Fundación CENIT para la Investigación en Neurociencias.
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Electrophysiological characterization of the microlesion effect after deep brain stimulation in patients with parkinson’s disease
Introduction: The microlesion effect after STN-DBS for Parkinson’s disease (PD) corresponds to a transient period of motor symptoms improvement after surgery, even with no stimulation being delivered.1,2 However, there are no studies probing the electrophysiological properties of this period. Recently available technology allowing continuous recording of neurophysiological activity from DBS electrodes3 provides an invaluable opportunity to interrogate and physiologically describe this period. The current work aims to characterize the electrophysiological signature of the microlesion effect in PD patients undergoing STN-DBS. Method: Using Brainsense technology, we continuously recorded local field potentials (LFPs) from 10 STN-DBS patients (20 hemispheres), from implantation day until stimulation was switched on, four weeks later. Data analysis was performed using the computational toolbox DBScope. Clinical data collected included PD phenotype, disease duration, age-of-onset and changes in MDS-UPDRS-III. Results: Median disease duration was 11 years; pre-operative MDS-UPDRS-III score was 54.4±13.3 and preoperative LEDD was 1291±418.6 mg. Study population clearly displayed microlesion effect, with significant reductions in MDS-UPDRS-III (-11.5 points, p=0.0098 med-off pre-op vs med-off/stim-off). Average frequency used for chronic sensing was 19.48Hz (beta). Temporal evolution of beta power displayed three clearly distinct periods: early dip, during which beta power decreases sharply to its minimum at 2.8±1.8 days; plateau, during which beta power remains low, lasting 12.7±2.3 days; late recovery, during which signal magnitude stars to slowly rebound. Temporal evolution of beta power was highly correlated across hemispheres. No correlation was found between duration of plateau and clinical variables. Discussion: Following the power of the beta-band, our study clearly demonstrates an electrophysiological microlesion effect, evolving throughout the first post operative weeks. This is the first electrophysiological description of the micro lesion effect with real-world, patient-derived data. The temporal window of signal rebound we describe may guide theoptimal timing for initiating neurostimulation after surgery. Conclusions: Further analysis on the electrophysiological signatures could potentially instruct adaptive-DBS protocols that entrain the STN physiology to recapitulate and prolong the beneficial clinical state that characterizes the microlesion period.
Derechos de autor 2025 Manuel J. Ferreira-Pinto, Carolina Soares, Pedro Melo, Ricardo Pérez, André Fernández, Carolina Silva, Manuel Rito, Paulo Aguiar, Clara Chamadoira https://creativecommons.org/licenses/by/4.0
Involvement Of Astrocytic Tetraploidy in Pharmacoresistant Epilepsy: Role Of The P2x7 Receptor
Introduction: Pharmacoresistant epilepsy is a significant public health problem, affecting 25–33% of patients who do not respond to current antiseizure treatments. This situation highlights the urgent need to identify new therapeutic targets. This study analyzes the role of astrocytic tetraploidy (a state with 4C DNA content) in pharmacoresistance, as well as its impact on neuronal excitability. Method: Two experimental models were used: (i) a human astrocyte cell line (CRL-8621), and (ii) primary astrocyte cultures obtained from resected cortical tissue of patients with pharmacoresistant epilepsy. The cell line was differentiated in serum-free conditions. Methodologies included immunocytochemistry to detect membrane receptors, and intracellular calcium homeostasis was assessed to evaluate receptor functionality. Results: Our results show that purinergic P2X7 receptors are present in the cell line and their expression significantly increased after serum deprivation and differentiation. The presence of tetraploid astrocytes was confirmed, and functionally, they responded to various stimuli such as KCl, bradykinin, ATP, and Bz-ATP. Similarly, primary astrocytes expressed P2X7 receptors and functionally responded to the agonists Bz-ATP and ATP. Discussion: Altogether, the results suggest that tetraploid astrocytes are functional and may be involved in pharmacoresistant epilepsy. These findings may contribute to identifying new therapeutic targets of interest in the future.
Derechos de autor 2025 Laura Cerrada Gálvez, Emma Downes, Marcos Navares-Gómez, María Francisca Cano Abad, Carmen Ovejero-Benito, Cristina Torres Diaz https://creativecommons.org/licenses/by/4.0
Study of the Mechanism of Tetraploid Astrocyte Generation in Pharmacoresistant Epilepsy using an In Vitro Model
Introduction: Epilepsy is a common chronic neurological disorder, and 25–33% of patients develop pharmacoresistant epilepsy (PRE). Its etiology remains unclear, highlighting the need to study molecular changes in the epileptogenic zone. Neurosurgical resections in PRE provide access to affected tissue, revealing an increased presence of tetraploid (4C) astrocytes. This study aims to explore their generation using an in vitro model to complement findings from neurosurgical samples Method: The human astrocyte cell line CRL8621 was differentiated under serum-free conditions. Astrocyte markers (NDRG2, GFAP, GLUT1, AQP4, TrkB, GABA BR2, EAAT2, GABA T3, and P2X7) were assessed by immunocytochemistry in both differentiated and undifferentiated cells. Differentiated cells were exposed to three types of stimuli: trophic factors (NGF, BDNF, and their combination), pro-epileptogenic agents (LPS, kainate, bicuculline), and antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam). Tetraploidy was quantified by flow cytometry following ethanol fixation and propidium iodide staining. Results: Differentiated astrocytes retained their astrocytic markers. Significant differences were observed in the total percentage of cells with and without serum (N=8), with a lower number in the latter; however, there was a significant increase in diploid astrocytes and a decrease in those greater than 4C. The optimal time for treatment and fixation was found to be 48–72 h and 96 h, respectively. Regarding the trophic factor treatments (N=4), no significant differences were found, although a slight decreasing trend in diploid astrocytes was observed in the presence of BDNF. Similarly, treatments with pro-epileptogenic factors and antiepileptic drugs (N=4) did not produce significant changes in the proportion of tetraploid cells. Discussion: A serum-free in vitro model using the CRL8621 astrocyte line was optimized to study tetraploid astrocytes in PRE. The results complement neurosurgical findings, showing that the tested stimuli did not alter the astrocyte cell cycle. Conclusions: Further studies, ideally alongside neurosurgical tissue, are needed to identify factors influencing tetraploidy. Therefore, further complementary studies using this model — ideally in conjunction with neurosurgically obtained tissue — are needed to identify stimuli that influence tetraploidy.
Derechos de autor 2025 Laura Cerrada-Galvez, Inés Gemperle Sánchez Del Corral, Rosario Lopez-Rodriguez, Maria F Cano-Abad, M Carmen Ovejero-Benito, Cristina Torres Diaz https://creativecommons.org/licenses/by/4.0
Deep-Brain Stimulation of the Human Nucleus Accumbens-Medial Septum Enhances Memory Formation
Introduction: Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Method: Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. Results: An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Discussion: Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.
Derechos de autor 2025 Svenja Treu, Juan Barcia, Cristina Torres Diaz, Anne Bierbrauer, Javier González Rosa, Cristina Nombela, José Pineda-Pardo, Daniel Torres https://creativecommons.org/licenses/by/4.0
Long-Term Clinical Changes of Nacc/Alic DBS in OCD Patients: Evolution of Improvement after more than three years of Continuous Stimulation
Introduction: Deep brain stimulation (DBS) is an effective therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). Previous studies have primarily documented efficacy in the short and medium-term, typically up to one year after DBS. However, its long-term effects remain unclear. Our aim is to identify and quantify improvement following long-term follow-up of more than three years, and assess changes—whether improvement or worsening—after the first postoperative year in OCD patients treated with DBS. Method: Thirty patients diagnosed with resistant-treatment OCD who underwent Nucleus Accumbens (NAcc) and Anterior Limb of the Internal Capsule (ALIC) DBS surgery at University Hospital Cologne were included in this study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was applied to assess clinical baseline and follow-up after surgery. A retrospective, observational study between 2004 and 2022 was conducted. Clinical outcomes were assessed at three time points: T0 (baseline), T1 (one year post-surgery), and T2 (three or more years post-surgery). Y-BOCS scores were used to classify severity into three categories: extreme (32–40 points), severe (24–31 points), and moderate (16–23 points). Patients with Y-BOCS score reductions above 35% were considered full responders. Scores and percentage reduction of symptoms were compared and analyzed using repeated measures ANOVA. All data were disclosed with informed consent of the patients. Results: Patients with extreme (n=15) and severe (n=12) symptoms demonstrated statistically significant improvements (p < 0.001) across all three follow-up time points. Full responders (n=22) showed significant differences between baseline (T0) and latest follow-up (T2), as well as between one year post-surgery (T1) and latest follow-up (T2) (p < 0.001). Among the three severity categories, 80%, 66.6%, and 77.7% of patients with extreme, severe, and moderate symptoms were full responders, respectively. A significant response across the three time points was not found among non-responders (p > 0.05). Among full responders at long-term follow-up (T2), 8 of 22 patients did not meet full-responder criteria after the first year of stimulation (T1). Discussion: Based on our findings, DBS for OCD showed meaningful, sustained benefits for patients with the most severe symptoms, as they consistently improved over time. Full responders experienced clear long-term gains, even if some did not show full improvement in earlier stages. The majority of patients across all symptom severity levels ultimately responded well to the intervention. In contrast, those who did not respond showed little to no measurable change throughout the follow-up period, highlighting a distinct difference in treatment outcomes between responders and non-responders. Conclusions: Results one year after surgery are not always definitive. Significant symptom reduction in the first year usually leads to greater reduction long-term. If this threshold is not reached, results are not necessarily final, but the chance of worsening after early improvement remains low.
Derechos de autor 2025 Fátima Ximena Cid Rodríguez, Rabea Schmahl, René Márquez Franco, Ursua Soriano, Antonio Marvin, Jens Kuhn, Veerle Visser-Vandewalle, Pablo Andrade https://creativecommons.org/licenses/by/4.0
Field H1 of Forel vs Subthalamic Nucleus Electrical Stimulation in Parkinson’s Disease: Long-Term Effects on Motor Symptoms and Quality of Life
Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) relieves motor symptoms, including levodopa- responsive gait disorders in Parkinson’s disease (PD). Traditionally, STN-DBS is not indicated to treat severe, clinically resistant axial symptoms. In this scenario, field H1 of Forel (FF) stimulation (FF-DBS) is likely a feasible option, given it improves motor symptoms, including freezing of gait (FOG), as shown by a short-term study. However, no data are available about the long-term effects of this therapy. Finally, no study has compared the long-term effects of FF and STN-DBS. Method: We analyzed 22 patients (10 FF-DBS, 12 STN-DBS). Motor symptoms (MDS-UPDRS III), gait (FOG score), cognition (Mattis DRS), quality of life (PDQ-39), and levodopa equivalent daily dose were assessed. Outcomes between FF-DBS and STN-DBS were compared. Results: The mean follow-up was 6.18 years (95% CI: 5.57–6.78). Compared with the preoperative period, patients with FF had an average reduction of 32.2% in the MDS-UPDRS III scores (p < 0.01), a decrease of 35.3% in the FOG scores (p < 0.01), and an improvement of 25.9% in the PDQ-39 (p < 0.01). There was a 7.5% decrease in cognition (p < 0.01). Levodopa equivalent dose (LED) was reduced by 26.3% (p < 0.01). The STN group had an average reduction of 39.4% in the MDS-UPDRS III scores (p < 0.01), a decrease of 23.7% in the FOG scores (p < 0.01), and an improvement of 33.2% in the PDQ-39 scores (p < 0.01). Cognition decreased by 1.6% (p < 0.01) and LED by 15.06% (p = 0.02). Patients with FF-DBS were older than those with STN-DBS at the time of surgery: 61.2 years and 55.7 years, respectively (p = 0.02), and had longer duration of disease (p = 0.02). Patients with FF-DBS had a greater reduction in FOG (p = 0.02) than did the STN group and presented with a greater decrease in cognition (p < 0.01) after five years. STN-DBS had a greater effect on quality of life. Discussion: Both FF-DBS and STN-DBS produced long-term motor improvements and enhanced quality of life in Parkinson's patients. While general motor benefits were similar, FF-DBS showed greater improvement in axial symptoms and FOG, but with a higher cognitive decline. FF-DBS also required lower energy, suggesting a potential economic advantage. Patient selection was key, with FF-DBS typically applied in more advanced cases. These findings support FF-DBS as an effective alternative for axial symptoms, but further randomized studies are needed. Conclusions: Both FF-DBS and STN-DBS relieved motor symptoms and improved quality of life over a long-term period. Patients with FF-DBS had a higher reduction in both FOG and in LED than did those with STN-DBS. These data support our hypothesis that FF-DBS is a safe and efficient option for treating motor symptoms in PD, including FOG in advanced stages.
Derechos de autor 2025 Fabio Luiz Francheschi Godinho, Ricardo Iglesio, Kaito Laube, Juliana Rodrigues https://creativecommons.org/licenses/by/4.0
TMS Multi-Target con Estimulación Tipo Theta Burst para Tinnitus Subjetivo Crónico: Estudio Piloto
Introducción: El tinnitus subjetivo crónico representa una condición compleja sin tratamientos de primera línea validados. Estudios previos han demostrado que la estimulación magnética transcraneal (TMS) puede modular la red cortical implicada en su génesis y mantenimiento.1 En ese contexto fue desarrollado un protocolo de estimulación multisitio con resultados positivos y significativos.2 Este estudio piloto evalúa la replicación de dicho protocolo con una modificación: el reemplazo de la estimulación prefrontal de 20 Hz por estimulación tipo intermittent theta burst stimulation (iTBS) de menor duración por la misma cantidad de pulsos, cambio validado en otras patologias.3,4 Método: Se trata de un estudio prospectivo con cinco pacientes con tinnitus crónico subjetivo, de entre 3 meses y 10 años de evolución. Los criterios de exclusión incluyeron tinnitus objetivo, comorbilidad psiquiátrica o neurológica inestable, y contraindicaciones para TMS. La intervención consistió en 10 sesiones sobre tres targets: cortezas temporoparietales bilaterales (1Hz) y corteza dorsolateral prefrontal izquierda (iTBS). Se utilizaron dos instrumentos validados para evaluar el impacto del tinnitus: el Tinnitus Handicap Inventory (THI)5 y el Cuestionario de Tinnitus (TQ). Las evaluaciones se realizaron en los días 1 (pretratamiento), 12 (post inmediato), 19 (7 días post) y 42 (30 días post). Resultados: El promedio del puntaje total en THI se redujo un 36% al día 12, 60% al día 19 y 48% al día 42. Las subescalas funcional, emocional y catastrófica reflejaron mejoras sostenidas, destacándose la reducción funcional (66%) al día 19. En el TQ, se observó disminución del porcentaje de tiempo consciente del tinnitus (37% al día 19 y 24% al día 42). La intensidad percibida del acúfeno disminuyó inicialmente, con cierta variabilidad individual al mes de seguimiento. El componente de irritabilidad mostró una reducción significativa al día 19 (45%). Discusión: Este estudio piloto sugiere que la aplicación de un protocolo de TMS multi-target con iTBS es factible y potencialmente eficaz para reducir el impacto percibido del tinnitus. La modificación del protocolo de Lehner permitió una reducción sustancial en los tiempos de estimulación sin evidenciar pérdida de eficacia. Las mejoras más marcadas se observaron en las dimensiones funcional y emocional del THI, así como en el porcentaje de tiempo de conciencia del ruido. La evolución clínica mostró una respuesta sostenida durante las primeras semanas y un patrón individual variable al mes, lo que sugiere la necesidad de protocolos de refuerzo o seguimiento más prolongado. La no inferioridad de iTBS frente a las frecuencias de estimulación de 10-20 Hz descrito en otras patologías también es consistente con nuestro estudio.3,4 Conclusiones: El protocolo de TMS multi-target con iTBS podría constituir una alternativa terapéutica prometedora y eficiente para el tinnitus subjetivo crónico. Se requieren estudios controlados y con mayor tamaño muestral para validar estos hallazgos preliminares y optimizar parámetros de estimulación
Derechos de autor 2025 Franco Moscovicz, Alejandro Idraste, Fabian Piedimonte https://creativecommons.org/licenses/by/4.0
Optimizing GPi-DBS Electrode Placement: Cortical Visual Evoked Potentials as a Reliable Adjunct to Microelectrode Recording for Delineating The Ventral Pallidal Border
Introduction: Precise electrode placement is critical for successful Globus Pallidus Internus (GPi) Deep Brain Stimulation (DBS). However, accurately identifying the ventral GPi border near the optic tract (OT) is challenging. Microelectrode recording (MER) signals can be ambiguous in dystonia,1 and the common use of general anesthesia precludes patient feedback for OT localization.2 We investigated direct OT stimulation with cortical visual evoked potential (CVEP) recording as an objective method to delineate the ventral GPi boundary and optimize electrode placement. Method: Nine patients undergoing bilateral GPi-DBS, some under general anesthesia, were prospectively studied with ethics approval. After initial MER-guided targeting, direct monopolar stimulation (3 Hz, 50μs, 1-3mA) was delivered near the OT to elicit CVEPs, recorded from occipital scalp electrodes. The N40-P70 wave amplitude was correlated with electrode position. The final DBS lead was placed immediately dorsal to the site of maximal CVEP amplitude. Post-operative MRI verified placement, and clinical outcomes were assessed at follow-up. Results: Direct OT stimulation consistently elicited N40-P70 CVEPs in all 18 hemispheres. Amplitudes increased significantly with proximity to the OT while latencies remained stable, providing a reliable localization signal. CVEP-guided placement resulted in optimal ventral GPi electrode locations confirmed on post-operative imaging. All patients had significant clinical improvement without visual side effects. Discussion: Our results show CVEP monitoring is a reliable method to define the ventral GPi limit, overcoming the limitations of subjective visual phosphenes, especially under general anesthesia where patient feedback is absent.1,3 This is particularly useful in dystonia surgery where MER signals can be ambiguous.2 Using an objective landmark for the OT enhances safety by preventing unwanted stimulation and avoiding deep exploratory penetrations, confirming its utility as a practical intraoperative tool.3 Conclusions: Direct OT stimulation with CVEP monitoring is a safe and effective adjunct to MER for GPi-DBS. It refines targeting by providing a clear physiological landmark for the ventral GPi border, improving accuracy and safety, especially for patients under general anesthesia.
Derechos de autor 2025 Ahmed Aly, Kaarthigan Masilamany, Surajit Basu https://creativecommons.org/licenses/by/4.0
DBS Data Synchronization with Continuous Audio and Video for Psychiatric Biomarker Discovery
Introduction: Obsessive-compulsive disorder (OCD) and treatment-resistant bipolar depression (TRBD) constitute some of the most challenging psychiatric disorders to treat, as a significant proportion of patients demonstrate poor response to pharmacological strategies alone or in combination with psychoterapeutic approaches.1 Deep brain stimulation (DBS) is a potential therapeutic approach for select patients, although clinical outcomes remain inconsistent. To improve treatment efficacy, clinicians need to gain a deeper understanding of the neural activity and associated behavioral outcomes that correspond to distinct symptom profiles.2 One of the major hurdles in any effort to explore psychiatric neuromodulation is linking neural activity with behavior that we can observe. Examining correlated neural features with behaviorial information may provide biomarkers to inform DBS interventions.3-5 The present study introduces a platform that integrates video, audio, and neural data, including theta-band activity and spectrograms, all collected during real-world observations. This multimodal data approach enables clinicians to examine brain-behavior interactions with greater precision, facilitating the development of more individualized and effective treatment strategies. Objective: to validate the feasibility of frame-level synchronization of video, audio, and intracranial signals during real-world clinical sessions, and to demonstrate its potential to support behavioral–neural biomarker discovery for DBS in OCD and TRBD. Method: We implemented a hardware-based synchronization system designed for ecological clinical environments, that interfaces continuous high-definition video (FLIR Blackfly), high-fidelity audio, and direct neural recordings from implanted DBS systems. As shown in Figure 1, an Arduino-based controller generates a unique frame ID that increases sequentially, embedding it into one audio channel. This ID serves as the common temporal reference to align video and audio streams, which are later synchronized with the neural recordings. This platform aligns: Patient video recordings capturing spontaneous behavior and facial expressions; multichannel audio, including verbal responses and environmental context; intracranial electrophysiology from DBS electrodes. By extracting the frame ID from the audio channel, all modalities can be aligned with sub-frame accuracy. This approach remains robust to environmental noise and brief recording outages, which is crucial for long term clinical monitoring. The resulting output is processed and merged into a single synchronized outputs for subsequent behavioral annotation and biomarker analysis. Results: In recent recordings, the system was able to constantly align continuous video, audio, and neural signals over sessions lasting up to one hour. The system was validated across five patient sessions, consistently achieving stable synchronization throughout. Each dataset contained thousands of precisely matched frame identifiers, ensuring accurate temporal alignment across all modalities. The resulting synchronized outputs (Figure 2) allowed frame-by-frame correlation of patient behavior, speech patterns, and neural activity without perceptible desynchronization. Across recordings, alignment error remained below one frame (<33 ms), ensuring temporal precision sufficient for clinical and research analysis. Discussion: Synchronizing neural, behavioral, and contextual data enables real-time insight into brain–behavior relationships, helping identify biomarkers that can inform and refine DBS treatment. In the future, synchronized datasets could be integrated into clinical routines by allowing physicians to review neural activity alongside patient behavior and speech, providing a more objective complement to standard psychiatric assessments. One limitation is that the system has so far been validated in sessions of about one hour, which is well suited for proof-of-concept but more challenging to scale to recordings lasting several hours. Conclusions: This platform demonstrates the feasibility of precise multimodal synchronization in DBS patients, providing clinicians with richer, time-aligned datasets to link behavior and neural activity. These results lay the groundwork for future clinical studies aimed at validating multimodal biomarkers and testing whether such data can inform adaptive DBS programming.
Derechos de autor 2025 Maria Agustina Amilibia, Raphael A. Bechtold, Yewen Zhou, Wayne K. Goodman, Sameer A. Sheth, Jeffrey Herron, Nicole R. Provenza https://creativecommons.org/licenses/by/4.0
Optimization of DBS Based on Structural Brain Connectivity in Pediatric and Adolescent Patients with Inherited and Adquired Dystonia
Introduction: Dystonia in pediatric patients presents unique clinical and neuroanatomical challenges, often involving complex network-level dysfunctions beyond isolated basal ganglia abnormalities.1 Understanding the structural connectivity differences between acquired and inherited dystonia is essential for the planning of DBS.2 This study investigates the structural connectivity in inherited and acquired dystonia using quantitative probabilistic tractography and connetomic measurements. Method: We analyzed 44 pediatric dystonic patients treated with DBS at the University Hospital Cologne. Individualized structural connectivity connectomes matrices were generated with a focus on key motor and associative regions. Comparative analyses were performed between patients with inherited versus acquired dystonia.3-10 Results: Preliminary findings reveal that a total of 44 patients were included and 13 presented complete pre- and 12-month postoperative BFMDRS scores. The mean preoperative BFMDRS score was 87.08, and the postoperative score was 73.17, yielding a mean clinical improvement of 13.92 points. Both Wilcoxon (p = 0.012) and paired t-test (p = 0.045) analyses confirmed a statistically significant reduction in dystonia severity following DBS. Subgroup analysis revealed that patients with inherited dystonia experienced the greatest median clinical improvement. Patients with acquired dystonia exhibited reduced streamline density and fractional anisotropy (FA) in thalamo-cortical and cerebello-thalamic pathways (Wilcoxon p < 0.05). Discussion: A statistically significant reduction in BFMDRS score, suggest efficacy of DBS in the GPi for improving motor symptoms. Especially in pediatric dystonia inherited dystonia compared to acquired dystonia. Conclusions: This study demonstrates that pediatric dystonia subtypes are associated with distinct patterns of structural brain network disruption. These findings highlight the importance of connectome-based characterization for phenotyping dystonia and optimizing patient-specific DBS targeting. Structural connectivity biomarkers may improve patient selection and predict therapeutic response in children undergoing DBS.
Derechos de autor 2025 Rene Marquez Franco, Ricardo Loucão, Lea Hagelschuer, Fátima Ximena Cid Rodríguez, Rabea Schmahl, Pablo Andrade, Veerle Visser-Vandewalle, Anne Koy https://creativecommons.org/licenses/by/4.0
Network-Specific Structural Connectivity of NAc/ALIC, MFB, and AMSTN in Treatment-Resistant OCD
Introduction: DBS has emerged as an effective therapy for treatment-resistant OCD (trOCD), yet clinical response remains heterogeneous. Increasing evidence suggests that therapeutic outcomes may depend on the specific functional networks modulated by each DBS target.1 This study investigates how distant structural connectivity of 3 commonly used targets: nucleus accumbens/anterior limb of the internal capsule (NAc/ALIC), medial forebrain bundle (MFB), and anteromedial subthalamic nucleus (amSTN), correspond to distinct functional sub-networks, potentially mediating domain-specific symptom relief.2-5 Method: We analyzed 22 trOCD patients who underwent DBS at the University Hospital Cologne. We performed patient-specific probabilistic tractography and connectomic analysis. Structural connectivity matrices were generated with validated atlases. Key metrics included streamline counts, fractional anisotropy (FA), and mean diffusivity (MD) across functionally defined a priori regions. Statistical comparisons between targets were conducted using Kruskal–Wallis and post hoc pairwise tests. Results: Distinct structural connectivity profiles were identified for each DBS target. NAc/ALIC showed strong connectivity with frontolimbic regions (medial OFC, insula, rACC; p < 0.001). MFB was linked to mesolimbic/reward-related areas (pallidum, rostral middle frontal cortex; p < 0.001). amSTN connected preferentially to motor-executive regions (precentral/paracentral gyri; p < 0.001). FA was significantly higher in amSTN and MFB pathways versus NAc/ALIC (p < 0.05). Discussion: Distinct structural connectivity profiles were observed for each DBS target. NAc/ALIC was associated with affective and cognitive control networks, MFB with reward-related circuits, and amSTN with motor-inhibitory pathways. These differences may explain the target-specific clinical responses observed in OCD and underscore the importance of network-informed DBS planning. Conclusions: Our results support the use of patient-specific tractography to guide DBS target selection based on symptom domains. This strategy may improve treatment outcomes by aligning stimulation sites with the neural circuits underlying individual clinical symptoms.
Derechos de autor 2025 Rene Marquez Franco, Luis Ruelas, Ricardo Loucao, Rabea Schmal, Fátima Ximena Cid Rodríguez, Petra Heiden, Veerle Visser-Vandewalle, Pablo Andrade https://creativecommons.org/licenses/by/4.0
Auditory Single-Unit Responses in the STN Provide Sensorimotor Context for Speech
Introduction: The basal ganglia (BG) have traditionally been implicated in movement initiation, selection, and termination,1 yet their contribution to speech motor control remains under-explored.2 Recent intraoperative recordings from our group and others demonstrate articulator-specific activation of the subthalamic nucleus (STN) during speech production.3-5 Furthermore, our recent work analyzing cortical evoked potential following STN stimulation suggests monosynaptic projections from the superior temporal gyrus (STG) to the STN,6 possibly via the hyperdirect pathway.7 We hypothesized that STN single units track auditory cues, providing a sensorimotor context relevant to speech. Method: We conducted intraoperative recordings in Parkinson’s disease (PD) patients undergoing awake DBS surgery. Two cohorts were studied: Cohort 1 (n = 25, 21M/4F, age 65.4±7.1y, IRB #20070368), from 2017–2019 at The University of Pittsburgh (Pitt); Cohort 2 (n = 23, 17M/6F, age 63±9y, IRB #2019P003841), from 2020–2024 at MGH. Microelectrode recordings (MER) captured STN single-unit activity during an auditory cue presentation and speech production tasks. Sorted units (Plexon) were required to meet well-defined stability and isolation criteria. Instantaneous firing rates (FR) were analyzed in 50ms windows, and significant deviations from baseline were detected (permutation test, p < 0.05, FDR corrected). Results: In Cohort 1, participants performed a consonant-vowel (CV) syllable triplet repetition task. As previously reported,4 STN units modulated their FR during speech production. Interestingly, we identified STN neurons whose FR were modulated by the auditory presentation of the CV syllables. A subset of these auditory-responsive units exhibited phoneme and sequence specificity; notably, all these auditory-feature-encoding units were activated during overt speech. In a second task (Cohort 2), subjects read aloud sentences in either a QUIET condition or in cocktail-party NOISE to elicit the Lombard effect (i.e., an involuntary increase in speech volume with background noise). We replicated in this data our findings of speech-related STN modulation. However, although the Lombard effect was robustly elicited, units that modulated their FR during speech did not show increased activity in the NOISE condition. Interestingly, we discovered an independent population of units whose FR scaled with background noise level. Discussion: These data position the STN as a site of integration of acoustic information into BG loops governing speech motor control. The fact that only production-active neurons encode phonemic and sequence details during listening suggests these units carry sensorimotor information relevant for fluent articulation. Noise-sensitive units may underlie automatic adjustments in vocal effort (Lombard effect). Given that DBS often enhances speech volume yet impairs articulation precision and intelligibility, we propose a model in which BG output modulates articulatory gain, prosody, and volume based on sensorimotor context. Conclusions: The STN is a key BG input nucleus whose neurons encode acoustic information regarding phones, sequence, and background noise. These auditory single-unit responses suggest the STN provides essential sensorimotor context for speech motor control.
Derechos de autor 2025 Alan Bush, Yanming Zhu |, Price Latane Bullock, Matteo Vissani, Robert Mark Richardson https://creativecommons.org/licenses/by/4.0
Evoked and Spontaneous High-Frequency Biomarkers for DBS Surgery And Programming
Introduction: Beta oscillations are established biomarkers of rigidity and bradykinesia in Parkinson’s disease (PD).1-3 However, beta-band exhibits considerable intra- and inter-patient variability and correlates only partially with the spectrum of PD motor signs or clinical response to DBS.4 More reproducible biomarkers, directly tied to network dynamics evoked by stimulation, are needed to optimize DBS frequency, waveform, and spatial patterns of stimulation for individual patients. Here we assess two promising biomarkers - high-frequency oscillations (HFOs)5-7 and evoked resonant neural activity (ERNA),8-12 examining their spatial distribution and co-occurrence in the BG. Method: We recorded intraoperative LFPs from directional DBS leads in PD patients undergoing awake surgery. Passive and evoked potentials (EP), obtained after bursts of DBS-like stimulation, were recorded. Cohort 1, 29 subjects (University of Pittsburgh, 2017–2019); Cohort 2, 9 subjects (MGH, 2024–2025). We quantified resting-state power spectra and evoked responses, focusing on HFOs and ERNA in STN, GPi, and VIM. Spectral features were extracted via a custom implementation of specparam,13,14 and EP were analyzed using MATLAB and R. Statistical analyses employed linear mixed-effects models. We developed two computational models of the BG network in Neuroblox: a biophysically detailed H-H model,15 and a Next-Generation Neural Mass Model. Results: Both HFOs and ERNA were robustly detected in both the STN and GPi, but not in VIM. Within the STN, HFOs exhibited clear spatial clustering, with “fast” (300-350 Hz) oscillations localized ventrally to “slow” (250-300 Hz) oscillations. ERNA waveforms, measured across the ventral and dorsal ring contacts, were remarkably consistent across stimulation from directional segments, suggesting activation of a single circuit. Failure to evoke ERNA in the STN was predictive of suboptimal lead placement. Our computational models of the STN and GP network successfully recapitulated spontaneous HFOs and the temporal dynamics of ERNA. Discussion: HFOs and ERNA coincide in frequency and co-occur across patients, suggesting a common neural substrate. We hypothesize that spontaneous HFOs reflect intrinsic STN<=>GP dynamics, which are enhanced by DBS, manifesting as ERNA. Our computational models capture these dynamics, providing mechanistic insight. Conclusions: High-frequency intraoperative biomarkers could help confirm accurate lead placement. ERNA can be recorded in less than 200ms per trial, enabling time-efficient exploration of stimulation parameters. Model-based fitting of patient-specific HFO and ERNA data can enable in-silico optimization of DBS settings, streamlining DBS programming.
Derechos de autor 2025 Alan Bush, Matteo Vissani, Abigail Zuckerman, German Abrebaya, Clemens Neudorfer, Helmut Strey, Lilianne Mujica-Parodi, Robert Mark Richardson https://creativecommons.org/licenses/by/4.0
Integrating Qualitative and Quantitative MRI Analysis for Optimizing DBS Candidate Selection in Patients with Disorders of Consciousness
Introduction:Disorders of consciousness (DoC) encompass a range of clinical conditions with overlapping presentations, often leading to diagnostic uncertainty. While advanced neuroimaging techniques such as fMRI and PET have improved diagnostic accuracy, they are not routinely accessible. This study aimed to evaluate whether conventional structural MRI, through combined qualitative and quantitative analysis, could support more accurate diagnosis and improve the selection of patients for deep brain stimulation (DBS) as a therapeutic intervention. Method: We prospectively included 50 patients with DoC who underwent standardized clinical, neurophysiological, and structural MRI evaluations. Patients were classified as DBS candidates or non-candidates based on predefined clinical and neurophysiological criteria. MRI was assessed qualitatively for features such as cortical atrophy, ventricular enlargement, leukoaraiosis, and thalamic or brainstem atrophy. Quantitative volumetric analysis was performed using the FreeSurfer pipeline. Results: Qualitative indicators, such as leukoaraiosis, corpus callosum lesions, thalamic and diffuse cortical atrophy, and ventricular enlargement, were significantly correlated with DBS candidacy. Quantitative analysis revealed that ventricular volume, total gray matter, CSF, supratentorial volume, and striatal volume were predictive of DBS eligibility. A combined model integrating both qualitative and quantitative parameters showed the highest predictive value. Discussion: These findings highlight the potential of widely available structural MRI to bridge the gap between complex neuroimaging and practical clinical decision-making. The integration of structural markers into routine diagnostic workflows may enhance personalized treatment strategies for patients with DoC. Conclusions: Structural MRI, when analyzed using a combined qualitative and quantitative approach, provides meaningful diagnostic and prognostic information in DoC. This method may enhance the selection of appropriate candidates for DBS and improve clinical outcomes. Future multicenter research is warranted to validate these findings and establish standardized imaging-based criteria.
Derechos de autor 2025 Marina Raguž, Petar Marčinković, Hana Chudy, Valentina Galkowski , Maja Majdak, Darko Chudy https://creativecommons.org/licenses/by/4.0
Beyond Motor Function: What is the Role of Quantitative Electroencephalography in the Assessment of Amyotrophic Lateral Sclerosis? – A Case Report
Introduction: Amyotrophic lateral sclerosis (ALS) primarily affects motor neurons, but evidence shows that its progression may also compromise non-motor networks, potentially leading to cognitive dysfunction. In this context, quantitative electroencephalography (qEEG) emerges as a valuable, non-invasive, and cost-effective method for analyzing brain oscillatory activity. By detecting subtle changes in cortical rhythms, qEEG aids in the early identification of neurophysiological alterations, supports monitoring of disease progression, and may guide therapeutic strategies. Clinical description: G.S.V.R.J., a 56-year-old male diagnosed with ALS in October 2024, exhibits early-stage motor difficulties with minimal impact on speech and mobility. In the following month, under neurological follow-up without pharmacological treatment, he participated in a pilot study at a university hospital, where qEEG was performed to assess brain activity and detect pathological changes. Recordings during resting state (eyes closed and open) revealed a global reduction in alpha band activity, with decreased spectral power (z-score < -2.3), hypoconnectivity (z-score < -1.96), and asymmetry in occipital alpha peak amplitude (z-score -1.11 left vs. 0.04 right), compared to normative values for sex and age. These findings may reflect cortical hyperexcitability due to an imbalance between inhibitory and excitatory circuits, as well as thalamo-cortical dysfunction. In addition, altered posterior dominant rhythm — relevant for cognitive assessment — and elevated frontal power ratios (theta/beta, theta/alpha, delta/alpha) were observed and associated with reduced attention and cognitive performance. Discussion: Although G.S.V.R.J. is currently asymptomatic regarding these issues, compensatory neural reorganization may keep the condition subclinical. Nonetheless, qEEG indicators should be considered in prognosis, especially given the risk of frontotemporal dementia. Non-invasive interventions such as neurofeedback and photobiomodulation, guided by qEEG, may help modulate affected frequencies and preserve quality of life. Conclusions: This case highlights qEEG’s potential to detect early neurophysiological changes in ALS. Identifying deviations in alpha activity and frontal power ratios can support broader clinical assessment, enable timely intervention, and ultimately contribute to improving personalized patient care.
Derechos de autor 2025 Clara Costa, Lucas Longo Ferreira, José Geraldo Medeiros Netto, Caio Araujo De Souza, Bruno Lima Pessôa https://creativecommons.org/licenses/by/4.0
Surgical Treatment of Holmes Tremor: Case Report, Systematic Review, and Meta-Analysis
Introduction: Holmes Tremor (HT) is a rare, disabling, low-frequency tremor tipically arising from brainstem lesions. Pharmacological treatments often fail to provide sufficient relief, leading to the use of surgical strategies, particularly deep brain stimulation (DBS) and lesional procedures. This study presents a rare case report of HT in a patient who underwent both lesional treatment and subsequent DBS. Additionally, it offers the first meta-analysis directly comparing the outcomes of lesional procedures and DBS in the treatment of HT. Clinical description: A systematic review and meta-analysis were conducted following PRISMA guidelines, encompassing studies from five databases published between 1992–2024. The primary outcome was tremor improvement following DBS or lesional surgery, assessed through standardized tremor rating scales such as the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore for tremor. Meta-regression was performed to explore potential predictors of surgical response. Additionally, we report a rare clinical case of HT managed with a staged approach—initial posterior subthalamic area (PSA) lesioning followed nine months later by DBS targeting both the ventral intermediate nucleus (VIM) and PSA -ilustratting decision-making, and surgical outcomes. Discussion: The meta-analysis included eleven studies comprising a total of 168 patients (96 DBS, 72 lesion), showing an overall tremor improvement of 70.2%. DBS resulted in a higher mean reduction in tremor scores (mean difference: 3.95 points; 95% CI: 2.91–5.00) compared to lesional procedures (mean difference: 2.18 points; 95% CI: 0.24–4.12), despite substantial heterogeneity. Older age and longer tremor duration were significantly associated with less favorable outcomes. The reported case illustrates the practical challenges in treating HT, showing that lesion alone yielded partial benefit, while subsequent DBS provided significant additional improvement. Conclusions: Both DBS and lesional procedures are effective treatment options for HT. DBS may offer superior tremor control, however lesional interventions remains an important option, especially in resource-limited settings or when DBS is not feasible. Our case underscores the utility of a personalized, stepwise surgical approach to optimize outcomes in this challenging conditions.
Derechos de autor 2025 Juliana Rodrigues, Kaito Carvalho Laube, Murillo Martins Correia, Emanuele Pires Canela Dos Santos, Rubens Cury, Reitor Carlos Gilberto Carlotti, Ricardo Ferrareto Iglesio, Fabio Luiz Francheschi Godinho https://creativecommons.org/licenses/by/4.0
The Role of Preoperative Immunonutritional Scores in Predicting Complications after STN DBS in Parkinson’s Disease
Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with systemic inflammation, immune dysregulation, and malnutrition, all of which may influence surgical outcomes. Subthalamic nucleus deep brain stimulation (STN DBS) is a widely used treatment for advanced PD, yet postoperative complications remain a concern. This study evaluates the predictive value of preoperative immunonutritional markers—including the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score, Aggregate Index of Systemic Inflammation (AISI), Lymphocyte-to-Monocyte Ratio (LMR), and Systemic Inflammatory Response Syndrome (SIRS) - for the risk of extracranial complications following STN DBS. Method: A retrospective cohort study was conducted on 138 PD patients who underwent STN DBS. Clinical and laboratory data were analyzed to assess the association between preoperative immunonutritional markers and postoperative complications, including infections, wound healing disturbances, and surgical revisions. Logistic regression and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive power of these markers. Results: SIRS emerged as the strongest predictor of complications (aOR = 6.99, 95% CI = 1.844–26.509), emphasizing the critical role of systemic inflammation in surgical outcomes. HALP, AISI, and LMR also demonstrated significant predictive potential, with HALP (AUC = 0.69) and LMR (AUC = 0.73) being the most robust predictors of complications. While albumin alone was not a significant predictor, it correlated with inflammatory markers and comorbidities, underscoring its role in broader risk assessments. Discussion: SIRS emerged as the strongest predictor of complications (aOR = 6.99, 95% CI = 1.844–26.509), emphasizing the critical role of systemic inflammation in surgical outcomes. HALP, AISI, and LMR also demonstrated significant predictive potential, with HALP (AUC = 0.69) and LMR (AUC = 0.73) being the most robust predictors of complications. While albumin alone was not a significant predictor, it correlated with inflammatory markers and comorbidities, underscoring its role in broader risk assessments. Conclusions:This study underscores the value of preoperative immunonutritional markers in predicting complications following STN DBS in PD patients. Incorporating these markers into clinical risk stratification may enhance preoperative planning and personalized postoperative care, ultimately improving surgical outcomes. These findings, while promising, warrant validation through prospective, multicenter studies to refine predictive models and enhance patient outcomes.
Derechos de autor 2025 Marina Raguz, Marko Tarle, Petar Marcinkovic, Darko Oreskovic, Vladimira Vuletic, Darko Chudy https://creativecommons.org/licenses/by/4.0
A Human Brain Network Linked to Restoration of Consciousness after Deep Brain Stimulation
Introduction: Disorders of consciousness (DoC) are characterized by severe impairments of arousal and awareness. Deep brain stimulation (DBS) has emerged as a potential therapeutic option, but clinical outcomes remain inconsistent. This variability may stem from differences in patient characteristics, electrode placement, or the specific brain networks modulated by stimulation. Method: We investigated 40 patients with DoC who underwent DBS targeting the centromedian-parafascicular complex of the thalamus. Structural MRI was used to assess gray matter preservation, and electrical field modeling was applied to estimate the spatial extent of stimulation. Connectivity analysis was conducted to identify common cortical targets associated with positive outcomes. Results: Improvements in consciousness were linked to greater gray matter preservation, particularly within the striatum. Electrical field modeling showed that the most effective stimulation sites extended ventrally below the centromedian nucleus, engaging the ventral tegmental tract—an important pathway connecting the brainstem and hypothalamus. Furthermore, these effective sites were functionally connected to a cortical network overlapping with regions previously associated with impaired consciousness in conditions like seizures and stroke. Discussion: These results suggest that targeting a subcortico-cortical network—including the ventral tegmental tract and its cortical projections—may be critical for therapeutic response in DBS for DoC. Incorporating imaging-based network analysis into DBS planning could enhance patient selection and electrode targeting, improving clinical outcomes. Conclusions:This study highlights the importance of structural integrity and precise network engagement in successful DBS treatment for DoC. The findings support future clinical trials and provide a framework for refining DBS targets based on a therapeutic consciousness network.
Derechos de autor 2025 Aaron E.L Warren, Marina Raguz, Darko Chudy, John D. Rolston https://creativecommons.org/licenses/by/4.0
Delayed Intracerebral Hemorrhage after DBS for Parkinson’s Disease
Introduction: Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for advanced Parkinson’s disease (PD), offering significant symptomatic relief. Although DBS is generally considered safe, it carries risks, including the potential for delayed complications such as intracerebral hemorrhage (ICH). Method: We present a rare case of a 67-year-old male with PD who developed delayed ICH after undergoing bilateral STN DBS. Initially, the patient showed no neurological deficits postoperatively, with imaging confirming correct lead placement and no signs of hemorrhage. However, on the second postoperative day, the patient developed sudden right-sided hemiparesis. A CT scan revealed ICH alongside the left lead. The hemorrhage was managed conservatively, and the patient underwent extensive physical therapy, leading to significant improvement. Over the next two weeks, the patient’s condition improved, and follow-up CT scans showed complete resolution of the ICH. At this point, the left lead stimulation was initiated, further improving the patient’s PD symptoms. This case illustrates the potential for delayed ICH following STN DBS, emphasizing the need for ongoing monitoring and individualized treatment strategies. Discussion: This case highlights that even in the absence of immediate postoperative abnormalities, delayed hemorrhagic events can occur, underscoring the dynamic nature of post-DBS recovery. Identifying risk factors for delayed ICH and establishing standardized monitoring protocols may help mitigate such events and guide early intervention. Conclusions:This case underscores the importance of vigilant postoperative monitoring and individualized management strategies in STN DBS patients. Early detection and appropriate management of complications such as ICH are crucial for minimizing risks and ensuring optimal patient outcomes. The potential for delayed complications highlights the need for continuous follow-up, even in the absence of immediate postoperative issues.
Derechos de autor 2025 Hana Chudy, Marina Raguz, Petar Marcinkovic, Valentino Racki, Elisa Papic, Mario Hero, Vladimira Vuletic, Darko Chudy https://creativecommons.org/licenses/by/4.0
From Diagnosis to Relief: Multidisciplinary Protocol and Neuromodulation for Refractory Facial Pain
Introduction:Refractory facial pain (RFP) is a complex clinical entity often resistant to standard pharmacological and surgical treatments. Due to its multifactorial etiology and overlapping symptomatology with dental, neurological, ENT, and musculoskeletal disorders, accurate diagnosis and effective treatment remain challenging. To address this, we implemented a structured multidisciplinary team (MDT) approach aimed at improving diagnostic accuracy and optimizing therapeutic outcomes. Method: A comprehensive MDT protocol was developed and implemented at Dubrava University Hospital. The MDT includes experts from neurosurgery, neurology, psychiatry, otorhinolaryngology, maxillofacial and oral surgery, anesthesiology, radiology, and physical medicine. The protocol is organized into three escalating treatment lines: (1) Diagnostic clarification and pharmacological therapy, (2) Interventional pain management, and (3) Advanced neuromodulatory and surgical options. Patients are referred via a centralized MDT email system and undergo coordinated assessment and individualized treatment planning. Regular follow-ups are conducted to evaluate clinical response and determine progression through therapeutic lines. Results: To date, a number of patients with refractory facial pain have completed the MDT evaluation and treatment process. Diagnostic precision was significantly improved, enabling the exclusion of secondary causes and appropriate patient stratification. Several patients progressed to the third treatment line and were treated with motor cortex stimulation (MCS). These patients demonstrated marked reduction in pain intensity and significant improvements in quality of life, with minimal adverse effects. Clinical success was most evident in cases with confirmed neuropathic pain phenotypes.Discussion: These findings suggest that a structured MDT framework not only enhances diagnostic clarity but also ensures timely access to advanced treatments for appropriate candidates. The collaborative decision-making process promotes individualized care and may serve as a model for managing other complex chronic pain conditions. Conclusions:The structured MDT approach offers a systematic and effective framework for managing refractory facial pain. It facilitates accurate diagnosis, reduces unnecessary diagnostics, and enables timely initiation of advanced treatments, such as MCS, for carefully selected patients. Our early clinical experience supports the continued development and potential expansion of this protocol as a model for comprehensive facial pain management.
Derechos de autor 2025 Marina Raguz, Marko Tarle, Koraljka Hat, Petar Marcinkovic, Igor Cvrljevic https://creativecommons.org/licenses/by/4.0
Stimulating Recovery: Two SCI Stories Redefining the Limits of SCS
Introduction: Spinal cord injury (SCI) remains a devastating condition with limited options for functional recovery and chronic pain management. Traditionally, spinal cord stimulation (SCS) has been reserved for refractory neuropathic pain; however, emerging evidence suggests its potential in promoting motor recovery and autonomic function in SCI patients. This report presents two illustrative cases exploring both conventional and novel indications for SCS. Method: We describe two patients with SCI who underwent SCS implantation. The first, a middle-aged male with post-traumatic SCI due to a gunshot wound, presented with intractable neuropathic pain. The second, a young adult female with complete paraplegia following a motor vehicle accident, was selected for neuromodulation targeting motor and sensory improvement. Both patients underwent comprehensive clinical evaluation, imaging, psychological assessment, and intraoperative neuromodulation testing. Outcomes were assessed using pain scales, spasticity grading, and functional mobility indices. Discussion: The first patient experienced a significant reduction in pain intensity (VAS from 9 to 3) and decreased reliance on opioids within the first three months post-SCS. The second patient, despite complete motor paraplegia (AIS A), demonstrated unexpected early gains in trunk control, reduced spasticity, and subjective improvement within three months of stimulation onset. No device-related complications were observed. Conclusions: These two cases underscore the expanding therapeutic potential of SCS in SCI. While pain relief remains a well-established indication, neuromodulation may potentially offer functional benefits even in complete SCI. These observations advocate for broader research into the neuroplastic and rehabilitative effects of SCS and encourage reconsideration of candidacy criteria in the SCI population.
Derechos de autor 2025 Andrea Blažević, Darko Chudy, Raguz, Marina https://creativecommons.org/licenses/by/4.0
Hacia la Protocolización del TMS para Dolor Crónico Central. Revision Bibliográfica y Propuesta de Algoritmo Clínico.
Introducción: El dolor neuropático representa uno de los mayores desafíos clínicos en el campo del dolor crónico con elevada prevalencia y baja respuesta a tratamientos farmacológicos convencionales. La estimulación magnética transcraneal repetitiva (rTMS, por sus siglas en inglés) ha surgido como una estrategia de neuromodulación no invasiva con creciente evidencia de eficacia en aliviar la sintomatología. En este trabajo se revisa el estado del arte en TMS para dolor crónico, se destacan los principales aportes del Dr. Jean-Pascal Lefaucheur y se propone un algoritmo clínico basado en la evidencia para guiar su implementación en la práctica médica. Método: Se realizó una revisión crítica de la literatura científica actualizada, con énfasis en ensayos clínicos, metaanálisis y consensos internacionales sobre el uso de rTMS en dolor. Se identificaron variables predictoras de respuesta terapéutica y se sistematizaron los parámetros de estimulación más efectivos. A partir de esta revisión, se elaboró un algoritmo clínico integrador (“TMS Pain-RoadMap”) que incorpora predictores clínicos y propone un flujo lógico de evaluación, aplicación y seguimiento del tratamiento. Resultados: La estimulación de M1 y de corteza pre frontal con rTMS de alta frecuencia ha mostrado eficacia significativa en dolor neuropático con componente central, fibromialgia y otros síndromes de dolor crónico, alcanzando niveles de recomendación A según guías internacionales. Estudios recientes demostraron que dos variables negativas: depresion mayor y localización distal del dolor en extremidades inferiores; y una variable positiva: magnificación del dolor (Escala PCS), pueden predecir la respuesta al tratamiento con alta sensibilidad (85%) y especificidad (84%). El algoritmo propuesto permite seleccionar pacientes candidatos, definir fases de inducción, evaluar respuesta y establecer estrategias de mantenimiento o modificación del protocolo según la evolución clínica. Discusión: El desarrollo de modelos clínicos basados en predictores de respuesta representa un avance hacia la personalización del tratamiento con TMS en dolor crónico. El algoritmo presentado se basa en bibliografía robusta y facilita una toma de decisiones clínica más racional y eficaz. Conclusiones: El TMS es una herramienta eficaz y segura para el tratamiento de algunos sub tipos de dolor cronico. Su protocolización, basada en evidencia y variables predictivas, puede mejorar significativamente la selección de pacientes y los resultados terapéuticos. El “TMS Pain-RoadMap” constituye una propuesta concreta para avanzar en una medicina de precisión en dolor crónico.
Derechos de autor 2025 Franco Moscovicz, Carolina Moltedo, Fabian Piedimonte https://creativecommons.org/licenses/by/4.0
Connectivity Analysis of Brain Circuits Modulated by Electrical Stimulation of the Ventral Capsule and Ventral Striatum in Patients with Obsessive-Compulsive Disorder
Introduction: Deep brain stimulation (DBS) targeting the ventral capsule/ventral striatum (VC/VS) is an emerging treatment for treatment-resistant obsessive-compulsive disorder (OCD). However, approximately 40% of patients fail to achieve significant symptom relief. Variability in clinical outcomes may reflect individual diferences in the modulation of neural circuits. This study investigated the neural circuits modulated by VC/VS stimulation and their relatioship to treatment response. Clinical description: Nine patients with treatment-resistant OCD underwent VC/VS DBS at the University of São Paulo between 2016 and 2024. Symptom severity was assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) preoperatively and one year postoperatively. Lead localization was reconstructed using LeadDBS 3.0, by co-registering postoperative CT scans with preoperative MRIs in MNI space. The volume of tissue activated (VTA) was estimated for each patient. Imaging preprocessing was performed using FSL; T1-weighted images were co-registered with diffusion tensor imaging (DTI), and probabilistic tractography was performed using each VTA as a seed. Cortical regions were labeled using the Automated Anatomical Labeling 3 atlas. Results: Five patients were responders, and four were non-responders after one year. Among responders, right-sided VTAs were located more laterally within the anterior limb of the internal capsule (ALIC). Tractography revealed that stimulation consistently engaged fibers projecting to the medial orbitofrontal cortex (mOFC), superior and middle occipital cortices, and anterior thalamic nuclei. Figura 1: VTA-activated tract reconstructions to cortical targets using FSL tractography. Left in red, right in blue. Discussion: VC/VS DBS modulates a distributed network implicated in the pathophysiology of OCD. Notably, enhanced connectivity to the mOFC—a region associated with salience processing and goal-directed decision-making—was observed in all patients. Connectivity with occipital areas may reflect broader engagement of sensory-associative networks, though the functional relevance of this finding remains unclear. Conclusions: Lateral stimulation within the ALIC is associated with improved clinical response and involved fibers projecting to the mOFC, anterior thalamus and occipital cortex. These findings support the strategy of targeting connectivity informed networks, rather than anatomical sites, to optimize DBS outcomes in OCD.
Derechos de autor 2025 Kaito Laube, Ricardo Iglesio, Paula Ricci Arantes, Euripedes Miguel, Marcelo Hoexter, Carlotti Junior Gilberto, Antonio Carlos, Lopes Carlos, Fabio Godinho https://creativecommons.org/licenses/by/4.0
Pallidotomy for Post-Stroke Hemidystonia with Tongue Myorhythmia: A Potential Therapeutic Approach
Introduction: Myorhythmia is a rare hyperkinetic disorder characterized by slow (1–4 Hz), rhythmic involuntary movements, often linked to brainstem lesions such as pontine infarcts.¹ Post-stroke pontine damage can cause hemidystonia and tongue myorhythmia, both typically resistant to medical therapy.¹,² We report a case where stereotactic pallidotomy, performed primarily for hemidystonia, led to significant improvement of coexisting myorhythmia, suggesting a potential therapeutic benefit. Clinical description: A 62-year-old woman developed progressive right hemidystonia and complex myorhythmia four months after sustaining a left pontomesencephalic ischemic stroke. Neurological examination revealed right-sided hemiparesis, spasticity, severe dysarthria, and rhythmic involuntary movements (~3 Hz) involving the limbs, tongue, and soft palate. Given refractoriness to pharmacological treatment, the patient underwent stereotactic pallidotomy targeting the internal globus pallidus (GPi). Intraoperatively, immediate suppression of myorhythmia was observed, with sustained improvement at three months post-procedure, including a marked visual reduction of tongue tremor and only mild residual palatal involvement, giving an enhanced gait and overall quality of life. Discussion: Discussion: Differentiation of myorhythmia from Parkinsonian or dystonic tremor, and myokymia is crucial and relies on clinical evaluation supported by electromyography and imaging.¹ Pontine infarcts are a well-recognized cause of myorhythmia, typically showing limited response to pharmacological therapies. In this case, stereotactic pallidotomy was primarily performed to address hemidystonia³ but unexpectedly improved coexisting myorhythmia, which was not previously described in the literature. Tremor analysis of the limbs, using the iPhone StudyMyTremor application, revealed a significant postoperative reduction in amplitude (from 11.37 mm to 1.94 mm), power (from 116.26 mW to 24.28 mW), and synchronization (from 194.01 to 3.18), with minimal change in frequency (3.03 Hz preoperatively and 3.73 Hz postoperatively), resulting in substantial functional improvement to the patient. Conclusions: This case underscores pallidotomy’s potential as a therapeutic strategy for refractory post-stroke hyperkinetic movement disorders, particularly when myorhythmia coexists with dystonia, with significant reductions in tremor amplitude, power, and synchronization, contributing valuable insight to clinical practice.
Derechos de autor 2025 Caio Araujo De Souza, João Carlos Amorelli B. A. Figueira, Fernanda Lopes De Paula, Lizen Clare André Moreira, Laís Dantas, Maria Clara Amadeu, Rosana Siqueira Brown, Bruno Lima Pessôa https://creativecommons.org/licenses/by/4.0
Selective Dorsal Rhizotomy for the Treatment of Spasticity Associated with HIV Encephalopathy (Hive) in 15 Pediatric Patients
Introduction: Vertical transmission of HIV has decreased in developed countries but remains prevalent in developing nations. HIV-associated encephalopathy (HIVE) leads to severe neurological sequelae, including spasticity. Selective dorsal rhizotomy (SDR) is known to reduce spasticity and improve motor function in children with cerebral palsy, but its use in HIVE has not been well studied. This is the first study to evaluate the outcomes of SDR in children and adolescents with HIVE MATERIALS AND METHODS. A retrospective cohort study was conducted at two specialized centers, including 15 pediatric patients with progressive subacute HIV-associated encephalopathy and spasticity, who underwent selective dorsal rhizotomy between 2010 and 2022. The variables evaluated included the Gross Motor Function Classification System (GMFCS), the Functional Mobility Scale (FMS), the Gillette Functional Assessment Questionnaire (FAQ), and the Ashworth Scale (EAM) to measure muscle tone. Method: 1- Operative Technique Selective dorsal rhizotomy (SDR) was performed under general anesthesia with the patient in the prone position. Subdermal electrodes were placed in specific muscles for intraoperative mapping. A laminotomy was carried out from L2 to S1, and after opening the dura mater, the dorsal roots from L2 to S1 were identified. Radicles with the lowest stimulation threshold were selected for rhizotomy. In most cases, 25% of the root was sectioned, guided by neurophysiological monitoring. The laminae were fixed using titanium bone plates. Patients remained on bed rest for two days before beginning mobilization. All patients underwent intensive motor rehabilitation following SDR. 2- Functional Outcomes The mean age was 11.8 ± 3.12 years. At the 24-month follow-up after SDR, a significant reduction in spasticity was observed across all muscle groups, as measured by the Modified Ashworth Scale (MAS) (p < 0.001). Most children (94%) maintained the same GMFCS level at 24 months postoperatively, while 6% improved by one level. No significant long-term differences were found in the Functional Mobility Scale (FMS). General ambulatory function, as measured by the FAQ, showed a statistically significant improvement in many participants. Discussion: The results demonstrate a significant reduction in spasticity and improvements in functional capacity, suggesting that selective dorsal rhizotomy (SDR) is a viable treatment option for managing spasticity in this patient population. When combined with an intensive physiotherapy program, SDR can lead to substantial improvements in the quality of life of patients with HIV-related encephalopathy. Conclusions: Selective dorsal rhizotomy (SDR) is effective in reducing spasticity and improving motor function in children with HIV-related encephalopathy, offering a promising treatment option to enhance their quality of life. Long-term studies with larger patient cohorts are needed to confirm these findings.
Derechos de autor 2025 Facundo Villamil, Ricardo Nazar, Fernando Ford, Clara Duffy, Beatriz Mantese https://creativecommons.org/licenses/by/4.0
Neuromodulation for Drug-Resistant Chronic Cluster Headache: Efficacy and Safety in a Series of Four Cases
Introduction: Chronic cluster headache (CCH) is a severely disabling form of trigeminal autonomic cephalalgia, often refractory to pharmacological treatment. In recent years, peripheral neuromodulation through occipital (ONS) and supraorbital (SON) nerve stimulation has emerged as a promising alternative for selected drug-resistant patients. Method: To describe the clinical outcomes of patients with refractory cluster headache treated with occipital nerve stimulation (ONS), and to evaluate the potential benefits of combining supraorbital nerve stimulation (SONS) in selected cases. Discussion: These findings are consistent with previous reports supporting the efficacy of peripheral neuromodulation for refractory CCH. The high responder rate and absence of adverse events reinforce the role of ONS and SON as safe and effective options in carefully selected cases. Despite the limited sample size, the sustained improvement observed justifies further investigation into optimization parameters and predictors of response. Conclusions: Occipital and supraorbital nerve stimulation proved to be a safe and effective treatment for refractory chronic cluster headache, resulting in a significant reduction in attack frequency and high patient adherence.
Derechos de autor 2025 Facundo Villamil, Enzo StefanoParisi, Maximiliano Nuñez, Jorge Mandolesi, Oscar Stella https://creativecommons.org/licenses/by/4.0
Assessing Basal Ganglia Circuitry Function in Parkinson’s Disease: Phenotypic and Movement-Dependent Periodic and Aperiodic Activity in Human STN-LFP Recordings
Introduction: Parkinson’s disease (PD) presents distinct motor phenotypes—tremor-dominant (TD) and postural instability/gait disorder (PIGD)—which differ in prognosis and response to deep brain stimulation (DBS).¹ Identifying electrophysiological markers reflecting these phenotypes and motor states is essential for optimizing adaptive DBS.² Traditional analyses of subthalamic nucleus local field potentials (STN-LFPs) often conflate oscillatory (periodic) and broadband (aperiodic) activity, potentially masking key neural dynamics.³ This study investigates whether parameterizing STN-LFPs into periodic and aperiodic components enhances detection of phenotype- and movement-specific features in PD. Method: STN-LFPs were recorded intraoperatively from 35 hemispheres in 22 PD patients (15 TD, 20 PIGD) during rest and voluntary upper-limb movement. Power spectral density was used to isolate periodic (alpha, low beta, high beta) and aperiodic (offset, decay exponent, knee frequency) components (Figure 1). Periodic power was analyzed with and without aperiodic adjustment to improve oscillatory signal precision. Mixed-design ANOVA assessed effects of phenotype and motor state. Logistic regression tested phenotype classification using spectral features. Correlations with UPDRS-III subscores were explored. Result: TD patients showed movement-related suppression in adjusted low beta power (p = 0.003), while PIGD showed elevated high beta power at rest (p = 0.056). Aperiodic parameters significantly differentiated TD and PIGD during movement. In PIGD, aperiodic features also separated rest from movement. Rigidity was correlated with periodic and aperiodic features (e.g., high beta, þ = 0.601). A logistic model combining adjusted low and high beta with exponent decay achieved strong phenotype classification (AUC = 0.83) (red area in Figure 2). Discussion: Decomposing STN-LFPs into periodic and aperiodic components revealed phenotype- and movement-specific patterns in PD. Adjusting for aperiodic activity enhanced interpretation of canonical power bands, revealing phenotype–condition interactions, particularly in low beta. The spectral exponent and knee frequency showed distinct responses to movement: flatter exponents (greater excitation) in TD and steeper ones (enhanced inhibition) in PIGD. Combined periodic and aperiodic metrics outperformed periodic-only models in phenotype and movement condition classification, underscoring the clinical value of aperiodic features. Conclusions: Spectral decomposition of STN-LFPs improves detection of phenotype- and movement-specific neural dynamics in PD. These findings support incorporating spectral parameterization into adaptive DBS strategies.
Derechos de autor 2025 Fabio Godinho, Luiz Ricardo Trajano Da Silva, Carlos Carlotti, Eberbal Figueiredo, Sheila Guimarães Rocha, Diogo Soriano https://creativecommons.org/licenses/by/4.0
Evaluation of the Long-Term Response and Pain-Free Survival Rate in Refractory Trigeminal Neuralgia after Cyberknife Radiosurgery: A Retrospective Analysis of a Case Series.
Introduction: Cyberknife® radiosurgery (CK-SRS) represents an effective treatment modality for refractory trigeminal neuralgia (TN) in patients who are suitable candidates for the procedure. The aim of this work is to report the long-term response and pain/numbness free survival rate in patients with refractory TN at 1 month (n=23), 1 year (n=20) and 2 years (n=10) post-treatment, as well as possible complications. Method: This study analyzed 23 patients with refractory TN treated with CK-SRS at our clinic from September 2022 to May 2025. They received a single dose of 90 Gy with CK, except for one case of re-irradiation at 75 Gy. Baseline facial pain and at 7, 15 and 30 days, as well as 1 to 2 years post-treatment was evaluated using the Visual Analog Scale, while the BNI Pain Intensity and Facial Numbness Score were obtained before treatment and at latest follow-up for patient outcomes. Other toxicities besides facial numbness were assessed. Result: The mean follow-up of this cohort was 18 months. The change in BNI was toward pain reduction in 21 of the 23 patients (91.3%), from BNI I to II with fewer cases toward IIIa or IIIb, while one remained the same (IV) and one worsened (IV to V). Initially patients reported severe pain with a mean VAS score of 10 (range 8-10). Early responses after SRS (7-30 days) showed a significant reduction in pain (p<0.001), as most patients' scores dropped to 4-6. At one year, these results were sustained (p=0.065). Patients with a 2-year follow-up maintained pain reduction from year 1 (p=0.337), with scores predominantly 0-1, except for patients 1 and 2. The most common side effect was non-bothersome facial hypoesthesia, emerging early and persisting in 13 patients (56.5%). Pain-free survival rate showed at 6 months 87% of patients were pain-free (BNI I-II), and the estimates at 12 and 24 months were 68% and 60%, respectively. Five people had previously undergone other non-pharmacological treatment; their response was parallel to those who received SRS as a first option (p=0.921). Discussion: Immediate and successful pain relief has been reported at a median time of 7 to 30 days, others like Yomo et al. have reported at a median follow-up of 50 months an FPS score of 1.1 (SD 1.6) (P < 0.001). As a limitation, we highlight the scarce availability of articles on long-term pain response at 1 or 2+ years in refractory TN treated with CK-SRS. Conclusions:CyberKnife® radiosurgery proved to be a minimally invasive and effective treatment alternative with relatively rapid pain relief for patients with refractory TN, as evidenced by significant early reduction in VAS and BNI scores and sustained outcomes at 1 and 2 years.
Derechos de autor 2025 Ambar Perez Fernandez, Yeimy M Lebron Sanchez https://creativecommons.org/licenses/by/4.0
Comparing GPi Lesioning and DBS in Parkinson’s: Functional and QOL Impact
Introduction: Lesion-based procedures for Parkinson’s disease (PD) have resurged as viable alternatives to deep brain stimulation (DBS), particularly where access to neuromodulation is limited¹. This study compares GPi-DBS and GPi-RF regarding functional outcomes and quality of life (QoL), also evaluating cognitive safety. Method: A retrospective cohort of 102 patients with idiopathic Parkinson’s disease, treated between 2018 and 2022 at a single center, compared outcomes of GPi-DBS (n=46) and GPi-RF lesioning (n=54) with 18-month follow-up. Evaluations included the PDQ-39 and MoCA. Two RF patients could not attend final follow-up but were contacted remotely. The study was approved by the institutional ethics committee. Result: Both groups showed significant improvements in motor function (UPDRS-III) and overall quality of life (PDQ-39 total) at 18 months. GPi-DBS was associated with greater gains in the mobility domain, while GPi-RF yielded superior improvements in bodily discomfort and activities of daily living.Emotional well-being and cognitive QoL domains improved similarly in both groups, with no significant differences. Cognitive performance remained stable over time in both cohorts. Levodopa equivalent daily dose (LEDD) increased in the DBS group but remained unchanged in the RF group. Discussion: Both GPi-DBS and GPi-RF effectively improve functional outcomes and quality of life in Parkinson’s disease, with distinct profiles. DBS yielded greater gains in mobility, whereas RF lesioning resulted in superior outcomes in discomfort relief and independence in daily activities. The nature of RF lesioning may contribute to earlier clinical effects, particularly in axial symptoms, possibly due to immediate disruption of abnormal pallidal output. In this cohort, DBS did not demonstrate superiority over lesioning in cognition or quality of life domains. The absence of cognitive or emotional deterioration after lesioning, combined with its functional efficacy, highlights lesioning as a treatment strategy that merits consideration within a broader spectrum of care. Conclusions: This study supports the role of both GPi-DBS and GPi-RF as effective interventions for Parkinson’s disease, each with particular clinical strengths. Lesioning, in particular, may be considered a valid therapeutic option within a comprehensive care strategy. Further prospective studies are warranted to optimize patient selection, refine long-term expectations, and advance the technical precision of both procedures.
Derechos de autor 2025 Joao Paulo Brainer, Maria Eduarda Cavalcanti, Pedro Thadeu Brainer, Alessandra Mertens Brainer, Magela Magela, Mirian Carvalho Soares, Brainer Paulo Thadeu https://creativecommons.org/licenses/by/4.0
Gasserian Ganglion Stimulation in Refractory Trigeminal Neuralgia: A Single-Center Case Series
Introduction:Trigeminal neuralgia (TN) is a severe neurological condition characterized by intense, paroxysmal, and disabling facial pain. Management can be especially challenging in patients refractory to pharmacological and surgical therapies. Gasserian ganglion stimulation (GGS) has emerged as a potential alternative in such cases; however, its use remains limited and underrepresented in current literature. Objective. To evaluate the clinical efficacy, pain evolution, and impact on quality of life in a cohort of patients with refractory TN treated with Gasserian ganglion stimulation at our institution. Method:We conducted a retrospective observational study of 10 adult patients with refractory TN who underwent GGS between January 2008 and May 2025. Demographic data, clinical history, TN subtype (according to Burchiel’s classification), affected territories, trigger points, and prior treatments were analyzed. Pain intensity was assessed using the Visual Analog Scale (VAS) and Barrow Neurological Institute (BNI) pain scale preoperatively, immediately postoperatively, at six months, and at final follow-up. Quality of life (QoL) and reduction in medication use were also evaluated. A female predominance (73%) was observed, with a mean age at diagnosis of 50 years. Based on Burchiel’s classification, 50% had type I TN, and 20% had deafferentation pain. Prior interventions were reported in 72% (n=8), predominantly radiofrequency thermocoagulation. Preoperatively, 60% (n=6) experienced severe pain (VAS 8–10), 30% (n=3) moderate pain (VAS 4–7), and 10% (n=1) mild pain (VAS 1–3). Immediately postoperatively, 50% (n=5) reported moderate pain, 30% (n=3) severe, and 20% (n=2) mild. A significant reduction in pain was observed (p=0.002). On the BNI scale, 60% (n=6) had a score of 4 preoperatively; at six months, 80% (n=8) achieved BNI ≤3b. At final follow-up, 50% (n=5) reached BNI 2, 30% (n=3) BNI 3b, and 20% (n=2) BNI 1 (p=0.0018). Following surgery, 90% reported fair to excellent QoL. At six months, 82% had reduced medication use, with only 27% continuing pharmacological treatment at final evaluation. Discussion: GGS appears to be a viable alternative for patients with refractory TN, especially those with multiple failed interventions. Our results align with international findings regarding procedural safety, sustained pain relief, and medication reduction. A trend was observed between the number of trigger points and pain severity, suggesting possible predictive factors, though statistical significance was not achieved in this limited sample. Conclusions:Gasserian ganglion stimulation is a safe and effective option for treating refractory TN, providing significant pain relief, high clinical response, and sustained improvements in quality of life. These findings support its inclusion as a therapeutic alternative in complex, recurrent, or treatment-resistant cases.
Derechos de autor 2025 Facundo Villamil, Matias Solari, Maximiliano Nuñez, Oscar Stella https://creativecommons.org/licenses/by/4.0
Relationship Between MRI-Based Stereotactic Planning and Functional Localization via Microelectrode Recording in Subthalamic Nucleus Deep Brain Stimulation: A Case Series.
Introduction: Precise anatomical localization of the surgical target is essential in minimally invasive procedures such as subthalamic nucleus deep brain stimulation (STN-DBS). Correlating the stereotactic coordinates from preoperative MRI-based planning with intraoperative microelectrode recording (MER) findings helps achieve optimal functional localization without compromising clinical outcomes. This study not only reinforces existing scientific evidence but also aims to provide practical guidance for emerging surgical teams with limited resources or early-stage experience. Method: A retrospective observational study was conducted on patients with advanced Parkinson’s disease who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between January and June 2025. Six consecutive patients were included, all of whom had undergone preoperative MRI-based stereotactic planning and intraoperative microelectrode recording (MER). Result: The mean follow-up of this cohort was 18 months. The change in BNI was toward pain reduction in 21 of the 23 patients (91.3%), from BNI I to II with fewer cases toward IIIa or IIIb, while one remained the same (IV) and one worsened (IV to V). Initially patients reported severe pain with a mean VAS score of 10 (range 8-10). Early responses after SRS (7-30 days) showed a significant reduction in pain (p<0.001), as most patients' scores dropped to 4-6. At one year, these results were sustained (p=0.065). Patients with a 2-year follow-up maintained pain reduction from year 1 (p=0.337), with scores predominantly 0-1, except for patients 1 and 2. The most common side effect was non-bothersome facial hypoesthesia, emerging early and persisting in 13 patients (56.5%). Pain-free survival rate showed at 6 months 87% of patients were pain-free (BNI I-II), and the estimates at 12 and 24 months were 68% and 60%, respectively. Five people had previously undergone other non-pharmacological treatment; their response was parallel to those who received SRS as a first option (p=0.921). Discussion: Six patients (four men and two women) with advanced Parkinson’s disease who underwent STN-DBS were included. A total of 12 hemispheres were analyzed. A tendency was observed toward the need for more than one MER trajectory to achieve reliable functional localization of the STN. In most cases, two trajectories per hemisphere were required due to the absence of typical electrophysiological signals in the centrally planned trajectory. All patients presented elevated preoperative UPDRS-III scores, with evident subjective clinical improvement observed during postoperative follow-ups. However, quantitative postoperative data collection is still ongoing. Concordance analysis between the anatomically planned target (MRI-based) and the functionally determined target (MER), as well as the comparison between the location of the active contact(s) and the original planned coordinates, is currently in progress. Preliminary findings suggest that MRI-based planning did not always coincide with the optimal functional site determined intraoperatively through MER. Conclusions: In this case series of six patients with advanced Parkinson’s disease who underwent STN-DBS, multiple MER trajectories were required in most hemispheres to achieve accurate functional localization of the target. Preliminary data indicate that MRI-based anatomical planning does not always align with the intraoperatively determined optimal functional target. Ongoing concordance analysis and active contact comparison will provide further insight into the reliability and precision of each targeting method.
Derechos de autor 2025 Ambar Perez Fernandez, Alejandro Jimenez Marrero, Yerlin S. Heredia Pérez, Yeimy M. Lebron Sanchez https://creativecommons.org/licenses/by/4.0
Pituitary Radiosurgery for Management of Intractable Pain Syndromes: Overview of Reported Results
Introduction: Surgical hypophysectomy for management of intractable pain caused by metastatic cancer was introduced in 1953 by Luft and Olivecrona. Subsequently, less-invasive modifications of this technique were developed. Clinical applications of such treatment have reportedly resulted in pain relief in 40–100% of patients, but were frequently accompanied by major complications. Alternatively, pituitary radiosurgery (PR) targeting the junction of the pituitary stalk and gland attains comparable pain relief with minimal morbidity. 1-3 Method: The objective of the present review was analysis of the reported results of PR for management of intractable pain syndromes. From 1972 until 2022, 7 uncontrolled series involving small numbers of patients (from 7 to 27) and 3 case reports on clinical applications of such treatment were published. Result: Irradiation doses varied in different series from 140 to 200 Gy. No significant morphological changes of the pituitary stalk and gland were observed on MRI within 6 months after treatment. According to available publications, at least temporary pain relief after PR was noted in 68 of the 77 evaluated patients (88%), and was usually observed within few days after irradiation. The analgesic effects were most frequent and durable in the presence of metastatic bone disease, but were not limited to that pathological condition or to cases of hormone-dependent cancers. On the long-term follow-up after PR, hormonal changes were noted in 14-33% of patients, but panhypopituitarism was never reported. Diabetes insipidus was marked in 6-14% of patients. Reported neurological complications were limited to aggravation of numbness after thalamic stroke (accompanied by significant reduction of pain), and temporary abducent nerve palsy (one case each). There was one report on late osteonecrosis of the sellar turcica with rhinorrhea and meningitis at 9 years after PR. Treatment-related visual disturbances were never reported. Discussion: PR has demonstrated highly promising results in management of intractable pain syndromes caused by disseminated cancer (in particular, metastatic bone disease) and thalamic stroke. According to the available data, the analgesic effects of this procedure are comparable with those of both surgical and chemical hypophysectomy, but only a few associated side effects and complications are observed. The physiological mechanism beyond the analgetic effects of PR remains elusive. Moreover, the low-quality studies reported to date provide only level IV evidence of the efficacy of such treatment and do not support any meaningful clinical recommendations. Currently, at least 4 prospective clinical trials of such treatment are undergoing (in USA, France, and China), and their results are highly anticipated. Conclusions:Further clinical and basic investigations will bolster further developments in PR for management of intractable pain syndromes and expand its clinical role.
Derechos de autor 2025 Mikhail Chernov, Motohiro Hayashi, Yuichi Kubota https://creativecommons.org/licenses/by/4.0
Imaging Characteristics of the Affected Trigeminal Nerve in Cases of Trigeminal Neuralgia Caused by Pure Venous Conflict.
Introduction: The efficacy of neuroimaging for identification of the pure venous neurovascular conflict (NVC) in cases of trigeminal neuralgia (TN) is low. Possible identification of additional radiological characteristics that may support clinical diagnosis and help to determine indications for microvascular decompression (MVD) in such cases seems important. Method: The objective of our retrospective study1 was assessment of the imaging characteristics that may support the clinical diagnosis of TN caused by pure venous conflict. Preoperative axial constructive interference in steady state (CISS) images were analyzed in 30 patients with TN, and length, width, T2 hyperintensity, and shape of the cisternal segment of trigeminal nerve (CN V), as well as sizes of the trigeminal-pontine angle, trigeminal-petrous angle, and cerebellopontine cistern were evaluated on both sides. In all patients pure venous NVC as a cause of TN was confirmed during subsequent MVD performed between April 2007 and December 2019. Two-tailed paired t test and chi-square test were used for comparison of evaluated variables as appropriate. Result: On the affected side, the length of CN V was significantly shorter (mean 7.9 mm vs. 9.0 mm, P = 0.0249), whereas its width in midportion (mean 4.0 mm vs. 3.5 mm, P = 0.0022) and the size of the trigeminal-pontine angle (mean 55.30 vs. 48.80, P = 0.0052) were significantly larger. Other evaluated characteristics did not differ significantly between affected and nonaffected sides. Statistically significant odds ratio (OR) for the association with affected side was revealed for shorter length (OR 10.5, P = 0.0319) and larger width (OR 8.8, P = 0.0487) of CN V; the presence of either of these parameters (i.e., shorter and/or thicker CN V) provided the highest discriminative value (OR 19.3, P = 0.0063). Discussion: In patients with TN the length of CN V on the affected side is usually shorter compared with the nonaffected side,2,3 which well corresponds to results of this study. However, our data showed significantly greater trigeminal-pontine angle and larger width of CN V on the side of facial pain, which contravene previous reports.2,3 Of note, all former relevant investigations were mostly done in cases of NVC caused by compressing artery, which is clearly different from our series. It can be speculated that different types of NVC result in divergent changes of CN V and that in contrast to arterial compression, which may be due to the sharper trigeminal-pontine angle and frequently lead to the nerve root atrophy, venous conflict often causes stretching and/or local edema of CN V, which may appear on MRI as an increase of its width. Conclusions: Identification of shorter and/or thicker CN V on the affected side in patients with TN without an obvious offending vessel on MRI may suggest the presence of pure venous conflict and help with decision making about MVD.
Derechos de autor 2025 Mikhail Chernov, Amit Kumar, Yuichi Kubota https://creativecommons.org/licenses/by/4.0
Effectiveness of Proactive Microanatomy-Based Low-Dose Radiosurgery of Vestibular Schwannomas for Hearing Preservation in Patients with Neurofibromatosis Type 2
Introduction: The role of stereotactic radiosurgery (SRS) in management of vestibular schwannomas (VS) in patients with neurofibromatosis type 2 (NF2) remains unclear 1-3. In our University in such cases proactive low-dose SRS is performed. Method: The objective of this retrospective study was evaluation of the effectiveness of proactive microanatomy-based low-dose SRS of VS for serviceable hearing preservation in patients with NF2. The study cohort included 16 VS in 13 patients, who underwent SRS between January 2002 and March 2022. Median tumor volume was 0.56 cc (range, 0.12 - 2.75 cc). Hearing on the side of treated tumor corresponded to Gardner-Robertson classes I (12 cases) or II (4 cases). The prescription dose was 12 Gy (15 cases) or 11 Gy (1 case), and was delivered at 50% (13 cases) or >50% (3 cases) isodose line. Median maximal cochlear dose was 5.8 Gy (range, 2.2 - 8.2 Gy). Hearing preservation without deterioration and serviceable hearing preservation were evaluated. Result: Median posttreatment follow-up was 88 months (range, 30 - 226 months). Actuarial proportions of cases without hearing deterioration at 3, 5, and 10 years after SRS were, respectively, 0.81 ± 0.10, 0.67 ± 0.12, and 0.56 ± 0.14. Actuarial proportions of cases with serviceable hearing preservation at 3, 5, and 10 years after SRS were, respectively, 0.81 ± 0.10, 0.81 ± 0.10, and 0.67 ± 0.15. Gardner-Robertson class II hearing at the time of treatment and used prescription isodose of >50% showed statistically significant associations with subsequent hearing deterioration (P = 0.0242 and 0.0024, respectively) and serviceable hearing loss (P = 0.0047 and 0.0020, respectively). Specifically, actuarial proportions of cases with serviceable hearing preservation at 5 years after SRS in cases with Gardner-Robertson classes I and II hearing were 1.00 and 0.25 ± 0.22, respectively (P = 0.0009). Discussion: This study on SRS of NF2-associated VS demonstrates a significant difference in serviceable hearing preservation between cases with Gardner-Robertson class I and class II at the time of treatment. It can be suggested, that these patients should undergo SRS earlier, before development of the irreversible alteration of the cochlear nerve axons. For treatment planning it is important to understand the microanatomy of the tumor and adjacent structures, as well as presume possible chronology of the tumor growth. Conclusions: Gardner-Robertson class I hearing at the time of SRS for VS in patients with NF2 is associated with significantly higher chances of serviceable hearing preservation during subsequent long-term follow-up. It may advocate use of early proactive microanatomy-based low-dose SRS in such cases, particularly in younger individuals.
Derechos de autor 2025 Mikhail Chernov, Motohiro Hayashi https://creativecommons.org/licenses/by/4.0
Ultrasound Programmable Hydrogen-Bonded Organic Frameworks for Sono-Chemogenetics
Introduction: The precise control of mechanochemical activation within deep tissues using non-invasive ultrasound holds profound implications for advancing our understanding of fundamental biomedical sciences and revolutionizing disease treatments. However, a theory-guided mechanoresponsive materials system with well-defined ultrasound activation has yet to be explored. Here we present the concept of using porous hydrogen-bonded organic frameworks (HOFs) as toolkits for focused ultrasound (FUS) programmably triggered drug activation to control specific cellular events in the deep brain. Method: We have developed HOFs that could be precisely tailored and selectively activated through non-invasive ultrasound to facilitate remote medication manipulation, offering precise disease treatment in deep tissues. A theoretical model is developed to visualize the mechanochemical scission and ultrasound mechanics, providing valuable guidelines for the rational design of mechanoresponsive materials to achieve programmable control. To demonstrate the practicality of this approach, we encapsulate the designer drug clozapine N-oxide (CNO) into the optimal HOF nanocrystals for FUS-gated release to activate engineered G-protein-coupled receptors in the ventral tegmental area (VTA) of mice and rats and hence achieve targeted neural circuit modulation even at depth 9mm with a latency of seconds. Result: This work presents an ultrasound-activated HOF system with finely tuned interactions at the molecular level through modifying the chemical structure of interaction units. Through the manipulation of hydrogen bond density and the number of aromatic fused rings in the backbone structures of the organic ligands, a theoretical model is developed to explain the structure and functionality relationships in the HOFs, providing valuable guidelines for the precise and rational design of HOF building units at the molecular level to achieve on-demand and programmable drug activation under a desirable ultrasound pressure. By tuning HOF nanocrystals sensitivity to respond to focused ultrasoudn (FUS), we successfully achieve spatiotemporal control of deep brain neural circuits in both mice and rats with a latency of only seconds. The results demonstrate that HOF-enabled sono-chemogenetics can achieve a high temporal resolution and long-period neuromodulation while retaining the benefits of minimal invasiveness. Discussion: Our sono-chemogenetics technology is advancing toward applications in non-human primates and human disease treatment. While the current delivery of viruses and nanocrystals relies on local injection, FUS-mediated blood-brain barrier opening could reduce invasiveness, paving the way for future clinical applications of sono-chemogenetics. Conclusions: Our findings have demonstrated that our Ultrasound-activated HOF technology has the combination of high drug-loading content, high biostability, low immunogenicity and unique ultrasound programmability for non-invasive, precise medication therapy. Our technology is capable of releasing different types of molecule with designable medication activation sensitivity and resolution. .
Derechos de autor 2025 Huiliang Wang https://creativecommons.org/licenses/by/4.0
Warning Values of Intraoperative BAEP Monitoring During Microvascular Decompression for Hemifacial Spasm: A Tool for Safety and Functional Preservation
Introduction: Microvascular decompression (MVD) is the gold standard treatment for hemifacial spasm (HFS), but it carries a risk of auditory morbidity, primarily due to lateral traction on the eighth cranial nerve during exposure of the facial nerve. This study aimed to: (1) assess the incidence and mechanisms of hearing loss during MVD for HFS; (2) identify critical intraoperative changes in brainstem auditory evoked potentials (BAEPs) that predict postoperative outcomes; and (3) define practical intraoperative warning thresholds. Method: We retrospectively analyzed 100 patients undergoing MVD for HFS, including 84 with detailed intraoperative BAEP recordings and 34 earlier cases. BAEPs were continuously monitored, focusing on Wave I–V interpeak latency, Wave V latency shifts, and amplitude changes. Pre- and postoperative auditory function was evaluated using pure tone average (PTA). Correlations between intraoperative changes and hearing outcomes were analyzed to identify risk thresholds. Result: Hearing was preserved in 88% of monitored patients. Hearing loss occurred in 9.5%, and complete deafness in 2.3%. Wave V latency delay was the most sensitive intraoperative marker. Mean delay was 0.61 ms (±0.36) in patients without hearing loss, and 1.05 ms (±0.64) in those with hearing decline. Wave V abolition was associated with permanent deafness. Most BAEP changes occurred during cerebellar retraction. Earlier cases without systematic monitoring showed a higher deafness rate (3/7) than later ones (2/93). Discussion: BAEP monitoring reduces the risk of hearing loss by detecting reversible changes during MVD. We propose three intraoperative warning thresholds: • 0.4 ms Wave V delay – “watching” • 0.6 ms – “warning” • 1.0 ms or BAEP loss – “critical” These thresholds help prevent irreversible auditory damage in functional neurosurgery.
Derechos de autor 2025 Gustavo Polo, Andrei Brinzeu, Vincent Marneffe, Catherine Fischer, Marc Sindou https://creativecommons.org/licenses/by/4.0
Impact of Adverse Effects on Treatment Adherence to Cannabidiol in Patients With Dravet Syndrome: A Systematic Review
Introduction: Dravet Syndrome, a severe, genetic, and refractory epileptic encephalopathy, presents significant therapeutic challenges. While conventional treatments like valproic acid and clobazam have limited efficacy, cannabidiol (CBD) has emerged as a promising adjunctive therapy for seizure control. However, its long-term safety profile, associated adverse events (AEs), and sustained clinical impact require further investigation. This study critically evaluates CBD's effectiveness and safety in Dravet Syndrome treatment. Method: We conducted a systematic literature review following PRISMA 2020 guidelines, including English-language randomized controlled trials (RCTs) on Dravet Syndrome treated with CBD, valproic acid, or clobazam. Searches spanned major databases including PUBMED/MEDLINE, Web of Science, Scopus, Embase, Cochrane Library, LILACS, and Scielo. We extracted and qualitatively analyzed data on safety, AEs, discontinuation, and clinical benefits. Methodological quality was assessed using the ROB 2 (Risk of Bias 2) tool. Result: Ten clinical studies (n ≈ 1,276) were included, involving Dravet Syndrome patients treated with CBD (5–20 mg/kg/day) for 14 weeks to 3 years. Significant efficacy was observed, with mean seizure reductions from 38% to 85%. A 10 mg/kg/day CBD dose showed a 48.7% seizure reduction versus 26.9% with placebo, with fewer AEs than 20 mg/kg/day. AEs occurred in 94%–97% of patients, including diarrhea (up to 69%), fever (43%), decreased appetite (31%), and somnolence (28%). Hepatotoxicity (17%–22%) was primarily linked to concomitant valproate use, with 10 mg/kg/day CBD showing lower hepatic risk. Discontinuation rates ranged from 6%–9%, but retention fell to 45% over 3 years. Sedation (due to clobazam interaction) and hepatic toxicity were primary reasons for withdrawal,emphasizing dose adjustment and laboratory monitoring. Discussion: Our review, compared to other systematic reviews, found convergences in common AEs (somnolence, fatigue) as mild-to-moderate. However, discrepancies in rare AEs and methodologies were apparent, highlighting review heterogeneity. Polypharmacy in Dravet Syndrome complicates identifying specific drug interaction-related AEs. Many RCTs showed methodological fragilities, lacking standardized AE/quality-of-life scales, which undermines confidence in outcomes and may lead to underreporting. This issue is amplified by "scientific hype" and CBD's substantial financial impact, suggesting the need for greater transparency and rigor in future research. Conclusions:CBD's AEs generally have a limited impact on treatment discontinuation, with common symptoms usually well-tolerated at titrated regimens up to 20 mg/kg/day.
Derechos de autor 2025 Bianca De Almeida Maia Souza, Luys Antônyo Vasconcelos Caetano, Guilherme Marroques Noleto, Calderoni Carolina, Nenonena, Gisella De Deus Almeida Freire, Rebeca Pereira Dos Anjos https://creativecommons.org/licenses/by/4.0
Deep Brain Stimulation in Multiple System Atrophy: A Rare Case Report with Positive Clinical Response to STN-DBS
Introduction:Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar ataxia. Current treatment options are limited and fail to significantly alter the disease course. While deep brain stimulation (DBS) is widely accepted in the management of Parkinson’s disease (PD), its efficacy in MSA remains controversial, with only sporadic reports of clinical benefit. Method: A 53-year-old female patient presented with a 5-year history of rigidity and bradykinesia, initially responsive to Levodopa. She subsequently developed severe dyskinesias, dysphagia, dysarthria, and postural instability. Initially diagnosed with PD, the diagnosis was later revised due to clinical deterioration and MRI findings of pontine atrophy with the "hot cross bun sign," suggestive of MSA. In 2023, she underwent bilateral subthalamic nucleus (STN) DBS implantation using stereotactic techniques and microelectrode recording. The procedure was uneventful, and device activation occurred 14 days postoperatively. Following activation, complete control of dyskinesias was achieved, with immediate symptom recurrence upon DBS deactivation. Marked improvement in bradykinesia and gait was observed, with subsequent symptom stabilization. Rigidity and dyskinesia control have remained satisfactory to date, contingent upon continuous stimulation. Interestingly, shortly after surgery and before stimulation onset, the patient experienced a transient worsening of bulbar symptoms (dysphagia and dysarthria), with gradual recovery to preoperative baseline within two months. Over the long term, these symptoms have progressed slowly, though less severely than typically expected in MSA. To date, the patient has maintained sustained improvement in motor symptoms, representing a rare positive outcome in DBS for MSA. Discussion: Although MSA is traditionally regarded as poorly responsive to DBS, this case demonstrates that STN stimulation may yield significant motor benefits in selected patients, particularly when diagnostic overlap with PD exists. The favorable response highlights the importance of comprehensive, multidisciplinary evaluation in selecting candidates for DBS in complex neurodegenerative disorders. Conclusions: While DBS is not disease-modifying in MSA, it may serve as an alternative therapeutic strategy in carefully selected cases with predominant parkinsonian features, contributing to improved functional status and quality of life.
Derechos de autor 2025 Emanuele Canela, Isis Martin, Andrei Koerbel https://creativecommons.org/licenses/by/4.0
Use of Spinal Cord Stimulation in Movement Disorders: Evidence in Parkinson’s Disease, Parkinsonian Syndromes, and Dystonia
Introduction: Movement disorders such as Parkinson’s disease (PD), atypical parkinsonian syndromes, and dystonia (DT) impair motor control and significantly affect quality of life. Spinal cord stimulation (SCS), traditionally indicated for refractory chronic pain, has emerged as a promising therapeutic option for motor symptoms, especially in patients refractory or ineligible for deep brain stimulation (DBS). This study aims to systematically review the efficacy of SCS in these disorders, assessing benefits, limitations, and current evidence. Method: A systematic review following the PRISMA protocol was conducted. Databases PubMed, Embase, Scopus, Web of Science, Virtual Health Library (BVS/LILACS), and Cochrane were searched using descriptors in Portuguese and English such as “Spinal Cord Stimulation,” “Parkinson’s Disease,” “Dystonia,” and “Parkinsonian Syndromes.” Studies involving humans and animal models addressing SCS as a primary or adjuvant treatment were included. Studies focused exclusively on pain, other pathologies, inaccessible articles, and publications older than 20 years were excluded. Two independent reviewers performed screening on the Rayyan platform. Due to methodological heterogeneity, data analysis was qualitative. Result: A total of 61 studies were included. For PD, 46 publications were analyzed: 21 case reports, 18 case series, 2 case-control studies, and 5 preclinical studies. SCS demonstrated benefits particularly in axial symptoms such as freezing of gait (FoG), postural instability, and bradykinesia. Optimal results were observed with high-frequency stimulation (above 130 Hz) or burst mode, with implants preferably at high thoracic or cervical levels. In atypical parkinsonian syndromes, 10 studies were found (7 case reports and 3 case series) showing preliminary evidence of transient improvement in symptoms such as dysarthria, gait, and posture, especially in patients with multiple system atrophy (MSA). However, effects were limited by the small number of publications, short follow-up, and rapid disease progression. In DT, only 5 studies were identified (4 case reports and 1 case series), mostly predating DBS as the standard treatment. Isolated results, such as in complex regional pain syndrome associated with DT, suggest clinical improvement with SCS, indicating potential use as alternative or adjuvant therapy in specific contexts. Discussion: SCS emerges as a less invasive approach for patients with unsatisfactory response to conventional treatments. Its mechanism likely involves modulation of proprioceptive pathways and cortico-subcortical circuits, although pain relief may confound motor symptom assessment. Challenges include interindividual response variability, lack of standardized stimulation parameters (frequency, mode, implantation site), and scarcity of high-quality controlled studies. Burst stimulation is notable for its positive effects on symptoms such as FoG and tremor. Conclusions: SCS is a promising therapy for PD, parkinsonian syndromes, and DT, with benefits on motor symptoms and quality of life. Despite growing evidence, randomized controlled clinical trials are needed to validate efficacy, define optimal stimulation parameters, and elucidate mechanisms of action.
Derechos de autor 2025 Emanuele Canela, Isis Martin, Caroline Candido https://creativecommons.org/licenses/by/4.0
Axial Angulations of DBS Targets and Offering a New Design for Ben's Gun
Introduction: Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are primary targets in deep brain stimulation (DBS) surgeries for Parkinson’s disease (PD). Intraoperative macrostimulation helps to determine electrode positioning within the substructure of nucleus and its proximity to eloquent areas like internal capsule etc. Precise electrode placement in therapeutic areas is crucial to maximize benefits and minimize side effects, sometimes even necessitating intraoperative repositioning. So, we offer another improvement for DBS with a rotatable microelectrode array or so-called Ben’s gun. Method: The study included 52 patients (35 men and 17 women) diagnosed with PD. GPi or STN-DBS was performed between 2023 and 2025 at the same Turkish neurosurgery clinic. Magnetic resonance imaging (MRI) scans of patients were analyzed. In every patient medial border of both STN and GPi nuclei and angulation of these borders with midline were calculated. MRIs were evaluated with Stealthstation workstation S8 while angulations were calculated using a smartphone application. Result: In case-based evaluation, mean angulation of left GPi was 41,8 while right GPi was 42,3. Mean angulation of left STN was 39,8 while right STN was 42,2. Angulations were close to 45 degrees however except 5 cases, almost every case (n=47, %90.3) had 1 or more nucleus with angulation more than 5-degree deviation from 45 degree. In cerebral hemisphere-based evaluation, angulation of more than 100 nuclei of STN and GPi were evaluated. Mean angulation of GPi was 42,1 (30,7-54.9). Mean angulation of STN was 41,05 (29,2 – 51,2). Discussion: Using only two fixed electrode configurations reveals its major limitation during intraoperative macro- or microstimulation. For instance, employing a “+” configuration and stimulating a channel labeled as posterior does not necessarily correspond to the true posterior aspect of the nucleus but rather a posteriomedial position. In the case of the GPi, this could mean stimulation near the internal capsule, and for the STN, near the oculomotor nerve. Similar mismatches also occur with anterior, medial, or lateral channels. Therefore, to achieve more anatomically accurate and effective stimulation aligned with the individual nucleus’ orientation, it is essential to measure the angulation of the target nucleus preoperatively and adjust the orientation of Ben’s Gun microdrive accordingly. Conclusions: Ben’s gun microdrive may be only component of frame and DBS which was not improved since works of Benabid and colleagues. Optimal results in DBS, precise electrode repositioning must be based on the 3D anatomical topography of nuclei. These results suggest that STN and GPi had varying degree of angulation and using Ben’s gun microdrive only with “+” or “x” configurations may not be enough for this precision. We suggest a rotatable Ben’s gun microdrive which can be measured according to preoperative MRI.
Derechos de autor 2025 Ismail Simsek, Halit Anil Eray, Atilla Yilmaz https://creativecommons.org/licenses/by/4.0
The Effect of Linear Incision Technique on Infection and Cosmetic Results in Deep Brain Stimulation
Introduction: Deep brain stimulation (DBS) surgery is an effective method in the treatment of movement disorders. Different skin incisions such as bicoronal and semilunar are preferred in DBS surgery. However, linear incision is a less preferred method, especially if there is a foreign body under the skin, like DBS, and its effects on surgical recovery process, infection rates and cosmetic results have not been sufficiently studied. In this study, we aimed to evaluate the effect of the linear incision technique on electrode entry side we applied in DBS surgery on infection rates and cosmetic results. Method: We retrospectively analyzed 450 patients who underwent DBS surgery in 2021-2025 with the diagnoses of Parkinson's disease, essential tremor and dystonia in our clinic. All patients underwent intervention with linear incision technique by same senior surgeon. During surgery, the incisions were carefully closed in accordance with the anatomical layers. Special care was taken to suture the fascia, subcutaneous and skin tissues separately. Before the closure process, vancomycin powder was applied into wounds. No additional bone drilling applied around burr holes to countersink burr hole cap. Patients were evaluated for postoperative infection development and cosmetic results. Infection rates were compared with standard data reported in the literature. Results: Only 5 patients had minor skin problems which necessitate local procedure so electrode entry site infection rates were determined as 1.1%. This is comparable to the superficial infection rate of 1.5% reported in the literature (Morishita et al., 2017). Cosmetic evaluation revealed that the linear incision yielded aesthetically favorable outcomes. Compared to bicoronal and semilunar incisions, the linear approach resulted in smaller scars, avoided skin bulging, and better aligned with the natural hairline—benefits particularly appreciated by patients with sparse or no hair. However, further prospective studies with larger cohorts are needed to validate long-term cosmetic and clinical benefits. Discussion:The linear incision technique for electrode entry side in DBS surgery demonstrated a low infection rate of 1.1%, which is comparable to previously reported superficial infection rates of 1.5%, and provided cosmetically satisfactory results, even without any drilling for countersinking burr hole cap. Although linear incision is less preferred in cases where there is a foreign body under the skin, our closure technique may be effective in reducing infection rates. Conclusions: Our findings support the wider use of linear incision in DBS surgery, and more comprehensive studies are needed to clarify the advantages of this technique. Our closure technique appropriate to anatomical layers including fascia and the application of intra-wound vancomycin may be effective in reducing infection rates.
Derechos de autor 2025 Ismail Simsek, Halit Anil Eray, Habibe Yildiz, Huseyin Kuyuk, Atilla Yilmaz https://creativecommons.org/licenses/by/4.0
Retrocollis as Cervical Dystonia in Parkinson's Disease and Effect of Dbs: Case Series
Introduction: Dystonia can be seen in 30% or more of patients suffering with Parkinson’s disease (PD) and sometimes can precede overt parkinsonism. However, prevalence and clinical features of cervical dystonia (CD) in PD patients have not been well characterized and retrocollis is even rarely seen among these PD+CD cases. Pathological basis of association between CD and PD is not well understood while interplay of subthalamic nucleus (STN) and globus pallidus interna (GPi) is playing central role in both diseases’ pathophysiology. Interestingly, DBS for PD can cause dystonia such as blepharospasm and bilateral pallidal DBS for dystonia can result in features of parkinsonism. We aim to present case series of PD with retrocollis as CD and effect of deep brain stimulation (DBS) surgery on retrocollis. Method: We performed a single-center retrospective analysis of PD patients who underwent DBS surgery at our center and had retrocollis as a dystonic feature. Study included patients aged >18 years who were admitted between January 2024 and February 2025 for DBS surgery (n = 3). For each case, preoperative med-on and med-off UPRDS evaluations and postoperative patient records are evaluated. Results: Only 5 patients had minor skin problems which necessitatCase 1 was 61 years old male patient with right side onset PD, using levodopa+carbidopa (LD+CD) and clonazepam for hand tremor and cervical retrocollis. Operated for bilateral STN DBS. During programming sessions, patient had better response on lower contacts and higher frequency (180 Hz). It was possible to stop clonazepam and to reduce dosage of LD+CD after DBS. Case 2 was 55 years old female patient with right side onset PD, using LD+CD and rivotril for tremor, dyskinesia and cervicothoracal retrocollis. She had PD for 14 years. She operated for bilateral GPi DBS. During even second programming session, her dystonia cessated and it was possible to stop clonazepam and to reduce dosage of LD+CD after DBS. Case 3 was 61 years old male patient with left side onset PD. He had PD for 5 years and using levodopa+benserazid. His main complaints were tremor and cervical retrocollis which are responsive to challenge test. He had operated for bilateral STN DBS. After surgery, he especially benefited from tremors and also had a decrease in cervical retrocollis, although he still had to actively correct his posture while walking. Conclusions: CD is a frequent symptom in PD and our findings suggest that retrocollis as CD also can be seen in PD. Pathological bases of CD and PD in the GPi may explain how development and treatment of PD can ameliorate symptoms of CD. However, STN-DBS also can be useful in suppressing CD in PD patients, most probably due to interplay of STN with GPi. This has even more importance in tremor dominant PD cases. Frequency of retrocollis in PD, effect of STN-DBS on retrocollis and best programming parameters for this challenging symptomatology still needs studies with larger cohorts.
Brain Oscillation in Patients with Parkinson's Disease Underwent Different Treatment Scenarios
Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder with a complex and not yet fully understood etiology. One approach for its understanding is brain oscillations analysis, by which delta (0,5-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz) and gamma (>31 Hz) waves are evaluated by quantitative electroencephalography to comprehend brain function. This study aims to characterize the impact of each treatment on brain oscillatory activity. Method: This is a prospective, observational on cross-sectional ongoing study. So far, 21 participants were randomly selected from University Hospital Antonio Pedro, among which 7 patients are treated with clinical therapy, 12 were submitted to DBS surgery and 2 patients to pallidotomy. Tests are conducted both On and Off medication, DBS On and Off and pre and post-pallidotomy. Variables include sex, age, disease course length, disease subtype and side of onset, as well as EEG outcomes. Results: Preliminary results shows a predominance of male patients (76%), with age ranging from 65-70 years old, alongside with a disease course length from 3 up to 22 years. Most of the participants had a tremor-dominant onset (60%) with symptoms emerging from the left side (60%). We’ve analysed the qEEG in 4 patients (2 managed with DBS approach and 2 with conservative treatment). Regarding the clinical participants, the analysis revealed an important mean amplitude reduction in the delta wave band (µMedOFF = 4,256; µMedON = 2,898), as well as theta peek reductions with a lower standard deviation (µMedOFF 2,359 ± 2,152; µMedON 2,374 ± 1,848). Similar results were found on the surgical group, with a mean amplitude reduction in theta wave bands (µDBS-ONMed-ON 2,22 ± 1,319; µDBSOFFMedOFF 5,166 ± 6,167), but also a increase in beta and gamma mean amplitude (Beta: µDBSONMedON 1,447 ± 0,893; µDBSOFFMedOFF 1,034 ± 0,636 | Gamma: µDBSONMedON 0,539 ± 0,539; µDBSOFFMedOFF 0,220 ± 0,104). Discussion: Preliminary results shows a predominance of male patients (76%), with age ranging from 65-70 years old, alongside with a disease course length from 3 up to 22 years. Most of the participants had a tremor-dominant onset (60%) with symptoms emerging from the left side (60%). We’ve analysed the qEEG in 4 patients (2 managed with DBS approach and 2 with conservative treatment). Regarding the clinical participants, the analysis revealed an important mean amplitude reduction in the delta wave band (µMedOFF = 4,256; µMedON = 2,898), as well as theta peek reductions with a lower standard deviation (µMedOFF 2,359 ± 2,152; µMedON 2,374 ± 1,848). Similar results were found on the surgical group, with a mean amplitude reduction in theta wave bands (µDBS-ONMed-ON 2,22 ± 1,319; µDBSOFFMedOFF 5,166 ± 6,167), but also a increase in beta and gamma mean amplitude (Beta: µDBSONMedON 1,447 ± 0,893; µDBSOFFMedOFF 1,034 ± 0,636 | Gamma: µDBSONMedON 0,539 ± 0,539; µDBSOFFMedOFF 0,220 ± 0,104). Conclusions: These undergoing study results suggest that dopaminergic therapy and DBS jointly suppress pathological slow activity while restoring higher-frequency oscillations, which highlight the clinical value of oscillatory biomarkers for guiding personalized neuromodulation. Through this approach, we hope to facilitate the identification of pathological neural patterns and uncover new therapeutic targets.
Derechos de autor 2025 Adolphsson Lorena, Caio Araujo De Souza, José Geraldo Medeiros Netto, Lucas Longo, Rosana Brown, Bruno Lima Pessoa https://creativecommons.org/licenses/by/4.0
Toward an in Vivo Understanding of Addiction and Neuromodulation: Electrophysiologic Correlates of Neurochemicals During Opioid Administration in a Swine Model of Tractography-Guided Deep Brain Stimulation
Introduction: Dysregulation of mesolimbic dopamine pathways contributes to the pathophysiology of opioid addiction. Although intraoperative electrophysiology is routinely performed during deep brain stimulation (DBS), no existing clinical platform can record both electrophysiologic and neurochemical signals in parallel. Identifying electrophysiologic signatures of dopamine dynamics could clarify addiction mechanisms and support development of closed-loop DBS therapies. Method: The Multifunctional Apparatus for Voltammetry, Electrophysiology, and Neuromodulation (MAVEN) was used in an anesthetized swine model of frame-based, tractography-guided ventral tegmental area (VTA) DBS. A carbon fiber microelectrode (CFM) was stereotactically implanted in the swine nucleus accumbens (NAc) to record both tonic dopamine concentrations and local field potentials (LFPs). Tonic dopamine concentrations were measured using multiple cyclic square wave voltammetry (MCSWV) with the following parameters: initial potential -0.2 V, staircase increment +25 mV, square wave amplitude ±0.4 V, pulse duration 1.0 ms, five cyclic square waves per scan, and scan rate 0.1 Hz. Baseline and post-fentanyl recordings were performed. Results: Fentanyl administration resulted in increases in tonic dopamine concentrations in the NAc. Concurrent electrophysiologic recordings revealed increased power in lower-frequency LFP bands. Pre- and post-operative in vitro testing confirmed dopamine detection by the CFM. Discussion: This study demonstrates the feasibility of simultaneous neurochemical and electrophysiologic recording using MAVEN during tractography-guided DBS in a large-animal model of opioid administration. Conclusions: These results support the potential for neurotransmitters to serve as biomarkers of opioid intake in the development of closed-loop neuromodulation systems for opioid addiction and other neuropsychiatric disorders.
Derechos de autor 2025 Kristen Scheitler, Juan Rojas-Cabrera, Tyler Oesterle, Maximiliano Hawkes, Charles Blaha, Hojin Shin, Yoonbae Oh, Kendall Lee https://creativecommons.org/licenses/by/4.0
Emerging Applications of Spinal Cord Stimulation in Movement Disorders Beyond Parkinson’s Disease and Dystonia
Introduction: Movement disorders, such as essential tremor, spasticity, and other less prevalent conditions, significantly impact motor function and quality of life in many patients. Consequently, effective therapeutic alternatives are essential to improve clinical management. Spinal cord stimulation (SCS), traditionally used for chronic pain, has emerged as a promising therapeutic option in this context. This study aims to review the effectiveness of SCS in treating movement disorders, identifying its benefits, limitations, and future perspectives. Method: This systematic review followed the PRISMA protocol. A comprehensive search was performed in PubMed, Embase, Scopus, Web of Science, BVS (including LILACS), and Cochrane. The strategy included keywords such as “Spinal Cord Stimulation,” “Movement Disorders,” and “Essential Tremor.” Inclusion criteria encompassed articles, case reports, and books discussing SCS in movement disorders, focusing on publications from the last 20 years. Results: A total of 31 studies were included: 19 case reports, 11 case series, and 1 case-control study. SCS demonstrated promising results across various disorders. In refractory essential tremor, cervical SCS (C2) in burst mode led to sustained improvement for up to 23 months. In post-cervical fusion disorders, implants in C5–C6 and C7–T1, with frequencies of 39–52 Hz and pulse widths of 450–470 µs, eliminated symptoms immediately. In orthostatic tremor, thoracic SCS (T11–T12) reduced tremors by 30%–60% and improved postural stability. For spinocerebellar ataxia type 7, thoracic implantation (T11) with 130 Hz, 5 V, and pulse widths of 60–450 µs showed slight gait improvement. In patients with spasticity, SCS applied to the C2–C5, T9–T12, and L1 regions led to reduced muscle tone, pain relief, and functional improvement. In cases of spasticity due to cerebral palsy or spinal cord injury, muscle tone reduction was observed in all patients with spinal spasticity. In cerebral spasticity, the greatest benefits were seen in lower spastic paraparesis. The most effective parameters included frequencies of 40–130 Hz, pulse widths > 450 µs, and amplitudes up to 5 V. Discussion: SCS has shown potential in treating essential tremor and spasticity, particularly in refractory cases, likely due to modulation of motor circuits. It also presents a low rate of adverse effects. However, variability in stimulation parameters and implantation sites (cervical, thoracic, lumbar) challenges standardization. The lack of randomized trials and possible placebo effects, influenced by paresthesias, limit scientific validation. Although less invasive, broader clinical use of SCS in movement disorders requires controlled studies to optimize protocols and confirm its benefits. Conclusions: SCS is a promising therapy for movement disorders, especially essential tremor and spasticity. Nonetheless, technical and accessibility challenges demand further research to support its validation and wider clinical application.
Derechos de autor 2025 Emanuele Canela, Isis Martin, Caroline Silva https://creativecommons.org/licenses/by/4.0
Predictors of Pneumocephalus after Deep Brain Stimulation in Parkinson’s Disease: The Role of Intracranial Volume, Procedure.
Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, especially in the substantia nigra, leading to motor symptoms such as bradykinesia, tremor, and rigidity. Treatment involves dopaminergic medications and, in advanced stages, surgical options such as deep brain stimulation (DBS), typically targeting the subthalamic nucleus (STN) or internal globus pallidus (GPi). Stereotactic guidance is used to implant electrodes; however, factors such as pneumocephalus and cerebrospinal fluid (CSF) leakage may impair electrode positioning accuracy. Brain shift caused by these factors can affect the electrode placement and clinical outcomes. Thus, assessing the relationship between brain shift, atrophy, and pneumocephalus is key to optimizing DBS implantations. We aimed to analyze the potential correlations between pneumocephalus, brain atrophy, and brain shift in patients with PD undergoing DBS. Method: This retrospective study included patients diagnosed with PD who underwent DBS. Clinical and surgical data were collected from medical records. Surgical approach was classified as unilateral or bilateral lead implantation on the same day. Pneumocephalus and total intracranial volume (TIV) were manually segmented from postoperative CT images using 3D Slicer, whereas brain volume was obtained using CAT12. The brain index was defined as the ratio of the brain volume to TIV. Associations among the variables were assessed using multiple linear regression, and statistical significance was set at p < 0.05. Results: Thirty-eight patients (44 surgeries) with a mean disease duration of 12.9 years (SD = 3.54) were included. Most patients were male (70%), with 86% of the electrodes placed in the STN and 14% in the GPi. The regression model, which included TIV, brain index, sex, procedure duration, and DBS target, was significant (F(5,38) = 5.255; p < .001), explaining 40.9% of the variance (R² = 0.409; adjusted R² = 0.331). The Durbin-Watson statistic (1.786; p = 0.426) indicated no autocorrelation of residuals. TIV (β = −0.456; p = 0.024) and procedure duration (β = 0.328; p = 0.022) were significant predictors of pneumocephalus. Female sex was also associated with a lower PV (p = 0.003). Brain index (p = 0.602) and DBS target (p = 0.307) were not statistically significant. Multicollinearity was not detected (VIF < 3.2; Tolerance > 0.3). Discussion: Pneumocephalus after DBS in PD patients was influenced by TIV, surgical duration, and sex. Larger cranial volumes are associated with reduced pneumocephalus, whereas longer procedures lead to greater air accumulation. Female patients showed a trend toward lower pneumocephalus volumes. Brain atrophy, as reflected by the brain index, was not a significant factor, suggesting that brain shift may occur independently of preoperative brain volume shrinkage. Conclusions: The findings underscore the relevance of anatomical and procedural factors in DBS planning and highlight the need for strategies to minimize pneumocephalus and its impact on electrode accuracy. Although TIV influenced pneumocephalus, a relatively larger CSF space, indirectly measured as brain atrophy, did not influence postoperative intracranial air in head CT imaging.
Derechos de autor 2025 Ana Victoria Calado Godoy, Leonardo De Favi Bocca, Renato Barradas Rodrigues Renato, Thiago, Pereira Rodrigues, Carolina, Candeias Silva, Ricardo, Ricardo Silva Centeno https://creativecommons.org/licenses/by/4.0
Lead-DBS Demonstrates Sensory-Motor Nucleus Stimulation: A Real-Life Simulation of a Computerized Tool in Parkinson’s Disease
Introduction: Medical literature consistently identifies the sensorimotor region within the subthalamic nucleus (STN) and internal globus pallidus (GPi) as the optimal targets for Deep Brain Stimulation (DBS) in Parkinson’s disease. Accurate electrode placement and adequate stimulation of these regions are directly associated with better clinical outcomes. To assess surgical precision and stimulation effects, neuroimaging-based software tools such as Lead-DBS can localize electrode positions and estimate the volume of tissue activated (VTA). In this study, we applied Lead-DBS to a real-life Parkinson’s disease population to analyze electrode localization, simulate VTAs, and visually confirm stimulation overlap with the sensorimotor subregions. Method: We conducted a cross-sectional analysis of patients with Parkinson’s disease who underwent DBS surgery at a Brazilian neurosurgical center between 2022 and 2025. Preoperative high-resolution MRI and postoperative CT scans were processed using Lead-DBS software (version 3.2), following a standardized workflow including image coregistration, spatial normalization, and semiautomatic electrode reconstruction. ‘Sweetspot’ mapping was then conducted, taking into account the latest individual stimulation parameters. To improve anatomical interpretation, VTA data were exported to the 3D Slicer software (Version 5.8), overlaid on a T1-weighted atlas, and rendered using color-graded filters representing activation intensity. Results: Nineteen patients (38 electrodes) were included in the study, with 12 cases targeting the STN and seven targeting the GPi. Group electrode reconstruction demonstrated close anatomical proximity to the intended sensorimotor targets. Sweetspot simulation revealed predominant stimulation of the dorsolateral portion of both the STN and GPi, corresponding to the sensorimotor subregions. Discussion: Lead-DBS has proven to be a practical and accessible tool for postoperative electrode localization and stimulation field visualization in a real-life clinical population. The observed stimulation patterns were aligned with the established sensorimotor target zones reported in the literature. Nevertheless, further studies are warranted to validate its clinical predictive value. Conclusions: Lead-DBS effectively demonstrated stimulation of the sensorimotor subnuclei in a real-life Parkinson’s disease population, reinforcing its utility for anatomical and functional visualization in DBS surgery.
Ana Victoria Calado Godoy Carlos De Lima
Derechos de autor 2025 Renato Renato Barradas Rodrigues, Leonardo De Favi Bocca, Ana Victoria Calado Godoy Carlos De Lima, Thiago Garcia Varga, Rubens Mendes Martins Da Silva, Thiago Pereira Rodrigues, Carolina Candeias Da Silva, Ricardo Silva Centeno https://creativecommons.org/licenses/by/4.0
DBS for Aggressiveness, Results in a Series of 33 Patients
Introduction: Medical literature consistently identifies the sensorimotor Pathological refractory aggression poses a major clinical challenge. Despite advances in pharmacological and psychotherapeutic interventions, a significant proportion of patients continue to exhibit severe aggressive behavior, often with detrimental effects on their quality of life and social functioning. In this context, deep brain stimulation (DBS) has emerged as a potential therapeutic alternative for individuals who do not respond to conventional treatments. Method: We present a series of 33 patients with pharmacoresistant aggression who underwent DBS surgery at our institutions. All patients had previously failed multiple lines of pharmacological and behavioral therapy. The indication for DBS was based on the persistence of severe aggressive behavior that posed a risk to the patient or others, and on the lack of sustained response to standard treatments. Discussion: More than 90% of the patients exhibited a significant reduction in aggressive behavior following DBS implantation. Additionally, improvements in sleep and eating patterns were frequently observed. These findings suggest that DBS may be effective not only in managing treatment-resistant aggression but also in alleviating comorbid symptoms that contribute to overall patient dysfunction. Optimal outcomes likely depend on careful target selection, individualized programming, and multidisciplinary follow-up. Conclusions: Deep brain stimulation appears to be a promising therapeutic option for patients with refractory pathological aggression. The high response rate observed in this case series supports its consideration in complex clinical scenarios. Further controlled studies are needed to evaluate long-term efficacy and safety.
Derechos de autor 2025 Adriana Lucia Lopez Rios, William Hutchison- Duncan, Luisa Fernanda Aunca-Velasquez, Carlos Anibal Restrepo, Juan Sebastian Saavedra Moreno, Marta Navas García, Jose Antonio Fernandez-Alen, Cristina Torres Diaz https://creativecommons.org/licenses/by/4.0
Parkinson’s Disease and Neurotechnology: Emerging Surgical Approaches and Perspectives for the Next Decade
Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting motor and non-motor functions. In advanced or treatment-resistant cases, surgical strategies such as deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS) offer substantial symptomatic relief. With recent progress in neurotechnology, biomedical engineering, and molecular therapies, new surgical approaches are emerging. This narrative review explores the future of PD surgical treatment over the next 5 to 10 years, focusing on innovative and potentially disease-modifying strategies. Method: A narrative literature review was conducted across PubMed, Scopus, and Embase, selecting recent clinical trials, systematic reviews, and experimental studies. Keywords used: “Parkinson’s Disease”, “DBS”, “focused ultrasound”, “gene therapy”, “cell therapy”, “brain-computer interface”, “neurotechnology”, “future perspectives”. Articles were included based on relevance, innovation, and clinical applicability. Data were organized by thematic categories. No statistical analysis was applied. Results: DBS remains the gold standard, reducing motor fluctuations and medication dependency. Its use in earlier disease stages is gaining support. MRgFUS provides a non-invasive lesioning option, though it is irreversible. Technological advances such as adaptive DBS, directional leads, cortical recordings (ECoG), and multi-target stimulation increase therapeutic precision. 7-Tesla MRI and tractography enable stimulation of symptom-specific networks. BCIs and spinal neuroprostheses are under investigation for gait restoration and freezing control. In biological domains, gene therapies using viral vectors (AAV-GDNF, AADC, GAD) show neuroprotective effects. Optogenetics and chemogenetics (DREADD) allow remote control of neural circuits. iPSC-based cell therapies have demonstrated safety in early-phase trials. Gene correction (e.g., GBA1, LRRK2) and anti alpha-synuclein antibodies represent promising future strategies. Discussion: The field is shifting from symptomatic treatment to personalized, disease-modifying neurosurgical approaches. Integration of neuromodulation with biotechnology may alter disease trajectory. Adaptive DBS and multitarget designs optimize stimulation, while gene and cell therapies offer restoration of affected networks. However, high costs, device complexity, safety concerns, and ethical issues in placebo-controlled trials remain obstacles. Conclusions: Over the next 5 to 10 years, surgical care in PD is expected to evolve into a multimodal and individualized model, combining neurostimulation, biological therapies, and digital interfaces. These strategies aim not only to manage symptoms, but also to slow or modify disease progression, improving long-term autonomy and quality of life.
Derechos de autor 2025 Emanuele Canela, Ricardo Ferrarto Iglesio, Fabio Godinho https://creativecommons.org/licenses/by/4.0
Modelo para la Prescripción de los Contactos más Efectivos de los Electrodos Cerebrales Implantados en el Núcleo Subtalámico en Pacientes con Enfermedad de Parkinson
Introducción: La programación inicial de la estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) en enfermedad de Parkinson requiere la prueba sistemática de contactos (“contact testing”), lo que prolonga el tiempo hasta alcanzar un control óptimo de los síntomas y aumenta la carga asistencial. El objetivo de nuestro estudio fue desarrollar un sistema predictivo basado en los datos del microregistro multiunitario intraoperatorio y de las imágenes postoperatorias para seleccionar el contacto más efectivo del electrodo, reduciendo así el tiempo de programación y mejorando la calidad de vida del paciente. Método: Componentes del Sistema: Uso de imágenes pre y postoperatorias fusionadas de Tomografía Computarizada y de Resonancia Magnética para planeamiento estereotáctico. Microregistros multiunitarios intraoperatorios para la localización precisa del núcleo subtalámico. Análisis de datos con herramientas de visualización (mapas de calor, reconstrucción 3D) y algoritmos de machine learning (supervisado y no supervisado).Beneficios esperados: Disminución del tiempo de la consulta para la programación; selección más precisa y rápida de los contactos efectivos; mejora rápida en el control de síntomas como rigidez, temblor y bradiquinesia y optimización de recursos institucionales. Evaluación del modelo: Se utilizará una matriz de confusión para validar la precisión del sistema frente al método tradicional y se realizará un seguimiento comparativo entre la predicción del modelo y la evaluación del neurólogo. Implementación: El modelo fue implementado en un primer paciente en abril de 2024. Resultados: El modelo podría identificar correctamente el contacto más efectivo, coincidiendo con la selección final del equipo interdisciplinario. Esto permitira reducir el tiempo de programación inicial y lograr mejoría temprana de rigidez, temblor y bradicinesia. A su vez, el análisis preliminar mostró reducción en la utilización de recursos institucionales. Discusión: La integración de datos neurofisiológicos e imagenológicos permite una programación más rápida y precisa, coherente con reportes previos sobre el valor del MER y la imagen fusionada para optimizar la ECP. Consideramos que este proyecto puede dar a luz a una herramienta práctica y de extrema utilidad en el campo de la neuromodulación cerebral para el tratamiento de la enfermedad de Parkinson. Conclusiones: Con el presente modelo intentamos alcanzar en forma expeditiva y precisa la selección de los contactos más efectivos de los electrodos implantados y de esta manera, obtener resultados terapéuticos óptimos de forma precoz.
Derechos de autor 2025 Fabián Piedimonte, Nicolas Barbosa, Juan Pablo Travi, Nelson Ernesto Quintanal Cordero https://creativecommons.org/licenses/by/4.0
Clinical Outcomes of MR-Guided Focused Ultrasound for Movement Disorders: A Single-Center Experience in 48 Patients in Argentina
Introduction: Magnetic Resonance-guided focused ultrasound (MRgFUS) in functional neurosurgery is a non-invasive treatment for medically refractory movement disorders. While its efficacy has been well-established, further real-world evidence on clinical outcomes across different diagnoses and targets is essential to inform patient selection and optimize results. Moreover, while MRgFUS is a established procedure in high-income countries, its efficacy, safety, and feasibility remain largely uncharacterized in middle-income regions, particularly in Latin America. Method: We conducted a prospective analysis of data from 48 consecutive patients who underwent MRgFUS at our center in Argentina, between December 2024 and June 2025. Eligible patients presented with Parkinson’s disease, essential tremor, or pantothenate kinase-associated neurodegeneration. Preoperative evaluation included neurological assessment, MRI, and multidisciplinary case review. Procedures were performed using a 3T MR-compatible focused ultrasound system with stereotactic targeting based on the AC-PC coordinates system. The ventral intermediate nucleus (VIM) was targeted for tremor, and the nucleus subthalamicus (NST) for bradykinesia and rigidity. Clinical outcomes were assessed using physician-rated improvement and patient-reported symptom reduction. Statistical analysis included Kruskal-Wallis, Chi-square, and Pearson correlation, with p<0.05 considered statistically significant. Patient consent was obtained to share this information. Results: The cohort included 26 males (54.2%) and 22 females (45.8%) with a mean age of 69.2 ± 11.6 years. Parkinson’s disease was the most common indication (n=25, 52.1%), followed by essential tremor (n=22, 45.8%) and one case of pantothenate kinase-associated neurodegeneration. VIM was the primary target in 75.0% (n=36) of patients, NST in 20.8% (n=10), with two patients undergoing multi-targeting. There was a predominance of left-sided procedures (62.5%, n=30). On average, objective improvement was 92.9 ± 7.5%, and subjective improvement was 91.5 ± 8.1%, with a moderate but statistically significant correlation between the two (r=0.465, p=0.001). Only 4% (n=2) of patients experienced subtherapeutic results. Parkinson’s disease patients showed significantly greater objective improvement than those with essential tremor (96.0% vs 89.3%, p=0.001); subjective improvement followed a similar trend but did not reach significance (p=0.057). Efficacy was comparable between VIM and NST targets. Three patients (6.25%) experienced transient adverse events including gait instability, paresthesias, and mild pain, all of them resolved without intervention. Discussion: The described clinical outcomes reported from a single center in Argentina, covering a range of diagnoses and treatment targets, demonstrate the feasibility of implementing this technique in regions with limited access to cutting-edge technologies. MRgFUS provides robust symptom relief for movement disorders, particularly Parkinson’s disease and essential tremor, with high patient satisfaction and a favorable safety profile.
Derechos de autor 2025 Francisco Rivera, Nelson Ernesto Quintanal Cordero, Nicolas Barbosa, Sergio Pampin, Jose Luis Etcheverry, Gabriela Beatriz Raina, Augusto Grinspan, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
Stereotactic Targeting Precision in MR-Guided Focused Ultrasound: Anatomical Coordinates Analysis in Parkinson's Disease and Essential Tremor in Argentina
Introduction: Magnetic Resonance-guided focused ultrasound (MRgFUS) in functional neurosurgery is a non-invasive, incision-less alternative option which is being increasingly used for the treatment of medically refractory movement disorders. The therapeutic efficacy of MRgFUS for movement disorders depends on precise stereotactic targeting. While target selection is symptom-driven, understanding coordinates variability across targets, diagnoses, and hemispheres is essential for refining surgical planning. Method: We prospectively analyzed 48 consecutive patients undergoing MRgFUS for movement disorders at our center in Argentina, between December 2024 and June 2025, using the AC-PC (Anterior Commissure-Posterior Commissure) coordinates system. Preoperative planning was based on 1 mm isotropic T1- and T2-weighted MRI. Coordinates were defined in X (lateral), Y (anterior-posterior), and Z (superior-inferior) dimensions relative to PC. VIM (ventral intermediate nucleus) targets were selected for tremor-dominant symptoms; NST (nucleus subthalamicus) targets were used for bradykinesia/rigidity. Coordinate data and AC-PC distances were prospectively recorded. ANOVA and t-tests compared coordinates distributions across targets, diagnoses, and hemispheres. Pearson correlation assessed anatomical-clinical associations (p<0.05 considered statistically significant). Patient consent was obtained to share this information. Results: Complete stereotactic data were available for all 48 patients. Mean targeting coordinates were X=13.1 ± 4.5 mm, Y=7.2 ± 1.5 mm, and Z=1.1 ± 2.4 mm, with a mean AC-PC distance of 25.1 ± 1.4 mm. Within the VIM group, essential tremor and Parkinson’s disease patients demonstrated similar targeting precision, though Y-coordinates differed significantly (p<0.001). X-coordinates did not differ by hemisphere (p=0.935). The mean objective improvement was 92.9% ± 7.5, while the mean subjective improvement was 91.5% ± 8.1 (p=0.001). No significant correlations were found between anatomical coordinates and clinical outcomes (p>0.05). Discussion: The reported clinical outcomes from a single Argentinian center underscore the importance of meticulous preoperative surgical planning. MRgFUS stereotactic targeting demonstrates distinct coordinates profiles based on target type, diagnosis, and laterality, particularly in Y- and Z-axes. Despite this variability, consistent clinical outcomes suggest flexibility within anatomical bounds. Conclusions: These findings support refined, anatomy-guided targeting to optimize individualized treatment planning.
Derechos de autor 2025 Francisco Rivera, Nelson Ernesto Quintanal Cordero, Daniel Sarroca, Jake Olson, Daniel Dominguez, Jose Luis Etcheverry, Augusto Grinspan, Fabian Piedimonte https://creativecommons.org/licenses/by/4.0
Sequential Subthalamotomy and Thalamotomy Using MR-Guided Focused Ultrasound in Parkinson’s Disease: A Rare Case of Multitarget Lesioning for Mixed Motor Symptoms
Introduction: MR-guided focused ultrasound (MRgFUS) is a non-invasive therapeutic modality increasingly used for the treatment of movement disorders. While most interventions target a single nucleus, such as the ventral intermediate nucleus (VIM) or the subthalamic nucleus (STN), cases with mixed motor symptoms, such as tremor and bradykinesia, may require a more tailored approach. Multitarget MRgFUS remains rarely reported. Method: A 70-year-old right-handed male with an 8-year history of idiopathic Parkinson’s disease presented with right-predominant upper extremity and cephalic tremor, associated with significant bradykinesia and rigidity, refractory to optimized dopaminergic therapy. Preoperative neuropsychiatric evaluation confirmed candidacy for MRgFUS. Patient consent was obtained to share this information. Initial lesioning targeted the left STN using 3T MRI and CT fusion imaging. The anatomical coordinates were X=11.5, Y=10.2, Z=-4 mm, relative to PC. Stepwise sonications at 54–56°C were performed based on intraoperative clinical response. Significant improvement in bradykinesia and rigidity was observed, but residual tremor persisted. Subsequently, a left VIM thalamotomy was performed at coordinates X=14, Y=6.4, Z=2 mm, using a single sonication at 54°C for 6s. The STN lesioning resulted in marked improvement in contralateral bradykinesia and rigidity without adverse effects. However, tremor suppression was incomplete. Following the VIM lesion, complete resolution of tremor was achieved. The procedure was well tolerated, with no intraoperative complications. At one-month follow-up, the patient maintained sustained improvement in bradykinesia and rigidity, with complete tremor control. Mild right-sided ataxia was noted but did not interfere with daily functioning. Levodopa dosing was reduced, and no cognitive or psychiatric side effects were reported. Discussion: This case illustrates the feasibility and safety of multitarget lesioning -STN followed by VIM- in a single session. The approach enabled tailored symptom relief, reinforcing the value of intraoperative adaptability and expanding the potential role of MRgFUS in complex functional neurosurgery. Conclusions: In patients with Parkinson’s disease and refractory mixed motor phenotypes, single-target MRgFUS may provide limited relief. Thus, our sequential single-session approach may improve both symptom control and procedural efficiency, leading to substantial patient benefit.
Derechos de autor 2025 Francisco Rivera, Nelson Ernesto Quintanal Cordero, Sergio Pampin, Nicolas Barbosa, Jose Luis Etcheverry, Giselle Edith Vaisenstein, Augusto Grinspan, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
Anatomical and Clinical Correlates in MR-Guided Focused Ultrasound for Movement Disorders: A Prospective Cohort Analysis
Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a noninvasive alternative for the treatment of movement disorders such as Parkinson’s disease (PK) and essential tremor (ET). Understanding the relationship between patient age, gender, anatomy, targeting parameters, and clinical outcomes is key to optimizing therapeutic efficacy. Method: We prospectively analyzed 48 consecutive patients who underwent MRgFUS for functional neurosurgery, at our center in Argentina, between December 2024 and June 2025. Patient demographics, anatomical measurements, targeting coordinates, and clinical outcomes were collected. Pearson correlation and regression analyses were conducted to explore associations between variables. (p < 0.05 considered statistically significant). Patient consent was obtained to share this information. Results: The cohort consisted of 26 males (54.2%) and 22 females (45.8%) patients with a mean age of 69.2 ± 11.6 years (range: 25–88). Age did not differ significantly between diagnostic groups (PD: 68.4 ± 6.8 vs ET: 70.9 ± 13.0 years, p = 0.437) or targeting strategies (ventral intermediate nucleus-VIM: 70.5 ± 10.9 vs. nucleus subthalamicus-NST: 66.4 ± 6.4 years, p = 0.147), but was slightly positively correlated with AC-PC distance (r = 0.304, p = 0.04). No significant correlations were found between age and targeting coordinates or clinical outcomes. Males had significantly larger AC-PC distances than females (25.8 ± 1.3 mm vs 24.3 ± 1.1 mm, p < 0.001), though gender was not associated with clinical outcomes. The anterior AC-PC distance demonstrated a negative correlation with the Y-coordinate (r = –0.303, p = 0.048) and a positive correlation with the Z-coordinate (r = 0.450, p = 0.002), suggesting that individual anatomical variation influences target localization. Finally, a moderate but statistically significant positive correlation was confirmed between objective and subjective improvement measures (r = 0.474, p = 0.001), validating the consistency between physician assessment and patient-reported outcomes. Discussion: The reported clinical outcomes from a single Argentinian center highlight the importance of systematically recording variables such as age, sex, anatomical characteristics, and targeting parameters, and of incorporating these factors into the analysis to optimize outcomes and enhance the effectiveness of the procedure. Our results show a correlation between age and AC-PC distance, indicating that older patients have larger anterior commissure-posterior commissure measurements. The correlation between objective and subjective clinical improvement measures that we obtained validates the consistency between physician assessment and patient-reported outcomes. Conclusions: Our findings emphasize key anatomical and clinical correlations influencing MRgFUS targeting and possibly also clinical outcomes. These insights may guide personalized targeting strategies and improve outcome prediction in functional neurosurgery.
Derechos de autor 2025 Francisco Rivera, Nelson Ernesto Quintanal Cordero, Sergio Pampin, Nicolas Barbosa, Jose Luis Etcheverry, Tilden David, Augusto Grinspan, Fabian Piedimonte https://creativecommons.org/licenses/by/4.0
Target-Specific Thermal Dynamics in MR-Guided Focused Ultrasound for Movement Disorders: A Prospective Analysis of 39 Patients from Argentina
Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a non-invasive, incisionless option for treating medically refractory movement disorders. Despite its growing clinical use, limited evidence exists on how diagnosis and anatomical targeting influence technical demands and treatment efficacy. Clarifying these differences is crucial to improving patient-specific protocols. Method: We conducted a prospective analysis of 39 patients (mean age 70.6 ± 10.7 years; 56.4% male) who underwent MRgFUS for essential tremor (ET, n=21) or Parkinson’s disease (PD, n=18) at our center in Argentina, between December 2024 and June 2025. Target nuclei included the ventral intermediate nucleus (VIM, n=30), nucleus subthalamicus (NST, n=8), and dual targeting (NST+VIM, n=1). Technical parameters -number of sonications, energy delivery, thermal profiles- were compared across diagnostic and anatomical subgroups. Pearson correlation and t-tests analyses assessed associations or differences among procedural variables (p<0.05 considered statistically significant). Objective and subjective clinical improvements were recorded post-procedure. Patient consent was obtained to share this information. Results: All ET patients received VIM targeting, whereas PD cases were distributed between VIM (50.0%), NST (44.4%), and combined targeting (5.6%). The average number of sonications was consistent across groups (6.6 ± 1.8). Thermal parameters showed strong internal consistency, with maximum average temperature highly correlated with peak temperature (r=0.900, p<0.001). In contrast, energy delivery was moderately and inversely associated with thermal outcomes (r=-0.556 to -0.591, p<0.001), highlighting real-time thermal control as the principal procedural endpoint. ET cases required significantly greater energy delivery (25.30 ± 14.56 J) compared to PD (18.28 ± 7.87 J), a 38.4% increase (p=0.066), despite achieving slightly lower thermal thresholds (mean maximum average temperature: 54.5 ± 3.4°C vs 56.3 ± 2.2°C, p=0.059; mean maximum temperature: 58.0 ± 5.0°C vs 60.2 ± 3.4°C, p=0.128). Time at peak temperature was also shorter in ET (6.0 ± 2.0 s) than in PD (6.5 ± 1.7 s), a reduction of 8.4% (p=0.364). When comparing anatomical targets, NST ablations required longer thermal exposure than VIM (6.9 ± 1.7 s vs 6.1 ± 1.9 s; +12.7%, p=0.292) while utilizing 11.8% less energy (20.16 ± 10.15 J vs 22.86 ± 13.03 J, p=0.593), suggesting distinct thermodynamic demands based on target anatomy. Clinically, the cohort achieved substantial benefit, with a mean objective improvement of 92.9% ± 7.5 (p<0.001) and a mean subjective improvement of 91.5% ± 8.1 (p<0.001), supporting both technical efficacy and high patient satisfaction. Discussion: MRgFUS demonstrates high efficacy for both ET and PD, with over 90% average improvement in objective and patient-reported outcomes. Procedurally, consistent sonication counts support protocol standardization; however, energy and thermal requirements vary by diagnosis and target nucleus. While the reported differences did not reach statistical significance, we consider them worth presenting given that this is one of the first reports of this novel technique in Argentina. Conclusions: These findings reinforce thermal control -rather than maximal energy- as the determinant of success and support individualized treatment planning grounded in anatomical and pathophysiological context.
Derechos de autor 2025 Francisco Rivera, Nelson Ernesto Quintanal Cordero, Daniel Sarroca, Nicolas Barbosa, Sergio Pampin, Jose Luis Etcheverry, Augusto Grinspan, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
Intraprocedural Target Conversion from Pallidotomy to Pallidothalamic Tractotomy for Improving Thermal Efficiency in MR-Guided Focused Ultrasound for Parkinson’s Disease
Introduction: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) pallidotomy (GPi) is an established treatment for Parkinson's disease (PD). However, challenges like low-thermal efficiency, particularly due to skull density variations or off-midline target locations, can hinder effective lesioning. This report presents 3 cases of intraprocedural conversion from GPi pallidotomy to pallidothalamic tract (PTT) ablation due to inadequate thermal build-up. In all, the possibility of conversion was informed and consented by the patient previous to the procedure. Method: Case 1: A 49-year-old male with non-tremor PD and dyskinesias underwent left GPi MRgFUS. Despite optimal targeting, thermal mapping indicated insufficient temperature increase (max 48 °C). An immediate intraprocedural shift to PTT targeting resulted in a successful lesion and significant clinical improvement. Case 2: A 57-year-old female with PD and severe dyskinesia presented for left GPi MRgFUS. Initial sonications yielded suboptimal thermal profiles. Recognizing this low thermal efficiency, the target was redirected to the PTT. This conversion facilitated adequate thermal ablation, leading to marked improvement in rigidity, bradykinesia, and dyskinesias with no significant adverse events. Case 3: A 66-year-old male with asymmetrical PD and dyskinesias underwent left MRgFUS Pallidotomy, in whom low thermal response at the GPi (max 49°C) required intraprocedural redirection to PTT, achieving effective lesioning and symptomatic improvement. Discussion: These cases highlight non-invasive intraprocedural adaptability as a crucial strategy when encountering low-thermal efficiency during MRgFUS pallidotomy, allowing for effective treatment by converting to PTT ablation. This approach expands the therapeutic window for patients with challenging anatomical or thermal profiles. Conclusions: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) allows intraoperative redefinition of a new target whithout increasing risk.
Derechos de autor 2025 José Lorenzoni, Wilhelm Uslar, Marco Rattalino, Carlos Juri https://creativecommons.org/licenses/by/4.0
Post-Amputation Neuropathic Pain with Phantom Limb Phenomenon: Therapeutic Success with Spinal Cord Stimulation.
Introduction: Refractory neuropathic pain in amputation stumps represents a therapeutic challenge, particularly when conservative measures fail. Spinal cord stimulation (SCS) emerges as a promising alternative in selected cases of peripheral neuropathic pain, with evidence supporting pain intensity reduction and improvement in quality of life¹,². Method: A 28-year-old woman, with a past medical history of arterial hypertension, anxiety disorder, depression, and chronic neuropathic pain, presented with phantom limb pain in the right lower limb for several years. The pain was severe, daily, burning in nature, without radiation or relieving factors, and without infectious signs. She had previously received multiple pharmacological therapies at optimized doses (pregabalin, duloxetine, tapentadol), without satisfactory response, and achieved only partial control with gabapentin. She underwent an L5 nerve root block with transient benefit. Ultrasound was nonspecific, and lumbosacral MRI revealed mild degenerative changes at L4-L5 and L5-S1, including a right posterior disc protrusion at L4-L5, compressing the ventral surface of the dural sac and contacting the L5 root, and a disc bulge at L5-S1 contacting the ipsilateral root. Due to refractoriness and functional limitation, an epidural electrode was implanted for SCS at T8–T9, with laminectomy at T10 and generator placement in the left pre-gluteal region (3.4 mA; 120 μs; 1200 Hz). The patient showed significant pain improvement, gradual reduction of pharmacological therapy, progressive functional recovery, and enhanced quality of life. Discussion: This case highlights the potential of SCS in the management of neuropathic pain in amputation stumps, supporting studies demonstrating efficacy in refractory peripheral neuropathies¹ and severe neural injuries². Although literature specifically addressing amputees remains limited, broader research points to relevant relief in chronic neuropathic pain when conventional approaches fail¹,³. Conclusions: SCS may play a decisive role in controlling disabling post-amputation neuropathic pain. Careful patient selection and a multidisciplinary approach are essential to maximize outcomes, reduce medication dependency, and restore functionality.
Derechos de autor 2025 Isis Franco Martin, Igor Bagini Mateus, Isadora Sartoretto Meurer, Emanuele Pires Canela Dos Santos, Maria Antonia Cunha Figueiredo, Isabela Costa Ribeiro, Carolina Simão Martini, Giovanna Delcole https://creativecommons.org/licenses/by/4.0
Keyhole Temporal Lobectomy: Minimally Invasive Surgery for Medically Refractory Temporal Lobe Epilepsy
Introduction: Temporal lobe epilepsy (TLE) remains the most common form of focal epilepsy in adults. While traditional anterior temporal lobectomy (ATL) is effective, it often involves larger craniotomies and associated morbidity. Minimally invasive alternatives, such as keyhole temporal lobectomy (KTL), aim to reduce operative trauma while maintaining seizure control rates. This study evaluates the safety, efficacy, and functional outcomes of KTL in comparison to standard ATL. Method: We conducted a prospective analysis of 100 patients undergoing KTL for drug-resistant TLE between 2017–2025. All surgeries were performed via a 2 cm mini-temporal approach, using microrsocpic visualization. Preoperative evaluation included video-EEG, MRI, and neuropsychological testing. Primary outcomes included seizure freedom (Engel classification), cognitive function, operative time, hospital stay, and complication rates. Results: Seizure outcomes: At 12 months, 85 % of patients achieved Engel Class I outcomes, comparable to traditional ATL series. Discussion: Our findings suggest that KTL provides seizure outcomes comparable to standard ATL, with notable advantages in terms of recovery time, cosmetic satisfaction, and neurocognitive preservation. The use of neuronavigation allows for precise mesial resection through a limited corridor. This approach may be particularly valuable in young or professionally active patients, where minimizing neuropsychological sequelae and downtime is critical. Further randomized comparisons with open approaches are warranted to validate these findings across larger cohorts. Conclusions: Keyhole temporal lobectomy is a safe and effective alternative to traditional ATL in selected patients with TLE. It offers comparable seizure outcomes with reduced hospital stay, minimal cognitive morbidity, and improved cosmetic and recovery profiles. KTL represents a valuable addition to the minimally invasive epilepsy surgery armamentarium.
Derechos de autor 2025 Pavel Sebastian https://creativecommons.org/licenses/by/4.0
The use of Inertial Sensor Based System for Objective Assessment of Tremor in Parkinson’s Disease
Introduction: Parkinson's disease (PD) is a prevalent neurodegenerative condition characterized by the degeneration of dopaminergic neurons, with a significant impact on public health, particularly among the elderly. Despite the criterias for clinical diagnosis, there is no standardized approach for early diagnosis or continuous and objective assessment of tremor progression in PD. The current methods rely on subjective and limited assessments. The aim of this study is to evaluate the use of inertial sensor-based systems in assessing tremor progression and fluctuations in PD. Method: This study involved 12 PD patients and 12 healthy controls, assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) and the TREMSEN system, a inertial sensor-based device developed for high-resolution, objective quantification of tremor in clinical research. Results: The Kruskal-Wallis test revealed statistically significant differences in tremor amplitude (p < 0.05) between at least two of the groups (PD-OFF, PD-ON, controls) on both sides for all three spatial axes. In anteroposterior axis, Wilcoxon tests for multiple comparisons demonstrated significant differences observed for all comparison pairs during the posture maintenance task, the second resting period, the wrist adduction-abduction task, and the third resting period on both sides (p < 0.05). Spearman’s correlation for tremor amplitude exhibited a significant correlation with the clinical assessment scale (p < 0.05). Discussion: The results indicated that TREMSEN was effective in differentiating tremor between the groups, especially during rest and postural tasks, proving to be useful for the diagnosis and monitoring of PD. The correlation between tremor magnitude and the UPDRS scale suggests that the system can objectively reflect tremor severity. Conclusions: The findings reinforce the usefulness of TREMSEN in quantifying tremor and indicate the relevance of future studies on motor fluctuations with inertial sensors.
Nicoly Augusta Da Silva Quezada Dos Santos
Derechos de autor 2025 Nicoly Augusta Da Silva Quezada Dos Santos, José Geraldo Medeiros Netto, Clara Costa, Caio Araujo De Souza, Rosana Siqueira Brown, Ariana Moura Cabral, Adriano De Oliveira Andrade, Bruno Lima Pessôa https://creativecommons.org/licenses/by/4.0
Gamma-Tetha Local Field Potentials as Biomarkers in Treatment Resistant Depression on Bilateral Subgenual Corpus Callosum Deep Brain Stimulation. Integrated Behavioral, Neurophysiological and Clinical Effects
Introduction: Treatment-resistant depression (TRD) remains a significant therapeutic challenge globally. Although (DBS) has been an option for treatment, some suggests that a personalized approach base on main symptomatology and individual biomarkers, may yield more efficacious outcomes. Since 2013, our center at Rionegro San Vicente Fundacion Hospital Colombia, South America, has implemented a multidisciplinary neurofunctional program and performed bilateral subcallosal cingulate DBS (SCC-DBS) in 7 patients. Recently, 3 of these patients underwent device replacement with the PerceptTM RC neurostimulator Brain SenseTM technology, enabling advanced local field potential (LFP) recordings and behavioral and neurophysiological assessments. This study focuses on these 3 patients, each representing a distinct depressive phenotype: hypersensitive, stable, and anhedonic. We conducted comprehensive evaluations integrating emotional perception tasks, local field potential recordings, and longitudinal clinical profiling to elucidate the mechanisms and effects of SCC-DBS. Method: EMOTIONAL PERCEPTION TASK Patients viewed 10 standardized images 5 happy 5 sad in randomized order during two conditions stimON Chronic therapeutic stimulation and stim-OFF: 1 hour washout period. For each image, patients provided: Happiness rating 1 very sad to 10 very happy semantic association single-word descriptor and response latency measurement. Results: Behaviorally, SCC-DBS significantly enhanced positive image perception +9.5% and reduced negative bias −28% with a 34% improvement in emotional discrimination capacity. Neurophysiologically, stimulation led to increased gamma oscillations up to +175% suppressed theta activity up to −41.9% strongly correlated with affective improvements r = 0.76 and r = 0.71 respectively). Clinically 49.3% overall improvement in QofL with phenotype specific responses beta/gamma ratio was most effective in the hypersensitive patient theta-alpha phase-amplitude coupling relevant in the stable phenotype and high gamma power was a key biomarker in the anhedonic patient. Discussion: Our observations suggest that deep brain stimulation (DBS) of the (SCC) achieves therapeutic effects through frequency-specific, dissociable mechanisms. Gamma oscillations may facilitate long-term synchronization between the SCC and the nucleus accumbens, enabling positive valence encoding. Pathological theta hyperactivity during StimOFF states may reflect limbic-cortical dysrhythmia, consistent with the Broadway model of depressive hyperarousal. Theta suppression correlated with reduced connectivity between the amygdala and SCC may suggest normalized threat processing. All of this could have clinical application when programming real life patients, but more cases and scenarios are required for applicability across all individuals. Conclusions: We can suggest that SCC DBS may modulates affective circuits through frequency specific mechanisms gamma enhancement may facilitates positive affect and reward processing, while theta suppression may mitigates negative cognitive bias. The therapeutic response varies by depression phenotype, supporting a personalized neuromodulation approach guided by electrophysiological biomarkers. The use of Percept RC technology may enable real-time monitoring and biomarker identification. This optimized programming framework may have the potential to improve clinical outcomes in TRD and maybe establish SCC DBS as a targeted, phenotype-driven therapy.
Derechos de autor 2025 Adriana Lucia Lopez Rios, William Duncan Hutchison, Carlos Anibal Restrepo Bravo, Daniel Henao Lopez, Alejandro Aristizabal Gaviria, Luisa Fernanda Ahunca Velasquez, Juan Alexander Escobar Rincon, Jorge Holguin Holguin Lew https://creativecommons.org/licenses/by/4.0
Neuronal and Motor Activity in the Basal Ganglia During a Synchronization-Continuation Hand Tapping Task in Patients with Parkinson’s Disease
Introduction: Deep brain stimulation (DBS) of the STN is used for Parkinson’s disease (PD) patients refractory to medications. One symptom that is not significantly improved by DBS is freezing of gait (FoG) which, is implicated in performance in the synchronization-continuation task (SCT). The SCT consists of tapping in time with an external cue (like a metronome) and then continuing to tap without the external cue, requiring a shift from external to internal representations of rhythm. Studies have shown that patients with PD exhibit motor hastening in the continuation phase, with higher magnitude of hastening correlated to severity of FoG. To better understand the relationship between rhythmic control in the STN, medication, and DBS, 15 PD patients underwent the SCT while having both their motor behaviour and neural activity recorded. Method: Patients with DBS leads implanted in the STN underwent testing in four different conditions: M1S1 (Med ON/Stim ON), M0S0 (Med OFF/Stim OFF), M1S0 (Med ON/Stim OFF), and M0S1 (Med OFF/Stim ON), with Med OFF defined as 12hr off anti-Parkinson medication. Motor data was recorded using a triaxial accelerometer or a piezoelectric force detection device. Neural activity in the form of local field potentials was recorded using the PerceptTM technology. Results: Preliminary analysis of 3 patients showed motor hastening across all conditions, with greater magnitude in M0S0 (0.20 Hz) than M1S1 (0.12 Hz). Beta power was elevated in OFF states and reduced by medication or stimulation, while peak frequencies remained stable. In M0S0, beta power was highest during the listening phase, suggesting desynchronization with motor initiation. Discussion: Our findings align with prior reports of motor hastening in PD during the SCT. The greater hastening observed in M0S0 compared to M1S1 suggests that medication and DBS may help stabilize rhythmic motor output, while future analyses of M1S0 and M0S1 will clarify their individual effects. Spectral results also showed elevated beta power in M0S0 and suppression with medication or stimulation, consistent with existing literature. Conclusions: The results thus far confirm that motor hastening in the SCT is a common experience for patients with PD, and indicate that dopaminergic medication and DBS may help to reduce the degree of hastening. Additionally, the differences in beta oscillatory power across the different phases of the SCT, when combined with the behavioural results of the SCT, may help to better describe the role of the STN in rhythmic control, and how it is affected by PD.
Derechos de autor 2025 Daniel Henao Lopez, Adriana Lucia Lopez Rios, Juan Sebastian Saavedra Moreno, Carlos Anibal Restrepo Bravo, Carlos Ignacio Velez Arango, Luis Antonio Franco Vergara, Milad Lankarany, William Duncan Hutchison https://creativecommons.org/licenses/by/4.0
Novel DBS Target Trajectory Strategy for Treating Refractory OCD with Major Depressive Symptoms: From the Bed Nucleus of Stria Terminalis to the Ansa Subthalamica
Introduction: In 2009, the FDA approved DBS for treatment-refractory OCD, even before robust evidence for safety and efficacy for this indication was stablished. Different targets were proposed to modulate the circuits involved in OCD, with variable results in the literature. In the same way, DBS targeting for depression is not a resolved theme in the literature. We aim to describe a novel approach for targeting dual pathology (OCD + Major Depression), including more than one responsive structure in the trajectory. Clinical description: A 33-year old man with refractory and severe OCD associated major depression, was submitted to bilateral DBS, able to stimulate the bed nucleus of stria terminalis, anterior thalamic radiation, GPi, medial forebrain bundle and ansa subthalamica with a 8-contact electrode. Contact test was performed within 2-week interval, repeating depression and OCD scales for clinical evaluation. Pre and delayed post-operative MRIs were analyzed for cortical thickness. Discussion: All scales for depression and for OCD had remarkable improvement. Best Y-BOCS and depression scores were obtained with the stimulation of the ansa subthalamica (remission of depressive and OCD symptoms). Besides the clinical improvement, there was increase in average cortical thickness for 125 cortical areas (Desikan-Kiliani Atlas), reduction in 20 cortical areas and no change in 3 after 6 months of DBS on in the AS. The average of increase for both hemispheres was 0.19 mm. The increased thickness was more pronounced bilaterally in the cingulate gyrus, pre-central gyrus, precuneus and superior frontal gyrus and left subcallosal gyrus, reaching 0.5 mm in some frontal regions. In 2019, we have characterized the ansa subthalamica (AS), a fiber tract linking the anteromedial pole of the subthalamic nucleus (STN) and the ventral globus pallidus internus (GPi), both limbic.1 In 2020, we have described in patients submitted to lateral hypothalamic DBS for obesity in Prader-Willi syndrome that the activation of DBS settings in which the volume of activated tissue reached the AS (and not the MFB), were associated with manic symptoms in those patients.2 With the above concepts in mind, it was possible to plan a trajectory of an 8-contact DBS lead that would reach structures from the BNST to the AS. The best clinical effect was obtained in the ventral contacts, where there is a confluence of limbic fibers (AS and STN-frontal fibers), which might be responsible for the optimized effect in the present case, modulating both frontal - as we have presented elsewhere 3 - but also basal ganglia (STN-GPiam) networks. The cortical changes in thickness observed likely reflect beneficial neuroplasticity in response to DBS-induced modulation of limbic, motor and cognitive circuits and are consistent with the clinical improvement, emotional regulation, and restoration of cognitive control. Some increases in areas such the precuneus might indicate re-engagement of self-awareness and self-image networks (part of the default mode network), commonly suppressed in major depression. Other areas affected in OCD and depression such as motor cortex and area 25 also increased their thickness after the therapy. Conclusions: A novel strategy of targeting for OCD and Major Depression is hearby presented. The stimulation of the ansa subthalamica rendered good clinical outcomes, linked to plastic cortical changes and might be considered a potential target for investigation in OCD associated with major depressive.
Derechos de autor 2025 Eduardo Alho, Pablo Fruett, Paul Rodrigo Dos Reis, Adriana Gutterres Pereira, Paulo Roberto Franceschini https://creativecommons.org/licenses/by/4.0
Estimulación Cerebral Profunda del Globo Pálido Interno y del Núcleo Subtalámico en la Distonía Pediátrica: Una Revisión Sistemática y Metanálisis
Introducción: La estimulación cerebral profunda (ECP) dirigida al globo pálido interno (GPi) y al núcleo subtalámico (NST) se ha convertido en una opción terapéutica para pacientes pediátricos con distonía refractaria al tratamiento médico. Sin embargo, la evidencia sigue estando fragmentada en cohortes pequeñas y poblaciones heterogéneas. Método: Se realizó una revisión sistemática y un metanálisis de acuerdo con las directrices PRISMA. Se realizaron búsquedas en PubMed, Embase, Scopus, Web of Science y CENTRAL hasta agosto de 2025. Los estudios fueron elegibles si incluían pacientes pediátricos (<18 años) con distonía refractaria al tratamiento médico sometidos a estimulación cerebral profunda (ECP) dirigida al globo pálido interno (GPi) o al núcleo subtalámico (NST). El resultado principal fue el cambio porcentual en la puntuación BFMDRS-Motor a los 12 meses. Los resultados secundarios incluyeron el cambio porcentual medio en la puntuación de discapacidad de la BFMDRS a los 12 meses, la tasa de respuesta (mejora motora ≥50%) y la incidencia de eventos adversos graves (EAG). Los datos se agruparon mediante un modelo de efectos aleatorios en R Studio, y el riesgo de sesgo se evaluó con la herramienta ROBINS-I. Resultados: Catorce estudios cumplieron los criterios de inclusión, pero solo cinco fueron elegibles para la síntesis cuantitativa del resultado primario. En el caso de la GPi-DBS, la mejoría media agrupada en la BFMDRS-Motora a los 12 meses osciló entre el 60,2% y el 83,2% (I² = 86,1%), mientras que la BFMDRS-Discapacidad mostró una mejoría media agrupada del 40,8% al 79,5% (I² = 99,2%). Las tasas de respuesta (mejora motora ≥50%) oscilaron entre el 0% y el 89%, y la mayoría de las series informaron entre el 60% y el 80%. Se presentaron eventos adversos graves en aproximadamente el 15-20% de los pacientes. Un seguimiento a largo plazo de hasta 13 años confirmó un beneficio sostenido. Para la ECP-STN, la mejoría motora media agrupada fue del 63,8% (IC del 95%: 36,9-90,6; I² = 90,3%), aunque se basó únicamente en dos cohortes pequeñas. En general, el riesgo de sesgo entre los estudios se consideró de moderado a grave según la herramienta ROBINS-I. Conclusiones: Este metanálisis de un solo brazo sugiere que la ECP-GPi proporciona una mejoría motora y funcional significativa en la distonía pediátrica, mientras que la evidencia para la ECP-STN sigue siendo limitada. Los eventos adversos fueron relativamente frecuentes, pero manejables. Dado que la evidencia disponible se limita a estudios observacionales, se requieren más ensayos controlados aleatorizados para confirmar estos resultados y refinar la selección de los objetivos.
Derechos de autor 2025 Albert Gabriel Turpo Peqqueña, Josue Rodrigo Turpo-Peqqueña, Harlly Loza Chipa, Jahnie Madyson Supo Flores, Daniela Adriana Chávez Benavente, Guilherme Marroques Noleto, Gladys Huanca-Quispe, Richard Hernandez Mayori https://creativecommons.org/licenses/by/4.0
Update of Seven Cases of Refractory Cluster Headache Treated with Combined Occipital Nerve and Sphenopalatine Ganglion Stimulation with Good Mean Outcome in a Long Term Follow Up
Introduction: Cluster headache (CH) is an extremely debilitating and often difficult-to-treat headache disorder characterized by recurrent attacks of excruciating pain associated with cranial autonomic symptoms. Several invasive neuromodulation procedures have been evaluated in the past, but the combination of these procedures to maximize response has not been studied in groups of patients. This presentation aims to describe an update on the evolution of cases based on a recent publication of ours. Clinical description: This single-center, retrospective, observational study included seven patients (3F/4M) suffering from CCH, according to the diagnostic criteria of the current International Classification of Headache Disorders,1 and considered refractory based on the Consensus Statement of the European Headache Federation Between February 2010 and March 2021, these patients underwent implantation of electrodes for SPG and greater occipital nerve (GON) stimulation ipsilateral to the side of the pain (Figure 1). Patients with uncontrolled hypertension, cerebrovascular disease, congestive heart failure, cancer, or severe psychiatric disorders were considered ineligible for the procedure. The electrodes were implanted in a single surgery under general anesthesia. The mean follow-up time was 6.38 years ± 3,6 (maximum 12.6 years and minimum 1.3 years). Six out of the seven patients (86%) experienced good-to-excellent initial pain relief, defined as a egal or greater 50% reduction in VAS scores compared to baseline, together with marked clinical improvement in attack severity and functional impact as assessed by the treating physicians. Almost complete remission of symptoms was achieved in most cases, defined as the complete absence of cluster attacks or only rare, very mild episodes without significant functional impact. Discussion: Multiple techniques have been proposed to control CH symptoms, including ablative techniques as radiofrequency on the Gasser ganglion, SPG and GON.(7, 8) Peripheral Nerve Stimulation has been tried on SPG or GON, both isolately, Vagal Stimulation and High cervical Stimulation, with success, in reduced samples. Hypothalamic Deep Brain Stimulation was successfully tried, with low but significant morbi-mortality.(9, 10, 11) Here we report, for the first time, that combined invasive SPG and GON neurostimulation significantly and enduringly improves CCH symptoms in a series of refractory patients. Moreover, the number and severity of complications presented indicate that this approach is relatively safe compared to others of its kind, resulting in a convenient risk-benefit profile. Conclusions: Synergistic invasive SPG-GON stimulation appears to be a relatively safe and promising alternative for effective and long-lasting control of CCH.
Derechos de autor 2025 Juan Carlos Mario Andreani, Fabián Piedimonte, Osvaldo Bruera, Marco Lisicki, Diego Bashkansky https://creativecommons.org/licenses/by/4.0
Clinical Features of Pain Improvent in Five Patients with Traumatic Spastic Paraparesis and Neuropathic Pain Treated by Spinal Cord Stimulation
Introduction: The objective of this study is to study the long term characteristics of Pain evolution Refractory spasticity and pain are common complications in paraplegia and their treatment by spinal cord stimulation (SCS) has been widely reported in the international literature.1,2 However, although pain is present in 57% of cases of spastic paraplegia,3 little has been described about its independent evolution when treated by SCS.4 The aim of this presentation is to show preliminary results in four cases from an ongoing clinical trial. Clinical description: Five patients, 4 men and 1 woman with Spastic traumatic paraparesis (3 cases Asia C and 2 ASIA D Scale) at lower dorsal spinal level with Spasticity and Neuropathic Pain were treated by dorsal spinal cord stimulation. Pre and post interventional Ashworth and Penn scales assessments, as well as Visual Analogue Scale (VAS) were monthly performed, 3 months before and after surgeries. Results: Pre- and postoperative Ashworth and Penn scale assessments showed significant improvement, whereas the visual analogue scale showed little or no improvement during initial postoperative assessments, with modest improvement over time. Two patients regained some walking ability due to decreased severity of spasticity and spasms. Discussion: In our 5 cases, we found a more favorable evolution of spasticity and spasm frequency than in the improvement of pain. Improvement of neuropathic pain has been described in isolated cases of complete paraplegia (ASIA A).5 A recent extensive review describes the high prevalence of neuropathic pain in tetraplegics and below the lesion.6 Other authors,7,8 focused on spasticity have extensively described the pathophysiology of both. There are also authors who have extensively described the benefits and complications of spinal cord stimulation (SCS) in refractory spasticity.9,10,11 However, none of these works provide data on the parallel evolution of both neurological signs. Conclusions: While spasticity improved markedly and rapidly in our cases, pain showed unparalleled, slightly positive results, with some increase in benefits over time.
Derechos de autor 2025 Juan Carlos Mario Andreani, Guillermo Agustín Larrarte, Félix Barbone https://creativecommons.org/licenses/by/4.0
Age- and Sex-Related Variations of Skull Density Ratio (SDR) Among Latin American Patients with Parkinson Disease and Essential Tremor
Introduction: The Skull Density Ratio (SDR) is a key imaging biomarker used in determining eligibility for Magnetic Resonance-guided Focused Ultrasound (MRgFUS), especially in movement disorders such as Essential Tremor (ET) and Parkinson Disease (PD). While SDR is widely used in preoperative planning, its variability by age, sex, and diagnosis remains insufficiently described, particularly in Latin American populations. This study aimed to evaluate SDR distribution, stratify patients using clinically meaningful SDR intervals, and analyze age- and sex-related correlations in a cohort of Latin American patients referred for MRgFUS evaluation. Method: We retrospectively analyzed SDR data from 400 consecutive Latin American patients (36.5% female) assessed for MRgFUS treatment at a tertiary center in Santiago, Chile. All patients had confirmed diagnoses of PD or ET. SDR values were extracted from preoperative CT scans using standard MRgFUS planning software. Descriptive statistics were computed by sex and diagnosis. SDR values were stratified into four categories: <0.35, 0.35–0.39, 0.40–0.45, and 0.46, or more. Spearman correlations were calculated to assess relationships between age and SDR in the full cohort and by sex. Independent t-tests were performed to compare SDR across sex and diagnostic groups. Results: The mean age of the cohort was 63.2 years (SD ±10.9). Overall, 87% of patients had SDR over 0.40, with 26.5% in the 0.40–0.45 range and 60.5% with SDR 0.46 or more. SDR between 0.35–0.39 was found in 10% (n=40), and only 3.0% (n=12) had SDR below 0.35. No significant differences in mean SDR were observed between males and females within either diagnostic group. However, a moderate negative correlation between SDR and age was identified in females (p = 0.0042), suggesting an age-related decline in SDR among women. No such trend was observed in males. Discussion: This study provides the first detailed SDR characterization in a Latin American cohort with PD and ET. The high prevalence of favorable SDR is consistent with reports from North American and European populations, indicating similar anatomical suitability for MRgFUS in this region. The observed sex-specific correlation with age suggests a potential biological or structural difference in skull density dynamics between males and females. These findings underscore the importance of age- and sex- specific interpretation when considering SDR-based eligibility for MRgFUS. Conclusions: Most Latin American patients evaluated for MRgFUS in this cohort demonstrated favorable SDR profiles. The results support the broader implementation of MRgFUS programs across the region and highlight the need for prospective, outcome-based studies to refine SDR thresholds and better understand sex-based variability.
Derechos de autor 2025 Carlos Juri, Pamela Herrera, Carolina Sepúlveda, Elías Fernández, Wilhelm Uslar, Bárbara Wipe, Bárbara Espinoza, José Lorenzoni https://creativecommons.org/licenses/by/4.0
Ozono y Corticoides en Dolor Espinal: Estudio Comparativo.
Introducción: El dolor espinal crónico, tanto lumbar como cervical, es una causa frecuente de incapacidad y afecta considerablemente la calidad de vida de los pacientes. Los tratamientos intervencionistas con corticoides han demostrado eficacia a corto plazo, aunque limitada en duración. El ozono médico, por sus propiedades antiinflamatorias, antioxidantes y analgésicas, ha sido propuesto como terapia complementaria. Este estudio compara la eficacia del tratamiento con corticoides solos frente a la combinación de corticoides y ozono en el manejo del dolor espinal. Método: Se llevó a cabo un estudio clínico prospectivo, comparativo y no aleatorizado en 38 pacientes (edades entre 20 y 80 años) con diagnóstico de dolor espinal crónico de origen discal o facetario. Se dividieron en dos grupos: • Grupo A (n=16): recibió una única infiltración de corticoides (triamcinolona o dexametasona) guiada por fluoroscopía. • Grupo B (n=16): recibió la misma dosis de corticoide combinada con ozono médico (25–40 µg/mL), ajustado según técnica y localización anatómica. Se realizaron controles clínicos a 1, 3 y 6 meses utilizando la escala visual análoga (EVA) para el dolor y el índice de discapacidad de Oswestry (ODI) para la funcionalidad. También se documentaron eventos adversos y consumo de analgésicos. Resultados • A 1 mes, el Grupo B mostró una reducción del 65% en EVA frente al 45% en el Grupo A (p < 0.01). • A 3 meses, el Grupo B mantuvo una mejoría del 60%, mientras que el Grupo A disminuyó al 30%. • En ODI, el Grupo B evidenció una mejora funcional del 42%, superior al 25% del Grupo A. • El uso de analgésicos se redujo un 70% en el Grupo B frente al 40% en el Grupo A. • No se reportaron efectos adversos graves. Ambos grupos presentaron eventos leves y transitorios como cefalea o dolor local postinfiltración. Discusión: La combinación de ozono médico con corticoides mostró superioridad sobre el uso exclusivo de corticoides, logrando mayor alivio del dolor, mejor recuperación funcional y reducción significativa en el uso de analgésicos. Esta sinergia terapéutica se explica por la capacidad del ozono para modular el estrés oxidativo, disminuir citoquinas proinflamatorias y reducir la presión intradiscal, potenciando así el efecto antiinflamatorio de los esteroides. Nuestros resultados coinciden con meta-análisis y ensayos recientes que describen beneficios sostenidos y un perfil de seguridad favorable para la ozonoterapia en el tratamiento del dolor espinal. La ausencia de complicaciones graves en este estudio refuerza su viabilidad, especialmente en pacientes que requieren prolongar el efecto analgésico sin recurrir a múltiples infiltraciones con corticoides. Conclusiones: La combinación de ozono médico con corticoides ofrece beneficios clínicos superiores al uso exclusivo de corticoides en el tratamiento del dolor espinal crónico. Mejora de forma significativa el alivio del dolor, la recuperación funcional y la reducción del consumo de analgésicos, sin aumentar los riesgos para el paciente. Estos hallazgos respaldan la inclusión del ozono como terapia coadyuvante en protocolos intervencionistas del dolor espinal y motivan la realización de estudios más amplios y controlados.
Derechos de autor 2025 Ivan Castillo https://creativecommons.org/licenses/by/4.0
Tratamiento de la Escoliosis Neuromuscular, Espasticidad y Luxación Dolorosa de Caderas en un Tiempo Quirúrgico. Instrumentación Espino Pélvica, Rizotomía y Drezotomía
Introducción: La escoliosis neuromuscular, la espasticidad y la luxación dolorosa de caderas afectan hasta al 80 % de los pacientes con Encefalopatía Crónica No Evolutiva (ECNE) en sus formas más severas. El tratamiento quirúrgico de estas condiciones combinadas representa un gran desafío, especialmente en presencia de múltiples comorbilidades. El objetivo de este trabajo es presentar nuestra experiencia en el abordaje quirúrgico simultáneo de la escoliosis neuromuscular y la luxación espástica dolorosa de caderas, en el marco de un tratamiento multidisciplinario. Según nuestro conocimiento, se trata del primer reporte que describe esta estrategia combinada. Método: Estudio retrospectivo y analítico de 5 pacientes con ECNE y cuadriparesia espástica (GMFCS V), con edad promedio de 11,2 años, que presentaban escoliosis, espasticidad y luxación dolorosa de caderas, todas con indicación quirúrgica. Se realizó, en un solo tiempo quirúrgico, artrodesis espino pélvica instrumentada para corregir la deformidad espinal, asociada a rizotomía y drezotomía para el control del dolor y la espasticidad. Se evaluaron radiografías pre y postoperatorias, así como niveles de dolor y espasticidad. Resultados: Se obtuvo una corrección significativa de la escoliosis con buen balance espino pélvico en los planos coronal y sagital. La combinación de rizotomía y drezotomía permitió un control efectivo del dolor y la espasticidad en miembros inferiores. Estas mejoras facilitaron la sedestación, la higiene y los procesos de rehabilitación, impactando positivamente en la calidad de vida. Discusión: El tratamiento de pacientes con ECNE GMFCS V requiere un abordaje interdisciplinario, dada la coexistencia de dolor, deformidades ortopédicas, espasticidad severa, compromiso neurológico y otras comorbilidades que afectan la calidad de vida. En casos extremos con luxación dolorosa de caderas, escoliosis y espasticidad generalizada, las técnicas ortopédicas aisladas o el control del tono mediante toxina botulínica o bomba de baclofeno resultan insuficientes. En nuestra experiencia, la combinación de drezotomía y rizotomía dorsal selectiva, junto con la fusión espinal y la cirugía de caderas en un mismo tiempo quirúrgico, ofrece un abordaje integral y de alta complejidad que reduce la espasticidad, alivia el dolor y mejora de forma significativa el confort y la calidad de vida, incluso en los pocos casos que requirieron cirugía de rescate de caderas. Conclusiones: Este enfoque multidisciplinario representa una alternativa terapéutica integral y eficaz para pacientes con ECNE y alta complejidad clínica.
Derechos de autor 2025 Yamila Basilotta, Beatriz E Mantese https://creativecommons.org/licenses/by/4.0
Rizotomía Dorsal Selectiva: Análisis de dos Técnicas de Sección de Raíces Dorsales Sensitivas
Introducción: La rizotomía dorsal selectiva (RDS) es una cirugía irreversible, cada vez más utilizada para tratar los trastornos de la marcha en niños con encefalopatía crónica no progresiva, mediante la reducción de la espasticidad. Se ha observado que una mayor proporción de raíces seccionadas logra una mejor reducción de la espasticidad, aunque con el riesgo de efectos neurológicos adversos por desafección excesiva. Si bien existen estudios que documentan beneficios y complicaciones de la RDS a corto y largo plazo, no se han comparado técnicas en cuanto a su impacto sobre la marcha y la preservación de la fuerza muscular. Este estudio tuvo como objetivo analizar y comparar la eficacia de dos técnicas de RDS con monitoreo neurofisiológico intraoperatorio, mediante análisis de marcha tridimensional instrumentado. Método: Este estudio retrospectivo, aprobado por el Comité de Ética, incluyó pacientes con parálisis cerebral espástica que cumplieron: SDR realizada por el mismo neurocirujano (2009–2019), análisis de marcha 3D previo (<21 meses) y posterior (2–31 meses) a la cirugía, condición ambulatoria en ambas evaluaciones, ausencia de otras cirugías en ese intervalo y consentimiento para uso de datos. Se compararon dos técnicas bilaterales de L1 a S1: clásica (Peacock, sección de hasta el 50% de las raíces) y conservadora (Molenaers: L1 25%, L2–L4 33%, L5 25%, S1 15%). Todos los pacientes realizaron RM cerebral y de columna, evaluación urológica con ecografía pre y postmiccional (y estudio urodinámico si era necesario) y recibieron rehabilitación intensiva 5 días por semana durante un año. La espasticidad se evaluó con la escala de Ashworth modificada en cinco grupos musculares, y la fuerza muscular con la escala de Kendall. Resultados: Se estudiaron un total de 17 pacientes. Ambos grupos mostraron mejoras en el patrón de marcha y reducción de espasticidad. Sin embargo, los pacientes tratados con la técnica conservadora presentaron un aumento significativo (p = 0,04) en la potencia neta del tobillo (1,37±0,61 W/BW) frente a los operados con la técnica clásica (0,98±0,18 W/BW). Discusión: La rizotomía dorsal selectiva (SDR) reduce la espasticidad en parálisis cerebral, pero la evidencia sobre su impacto funcional a largo plazo es limitada. Este estudio comparó la técnica clásica (sección del 50% de las raíces) con una técnica conservadora (L1: 25%; L2–L4: 33%; L5: 25%; S1: 15%), evaluando resultados mediante análisis tridimensional de la marcha. Ambas lograron reducciones similares del tono y mejoras en el rango articular, sin diferencias clínicamente relevantes en el Gait Deviation Index. Sin embargo, la técnica conservadora preservó mejor la potencia neta del tobillo, evitando debilidad excesiva y optimizando el papel de los flexores plantares en la propulsión y estabilidad durante la marcha, lo que podría favorecer una rehabilitación más eficaz Conclusiones: La técnica conservadora no solo reduce la espasticidad, sino que favorece una mejor recuperación funcional para la rehabilitación y la marcha.
Simultaneous Unilateral MR-Guided Focused Ultrasound Pallidotomy and Thalamotomy for Severe and Tremulous Asymmetric Parkinson’s Disease
Introduction: Magnetic resonance–guided focused ultrasound (MRgFUS) has emerged as a minimally invasive therapeutic approach for movement disorders. A combined targeting approach involving the globus pallidus internus (GPi) and the ventral intermediate nucleus of the thalamus (Vim) in a single unilateral procedure may offer broader symptom control in Parkinson’s disease (PD) patients presenting with mixed motor symptoms, such as dyskinesia (DK) and tremor. Clinical description: We evaluated 7 patients with severe asymmetric Parkinson’s disease presenting with both dyskinesia and severe tremor who underwent unilateral MRgFUS lesioning of the globus pallidus internus (GPi) and the ventral intermediate nucleus of the thalamus (Vim) during the same treatment session. Motor function was assessed using the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III), before and after the intervention. Dyskinesia status (absent, present, or partially improved), UPDRS-IV scores, daily levodopa-equivalent dose (LED), and subjective perception of benefit were recorded during follow-up. The mean age was 67.4 ± 6.4 years, with a mean disease duration of 11.7 ± 4.7 years. The mean follow-up period was 3.4 ± 2.6 months (range 1–8). Baseline UPDRS-III scores averaged 49.6 ± 11.0, improving to 31.3 ± 10.3, corresponding to a 34.3% improvement (p < 0.05, Wilcoxon test). Mean UPDRS-IV scores improved from 9.0 ± 3.6 to 5.4 ± 1.9. The daily LED decreased from 802.1 ± 302.8 mg to 676.5 ± 250.1 mg. One patient developed a mild, transient lower limb paresis. No other major complications were observed during the follow-up period. Discussion: Unilateral MRgFUS lesioning of GPi+Vim yielded meaningful motor improvements and high patient-reported benefit rates in a short-term follow-up, with a reduction in both tremor and dyskinesia severity. These findings support the rationale for a combined target approach in selected PD patients, particularly those with disabling mixed motor features. The degree of UPDRS improvement is consistent with reported outcomes of single-target lesioning, suggesting that dual-target therapy may offer broader symptomatic coverage without a proportional increase in adverse events. Conclusions: In this small case series, unilateral MRgFUS GPi+Vim lesioning was associated with significant motor improvement and reduction in dyskinesia. Longer-term studies with larger cohorts are warranted to confirm durability, refine patient selection, and optimize targeting strategies.
Derechos de autor 2025 José Lorenzoni, Javiera Benavides, Carlos Juri https://creativecommons.org/licenses/by/4.0
Early Experience of Stereotactic Biopsy of Brain Lesion in Nepal
ntroduction: Stereotactic brain biopsy has recently been started in Nepal. Though the field has developed significantly in other parts of the world, Nepal still has a long way to go. This study describes the initial challenges, the technical constraints of starting the procedure in a tertiary center of Nepal. Method: This is a retrospective descriptive study performed at National Academy of Medical Sciences, Bir Hospital. Data were collected from patients' hospital records and analyzed. Results: A total of twenty four patients underwent stereotactic frame based biopsy between 2020 and 2022. Biopsy reports were positive in twenty two patients and in two patients the results were inconclusive. Discussion: The field of stereotactic brain surgery has been developing in Nepal and has been used mainly for brain biopsy in different patients. Conclusions: Despite logistics and technical constraints, stereotactic biopsy has been used in Nepal.
Derechos de autor 2025 Prabhat Jha https://creativecommons.org/licenses/by/4.0
Subthalamic Nucleus Stimulation after Cingulotomy for Refractory Obssesive-Compulsive Disorder
Introduction: Obssesive compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and repetitive behaviors performed to relieve distress related to obsessions. It is a prevalent psychiatric condition that affects 2-3% of the population and almost 30% of the patients can be refractory to first-line pharmacotherapy and psychotherapy. In these cases, neurosurgical procedures such as stereotactic lesioning and deep brain stimulation (DBS) are an option. Combining these treatments is relatively uncommon. The aim of this study is to report our experience with subthalamic nucleus (STN) stimulation in a patient that had previously undergone bilateral cingulotomy and relapsed. To our knowledge, this therapeutic approach has not been published in the literature before. Clinical description: 36 year-old male. OCD diagnosed more than twenty years ago with sexual and intra-psychic aggressive obsessions associated to compulsions dominated by mental rituals and repetitive hand movements. He required four hospital admissions, one of them after a major depressive episode with suicide attempt. Electro-convulsive therapy was carried out at that time. He received cognitive-behavioral therapy and complete pharmacological treatment. The patient had a severe OCD with 34 points in Yale-Brown Obsessive-Compulsive Scale (YBOCS). SPECT imaging showed bilateral prefrontal cortex hypoperfusion and right caudate nucleus hyperactivity. Ultimately, bilateral stereotactic cingulotomy was performed in 2011. The surgery resulted in dramatic improvement of his OCD and mood disorder. 1 year postoperatively YBOCS was reduced by 20 points (59% improvement) and depression remitted. However, 10 years later he showed progressive worsening of the OCD symptoms and mild depression. After several sessions of repetitive trans-cranial magnetic stimulation (rTMS) that had transient effect, the patient was still very disabled (YBOCS= 24). We proposed anteromedial subthalamic nucleus stimulation (amSTN DBS). He was implanted in December 2023 and the stimulator was turned on after one month with a conventional monopolar configuration at 130Hz and 60µs. Middle contacts were chosen according to the postoperative images and electrophysiological data. Interestingly, we found an unusual high power local field potential (LFP) in the theta band (7.81Hz) that was clearly reduced by increasing stimulation (Fig 1). During follow up we had to activate more dorsal contacts using a bipolar configuration due to a dysphoric-anxious reaction immediately elicited by ventral STN stimulation with amplitudes above 2.0mA. Micturition disturbances and subtle right upper limb dyskinesia were also observed. The former resolved with anticholinergic medication and the latter is not troublesome. The patient has now been followed for 20 months and reached YBOCS scores indicating mild OCD (12 points) with 50% improvement. There are no signs of depression. He is now able to work, live alone and take care of his daughter using low doses of medication. Discussion:Different targets, either for lesioning or DBS, have been proposed to treat refractory OCD. Most of them within the same neurobiological circuit involved in OCD pathogenesis. The ventral capsule (VC) and ventral striatum (VS- Nucleus accumbens) are frequently targeted regions. VC/VS DBS significantly decrease OCD symptoms with up to 46% improvement in YBOCS score. A randomized controlled trial of amSTN DBS demonstrated that active stimulation reduced YBOCS score by 11 points (40% improvement) compared to sham-stimulation and 75% of patients were responders. Metanalyses comparing both targets failed to show superiority of one over the other. However, amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. Capsulotomy and cingulotomy can effectively reduce OCD symptoms with similar results compared to DBS, although with higher incidence of adverse events, as these are irreversible and non-adjustable procedures. Our patient responses to cingulotomy and DBS were comparable to those in the literature and had a great impact in his quality of life. In this case, DBS acted as a rescue therapy after the disappearance of the cingulotomy effects and proved to be very helpful. Other cases of ventral capsule stimulation after capsulotomy have been reported with good results Conclusions:Either ablative or DBS techniques are effective to alleviate symptoms of severe treatment-resistant OCD. Combining these therapies after one of them has failed may be a reasonable option in selected patients.
Derechos de autor 2025 Federico Salle, Sebastian Lema, Aurana Erman, Silena Correa, Germay Rodriguez, Nicolas Legorburu, Humberto Prinzo https://creativecommons.org/licenses/by/4.0
Primer Reporte de la Asociación entre Enfermedad de Parkinson de Inicio Temprano Asociada a la Variante C.1192c>T del Gen GBA1 con Abordaje Terapeutico Mediante Neuro-Hifu por RMN Unilateral en Nucleo Subtalamico Derecho
Introducción: El gen GBA codifica la glucocerebrosidasa; variantes patogénicas aumentan el riesgo de enfermedad de Parkinson (EP), asociándose a inicio más temprano, progresión rápida y síntomas cognitivo-conductuales. Presentamos una paciente con EP de inicio temprano portadora de la mutación c.1192C>T en GBA-1, primera en recibir tratamiento avanzado con neuroHIFU por RMN en nuestro conocimiento. Clinical description: Mujer de 48 años, antecedente familiar de temblor en abuela materna. En 2019 comenzó con dolor, rigidez y bradicinesia en miembro superior izquierdo; único síntoma premotor: constipación. Sin hiposmia ni RBD. Inició rasagilina y pramipexol LP con buena respuesta. Panel genético confirmó variante heterocigota patogénica c.1192C>T en GBA-1. En 2022 se agregó levodopa; en 2023 presentó discinesias izquierdas, parcialmente controladas con amantadina. En julio 2025, ante wearing-off a las 2,5 horas y discinesias incapacitantes, se realizó subtalamotomía derecha por neuroHIFU, con mejoría de UPDRS III de 45/108 a 20/108 (55%). Se prolongó tiempo “on”, reduciendo dosis de levodopa y pramipexol LP, con control de discinesias. Única secuela inmediata: discinesias braquiales izquierdas transitorias. Discusión: Múltiples estudios han demostrado que los pacientes con Parkinson y mutaciones en el gen GBA1 tienen un mayor riesgo de desarrollar un deterioro cognitivo y síntomas psiquiátricos (como depresión, ansiedad, apatía, alucinaciones y hasta psicosis) a largo plazo, en comparación con pacientes sin esta mutación. Esta asociación es tan fuerte que la presencia de la mutación se considera un factor de riesgo independiente para la demencia y psicosis en la EP. Debido a este riesgo, la estimulación cerebral profunda (DBS) bilateral del núcleo subtalámico puede ser una opción de tratamiento pero considerándose que se tiene un riesgo aumentado de acelerar los síntomas cognitivos/psiquiátricos preexistentes en esta población de riesgo. Por ello, el uso de técnicas mínimamente invasivas y potencialmente más seguras, como la neuroablación por neuroHIFU unilateral del núcleo subtalámico, emerge como una alternativa prometedora. Esta opción permite mejorar los síntomas motores de forma significativa, con un menor impacto sobre la cognición y el estado neuropsiquiátrico, lo cual la hace especialmente atractiva para pacientes con perfiles genéticos de mayor vulnerabilidad, como los portadores de mutaciones en el gen GBA1. Conclusiones: El uso de neuroHIFU por RMN unilateral en NST en pacientes con EP de inicio temprano asociado a mutación del GBA-1 ha demostrado ser una alternativa segura y eficaz en los síntomas motores y mejorando la calidad de vida del paciente. En el caso de nuestra paciente, no se objetivaron efectos adversos relevantes en el seguimiento inmediato. Esto sugiere que esta técnica podría ser una opción prometedora para este subgrupo de pacientes.
Derechos de autor 2025 Jose Luis Alberto Etcheverry, Giselle Vaisenstein, Nicolas Barbosa, Nelson Ernesto Quintanal Cordero, Sergio Pampin, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
Spectral Analysis of Local Field Potentials in a Patient with Essential Tremor Treated with Deep Brain Stimulation in the Ventral Intermediate Nucleus of the Thalamus
Introduction: Deep Brain Stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is an established therapy for medically refractory essential tremor. Since 2014, 18 patients have undergone bilateral VIM DBS at our center in San Vicente Fundacion Rionegro Colombia. The recent availability of sensing devices such as the Percept RC has enabled direct analysis of local field potentials (LFPs) in vivo. We are presenting the characterization of the spectral dynamics of thalamic LFPs in our last patient with essential tremor implanted with the Percept RC system, comparing stimulation OFF and ON states across motor tasks. Method: A 72-year-old male with familial essential tremor underwent bilateral VIM DBS with a Percept RC neurostimulator. LFPs were recorded during three motor tasks: passive listening (15–45s), tapping with auditory cue (50–87s), and self-paced tapping (88–120s). Power spectral density (PSD) was computed using Welch’s method. Band-specific power was extracted for delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–100 Hz) bands. Peak frequency was also identified. Results: Resultados: Results: DBS ON induced distinct spectral changes. In passive listening, peak frequency shifted from 10.01 Hz to 23.19 Hz, with reduced alpha and beta power. During tapping with cue, low-frequency bands remained dominant, with slight increases in delta and theta. In self-paced tapping, peak frequency dropped from 21.73 Hz to 3.17 Hz, with increased delta and theta power and reduced alpha and beta activity. These findings suggest DBS modulates thalamocortical rhythms differently across motor states. Discusión: The spectral analysis may reveals that DBS stimulation induces significant modulation of thalamocortical activity. In passive listening, stimulation shifts the dominant frequency toward higher beta ranges while suppressing overall band power, suggesting a state of cortical desynchronization. During motor tasks, particularly self-paced tapping, DBS appears to reduce high-frequency activity and enhance low-frequency bands, possibly reflecting altered motor planning and execution. These observations may support the role of DBS in reshaping neural oscillatory dynamics and may support future strategies for optimizing stimulation parameters in essential tremor therapy. Conclusions: The observations on this case could show the feasibility of LFP spectral analysis using Percept RC in essential tremor. DBS alters oscillatory dynamics in a task-dependent manner, supporting its role in motor circuit regulation. These insights may inform future strategies for adaptive DBS and biomarker development.
Derechos de autor 2025 Adriana Lucia Lopez Rios, William Duncan Hutchison, Juan Sebastian Saavedra Moreno, Daniel Henao Lopez, Manuela Jaramillo Quintero, Manuela Pelaez Soto, Luis Fernando Botero Posada, Carlos Anibal Restrepo Bravo https://creativecommons.org/licenses/by/4.0
Spinal Cord Stimulation in a Complex Case of Post-Traumatic Brachial Plexus Injury: Pain Relief and Functional Impact
Introduction: Traumatic brachial plexus injury may lead to chronic refractory neuropathic pain and severe motor deficits, requiring complex therapeutic approaches, including neuromodulation. Spinal cord stimulation (SCS) has emerged as a promising alternative, with increasing evidence of its benefits in selected cases.¹⁻³ Clinical description: A 38-year-old male with chronic neuropathic pain and motor deficit in the right upper limb due to traumatic brachial plexus injury from a motor vehicle accident with root avulsion 7 years ago. He developed intense pain, weakness, and functional loss. In 2019, he underwent phrenic nerve transfer to the right biceps; in 2022, a sural nerve graft to the same limb. In 2021, two spinal cord stimulation electrodes were implanted, with partial symptom relief. Later, pain worsened—mainly in the right forearm—becoming refractory to morphine and associated with suicidal ideation. He was on Pregabalin, Chlorpromazine, Dipyrone, Clonidine, Lactulose, Methadone (with a history of opioid use disorder), and Mirtazapine. On neurological exam: global strength grade 5, except in the right upper limb (proximal grade 3, distal grade 4, and grade 0 in the hand), with hypotrophy, hypotonia (previous orthosis use), tactile hypoesthesia, and deep tendon reflexes 2+/4 globally, absent on the right upper limb. He was admitted for elective spinal cord stimulator generator replacement, maintaining previous programming (200 Hz; 350 µs; 4.0 mA) with electrode repositioning. Postoperatively, he had significant pain relief, improved quality of life and mental state, with no suicidal ideation, remaining under outpatient follow-up. Discussion: SCS has shown efficacy in reducing refractory pain, with good initial response in up to 86% of cases and sustained benefit in 69%, though it may decrease over time.¹ Recent reviews emphasize advances in mechanisms of action, including high-frequency stimulation and modulation of nociceptive pathways.² These reinforce the role of neuromodulation in chronic neuropathic pain.³ Conclusions: This case supports SCS as fundamental in selected cases of refractory neuropathic pain after brachial plexus injury,¹⁻³ especially with device revision. Multidisciplinary care and individualized selection are essential to optimize outcomes and quality of life.
Derechos de autor 2025 Isis Franco Martin, Igor Bagini Mateus, Julia Alvim Lage, Lucas Fernandes Neves, Emanuele Pires Canela Dos Santos, Isabela Costa Ribeiro, Delcole Delcole, Leonardo Galli Hamamoto https://creativecommons.org/licenses/by/4.0
Deep Brain Stimulation of the Internal Globus Pallidus in Primary Generalized Dystonia: A Case Report
Introduction: Primary generalized dystonia is a movement disorder characterized by involuntary and sustained muscle contractions, leading to abnormal postures and significant functional impairment. Deep brain stimulation (DBS) of the internal globus pallidus (GPi) has been recognized as an effective therapeutic alternative in cases refractory to pharmacological treatment.¹ Clinical description: A 32-year-old male patient, previously healthy, began experiencing involuntary muscle contractions at age 17, progressing to generalized dystonia over four years. The condition was refractory to multiple pharmacological treatments (anticholinergics, benzodiazepines, and baclofen). Neurological examination revealed severe torticollis, rotation and flexion of the trunk to the left, and dystonic movements in the limbs, with no other findings. The score on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was 78/120. After multidisciplinary evaluation, bilateral GPi DBS was indicated. The procedure was uneventful. Initial programming parameters were 130 Hz, 3.2 V, and a pulse width of 60 μs. In the first few weeks, there was progressive improvement in symptoms, achieving a 60% reduction in the BFMDRS score. The patient remains under follow-up, showing significant improvement in daily activities and continues outpatient care every three months. Discussion: GPi DBS proved to be highly effective in this case, supporting data from the literature regarding its indication in refractory primary dystonia.² Sustained clinical improvement over two years demonstrates not only the efficacy of the method but also the safety of the procedure when performed by an experienced team. Key aspects include careful patient selection, individualized programming adjustments, and rigorous follow-up to optimize outcomes.³ Conclusions: Deep brain stimulation of the GPi represents a safe and effective therapeutic alternative for patients with refractory primary generalized dystonia, providing long-lasting functional improvement and significant quality of life benefits.²,³
Derechos de autor 2025 Isis Franco Martin, Amanda Simionatto Fontana, Isabella Cristina Carvalho Corrêa, Luis Otávio Tabuas Bezerra, Bruna Durigan Baia, Julia Frizzo Zornitta, Ana Luiza Londero Schroder, Emanuele Pires Canela Dos Santos https://creativecommons.org/licenses/by/4.0
Functional Resection of the Mesial Temporal Lobe in Drug-Resistant Epilepsy: Case Report and Multidisciplinary Review
Introduction: Mesial temporal lobe epilepsy (MTLE) is the most common cause of drug-resistant focal epilepsy and is often linked to hippocampal sclerosis. Surgical resection of the epileptogenic zone is an effective and established treatment in functional neurosurgery, showing high long-term seizure freedom rates¹. Preserving cognitive and language functions, especially in the dominant hemisphere, requires careful planning with functional mapping and individualized approaches.² Clinical description: A 29-year-old man presented with epilepsy starting at age 10, marked by epigastric aura followed by oroalimentary automatisms and impaired awareness. He became resistant to multiple antiepileptic drugs. MRI revealed left hippocampal sclerosis, and video-EEG confirmed seizure onset in the left mesial temporal lobe. Neuropsychological tests showed verbal memory deficits. Wada test confirmed left-hemisphere language dominance with contralateral memory. An anterior left temporal lobectomy, including amygdalohippocampectomy, was performed. Intraoperative electrocorticography (ECoG) and neuronavigation with preoperative functional MRI (fMRI) were used to preserve eloquent cortex. The procedure was uneventful. The patient was discharged on the third postoperative day without neurological deficits. After 12 months, he was seizure-free (Engel class IA), with improved subjective memory and full social reintegration. Postoperative MRI confirmed adequate resection and preservation of key cortical areas. Discussion: Functional neurosurgery must balance seizure control and preservation of function. Multimodal evaluation with MRI, video-EEG, neuropsychological assessment, and functional imaging improves surgical outcomes.² Studies show 70–80% of MTLE patients achieve seizure freedom after surgery.¹ The combined use of fMRI and ECoG is critical for identifying eloquent cortex, especially in dominant hemispheres.³ Conclusions: Anterior mesial temporal lobectomy, guided by functional mapping and multidisciplinary evaluation, is a safe and effective approach for treating drug-resistant MTLE. Early surgical intervention improves long-term seizure control and quality of life with minimal functional morbidity.¹,²,³
Derechos de autor 2025 Isis Franco Martin, Talita Sousa Brito, Juliana Araujo Rech Lima, Thiago Bonafé, Matheus Souza Ribeiro, Marco Antonio Oliveira Santos Junio, Isadora Luiza Babinschi Dias De Souza, Emanuele Pires Canela Dos Santos https://creativecommons.org/licenses/by/4.0
Unilateral MR-Guided Focused Ultrasound Subthalamotomy in Parkinson’s Disease: Outcomes of 70 Consecutive Cases
Introduction: Magnetic resonance–guided focused ultrasound (MRgFUS) unilateral subthalamotomy is an emerging non-invasive lesioning modality for Parkinson’s disease (PD), targeting the subthalamic nucleus (STN) to improve motor performance and reduce dopaminergic medication requirements, thereby potentially mitigating long-term treatment complications. Method: We evaluated 70 consecutive PD patients who underwent MRgFUS unilateral subthalamotomy, with at least 3 months of follow-up. Variables assessed included age, disease duration, follow-up period, sex distribution, and post-procedural dyskinesia incidence. Primary endpoints were changes in levodopa equivalent daily dose (LEDD) and Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) scores in the OFF-medication state, from baseline to last follow-up. Paired t-tests were applied, with significance set at p < 0.05. Results: The cohort comprised 50 men and 20 women, with a mean age of 59.8 years (range, 33 to 79 years), a mean PD duration of 7.2 years (range, 2 to 16 years), and a mean follow-up of 6.3 months (range, 3 to 30 months). Mean LEDD decreased from 754.8 ± 495.8 mg to 575.0 ± 380.3 mg (p < 0.05), while UPDRS-III OFF scores improved from 42.8 ± 9.2 to 26.5 ± 7.8 (p < 0.001). Post-procedural dyskinesias were reported in 14.7% of cases, predominantly mild and self-limiting. Transient adverse events such as gait disturbance, dysarthria, paresis, dystonia/diskinesia were generally minor and resolved spontaneously in most instances. Adverse effects at the last follow-up were mild or moderate in 6 patients (8.5%). No procedure-related mortality, infections, or severe complications were observed. Discussion: In this large consecutive series, MRgFUS unilateral subthalamotomy demonstrated statistically and clinically significant improvements in both motor function and medication burden at short-term follow-up. The low incidence of mild, transient dyskinesias reinforces its safety profile. These findings are consistent with previous controlled trials and pilot studies, extending the evidence base for STN lesioning in PD. Limitations include the retrospective design, absence of a control arm, and relatively short follow-up; prospective, randomized studies are warranted to confirm efficacy and long-term durability. Conclusions: MRgFUS unilateral subthalamotomy is an effective intervention for advanced PD, yielding meaningful motor improvement and reduced medication dependency, without significant permanent adverse effects.
Derechos de autor 2025 Carlos Juri, Pablo Venegas, Wilhelm Uslar, Carolina Sepulveda, Barbara Wipe, Elías Fernandez, Tomás Rodríguez, José Lorenzoni https://creativecommons.org/licenses/by/4.0
Impact of Generator Replacement in a Patient with Advanced Parkinson’s Disease
Introduction: Deep Brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson’s disease (PD) who are refractory to optimized pharmacological therapy. Continuous stimulation is essential to maintain motor stability, and battery depletion can result in rapid clinical worsening. Recent studies confirm the long-term benefits of DBS on motor function, quality of life, and chronic neuromodulation.¹ Clinical description: A 62-year-old male with a 12-year history of PD (akinetic-rigid subtype) initially presented with freezing, bradykinesia, and early morning rigidity. Despite treatment with pramipexole, entacapone, multiple levodopa formulations, clonazepam, tramadol, melatonin, and amantadine, motor symptoms remained refractory. In 2022, he underwent bilateral DBS implantation in the subthalamic nucleus (STN), resulting in significant rigidity improvement. After generator battery depletion, the patient experienced progressive return of symptoms: worsening bradykinesia, chronic pain, and loss of independence in daily activities. Neurological examination showed severe bradykinesia, marked hypomimia, dysarthric speech, mild asymmetric tremor, and freezing. Cranial CT confirmed correct lead placement. The patient underwent generator replacement, programming was reestablished using standard bilateral STN parameters: 130 Hz, 60 µs pulse width, 2.8 V (left) and 3.0 V (right), in monopolar configuration (contacts 1–2 left, 9–10 right). Immediate postoperative improvement was noted, with reduced rigidity and bradykinesia. At one-month follow-up, the patient reported complete pain resolution, functional recovery, improved sleep, and high satisfaction. Discussion: This case illustrates the essential role of continuous DBS in motor control for advanced PD. Studies report sustained improvements in UPDRS-III and PDQ-8 scores after DBS¹. Patient selection based on clinical and imaging profiles remains key to optimal outcomes.² Generator replacement is safe and effective, with low complication rates.³ Conclusions: DBS generator replacement led to rapid functional recovery and quality of life improvement. This case reinforces the need for structured follow-up, early battery monitoring, and individualized DBS care.2,3
Derechos de autor 2025 Isis Franco Martin, Igor Bagini Mateus, Giovanna Novelli D. Kaczam, João Vitor Medeiros Lech, Giorgia Novelli D. Kaczam, Ana Luiza Londero Schroder, Rhaymysom Jasmy Gomes Abreu, Emanuele Pires Canela Dos Santos https://creativecommons.org/licenses/by/4.0
Sustained Relief of Central Pain after Stroke with Stereotactic Thalamotomy: A Case Secondary to Aneurysm Embolization.
Introduction:Central neuropathic pain is a debilitating condition resulting from lesions in the central nervous system, such as strokes, trauma, or neurovascular procedures. Its management represents a major clinical challenge, as it often does not respond to conventional pharmacological treatment. In refractory cases, functional surgical interventions, such as stereotactic thalamotomy, have been used with promising results, providing symptomatic relief and improvement in quality of life¹⁻³. Method:Male, 55 years old, with a history of chronic headache since childhood, presented with progressive worsening over the past six months, accompanied by vomiting. Neurological examination revealed anisocoria with reactive pupils and mild left-sided dysmetria. CT angiography showed an aneurysm of the left anterior inferior cerebellar artery (AICA). Endovascular embolization of an arteriovenous fistula and the aneurysm with liquid embolic material was performed, achieving good pedicle occlusion. After the procedure, imaging demonstrated interruption of flow in the left AICA, resulting in an ischemic stroke, with left peripheral facial paralysis, painful dysesthesia in the right hemibody (face, arm, and leg), and gait ataxia. Pain was partially controlled with Gabapentin and Carbamazepine. Due to refractoriness, stereotactic thalamotomy targeting the left Centromedian (CM) and Ventral posterolateral (VPL) thalamic nuclei was performed without complications. Initially, pain persisted, but the patient was informed about the possibility of delayed response. Over time, Duloxetine was introduced, leading to progressive improvement. After one year, there was significant relief of neuropathic pain. The patient currently remains on Gabapentin and Duloxetine, with occasional headaches and marked improvement in quality of life. Discussion:The management of central neuropathic pain requires an individualized approach. Many patients are refractory to standard pharmacological therapy². In such cases, functional neurosurgery, such as stereotactic thalamotomy targeting the CM and VPL nuclei, may be an effective alternative. Recent studies have shown favorable outcomes, with a low complication rate and sustained response¹,³. Conclusions:In cases of refractory central neuropathic pain, stereotactic thalamotomy represents a viable option. Continuous follow-up and personalized treatment are essential to improve clinical outcomes and quality of life.
Derechos de autor 2025 Isis Franco Martin, Igor Bagini Mateus, Henrique Aguiar Lima, Rafael Leão De Moraes, Emanuele Pires Canela Dos Santos, Bruna Dias Rocha, Paulo Luiz Da Costa Cruz, Paulo Niemeyer Soares Filho https://creativecommons.org/licenses/by/4.0
Mejora en Resultados de Biopsia Estereotactica en Tumores Cerebrales.
Introducción: Hemos trabajado en la técnica de biopsia estereotáctica desde 1992, tanto en el instituto de neurocirugía como en Clínica Alemana de Santiago. Presentamos una serie clónica prospectiva, hecha por el mismo equipo quirúrgico, en clínica alemana, siguiendo un protocolo y trabajo en equipo, junto a patólogos y neuro radiólogos. Analizamos los resultados en términos de mortalidad, eficacia y complicaciones y nos comparamos con series publicadas anteriormente. Método: Analizamos una serie prospectiva hecha en Clínica Alemana de Santiago, entre junio 2000 y julio 2025, desde que contamos con patólogo y software de planificación (stryker, medtronic s7 2010 y actualmente brain lab 2024), se trata de 103 casos (51 mujeres, 52 hombres) edad media 55 años (3 - 82 años), donde analizamos los resultados histológicos además de complicaciones: 2 casos con empeoramiento motor transitorio en postop. 1 caso de biopsia definitiva no diagnostico que hubo que repetir meses mas tarde una vez suspendido corticoides (linfoma primario en inmunocompetente). No hubo mortalidad en la serie, sin embargo, un caso hizo una hemorragia masiva luego de 7 días hecha la biopsia, en contexto de una trombofilia familiar con anticoagulantes orales. Comparamos estos resultados y nuestro proceso en pabellón con respecto a series anteriores. Discusión: La mejora en acceso a mejor tecnología como software de planificación, imágenes digitales y la mejora en conocimientos. Y destrezas, ha favorecido los mejores resultados de las biopsia estereotáctica, en su eficacia y en su seguridad para el paciente. Los resultados son comparables a la literatura actual. Las publicaciones muestran mejor eficacia, precisión y menor mortalidad en biopsias hechas con marcos versus sistemas de navegación, sin embargo, tal vez en niños menores de 2 años y lesiones de fosa posterior pueden tener ventajas los sistemas de navegación. Conclusiones: La biopsia estereotáctica de tumores cerebrales, hecha en un trabajo en equipo multidisciplinario, con un adecuado manejo tecnológico, es una técnica segura y efectiva en casos de tumores intra axiales cerebrales, profundos, pequeños y/o multicéntricos.
Derechos de autor 2025 Felipe Valdivia, Rodrigo Vallejo, José Miguel Montes, Rosario Fuenzalida, Elena Dulanto, Patricio Paredes, Marcela Gallegos https://creativecommons.org/licenses/by/4.0
Deep Brain Stimulation Programming Based on Local Field Potentials Detection in Parkinson Disease: A Single Center Experience
Introduction: Subthalamic nucleus DBS (STN-DBS) is an established effective therapy for refractory symptoms in Parkinson’s disease (PD). Perceptive devices that detect local field potentials (LFPs) in the vicinity of the stimulating electrodes allow identification and use of physiological biomarkers that help determining the best contact to stimulate,1 and allow chronic detection of signals for follow-up and further therapy adjustments. The investigator’s interest is to describe our center’s experience, Hospital San Vicente Fundacion Rionegro in the use of LFP-detecting devices in the programming of patients implanted with perceptive devices for STN-DBS in PD,2 the signals found in the first session and their stability over time, stimulation parameters used chronically and outcomes in terms of levodopa-equivalent daily dose (LEDDs) reduction post-operatively in the last visit. Method: Cross-sectional descriptive study involving patients with PD and STN-DBS. All patients implanted from March 2024 through June 2025 were included, LFPs were measured in the off-medication state. Variables measured included demographic, clinical (diagnosis, age at onset, disease duration, LEDDs, MDS-UPDRS-III scale) and physiological (frequency of interest FOI for sensing at first post-operative programming session, band and stimulation parameters). Data was collected on an Excel database, analyzed in JASP software 0.19.3v. Numeric variables are presented as mean (SD) and qualitative variables in absolute and relative frequencies. Results: 25 patients (50 electrodes) were included in the analysis. Mean age at implant was 63.7 (8.1) y, mean duration of disease was 10.8 (5.1) y. All patients were implanted bilaterally at the STN. 15 (60%) patients had right-sided predominant symptoms whereas 10 (40%) had left-sided predominance. Mean FOIs were 15.8 (7.7) Hz for right-STN electrodes and 17.5 (4.4) for left-STN electrodes. All electrodes in left hemispheres showed beta band activity on the off state whereas only 2 electrodes on right hemispheres showed different FOIs (7.8 Hz on a patient with left-predominant tremor and 36 Hz on a patient with left-sided biphasic dyskinesia). No significant LFP activity was found on two patients (8%). First programming was on average on day 19 (13) post-implant. Last follow-up was done 151(120) days post-operatively. Mean LEEDs reduction was 557 (369.6) mg. Discussion: From our knowledge, this is the first report on real world data of LFP-based programming in Latin America, with up to 1.3 years of follow-up. Our data align with previous works, with most patients exhibiting high beta-band activity in the STN related to the off state.3 Theta activity in the contralateral STN to refractory arm tremor was found in one patient and low gamma correlated with biphasic dyskinesia in other. Parameters remained stable and no change in contact stimulated was required. High-power beta oscillations helped in selection of contact for chronic stimulation in most patients.4 Conclusions: LFP-based programming is a useful and efficient tool for chronic programming of STN-DBS in patients with PD. FOIs are usually within the low beta range but should be determined individually based on clinical features.
Derechos de autor 2025 Adriana Lucia Lopez Rios, William Duncan Hutchison, Carlos Anibal Restrepo Bravo, Daniel Henao Lopez, Manuela Pelaez Soto, Luis Fernando Botero Posada, Carlos Ignacio Velez Arango, Juan Sebastian Saavedra Moreno https://creativecommons.org/licenses/by/4.0
Neuromodulación Espinal para el Tratamiento de Dolor Neuropático Crónico por Avulsión del Plexo Braquial
Introducción: El dolor neuropático crónico tras avulsión traumática del plexo braquial (APB) constituye un desafío clínico significativo, con mecanismos centrales y medulares complejos, escasa respuesta a fármacos y literatura limitada sobre neuromodulación. Tradicionalmente, se ha recurrido a la drezotomía, una técnica eficaz pero invasiva, mientras que la estimulación espinal (SCS) ha sido poco explorada en este contexto. Método: Presentamos una serie de tres pacientes con dolor neuropático crónico secundario a APB, tratados con diferentes modalidades de SCS. Todos lograron una reducción del dolor superior al 90 %, mejorando sustancialmente la calidad del sueño, reduciendo la medicación y prescindiendo de hospitalizaciones adicionales para manejo de crisis dolorosas; además se observó reinserción social plena. En cuanto a las modalidades utilizadas, dos pacientes fueron tratados con estimulación burst-DR™; y otro con estimulación subperceptiva de alta frecuencia con sistema Medtronic , todas con resultados consistentes en el control del dolor. Discusión: El dolor tras APB se sustenta en mecanismos medulares: hiperactividad neuronal en la sustancia gelatinosa y el tracto de Lissauer, expansión de campos receptivos por desinhibición, pérdida de interneuronas inhibitorias y activación glial, lo que genera sensibilización central y ectopia en la raíz dorsal. La drezotomia, que destruye estas neuronas hiperactivas en láminas I–V del asta dorsal, ha mostrado eficacia (66–87 % de alivio significativo en series amplias), aunque con riesgo de déficits sensoriomotores. En contraste, la evidencia para SCS en BPA es escasa: la revisión sistemática de Dombovy-Johnson et al. identificó 41 pacientes, con resultados variables y tendencia a recurrencia del dolor en seguimientos prolongados. Entre los factores que explican la baja difusión histórica de SCS se destacan: cobertura incompleta del dolor distal (particularmente en mano), dificultad técnica para el avance de electrodos en presencia de cicatrices intradurales, pérdida de eficacia a largo plazo, y la fisiopatología particular de la avulsión preganglionar, donde los mecanismos periféricos están abolidos y la eficacia dependería de vías supraspinales más complejas. Un aspecto distintivo de nuestra serie es la utilización de modalidades avanzadas de estimulación —burst-DR™ y alta frecuencia —, que hasta donde conocemos no habían sido reportadas previamente en pacientes con avulsión traumática de plexo braquial. Este hallazgo refuerza la hipótesis de que la limitación histórica de la SCS podría deberse más a los parámetros convencionales de estimulación que a la neuromodulación en sí. Conclusiones: Nuestra serie evidencia que la estimulación espinal, en sus diferentes modalidades, puede ofrecer control excepcional del dolor en avulsiones de plexo braquial, con impacto positivo en la calidad de vida. Estos hallazgos sugieren que la SCS, podría constituir una alternativa eficaz y menos invasiva a la DREZ-otomy, justificando la realización de estudios prospectivos que comparen ambas técnicas e investiguen de manera sistemática la respuesta a las ondas de estimulación modernas.
Derechos de autor 2025 Brenda Iglesias, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
Neurosurgical Intervention in Chronic Pain Secondary to Traumatic Cervical Spinal Cord Injury: Case Report
Introduction: Refractory chronic pain remains a persistent challenge, severely impairing quality of life and often requiring approaches beyond conventional pharmacotherapy. In recent years, neurosurgical techniques such as motor cortex stimulation (MCS), deep brain stimulation (DBS), and focused ultrasound-guided thalamotomy (FUS) have shown promising results in selected patients.¹⁻³ Clinical description: A 46-year-old female presented with chronic neuropathic pain secondary to traumatic cervical spinal cord injury sustained 3 years earlier. The patient described continuous burning and stabbing pain affecting the left hemibody, predominantly the upper limb, significantly limiting daily activities and sleep. Despite optimized pharmacological management, including gabapentin, duloxetine, amitriptyline, and opioid rescue therapy, pain persisted at 8–9/10 on the Visual Analog Scale (VAS). Functional assessment revealed impaired mobility, sleep disturbance, and depressive symptoms associated with chronic pain. Given refractoriness, a neurosurgical approach was proposed. After multidisciplinary evaluation, bilateral central lateral posterior (CLp) thalamotomy guided by MRgFUS was performed. The procedure was uneventful, with accurate targeting confirmed intraoperatively. Postoperatively, the patient reported partial relief, with VAS decreasing to 6/10. At 3 months, pain intensity improved to 5/10 with recovery of sleep quality. At 6 months, VAS stabilized at 4/10, reflecting >50% reduction compared to baseline, alongside improved activity tolerance and mood. Twelve months later, analgesia remained stable without neurological or cognitive adverse effects. The patient resumed light work and reported significant improvement in quality of life. Discussion: This case highlights the potential of CLp thalamotomy via MRgFUS in otherwise intractable neuropathic pain. Recent studies confirm that this minimally invasive approach may provide long-term pain relief with low complication rates.¹ DBS and MCS remain valid alternatives, particularly in patients with multifocal or complex pain.²⁻³ Careful selection and integration within multidisciplinary care are key to optimal outcomes. Conclusions: In refractory chronic pain, CLp thalamotomy guided by MRgFUS represents a safe and effective therapeutic option, capable of achieving sustained analgesia and functional recovery. Individualized neurosurgical strategies, supported by technological advances, are essential for improving outcomes.¹⁻³
Derechos de autor 2025 Isis Franco Martin, Ana Carolina Montanucci Da Silva, Isabela Ormond Bataglia Herrero, Isadora Sartoretto Meurer, De Lucas La Cruz Mota, Luis Otávio Tabuas Bezerra, Geovanna Saijo Cebalho Da Silva, Emanuele Pires Canela Dos Santos https://creativecommons.org/licenses/by/4.0
Longitudinal Evaluation of Quality of Life in Patients with Deep Brain Stimulation Therapy: Results and Lessons Learned From the Impact of Long Term Interdisciplinary Care in a Single Center
Introduction: This study aims to evaluate the impact of multidisciplinary interventions on the quality of life of 325 patients implanted with deep brain stimulation (DBS) therapy for various diagnoses in our center at Hospital San Vicente Fundacion Rionegro Colombia. Using the validated EQ-5D measurement scale, various dimensions of quality of life were assessed before and after intervention applied in conjuction with a multidisciplinary team with expertice in neurofunctional field. Method: Study Type: Longitudinal, retrospective. Patient Sample: 325 patients implanted with DBS therapy at San Vicente Fundación Hospital in Rionegro, Antioquia. Period of time: Since December 5 2012 to July 30 2025 . Measurement Scale: EQ-5D. Measurement Frequency: Before surgery, 6 months after, and annually thereafter. Discussion: Highly specialized interdisciplinary work enables comprehensive evaluation and treatment of complex neurological conditions, coordinated by a team of experts committed to improving patients' quality of life. Direct collaboration between surgical team and treating specialties was implemented for this sample of 185 patients with different diagnoses, including mainly movement disorders as Parkinson’s disease, essential tremor, dystonia, psychiatrist disorders as severe chronic refractory aggression, osbsessive compulsive disorder, depression, Tourette syndrome, and others as refractory epilepsy and thalamic pain. The program involves specialists from various clinical fields working together for shared and personalized decision-making, including: Neurology, Pain medicine, Neuropsychiatry, Psychiatry, rehabilitation team with physiotherapy, occupational therapy, seepch therapy and others. This neurofunctional care extends beyond the surgical process and works with a psychosocial team supporting patients and families throughout the process, consisting of Neuropsychology, Clinical psychology, Social worker, dietist. We cover in this way the bio psychosocial fields giving to the patients a holistic management and improving the daily activities and the quality of life scores in comparison with same before surgery. Conclusions: The observed improvement in patients can be attributed to a combination of therapeutic interventions and multidisciplinary support. The greatest improvement was seen in patients who adhered to multidisciplinary follow-up and DBS therapy. The study demonstrates that multidisciplinary interventions have a positive impact on patients' quality of life. Further evaluation of these approaches and exploration of new intervention strategies are recommended.
Derechos de autor 2025 Adriana Lucia Lopez Rios, Luisa Fernanda Ahunca Velasquez,, Manuela Pelaez Soto, Manuela Jaramillo Quintero, Carlos Anibal Restrepo Bravo, Maria Victoria Zea Medina, William Duncan Hutchison, Marcia Andrea Cadavid Buitrago https://creativecommons.org/licenses/by/4.0
Analysis of Globus Pallidus Internus Local Field Potentials in Dystonia Patients post Deep Brain Station Implantation
Introduction: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment for medically intractable dystonia. Dystonia clinical presentation is heterogenous and response to DBS is variable. DBS devices capable of recording local field potentials (LFPs) have recently become available for clinical use. Closed loop adaptive DBS (aDBS) has been used for Parkinsons’s disease by using beta peaks as a biomarker to alter stimulation in real-time to best suit the patient. Reliable biomarkers to use in aDBS algorithms for dystonia are yet to be established. We report findings from the use of a DBS system capable of recording LFPs in a single centre with the aim of identifying potential biomarkers that could be used in the optimal programming of DBS systems and potential use of aDBS in dystonia. Method: Clinical data and GPi LFPs were recorded from 3 patients with cervical dystonia implanted with Medtronic SenSight leads and Percept RC DBS systems from 10/01/24 to 26/07/24. GPi LFP data were collected using Medtronic BrainSense during the activation and programming visits. These data were exported and analysed in MATLAB to compute long term LFP timelines and power spectra, the latter with varying stimulation settings. Results: Long-term recordings of LFPs evidenced increased LFP power over time even while stimulation is turned off. Power spectra while stimulation was turned off evidenced significant oscillatory activity in the theta and alpha range but also increased activity across the beta frequency band. There was no clear correlation between the lateralisation of dystonic symptoms and theta-alpha power in the ipsilateral or contralateral hemisphere. When stimulation was turned on or increased, temporary increases in LFP power in the theta-alpha band, followed by a sustained decrease were seen in 2 patients. These increases in LFP power were also mirrored in the contralateral hemisphere. Fluctuations in beta band activity were also seen when the stimulation current was changed in 1 patient. Discussion: The effect of increased LFP power over time from the date of implantation while stimulation is turned off could be explained by the microlesion effect. Oscillatory activity in the theta-alpha band has been well documented previously and has been associated with dystonia severity. The role of pallidal beta oscillations in dystonia is contested but recent studies have suggested that there is a negative correlation between beta power in the GPi and dystonic severity and that the ratio of beta to alpha power correlates with potential benefit from DBS, and thus the presence of beta activity may present a useful biomarker for DBS and could potentially be used as a guide during implantation of DBS electrodes. The lack of correlation between interhemispheric differences in theta-alpha band power is likely a result of the small size of the sample. The effect of increased LFP power in the contralateral hemisphere to the one where stimulation was being increased provides some evidence for interhemispheric pallidal connections in dystonia which warrants further exploration. Conclusions: Our findings suggest that beta power and LFP dynamics such as bursting should also be considered as potential biomarkers to be used in future aDBS algorithms in dystonia alongside theta-alpha power.
Derechos de autor 2025 Nathan Anderton, Reiko Ashida, Petra Fischer, Mihaela Boca https://creativecommons.org/licenses/by/4.0
Estimulación Cerebral Profunda en Nucleos Subtalamicos para Enfermedad de Parkinson, Estudio de Seguridad
Introducción: La Estimulación Cerebral Profunda, usando de target el Núcleo Subtalámico (NST) bilateral, es el manejo estándar en algunos casos seleccionados, de pacientes con Enfermedad de Parkinson. La eficacia de esta técnica además de los criterios de selección los demostramos en una publicación anterior (Rev Med Chile 2018, 146:562-569). La presentación actual es un estudio de seguridad o de complicaciones de la técnica. Método: Revisamos los casos de pacientes operados luego de cumplir con criterios de selección estándar, pacientes con Enfermedad de Parkinson donde se les instalaron electrodos en ambos Núcleos subtalámicos para estimulación Cerebral profunda. Se trata de 47 pacientes con 94 electrodos, edad promedio de 54,4 años, 29 hombres y 18 mujeres. Todos siguen su seguimiento al menos al año de instalado. Se escogió como blanco los NST a ambos lados. Se hizo con técnica estereotáctica, software de planeación de blanco y trayectoria, usamos micro registro intra operatorio. Discusión: No tuvimos mortalidad relacionado a la intervención. La principal complicación fue la infección del sistema (2 casos) 4,2%, un caso presentó un edema transitorio de lóbulo frontal por trombosis venosa cortical relacionad al electrodo (1,1%), Fractura o desplazamiento de cables 3 casos (3,1%) Conclusiones: Este análisis de complicaciones o de seguridad, demuestra que es una técnica segura con un riesgo de complicaciones bajo, similar a lo reportado internacionalmente.
Derechos de autor 2025 Felipe Valdivia, Rodrigo Vallejo, Carolina Kunstmann, Jose Miguel Montes, Philippe Salles, Elena Dulanto, Juan Cristobal Nuñez https://creativecommons.org/licenses/by/4.0
Bilateral Centromedian Thalamic Nucleus Deep Brain Stimulation for Epilepsy in Children and Adults. 32 Cases and One Spectral Analysis Local Field Potentials During Emotional Stimuli
Introduction: This study evaluates the clinical efficacy and safety of bilateral deep brain stimulation (DBS) of the centromedian (CM) nucleus of the thalamus in 32 cases in a heterogeneous population of children and adults with drug-resistant epilepsy (DRE) performed in a single center in Hospital San Vicente Fundacion Rionegro Colombia. We also analized the last patient who was implanted with Percept PC battery that allow record local field potential from the centromedianos nucleos In this patient, LFPs were analyzed during both emotional discrimination and motor tasks, providing novel insights into thalamocortical network dynamics in epilepsy. These recordings revealed task-specific oscillatory patterns that may serve as potential biomarkers for future closed-loop neuromodulation strategies. Method: A retrospective analysis was conducted on 32 patients treated between 2017 and 2024. The primary outcomes included seizure frequency, seizure-free days, and quality of life, while surgical complications and mortality were also assessed. We also analyzes local field potentials (LFPs) in one of the patient who underwent percept PC battery. The recordings were obtained during a task involving the presentation of emotional images (five happy and five sad), with the DBS stimulator turned ON. Signals were segmented according to image presentation times and analyzed using Welch’s method. A 1/f correction was applied to the power spectra to compensate for the natural decline in power at higher frequencies. Results: The general results of DBS demonstrated a significant reduction in seizure frequency, from an average of 331.97 to 21.63 seizures per month (p = 0.001), representing a 93.45% median reduction. Seizure-free days increased from 9.1 to 60.77 days per month (p = 0.012), and 83% of patients reported improved life satisfaction. Device-related infections occurred in 9.3% of patients, and three deaths unrelated to DBS were recorded. In the patient implanted with percept PC, LFPs were analyzed during both emotional discrimination and motor tasks, providing novel insights into thalamocortical network dynamics in epilepsy. These recordings revealed task-specific oscillatory patterns that may serve as potential biomarkers for future closed-loop neuromodulation strategies. Discussion: In both hemispheres, DBS ON is associated with increased low-frequency power (especially in theta and alpha bands), suggesting enhanced thalamic responsiveness to positive emotional stimuli under stimulation.The DBS ON condition reveals increased power in both hemispheres, particularly in the low-frequency range (1–5 Hz) and mid-frequency range (15–25 Hz), suggesting that stimulation enhances thalamic responsiveness to emotionally salient stimuli. In contrast, the DBS OFF condition shows reduced spectral power, indicating diminished thalamocortical engagement during passive emotional processing. These findings suggest that DBS in the centromedian thalamus does more than suppress seizures—it may also restore or enhance physiological oscillations that are otherwise dormant or disrupted in epilepsy. The reactivation of low-frequency and mid-frequency bands could reflect a normalization of thalamocortical communication, which is critical for both conscious awareness and emotional processing. Conclusions: The findings support CM-DBS as a safe and effective therapeutic option for DRE, with significant improvements in seizure control and quality of life. The integration of Percept RC technology opens new avenues for personalized, biomarker-guided DBS programming. Further prospective studies are warranted to validate these results and explore the long-term benefits of adaptive neuromodulation in epilepsy.
Derechos de autor 2025 Adriana Lucia Lopez Rios, Carlos Anibal Restrepo Bravo, Luisa Fernanda Ahunca Velasquez, Daniel Henao Lopez, Manuela Pelaez Soto , Carlos Ignacio Velez Arango, William Duncan Hutchison, Juan Sebastian Saavedra Moreno https://creativecommons.org/licenses/by/4.0
Microvascular Decompression in an Elderly Patient with Refractory Trigeminal Neuralgia: Case Report
Introduction: Trigeminal neuralgia (TN) is characterized by severe, shock-like facial pain, often triggered by light stimuli. While pharmacological therapy (e.g., Carbamazepine or Oxcarbazepine) is effective for most patients, a significant proportion develop refractory pain requiring surgical intervention. Microvascular decompression (MVD) is considered the gold-standard etiological treatment, offering high long-term pain relief.1 Recent studies confirm its safety and effectiveness, especially in patients with well-defined neurovascular contact.2 Minimally invasive alternatives, such as percutaneous radiofrequency rhizotomy and stereotactic radiosurgery, are valid options in selected cases.3 Clinical description: A 64-year-old female presented with a 5-year history of right-sided facial pain, described as electric shock-like episodes affecting the maxillary and mandibular branches, with progressive worsening. Prior pharmacologic treatment included carbamazepine, oxcarbazepine, and baclofen, with only partial relief and significant side effects. Brain MRI revealed vascular contact between the superior cerebellar artery and the right trigeminal nerve root. Given the pain refractoriness and clear compressive etiology, MVD was indicated. Surgery was performed via a retrosigmoid approach with vascular dissection and interposition of a Teflon patch. The patient had no new neurological deficits and reported immediate and complete pain relief. At 6-month follow-up, she remained pain-free, with good control on low-dose carbamazepine monotherapy. She reported marked improvement in quality of life, resuming domestic and social activities without limitations or adverse effects. Discussion: Classical TN with neurovascular conflict is the most responsive subtype to MVD. Prospective studies show pain relief in up to 86% of cases, especially in patients with nerve morphological changes.2 A retrospective study showed that after 43 months, 83% achieved substantial relief, often with reduced medication.3 Compared to percutaneous techniques, MVD offers lower recurrence and fewer sensory complications.³ Proper patient selection and multidisciplinary assessment are key. Conclusions: MVD remains a safe, effective option for refractory TN with neurovascular conflict. This case illustrates the benefits of early surgical intervention, leading to pain remission, monotherapy, and significant quality-of-life gains.
Derechos de autor 2025 Isis Franco Martin, Fernanda Cittadella Alves, Juliana Araujo Rech Lima, Talita Sousa Brito, Isabela Ormond Bataglia Herrero, Yasmin Utuari De Oliveira, Bruna Durigan Baia, Emanuele Pires Canela Dos Santos https://creativecommons.org/licenses/by/4.0
Coronal Flair Magnetic Resonance Imaging for Delineation of the Subthalamic Nucleus: Validation with Intraoperative Microelectrode Recordings
Introduction: Accurate delineation of the dorsal and ventral borders of the subthalamic nucleus (STN) is critical for optimal deep brain stimulation (DBS) electrode placement in Parkinson’s disease. Although magnetic resonance imaging (MRI)-based targeting is widely employed, correlation of STN borders identified on coronal FLAIR MRI with intraoperative microelectrode recordings (MER) has not been previously validated. The objetive is to determine whether the dorsal and ventral borders of the STN identified on coronal FLAIR MRI correspond spatially with electrophysiological boundaries defined by MER. Method: We retrospectively analyzed 30 STN trajectories from 15 patients undergoing bilateral STN-DBS. Coronal FLAIR MRI was used to identify the dorsal and ventral borders of the hypointense STN, distinguished from the substantia nigra (SN) by a characteristic hypointense reentrant signal. These anatomical landmarks were compared with the onset and offset of neuronal activity determined intraoperatively by MER. Statistical analysis included descriptive measures (mean ± SD), Shapiro–Wilk test for normality, and Pearson correlation coefficients. Statistical significance was set at p < 0.05. Results: There was strong anatomical concordance between the dorsal FLAIR-defined border and MER onset, as well as between the ventral hypointense reentrant separating the STN from the SN and MER termination. The mean FLAIR-defined STN length was 5.92 ± 0.98 mm, compared to 5.42 ± 1.04 mm defined by MER. A significant positive correlation was found between FLAIR- and MER-defined lengths (r = 0.435, p = 0.016). The mean dorsal delta was 0.22 ± 1.13 mm and the ventral delta was -0.29 ± 0.85 mm. Table 1 summarizes the statistical results. Figure 1 illustrates the multimodal integration of FLAIR-based landmarks, MER, stereotactic planning, and postoperative reconstruction. Discussion: The use of FLAIR (Fluid-Attenuated Inversion Recovery) sequences has emerged as a critical advancement in DBS targeting, particularly for subthalamic nucleus visualization. FLAIR sequences offer superior contrast and reduced artifacts compared to conventional T2-weighted imaging. Three-dimensional SPACE FLAIR at 3T represents a significant advancement in STN visualization. This technique demonstrated superior clinical outcomes with 62.2% improvement in UPDRS scores compared to 43.6% with conventional T2-weighted Imaging. This method demonstrated 93% agreement with microelectrode recordings in contact location, according to some studies, and the correlation between imaging findings and electrophysiological recordings provides robust validation of targeting accuracy. Conclusions: The hypointense signal of the STN on coronal FLAIR MRI enables reliable identification of its dorsal and ventral borders. These MRI-defined boundaries show strong correlation with electrophysiological limits determined by MER, supporting the incorporation of FLAIR MRI into DBS surgical planning.
Derechos de autor 2025 Diogo Maldonado, Juliana Rodrigues, Fabio Luiz Franceschi Godinho, Everaldo Fernandes Celestrini https://creativecommons.org/licenses/by/4.0
Functional Neurosurgical Approach in Refractory Post-Traumatic Phantom Limb Pain: Case Report
Introduction: Phantom limb pain (PLP) is a form of chronic neuropathic pain affecting amputees, often described as burning, shooting, or electric-like sensations perceived in the absent limb. Pharmacological treatment (e.g., anticonvulsants, antidepressants, opioids) is frequently insufficient. Functional neurosurgery has emerged as a promising option for refractory PLP, with techniques such as thalamotomy, deep brain stimulation (DBS), and motor cortex stimulation (MCS) aiming to modulate dysfunctional central pain circuits. Clinical description: A 64-year-old female presented with a 5-year history of right-sA 41-year-old male underwent left transfemoral amputation following a motor vehicle accident two years prior. Since then, he experienced severe phantom limb pain (PLP), described as burning and electric shocks, with an average pain score of 9/10 on the Visual Analog Scale (VAS). He showed minimal response to gabapentin, amitriptyline, tramadol, and ketamine. Pain significantly interfered with sleep, prosthetic use, and social life, causing emotional distress. After multidisciplinary evaluation, a functional neurosurgical procedure was indicated. A stereotactic thalamotomy targeting the right ventroposterolateral (VPL) nucleus was performed using radiofrequency thermocoagulation. The procedure was uneventful. Postoperatively, pain decreased immediately to VAS 5/10, with gradual improvement over the following weeks. At 6-month follow-up, pain remained controlled at VAS 3/10, with no need for opioids and reduced gabapentin dosage. The patient reported improved function, resumed adapted work, and regained social engagement. Discussion: PLP involves peripheral, spinal, and supraspinal mechanisms, including maladaptive cortical reorganization. Stereotactic thalamic lesions in sensory nuclei like the VPL have shown effectiveness in reducing pain intensity in refractory cases. Deep brain stimulation and motor cortex stimulation are also effective options but carry higher complexity and cost. Proper patient selection and exclusion of psychiatric or functional pain syndromes are essential to ensure therapeutic success. Conclusions: This case highlights the efficacy of thalamotomy as a functional neurosurgical strategy for severe, post-traumatic phantom limb pain. An individualized, multidisciplinary approach allowed for significant pain control, functional recovery, and improved quality of life.
Derechos de autor 2025 Isis Franco Martin, Yasmin Utuari De Oliveira, Isabela Ormond Bataglia Herrero, Henrique Aguiar Lima, Joao Pedro Prado Salomão, Julia Alvim Lage, Isadora Luiza Babinschi Dias De Sou, Emanuele Pires Canela Dos Santos https://creativecommons.org/licenses/by/4.0
Evaluation by Stereoelectroencephalography (SEEG) of the Insular Region in Drug-Resistant Focal Epilepsies: Diagnostic Experience and Technique in the First Reported Cohort in Argentina
Introduction: The insula, due to its deep location, complex anatomy, and clinical interpretation, represents a challenge in the study of drug-resistant epilepsies. Method: Seventeen patients implanted between 2018 and 2025 with suspected insular involvement were included. Micromar® frames (2020–2023) and Leksell® frames (2023–2025) were used. Trajectories, number of contacts, ictal onset zone, thermocoagulations, and complications were analyzed. In addition, dissections were performed on six human hemispheres (Klingler technique) to validate safe trajectories. Results: During the study period, 218 electrodes were implanted, of which 56 (25.7%) targeted the insula, with 128 contacts in insular cortex. Accumulated experience enabled a transition from orthogonal trajectories (32 trajectories, covering opercular and insular regions, average of 2 insular contacts) to planning with both orthogonal and oblique trajectories (26 trajectories, exclusively insular coverage, average of 7 contacts). Discussion: Insular SEEG exploration has been increasingly reported worldwide, yet data from Latin America remain scarce. Our series, the largest in Argentina, confirms the feasibility and safety of insular implantation in drug-resistant focal epilepsy. Indications were based on semiology suggestive of insular onset or early propagation, and SEEG confirmed an insular ictal onset zone in one-third of cases. Technical refinement from orthogonal to oblique trajectories allowed denser sampling (up to 7 contacts/electrode) while avoiding vascular injury, with only one hematoma unrelated to insular electrodes. No procedure-related morbidity was observed. These findings reinforce the role of systematic insular exploration in SEEG protocols, given the limitations of non-invasive studies and the potential for therapeutic thermocoagulation when the insula is the primary ictal onset zone. Conclusions: Insular SEEG implantation is safe and feasible. Progressive technical optimization allowed denser coverage without increased morbidity. The possibility of identifying primary ictal activity and treating it through thermocoagulation supports its systematic inclusion in SEEG studies, despite its challenging anatomy.
Derechos de autor 2025 Facundo Villamil, Yamila Slame, Walter Silva, Gabriela Ugarnes, Abril Maria Laura Marone, Maria Victoria Piccirilli, Sofia Fariña, Marcelo Bartuluchi https://creativecommons.org/licenses/by/4.0
Primera Cirugía de Epilepsia en Temuco: Callosotomía Completa en Paciente con Epilepsia Refractaria y Crisis Atónicas, un Desafío Multidisciplinario
Introducción: La callosotomía es una cirugía desconectiva que secciona total o parcialmente el cuerpo calloso para limitar la propagación interhemisférica de descargas epilépticas; es una opción paliativa especialmente útil ante crisis atónicas con caídas. La epilepsia refractaria se define por el fracaso de dos esquemas antiepilépticos adecuados y tolerados para lograr libertad sostenida de crisis y afecta aproximadamente a un tercio de las personas con epilepsia. A nivel mundial, 50 millones de personas viven con epilepsia, con mayor carga en países de ingresos medios bajos; En Américas se estiman 5 millones, y Latinoamérica mantiene una carga significativa pese a descensos recientes. Reportamos el hito institucional de la primera cirugía de epilepsia realizada en el Hospital Dr. Hernán Henríquez Aravena Temuco, Chile, efectuada en diciembre de 2023: Callosotomía completa. Su ejecución implicó un desafío multidisciplinario, articulado a través de un comité de epileptología, neurología-UPC, neurocirugía, anestesia, UCI y rehabilitación, que permitió la toma de decisiones, la planificación y el seguimiento coordinado en un centro público regional. Método: Mujer rural, 23 años, con paquigiria bilateral y epilepsia refractaria multifocal; presentaba crisis atónicas diarias con caídas y lesiones, dependencia para AVD y supervisión 24 h. Recibía levetiracetam, topiramato y clobazam en dosis optimizadas (alergia a carbamazepina), sin control adecuado. Por la alta frecuencia de caídas, el impacto funcional y las barreras de acceso del contexto rural, el caso se discutió en comité multidisciplinario (epileptología/neurología-UPC, neurocirugía, anestesia, UCI y rehabilitación), que indicó callosotomía completa como estrategia paliativa. La cirugía se realizó en diciembre de 2023 sin incidentes mayores. En el posoperatorio cursó con síndrome de desconexión leve y transitorio (heminegligencia izquierda), con mejoría en la primera semana. La RM con tractografía confirmó sección completa del cuerpo calloso, verificando el objetivo quirúrgico. Al egreso: disminución marcada de crisis atónicas y ausencia de caídas; por preferencia familiar se mantuvieron los fármacos antiepilépticos. Discusión: La callosotomía consigue altas tasas de libertad de caídas y mejora la calidad de vida en epilepsias con crisis atónicas; la tractografía agrega verificación objetiva de la desconexión posquirúrgica y correlaciona con la respuesta clínica. Este caso constituye la primera cirugía de epilepsia en Temuco, viabilizada por un circuito multidisciplinario que permitió una decisión segura en una paciente joven y rural con tratamiento farmacológico óptimo pero ineficaz. Conclusiones: Este análisis de complicaciones o de seguridad, demuestra que es una técnica segura con un riesgo de complicaciones bajo, similar a lo reportado internacionalmente. Conclusiones: La callosotomía completa fue factible y segura en un hospital público regional, con reducción significativa de crisis y abolición de caídas, marcando el inicio institucional de un programa de cirugía de epilepsia con enfoque multidisciplinario y verificación imagenológica del resultado.
Derechos de autor 2025 Jaime Antonio Leñero Navarrete, Claudio Parada Muñoz https://creativecommons.org/licenses/by/4.0
Neuronal and Motor Activity in the Basal Ganglia During a Synchronization-Continuation Hand Tapping Task in Patients with Deep Brain Stimulation for Parkinson's Disease
Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used for Parkinson's disease (PD) patients refractory to medications. One symptom that is not significantly improved by DBS is freezing of gait (FoG) which, is associated with a festination behaviour in the synchronization-continuation task (SCT). The SCT consists of three 30s phases: listening while still, tapping in time with an external cue (like a metronome), then continuing to tap without the external cue, requiring a shift from external to internal representations of rhythm. Studies have shown that patients with PD exhibit motor hastening in the continuation phase, with higher magnitude of hastening correlated to severity of FoG. To better understand the relationship between rhythmic control in the STN, medication, and DBS, 15 PD patients underwent the SCT while having both their motor behaviour and neural activity recorded. Method: Patients with DBS leads implanted in the STN underwent testing in four different conditions: M1S1 (Med ON/Stim ON), MOSO (Med OFF/Stim OFF), M1SO (Med ON/Stim OFF), and MOS1 (Med OFF/Stim ON), with Med OFF defined as 12hr off anti-Parkinson medication. Motor data was recorded using a triaxial accelerometer or a piezoelectric force detection device. Neural activity in the form of local field potentials was recorded using the PerceptTM technology. Motor and neural local field potential (LFP) data were synchronized using Spike2 and analyzed using Python and R. Results: Preliminary analysis of 3 patients showed motor hastening across all conditions, with greater magnitude in MOSO (0.20 Hz) than M1S1 (0.12 Hz). Beta power was elevated in OFF states and reduced by medication or stimulation, while peak frequencies remained stable. In MOSO, beta power was highest during the listening phase, suggesting desynchronization with motor initiation. Discussion: Our findings align with prior reports of motor hastening in PD during the SCT. The greater hastening observed in MOSO compared to M1S1 suggests that medication and DBS may help stabilize rhythmic motor output, while future analyses of M1S0 and MOS1 will clarify their individual effects. Spectral results also showed elevated beta power in MOSO and suppression with medication or stimulation, consistent with existing literature. Conclusions: The results thus far confirm that motor hastening in the SCT is common in patients with PD, and indicate that dopaminergic medication and DBS may help to reduce the degree of hastening. Additionally, the differences in beta oscillatory power across the different phases of the SCT, when combined with the behavioural results of the SCT, may help to better describe the role of the STN in rhythmic control, and how it is affected PD.
Estimulación Talámica Anterior en Epilepsia: Eficacia Terapéutica y Optimización del Blanco Quirúrgico
Introducción: La epilepsia afecta a más de 50 millones de personas a nivel mundial y el 40 % de los casos son resistentes al tratamiento farmacológico (EFR). La estimulación cerebral profunda (ECP) del núcleo talámico anterior (ANT) es una opción terapéutica prometedora y eficaz para el tratamiento de aquellos pacientes con EFR multifocal, generalizada o, incluso, focal pero refractario a tratamiento quirúrgico previo. El objetivo del presente estudio es evaluar la respuesta del tratamiento quirúrgico con ECP-ANT en paciente con epilepsia farmacorresistente proponiendo una técnica de planificación de target y trayectoria modificada. Método: Estudio analítico, longitudinal, retrospectivo, muestreo no probabilístico consecutivo que incluye pacientes con epilepsia farmacorresistente tratados con ECP-ANT durante el período de enero del 2021 a julio del 2024 en Fundación Favaloro, con un seguimiento mínimo de 6 meses. Se introdujo una modificación a la técnica quirúrgica en la planificación para que el extremo inferior de la cánula quede debajo del piso del ventrículo lateral, evitando la pérdida de LCR al retirar el introductor interno con la consiguiente modificación de la anatomía cerebral y de las coordenadas del target. Resultados: Se incluyeron 8 pacientes que se sometieron a cirugía de ECP-ANT con una mediana de edad al implante de años 28,5 (RIC 19,75) 50% de sexo femenino. La mitad de estos pacientes presentaron epilepsia multifocal y cinco de ellos (62.5%) ya se habían sometido a procedimientos quirúrgicos previos, exhibiéndose un promedio de 14.75 años de dilación entre el diagnóstico de epilepsia y la primera cirugía. Se demostró reducción significativa de crisis epilépticas totales al 52% respecto al basal/prequirúrgico a los 6 meses, un 30.86% al año, 28.4% a los 18 meses y 28.3% teniendo en cuenta el tiempo máximo de seguimiento, obteniéndose respuesta en el 100% de los participantes al máximo seguimiento. Conclusiones: La cirugía de ECP-ANT en nuestra cohorte ha producido una eficacia notable en la reducción de las crisis epilépticas con resultados equiparables a los expuestos en la bibliografía actual, incluso lográndose respuesta en el total de los participantes. La protocolización y modificación de la técnica quirúrgica permitió un correcto posicionamiento de los electrodos en el núcleo anterior del tálamo. Contando el presente estudio con un seguimiento acotado en el caso de alguno de los participantes, sería menester corroborar que se mantenga alto el porcentaje de respuesta a lo largo del seguimiento e, incluso, al aumentar el número de pacientes sometidos a ECP-ANT en nuestro centro.
Derechos de autor 2025 Martin Uranga Vega, Federico Bocassi, Francisco Fuertes, Esteban Robledo, Matias Andres Rojas, Jorge Mandolesi https://creativecommons.org/licenses/by/4.0
Impacto de la Cirugía Funcional en la Calidad de Vida de Pacientes con Enfermedad de Parkinson
Introducción: La enfermedad de Parkinson (EP) es el segundo trastorno neurodegenerativo más frecuente, con alta prevalencia mundial y marcado impacto en la calidad de vida debido a síntomas motores como no motores. El tratamiento farmacológico inicial ofrece beneficios, aunque su eficacia disminuye con los años, debido principalmente a disquinesias y fluctuaciones motoras. En este contexto, la cirugía funcional (ablativa o de estimulación cerebral profunda) se plantea como alternativa. El objetivo de nuestro estudio es determinar el impacto de los procedimientos quirúrgicos en la calidad de vida de los pacientes con enfermedad de Parkinson mediante la valoración del cuestionario PDQ39. Método: Se diseñó un estudio observacional retrospectivo que incluyó pacientes con EP intervenidos quirurgicamente entre 2019 y 2022 en el Hospital Nacional Prof. Alejandro Posadas. Se establecieron los siguientes criterios de inclusión: Paciente con diagnóstico de enfermedad de Parkinson, que posea evaluación con cuestionario PDQ 39 pre y postquirúrgico y, haya sido intervenido quirúrgicamente dentro de los límites de tiempo preestablecido. La evaluación postquirúrgica no fue sistematizada previamente por lo que el tiempo de evaluación difiere en un periodo de 2 a 5 años. Resultado: De los 108 pacientes evaluados, 39 cumplieron criterios de inclusión. La edad promedio fue de 56 años y el tiempo medio de evolución de la enfermedad de 10,3 años. Se realizaron 22 cirugías ablativas y 17 DBS. El mayor beneficio se observó en el ítem estigma social (mejoría del 56%), seguido de actividades de la vida diaria y movilidad (20–26%). La DBS mostró mejor impacto en movilidad frente a la cirugía ablativa. Por el contrario, cognición y comunicación presentaron deterioro, especialmente tras DBS bilateral. La psicoprofilaxis prequirúrgica se asoció con mejores resultados en dominios emocionales y sociales. Discusión: El cuestionario PDQ-39 contiene 39 ítems agrupados en 8 dominios: movilidad, actividades de la vida diaria, bienestar emocional, estigma, apoyo social, estado cognitivo, comunicación, malestar corporal. Los hallazgos de nuestro estudio difieren parcialmente de la literatura, donde el estigma social suele mostrar baja mejoría siendo en nuestro estudio el dominio que presentó mayor mejoría global. Se concuerda que tanto el ítem de apoyo social como de comunicación y cognición presentan detrimento, pero con la salvedad de que aquellos pacientes que realizaron psicoprofilaxis prequirúrgica, el impacto positivo en los ítems mencionados fue mayor que en aquellos pacientes que no realizaron la misma. Los procedimientos bilaterales, en especial DBS, mejoraron movilidad y malestar corporal, aunque a expensas de mayor deterioro cognitivo y de comunicación. En nuestra serie se pudo observar que los pacientes que fueron intervenidos a los 7 años de evolución presentaron mayor impacto positivo sobre la calidad de vida que aquellos en los que se realizó previo y posterior a este tiempo. Conclusiones: La cirugía funcional representa una mejoría en la calidad de vida global de los pacientes con enfermedad de Parkinson. Mejorando significativamente el estigma social y las actividades de la vida diaria. La psicoprofilaxis prequirúrgica representa un pilar fundamental para el éxito quirúrgico. No obstante, creemos que la realización de un estudio doble ciego reforzaría los resultados obtenidos.
Derechos de autor 2025 Paula Camila Paez, Sergio Pampin, Santiago Driollet Laspiur, Katherine Palma, Lucas Cornejo, Maria Fernanda Lopez https://creativecommons.org/licenses/by/4.0
Biomechanical Characterization Before, During, and after Freezing of Gait Episodes In Parkinson's Disease
Introduction: Freezing of gait (FoG) is a disabling and episodic phenomenon in Parkinson's disease (PD), leading to falls, reduced mobility, and impaired quality of life (1). Although multiple studies have described FoG occurrence, little is known about biomechanical alterations immediately preceding and following freezing episodes (2). Recent advancements in wearable sensors have enabled the objective quantification of FoG using parameters such as the Freezing Ratio (3), but the dynamic transitions around freezing events remain poorly characterized. Method: We analyzed a dataset comprising individuals with PD assessed during two home visits. Each participant was evaluated in Off-medication. During the assessments, participants wore a triaxial accelerometer (Ax3, Axivity) placed on the lower back sampling at 100 Hz. The protocol included multiple gait and turning tasks designed to provoke freezing, such as 4-meter walk, Timed Up & Go (single and dual-task), repeated turning tasks, and Hotspot walking trials through individualized freezing-prone environments. For the present analysis, episodes of continuous walking where freezing events were identified were segmented into three phases: Pre-FoG (2 seconds before onset), During FoG (identified by visual inspection and acceleration patterns), and Post-FoG (2 seconds after resolution). The FoG Ratio, as described by Mancini et al. (3), was calculated based on the power spectral density of the anteroposterior (AP) accelerations, comparing high-frequency (3–8 Hz) to low-frequency (0.5–3 Hz) components. Results: The observed reduction in acceleration amplitude prior to freezing suggests an early impairment in postural adjustments and gait rhythm preceding FoG onset, possibly reflecting deficits in motor planning or anticipatory control. The elevated AP FoG Ratio during freezing confirms its utility as a specific marker of the freezing state, consistent with prior literature validating its clinical relevance (3). The post-freezing recovery phase exhibited a rapid normalization of biomechanical parameters, highlighting the transient and abrupt nature of FoG events. These biomechanical signatures may reflect the interplay between supraspinal gait control mechanisms and the impaired dynamic coordination that characterizes FoG. Discussion: Our study provides novel evidence of biomechanical alterations not only during but immediately before and after FoG episodes. The distinct pre-FoG signature observed may serve as a critical window for predictive algorithms and real-time interventions aimed at preventing freezing events. The use of wearable sensors and spectral analysis of accelerometry data offers a feasible and ecologically valid approach for continuous FoG monitoring in natural environments. Conclusions: Repeated measures ANOVA revealed significant differences across the three phases in all acceleration axes (AP, ML, and VT). Post-hoc Bonferroni comparisons demonstrated that pre-FoG phases were characterized by significantly reduced acceleration amplitudes compared to post-FoG periods across all axes (p < 0.05). Notably, for the AP axis, the During FoG phase exhibited significantly different FoG Ratio values compared to both Pre- and Post-FoG phases (p < 0.05), indicating increased high-frequency oscillations corresponding to the characteristic trembling observed during freezing episodes. These findings support the FoG Ratio’s sensitivity in capturing freezing severity and transition dynamics.
Derechos de autor 2025 Barbosa Jaci, João Antonio Marques Costa, Brenda Luciano De Souza Silva, Thayna Magalhães Novaes, Daniel Boari Coelho https://creativecommons.org/licenses/by/4.0
Walking again with Epidural Spinal Stimulation: A Prisma-Guided Synthesis of Human Walking Outcomes (2020-2025)
Introduction: Spinal cord injury produces profound motor deficits that remain refractory to conventional rehabilitation. In recent years, epidural electrical stimulation targeted to lumbosacral circuits has enabled standing and overground stepping from early postoperative sessions, with additional gains after task-specific rehabilitation. Building on these advances, we synthesized contemporary human evidence (2020-2025) focused specifically on walking outcomes to clarify clinically meaningful effects and practical levers for protocol standardization. Method: Design: Systematic review compliant with PRISMA guidelines. Data sources: PubMed and Google Scholar (Jan 2020-Sep 2025). Eligibility: Original human studies of surgically implanted epidural stimulation reporting walking outcomes (walking speed, six-minute walk distance, Timed Up and Go, symmetry index, and overground ambulation). Trials, before-after studies, and case series/reports were included; animal studies, non-epidural stimulation, technical notes only, and reviews were excluded. Two reviewers screened and extracted data. Given heterogeneity, we used a structured synthesis without meta-analysis based on pre-specified clinically important differences: speed > 0.10 m/s, six-minute walk distance > 50 m, Timed Up and Go -3 s, symmetry index > 20% improvement; overground ambulation summarized as achieved vs not achieved. Results: Eight studies met criteria (single-patient reports to a 25-patient series; total 38 participants), spanning incomplete and motor-complete injuries. Across designs, most reports showed clinically important gains in walking speed and/or six-minute walk distance; incomplete-injury cohorts frequently improved symmetry. Crucially, overground ambulation was newly achieved or clearly upgraded in several reports, including motor-complete cases. Three convergent signals emerged that likely facilitate ambulation: ventral lead placement enabling rapid distance walking within weeks; high-frequency paradigms reducing spasticity and improving inter-joint coordination; and intent-coupled adjuncts (robotic training or brain-spine interfaces) promoting naturalistic gait and task generalization (uneven terrain, stairs). Adverse events were infrequent and mostly minor. Certainty is limited by small samples, non-randomized designs, heterogeneous co-interventions, and variable outcome timing. Discussion: Converging human evidence indicates that epidural stimulation can acutely unlock stepping and produce training-mediated gains over weeks to months. Emerging paradigms-ventral targeting, high-frequency modulation, and intention-coupled assistance-appear to broaden candidacy and improve gait quality, but require standardization across centers. Conclusions: Epidural stimulation is associated with clinically meaningful restoration of ambulation after spinal cord injury, from incomplete to motor-complete cases. Multicenter comparative studies should standardize targets and dosing, pre-specify common walking endpoints (speed, six-minute walk distance, symmetry, overground status), and stratify by impairment level, lesion topology, and use of ventral/high-frequency approaches and intention-coupled adjuncts.
Derechos de autor 2025 Eriko Kamijo, Shiro Horisawa https://creativecommons.org/licenses/by/4.0
Intrathecal Opioid Trialing Protocol Combining PCA Bolus and Continuous Infusion with an Efficacy/Safety Self-Evaluation Chart. Clinical Experience
Introduction: Spinal cord injury produces profound motor deficits that remTo describe the clinical utilization of an IT opioid trialing protocol using PCA IT bolus and a continuous infusion and patient self-evaluation chart. Method: We describe our 13-patient clinical experience using an Intrathecal Opioid trialing Protocol with a portable PCA external pump combining Continuous Infusion + PCA bolus that resembles an implanted pump functionality. A self-evaluation chart allows patients to report side effects and pain ratings, and patient satisfaction is rated. The chart is signed in front of a witness as an agreement to proceed with internal pump implantation. Discussion: All 13 patients were chronic non-malignant pain patients (5 FBSS, 2 Spinal Cord Injury, 5 Lumbar Spinal Stenosis, 1 Rheumatoid Arthritis) requiring high dose oral opioids with inadequate pain control. Eight patients were female and three males with an average age of 70 yr. (36 – 90 yrs.). Eleven trials lasted three days, one trial was stopped at day two because the patient had urinary incontinence (she had a previous gynecologic surgery that altered her sphincter anatomy) and one patient required an extra day because the need of additional baclofen boluses in trial day and day three for spasticity related pain. All trials had at least 24 hr. of a continuous infusion before ending. Preservative free morphine was used in all trials. Dose requirements were low compared to most bolus doses described in the literature. All positive trials started with a pain rating VAS ≥ 8 and final VAS ≤ 3. Patient satisfaction was Very Satisfied in 7, Moderately Satisfied in 3 and Unsatisfied in 3. No serious side effects were observed. Most common side effects were itching (7 patients), nausea (4 patients) and urinary retention (4 patients).They resolved with dose adjustments by the end of the trial. Three patients required urinary catheterization after the first bolus dose was administered, one of them did not resolve lowering the morphine dose, and the other two recovered spontaneous micturition after dose adjustment. It is important to mention that one female patient that had a previous urinary incontinence surgery suffered intolerable incontinence that required catheter removal. It has been described that low IT morphine doses can increase bladder muscle activity, leading to incontinence when sphincter activity is altered. Three patients did not get a pump implanted. One of them because of unrelated health problems. The other two patients suffered urinary retention requiring intermittent catheterization and it was not possible to get an analgesic response. Conclusions: Prior to implantation of an internal IT pump, a successful trial is usually required. Consensus recommendation is that until RCT are developed each practitioner should use a trialing protocol based on safety, adherence to safe algorithmic principles, and proper patient monitoring. Described trial methodologies are IT single bolus, IT multiple bolus or IT continuous infusion. No combined methods using PCA boluses and continuous infusion were found in the literature. This 3-day trialing technique provides an opportunity to assess IT opioid response with a safer and reliable methodology. Patient self-involvement and final agreement allows a more objective evaluation and helps decision making for internal pump implant. Even our small sample size does not allow to draw any conclusions, it is remarkable that very low doses were required with minor and reversible side effects with good patient satisfaction.
Derechos de autor 2025 Diego Bashkansky, Diana Ciaffone, Nicolás Barbosa, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
Modulation of Cortical Oscillatory Activity Underlies Sustained Improvement in Segmental Dystonia with Pallidal Deep Brain Stimulation
Introduction: Segmental dystonia often responds only partially to deep brain stimulation (DBS), sometimes requiring additional or “rescue” strategies for sustained benefit. We report a 58-year-old woman with adulthood-onset idiopathic isolated focal upper limb dystonia, refractory to medications and botulinum toxin, who achieved long-term improvement after a novel approach: implantation of two electrodes within the same unilateral globus pallidus internus (GPi). This configuration yielded marked and durable relief, maintained for over nine years. To explore underlying mechanisms, we performed high-resolution quantitative EEG (qEEG) and connectivity analyses paired with clinical observations. Clinical description: The patient developed painful dystonic contractions of the dominant right upper limb at age 48. Family history was negative. Despite 3–4 years of medical therapy and botulinum toxin, symptoms persisted. At age 58, unilateral DBS of the left GPi was performed with two electrodes in the same nucleus. This dual-electrode strategy provided striking and sustained benefit: pain markedly decreased, and involuntary movements nearly disappeared. qEEG revealed distinct patterns OFF vs ON stimulation. In the OFF state, dystonic movements correlated with asymmetric oscillations, including a prominent delta peak in left parietal/central cortices, reduced beta power (13–30 Hz), and mild gamma activity in the left motor cortex. ON stimulation reorganized cortical activity: delta abnormalities subsided; beta activity increased symmetrically in central–parietal regions, and gamma activity diminished. Connectivity analysis confirmed this reorganization: OFF showed hyper-connectivity in left central beta-2 networks and hypo-connectivity in short-range circuits, whereas ON restored beta-2 coherence, reduced gamma connectivity bilaterally, and produced more symmetrical, stable network dynamics. These changes coincided with complete resolution of dystonic movements. Discussion: DBS of the GPi or STN is established for generalized and segmental dystonia, but focal presentations remain less studied. Dual-target strategies (GPi plus thalamus) have been attempted, yet this is the first description of two electrodes within one GPi for limb dystonia. The long-term benefit suggests that dual-electrode placement may improve modulation of the pallidal sensorimotor territory. Oscillatory findings support this: DBS restored physiologic beta synchronization, reduced pathological low-frequency activity, and suppressed abnormal gamma coupling, mirroring the patient’s clinical outcome. Conclusions: This case demonstrates the potential value of dual-electrode GPi stimulation in refractory focal dystonia, with sustained benefit over nine years. It also highlights qEEG as an exploratory biomarker to capture stimulation-induced reorganization and guide personalized DBS strategies.
Derechos de autor 2025 Erich Talamoni Fonoff, Pedro Melo Barbosa, Maria Gabriela Ghilardi, Francielly Ferreira Santos, Alexandre Maira Santos, Bruno Lima Pessoa https://creativecommons.org/licenses/by/4.0
When one Target is Not Enough: Combined DBS and Spinal Cord Stimulation for Refractory Gait and Dystonia in Parkinson’s Disease
Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that remains a therapeutic challenge. Levodopa is the cornerstone of treatment, yet many patients become refractory and require surgical interventions such as deep brain stimulation (DBS). While DBS provides substantial benefit, its effects may be incomplete, particularly for symptoms such as foot dystonia, freezing of gait, and pain. In this context, spinal cord stimulation (SCS) has emerged as a potential adjuvant. This report explores its value in a patient with PD refractory to conventional treatments. Clinical description: A 47-year-old man with a 10-year history of PD initially presented with asymmetric symptoms in the left upper limb, later spreading to the right with lower intensity. Over time, he developed rigidity, pain, dystonia, speech impairment, freezing in the OFF state, poor sleep, mild mood changes, despite optimized medication treatment. Bilateral STN DBS provided initial benefit, but rigidity and dystonia worsened within a year. Subsequent bilateral GPi DBS with right STN repositioning improved dystonia and rigidity/tremor by ~40%, though freezing persisted. Due to persistent pain in the left limbs, SCS was implanted using Microburst™ stimulation (T8–T10) and Fast™ stimulation (T2–T4). Timed Up and Go (TUG) and gait analyses showed progressive improvement, and reclassification of fall risk from high to low. The patient experienced marked improvement in gait, UPDRS (80%), foot dystonia (95%), and pain (100% -lower limb and 70% -upper limb). Discussion: Although traditionally used for pain, SCS may also improve motor symptoms and dystonia.Case reports describe improvements in gait and freezing, suggesting modulation of sensorimotor networks that may complement DBS. Controlled trials, however, have yielded inconsistent results, reflecting variability in patient selection and stimulation parameters. Still, this case shows how SCS may serve as an adjuvant after DBS, especially when pain, dystonia, and gait dysfunction coexist. It underscores how individualized neuromodulation can extend therapeutic benefit beyond conventional targets. Conclusions: SCS may unlock therapeutic potential beyond pain control in PD, offering meaningful gains in gait and dystonia where medication and DBS fall short. This case reinforces the promise of combined neuromodulation, while highlighting the need for rigorous clinical trials to define its role in advanced PD care.
Derechos de autor 2025 Emanuele Canela, Barbosa Jaci, Sara Casagrande, Vivian Milanese, Vanessa Milanese https://creativecommons.org/licenses/by/4.0
Probing Dopaminergic Modulation via Subthalamic Stimulation: A Preclinical Perspective
Introduction: Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the gold standard symptomatic treatment for patients with levodopa therapy-induced complications in Parkinson’s disease (PD). However, even though the efficiency of DBS is well recognized, to this date, it is not clear the influence of subthalamic stimulation on the dopaminergic system. Hence, the aim of this study is to investigate the effect of STN-DBS on striatal dopaminergic system in a rodent model of PD. Method: This work was approved by the Ethics Committee on the Use of Animals at Hospital Sírio-Libanês (CEUA 2016/04). Male Wistar rats were subjected to the 6-hydroxydopamine (6- OHDA)-induced model of PD (left striatum, 12 ug) followed by the immediately ipsilateral implantation of STN electrode. Animals were divided into four groups: (i) Control (striatal saline + no electrode implantation), (ii) PD (striatal 6-OHDA + no electrode implantation), (iii) PD+DBS OFF (striatal 6-OHDA + STN electrode implantation but not stimulated) and (iv) PD+DBS ON (striatal 6-OHDA + STN electrode implantation + active stimulation). PD+DBS ON animals were stimulated 2h/day for 5 days (130 Hz, 60 µs, 0.1 mA). Motor evaluation was performed using cylinder test, immobility in the bar and open field test (OFT). Microdialysis samples were collected before the first and after the last session of DBS (7 and 12 days after the surgical procedure, respectively). After the last stimulation, animals were evaluated in apomorphine- induced rotation. Then, fresh and fixed tissue were for the evaluation of dopaminergic receptors (DR) expression, tyrosine hydroxylase immunoreactivity (TH-IR) and labelling of neuronal number. One and two-way ANOVA were used to statistically evaluate the results, where p<0.05. Results: As expected, STN-DBS attenuated motor complications in the PD model, confirming its efficacy in our preclinical setup. Untreated PD animals showed increased striatal D1R and D2R expression (p<0.01 vs. control). Electrode implantation per se reduced this increase, while stimulated animals exhibited a significantly higher D1R/D2R ratio. PD and PD + DBS OFF groups showed a 30–50% reduction in striatal dopamine release between days 7 and 12 post- surgery (p<0.01 vs. baseline), whereas PD + DBS ON animals maintained baseline dopamine levels (p>0.05). Dopaminergic changes in non-treated PD animals were accompanied by reduced TH-IR in the substantia nigra (SN) and striatum (p<0.001 vs. control). In contrast, STN- DBS increased TH-IR in the SN and suppressed PD-induced contralateral rotations upon apomorphine administration, without interfering with the number of neurons in the SN. Discussion:STN-DBS has the unique capability to reduce the equivalent dose of levodopa therapy, enabling the management of dyskinesia. Here we show that STN-DBS modulates dopaminergic circuitry by increasing the D1R/D2R ratio, promoting the switch from an anti- movement to a pro-movement setting while preventing the dopaminergic attenuation in the nigrostriatal pathway. Conclusions: STN-DBS, rather than exerting a “neuroprotective” effect, facilitates a range of neuroplastic mechanisms promoting the modulation of dopaminergic surviving neurons. The enhanced activity of the direct motor pathway, driven by a more pronounced DR1 receptor response may partly explain the reduced levodopa dosage required to manage motor complications in PD.
Derechos de autor 2025 Ana Carolina Campos, Mc Carvalho, Raquel Martinez, Erich Talamoni Fonoff, Clement Hamani, Rosana Lima Pagano https://creativecommons.org/licenses/by/4.0
Biomechanical Evaluation before and after Repetitive Transcranial Magnetic Stimulation (rTMS) in a Patient with Atypical Parkinsonism (Suspected MSA): Case Report
Introduction: Atypical parkinsonism, including Multiple System Atrophy (MSA), is characterized by postural instability, high risk of falls, and refractoriness to conventional treatments. Repetitive transcranial magnetic stimulation (rTMS) has been investigated as an adjuvant strategy for motor symptoms in parkinsonian syndromes. Wearable sensor technologies allow objective gait quantification, providing reproducible measures for intervention assessment. Clinical description: A 63-year-old woman with a clinical diagnosis of atypical parkinsonism, under investigation for MSA. The protocol included rTMS applied for five consecutive days (July 21–25, 2025), in two daily sessions (10 sessions in total): - Left dorsolateral prefrontal cortex (F3): 10 Hz, 1800 pulses/session. - Supplementary motor area (SMA): 10 Hz, 3000 pulses/session. - Spinal stimulation: 50 Hz, 20 pulses, 20 series, 2-second intervals between series. Each session was followed by neurofunctional physiotherapy focused on gait and balance. Assessments included gait analysis with an inertial sensor (Baiobit®, Sensor Medica, Italy), extracting spatiotemporal parameters (velocity, cadence, step length, symmetry, and propulsion), as well as the standardized Timed Up and Go (TUG) test. Discussion: Following the intervention, significant clinical and functional improvements were observed. In the TUG, fall risk decreased from high (pre) to low (post), and functional independence improved from semi-independent to independent. Gait analysis demonstrated improvements in symmetry (0 → 85%), cadence (+88.7%), and propulsion (0 → 10). Velocity increased (3.3 → 5.9 m/s; +78.8%), while step length remained slightly reduced (-3.2%), suggesting a cautious gait pattern. These findings reinforce evidence supporting the benefits of rTMS in movement disorders and highlight the role of wearable sensors in providing objective clinical outcomes. Even in non-idiopathic parkinsonian syndromes, neuromodulation may contribute to functional improvement and gait safety. Conclusions: The rTMS protocol combined with neurofunctional physiotherapy resulted in objective improvements in gait and reduced fall risk in a patient with atypical parkinsonism (suspected MSA). This case highlights the potential of neuromodulation as a symptomatic therapeutic resource in refractory parkinsonian syndromes.
Derechos de autor 2025 Barbosa Jaci, Sara Carvalho Barbosa Casagrande, Tarciana Aureliano Toscano De Olive, Vanessa Milanese Holanda https://creativecommons.org/licenses/by/4.0
Radiosurgery for Intracranial Meningiomas, Chilean Gamma Knife Experience
Introduction: Intracranial meningiomas (IM) represent the most prevalent primary central nervous system (CNS) tumors in adults, with an incidence rate ranging from 8.58 to 9.15 cases per 100,000 individuals. Small and medium-sized IM treatment standard options encompass radical surgery; however, this may not always be feasible due to surgical risks and patient preferences. In contrast, SRS stands out as an effective tool for managing tumor growth and alleviating symptoms. This holds particular significance in countries with long surgical waitlists, providing a cost-effective and low complication alternative. Method: This is a retrospective, single-center study involving 201 consecutive patients managed with GKRS for IM from 2011 to 2023. In the other Clínica Dávila Gamma Center in Chile. other series of patients were also included from 2014 to 2023. All data were collected in a prospective registry from the clinical patients records and then analyzed retrospectively. From this consecutive cohort, only 43 patients were selected for further analyses that had macroscopic tumors on baseline MRI, and additional post-SRS follow-up MRI with volumetric calculation. In the procedure room and under local anesthesia, patients underwent placement of a Leksell stereotactic frame. Stereotactic brain CT scanning was then obtained and fused in the Leksell Gamma Plan. with the preoperative, thin slice (1 mm) axial, and coronal pre- and post-contrast administration brain MRI for treatment planning. The radiosurgical plan was formulated by the treating neurosurgeon in conjunction with a medical physicist. All patients were treated in an ambulatory setting with single-session SRS using the Leksell Gamma Knife 4C (Elekta Instruments AB) in Centro Gamma knife and the Leksell Gamma Knife perfection in Clínica Dávila . A medial marginal dose of 12.8 Gy (range from 12 to 15 Gy) was delivered in a single session with a median prescription isodose line of 48.3% (range from 35 to 60%) Routine clinical and radiologic follow-up was obtained at approximately 6-month intervals following GKRS. Tumor volumes were calculated on T1 post-contrast MRI sequences. Tumor stability (i.e., tumor control) was defined according to the RANO criteria. Statistical analyses were performed with GraphPad Prism 9 and IBM SPSS statistics. For all statistical tests, a p-value of <0.05 was considered as statistically significant. Change in meningioma volume at last brain MRI was compared to the pre-GKRS MRI before SRS. A total of 70% were skull base meningioma, and 30% were non-skull base meningioma. Only one patient from the non-skull base IM presented transient edema as a complication of SRS (2.3%). Results: Our results showed that there is a statistically significant tumor volume reduction in the skull base IM group (mean initial volume: 5.32 cm3/last follow-up volume: 4.34 cm3). This tendency was not evident in the non-skull base group (mean initial volume: 5.78 cm3/last follow-up volume: 5.36 cm3). Also, at the volumetric follow-up, all the patients at least achieved a stable disease according to RANO, as shown in Figure B. The mean tumor volume change at 24 months post SRS was −10,6 and −23,9% for non-SB and SB meningiomas, respectively. Discussion: Our small series shows similar results to the literature (as shown in this review). To our knowledge, this is the first Chilean report of IM patients’ outcomes with GK SRS. All the patients were managed in an ambulatory setting. In our series, there was a low incidence of SRS-related compilations. The long-term outcomes were satisfactory because all the samples achieved at least a stable disease stage. This means that the radiosurgical procedure could achieve tumor control. Interestingly, the skull base group showed a statistically significant tumor volume reduction, as well as other reported series. Of the collected cases, the most common IM treated with GK SRS was skull base IM. Among these, more than 50% were tentorial, cerebellopontine angle, and petroclival meningiomas. The posterior fossa tumors are located in a critical region considering the presence of the brainstem, and in close relation with cranial nerves and vertebrobasilar circulation. Moreover, IM surgery is associated with more complications which may explain why SRS is preferred for skull base compared to non-skull base IM. From an economic perspective, several reports have revealed that SRS treatment is less expensive than microsurgery. The Dutch study of Tan et al. demonstrated that initial treatment cost is about five times higher for microsurgery ($12,288 euros) compared to SRS ($1547 euros for LINAC radiosurgery and $2412 euros for GK radiosurgery). For this reason, our attention is directed toward SRS as an economically viable treatment option within the domain of public health and neurosurgery. By prioritizing SRS, we aim to adopt a therapeutic approach that not only proves effective in addressing health issues but also demonstrates cost-effectiveness on a larger scale and well-being of individuals Conclusions: In conclusion, primary SRS emerges as a safe and valuable therapeutic option for addressing small to medium-sized symptomatic intracranial meningiomas. It boasts a high degree of tumor control while maintaining low complication rates and ensuring favorable long-term functional outcomes. It is indicated in tumors classified as WHO grade I IM that cannot be resected without important morbidity and mortality, in patients that are poor surgical candidates or by patient preferences with delayed and low radiotoxicity. Also, SRS can be used as adjuvant therapy in gross total and subtotal resection as well as recurrent small IM. There are several limitations of this study, first, it is a retrospective case series of two-center experience. Also, there is a low consecutive follow-up of patients that diminished our sample size of collected cases. Furthermore, as an ambulatory therapy from epidemiological point of view, it has a place in resolving the surgical waiting list that is long, especially in countries with less neurosurgical facilities with a safe and low toxicity technique.
Derechos de autor 2025 Gustavo Zomosa, Lucas Gonzalez-Johnson, Catalina Rojas-Sole, Gonzalo Lene Troncoso, Macarena Rojas, Jose Lorenzoni, Luz Oñoro, Andrés Fasssler https://creativecommons.org/licenses/by/4.0
Estimulación Cerebral Profunda (ECP) de Núcleo Intermedio Ventral del Tálamo (VIM)/Zona Incerta (ZI) Bilateral en un Caso de Temblor Ortostático (TO): Primera Cirugía en Argentina y Revisión de la Literatura
Introducción: El TO es un temblor de rara aparición, de alta frecuencia que se manifiesta en tronco y miembros inferiores (MMII) cuando el paciente se pone de pie. Suele asociarse a inestabilidad y miedo a caerse, aunque raramente sucede. Se lo clasifica en primario (puede asociar temblor en miembros superiores MMSS) y plus (asocia otros síntomas neurológicos como parkinsonismo). La fisiopatología es desconocida, sugiriéndose un compromiso principalmente en el circuito cerebelo-tálamo-cortical. En casos leves o de poco tiempo de evolución, suelen responder a fármacos antiepilépticos y benzodiacepinas, pero cuando es moderado a grave, avanzado o el paciente experimenta efectos adversos de la medicación, se vuelve problemático. Hay pocos casos descriptos en la literatura que han sido operados (ECP de VIM), con resultados que parecerían ser poco alentadores, y sólo 4 con ECP VIM/ZI. Nuestro objetivo es describir un caso de temblor ortostático operado con un doble blanco quirúrgico y muy buena respuesta terapéutica, y realizar una revisión de la literatura. Descripción clínica: Se describe el primer caso de TO operado de Argentina con ECP de VIM/ZI. Paciente femenina de 46 años, que consultó por temblor en miembros inferiores (MMII) de 8 años de evolución que se desencadenaba con la bipedestación y deambulación, cesaba al sentarse, acostarse o apoyarse sobre objetos. Asociaba sensación de inestabilidad y caídas. Se encontraba en tratamiento con propranolol 200 mg y clonacepam 2 mg/día con tendencia a la hipotensión. Había recibido pregabalina, pramipexol y gabapentin, con escasa respuesta y efectos adversos. Tenía antecedentes de temblor postural y acción leve en ambos miembros superiores (MMSS) desde la juventud, y, tanto su madre, tío materno y su hijo presentaban temblor de similares características en MMSS Al examen físico se observó temblor de alta frecuencia en MMII con la bipedestación inmediata, signo del dobladillo, marcha inestable y asistida. Temblor postural y de acción en ambos MMSS. La resonancia magnética de cerebro fue normal. El registro EMG de miembros inferiores durante la bipedestación mostró contracción simultánea de los músculos agonistas y anatagonistas con una frecuencia de 13 a 18 Hz en tibial anterior, gemelos, cuádriceps y bíceps femoral compatible con TO. Considerando los efectos adversos farmacológicos y la alteración sustancial en la calidad de vida, se realizó una cirugía de ECP de VIM/ZI con excelentes resultados a casi 1 año de la misma. Se abordaron las estructuras VIM/ZI en forma bilateral con un electrodo octopolar direccional a cada lado que involucró en forma simultánea a ambos núcleos Obtuvo un muy buen efecto lesión por 2 semanas, lo que suele pronosticar buena respuesta a la ECP. Se evaluó tanto en el pre como post quirúrgico con la escala de Impresión global de cambios en el paciente, familiar y médico, (siendo 0 gran empeoramiento y 6 gran mejoría), tiempo de latencia de inicio del temblor y tiempo duración al estar de pie, con óptimos resultados. Conclusiones: Si bien hay poca experiencia a nivel mundial de ECP y TO, se debería considerar en aquellos pacientes severamente afectados o con efectos adversos farmacológicos o intolerancia a los mismos. En el caso de nuestra paciente, se abordaron las estructuras VIM/ZI en forma bilateral con buena respuesta al momento, por lo que sugerimos tener presente este blanco quirúrgico en caso de TO refractario.
Derechos de autor 2025 Cynthia García Fernández, G Raina, R. Maiola, C. Paleka, B. Vera Barros, A. Pardal, G. Cersosimo, S. Pampin, F. Pedimonte https://creativecommons.org/licenses/by/4.0
Deep Brain Stimulation for Post-Traumatic Cerebellar Ataxia and Anterograde Amnesia: Multitarget Approach with 6 Electrodes, Electrophysiological and Tractographic Validation
Introduction: Post-traumatic cerebellar syndromes and memory disorders are highly disabling and refractory to conventional therapy. Deep brain stimulation (DBS) has shown therapeutic benefit in movement disorders, but its application in cerebellar and limbic circuits remains experimental. We report a pioneering case combining bilateral ventral intermediate nucleus (VIM) and Dentate nucleus (DN) stimulation for severe cerebellar ataxia and fornix stimulation for anterograde amnesia secondary to traumatic brain injury (TBI), supported by intraoperative electrophysiology. Clinical description: A 32-year-old male with severe TBI developed refractory pancerebellar syndrome (intention tremor, dysmetria, gait ataxia) and profound anterograde amnesia. MRI showed cerebellar and brainstem atrophy, hippocampal shrinkage, and thalamic involvement. DBS was proposed targeting the dentate nucleus bilaterally and the fornix. Microelectrode recordings in the VIM revealed multiple tremor cells with rhythmic bursting and low-frequency local field potentials (LFPs), confirming pathological oscillatory activity. Postoperative programming achieved marked reduction in tremor amplitude and improved motor coordination. Memory deficits persisted but showed mild improvement in short-term recall. Discussion: VIM trajectory was deliberately planned at a deeper level to engage the dendrorubrothalamic tract (DRETT) 3, a major cerebellothalamic pathway implicated in tremor generation. This approach aimed to modulate pathological oscillatory activity transmitted from the dentate nucleus through the red nucleus to the thalamus, optimizing tremor control. Dentate stimulation has shown variable success in ataxia, while fornix stimulation is primarily described in Alzheimer’s disease. Our findings suggest potential synergy, though cognitive recovery remains limited. Literature on combined approaches is scarce, underscoring the need for controlled trials. Conclusions: This case demonstrates the feasibility of combining cerebellar and limbic DBS targets for complex post-traumatic syndromes. DBS targeting DN, DRETT and fornix may offer benefit in refractory cerebellar ataxia with coexisting memory impairment after TBI. Intraoperative microrecording and LFP analysis provide valuable biomarkers for optimizing targeting and programming.
Derechos de autor 2025 William Omar Contreras López, Fabián Piedimonte, Juan Esteban Rosales, Paula Alejandra Navarro González, Nicolás Moreno Guerra https://creativecommons.org/licenses/by/4.0
Deep Brain Stimulation for Disorders of Consciousness after Global Cortical Ischemia: Bilateral CM-PF and Posterior Hypothalamic Targeting with Neurophysiological Validation
Introduction: Post-anoxic brain injury is a major cause of prolonged disorders of consciousness (DoC) and minimal functional recovery despite intensive rehabilitation. We report a case of advanced neuromodulation in a patient with chronic minimally conscious state (MCS) following global cortical ischemia secondary to cardiorespiratory arrest. Clinical description: A 57-year-old female with a history of perioperative hypoxic-ischemic encephalopathy presented with persistent MCS for over 12 months. MRI demonstrated extensive ischemic damage involving bilateral occipital cortex, frontal lobes, and centrum semiovale. PET scan revealed generalized cortical hypometabolism. Long-term video-EEG telemetry showed preserved occipital alpha activity, indicating partial integrity of thalamocortical projections—a recognized predictor of recovery potential in selected candidates for DBS. Based on clinical and neurophysiological criteria, bilateral deep brain stimulation was proposed targeting two complementary neuroanatomical structures: Centromedian-Parafascicular (CM-Pf) complex of the thalamus, and Posterior hypothalamic area (PHyp). Discussion: The synergistic combination of CM-Pf, to restore thalamocortical connectivity and frontoparietal networks activation implicated in consciousness, and PHyp to modulate arousal and active monoaminergic pathways, improving wakefulness, visual tracking, vocalization, and cortical excitability, has demonstrated sustained functional benefits in chronic MCS, including recovery of command-following, reduction of spasticity, and progress in communication. At microelectrode findings, PHyp confirmed neuronal activity consistent with the hypothalamic region. During intraoperative stimulation, BIS index increased from 36 to 95, accompanied by autonomic changes (blood pressure and heart rate modulation). CM-Pf revealed neurons with intermediate firing patterns, supporting accurate CM-Pf localization. Conclusions: This case of Dual-target DBS involving CM-Pf and PHyp represents a feasible therapeutic strategy for refractory DoC, neurophysiological markers such as preserved alpha rhythms and tractographic validation are essential for patient selection and surgical planning. Integration of microrecording and neurophysiological monitoring enhances accuracy and may expand DBS indications beyond movement disorders. Further studies are needed to confirm long-term outcomes and refine stimulation paradigms for DoC.
Spatio-Temporal Hypomimic Deep Descriptor to Discriminate Parkinsonian Patients
Introduction: The hypomimia is a main clinical sign of Parkinson disease that describes motor patterns associated with the reduction and progressive loss of facial expression. This clinical sign constitutes a main biomarker to support diagnosis, even at early stages, and to establish progression and description of the disease. In clinical routine, the evaluation of such signs remains subjective or limited to the description of some landmarks that poorly describe little expressions correlated with the disease. This work introduces a new digital biomarker, expressed as a spatio-temporal convolutional representation that learns facial movement patterns to discriminate between Parkinson and control patients. Clinical description: This paper implements a 3D convolutional representation, inspired by the net scheme of I3D. This representation was here trained to automatically identify Parkinsonian facial patterns, using a supervised end-to-end scheme. From such representation it is possible to discriminate patterns but also to recover spatio-temporal activations that enhance spatial regions with major correlation with the disease. The trained volumetric network demonstrated distinct activation patterns between groups. In Parkinson’s patients, the model concentrated on restricted facial regions (eyes, nose, mouth), reflecting reduced expressivity and limited dynamic movement. In contrast, control participants elicited broader and more diverse activation across facial areas. The ablation analysis varying temporal resolution showed that a configuration using 14 frames per video yielded the highest classification performance. Compared with a standard 2D ResNet-50 model and previously reported static-feature approaches, the proposed 3D spatio-temporal descriptor achieved superior discrimination. The learned embedding space further showed clear separation between patients and controls. Discussion: These findings suggest that the reduced activation spread in Parkinson’s patients corresponds to clinical hypomimia characterized by facial rigidity and diminished micro-movement dynamics. The improved performance at lower temporal resolution indicates that moderate temporal subsampling facilitates the detection of subtle motion deficits inherent in hypomimic expression. The superiority of the spatio-temporal method over static models supports the relevance of capturing dynamic facial patterns rather than isolated frames or manually selected landmarks. The embedding distribution also suggests potential alignment with clinical severity markers, indicating that this approach may serve as a complementary digital biomarker for disease characterization and monitoring. Conclusions:This work introduced an end-to-end method for learning a spatio-temporal representation of facial patterns in video. The proposed method outperformed similar approaches for Parkinson detection in video sequences. The analysis of attention maps in intermediate layers highlighted facial regions associated with the neural network’s prediction. These regions could provide support to clinicians’ evaluation and further patient’s monitoring. In this research we also collected, to the best of our knowledge, the first audiovisual dataset of Parkinson’s patients and control subjects with diagnosis stage annotations. This dataset will enable the exploration of computational methods for multi-modal analysis.
Derechos de autor 2025 William Omar Contreras López, Brayan Valenzuela, Jhon Arevalo, Fabio Martínez https://creativecommons.org/licenses/by/4.0
Tractography‑Guided Multitarget DBS with Multiple Independent Current Control Combining Linear and Directional Electrodes in Resistant Depression and Anxiety
Introduction: Treatment-resistant depression (TRD) is a chronic and severe form of major depressive disorder with limited therapeutic options. One-third of TRD patients fail to respond to pharmacological and psychotherapeutic interventions. Deep Brain Stimulation (DBS) is a promising therapy for TRD patients, but its clinical results have been highly variable in multiple studies focused on single target interventions, suggesting suboptimal targeting of the circuits implicated in TRD. Connectomics approaches have emerged to enable an individualized planning of symptom-specific circuits targeting in TRD with promising results. We report a case of Multitarget DBS involving six neural tract including subgenual cingulate cortex, Brodmann area 25 (SGC25) and anterior limb of the internal capsule (ALIC) with distal extension toward the nucleus accumbens (NAc) stimulation. Clinical description: A 34-year-old woman presented with a chronic psychiatric history dating back to age 10, when she developed disordered eating behaviors, bulimia nervosa type 1 and later anorexia nervosa at 15 years managed with limited success. Over the ensuing years, she experienced recurrent major depressive episodes, generalized anxiety disorder, panic attacks, social phobia, and agoraphobia. Despite multiple evidence-based psychiatric interventions—including cognitive behavioral therapy and sequential pharmacotherapy with selective and multiple serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors—her symptoms remained refractory or transient improvement. At evaluation, affective lability, anhedonia, hopeless, and intrusive anxiety are presented persistently. Given the TRD diagnostic, a multidisciplinary team recommended an innovative multitarget DBS approach using Multiple Independent current control (MICC). Discussion: This case illustrates the potential of simultaneous modulation of interconnected affective and cognitive circuits implicated in TRD. The ALIC-NAc target was selected to precisely modulate anxiety and reward-related networks, while the SGC25 was chosen to engage affective regulation pathways including medial forebrain bundle (MFB), dorsal longitudinal fasciculus (DLF), and anterior thalamic radiation (ATR), all described with antidepressant effect in DBS for TRD. MICC technology enabled tailored stimulation according to TRD individual evolution explaining the observed multidomain symptomatic improvement across scales. At four-month follow-up, Hamilton Depression Rating Scale (HDRS-17) scores improved by 65%, Montgomery–Åsberg Depression Rating Scale (MADRS) by 70%, with additional improvement in Beck inventory depression and anxiety scales (BDI and BAI). Conclusions: This novel single-case study supports the feasibility and clinical benefit of multitarget MICC-DBS guided by connectomics in TRD. Individualized modulation of SGC25 and ALIC-NAc may improve cognitive and anxiety predominant symptoms in TRD patients. Further studies are needed to replicate these findings in a well-selected cohort of TRD patients to validate the individualized multitarget MICC-DBS modulation and its progressive capacity to improve symptoms in TRD. Coronal postoperative MRI with tractography overlay demonstrating bilateral multitarget DBS electrode trajectories. Directional Cartesia™ leads were placed in the SGC25, while linear Vercise™ leads traversed the ALIC with distal contacts in the NAc. Patient-specific tractography highlights key white matter pathways: MFB (blue), ATR (green), and DLF (red), confirming engagement of fronto-limbic and reward circuits relevant to depression and anxiety modulation. (Figure 1).
Derechos de autor 2025 William Omar Contreras López, Paula Andrea Millán Giraldo, Nicolás Moreno Guerra, Juan Esteban Rosales https://creativecommons.org/licenses/by/4.0
Integrating Synchronized Dysarthria and Hypomimia Deep Patterns to Quantify Parkinson Disease
Introduction: Parkinson’s disease (PD) is a progressive neurological disorder that often leads to impairments in speech (dysarthria) and facial expressiveness (hypomimia). These signs are clinically relevant but often evaluated subjectively. Current methods treat these impairments separately. We propose a multimodal deep learning framework that jointly analyzes audio and video data to detect patterns associated with dysarthria and hypomimia. Method: Facial movement and voice signals were encoded using deep neural representations to identify PD-related patterns. A retrospective study involved 14 native Colombian Spanish speakers: 7 PD patients (mean age 65 ± 4, 4M/3F) and 7 controls (mean age 61 ± 3, 2M/5F). Diagnoses were confirmed by a neurologist and partially labeled via the Hoehn and Yahr scale; 2 patients were off medication and 5 under Levodopa. Data were acquired in controlled conditions using a Nikon D3500 camera (1080p, 60 fps) with monaural audio (48 kHz). Participants performed vowel, phoneme, and word tasks to elicit PD symptoms. This is the first Spanish-speaking synchronized audio-video corpus for PD orofacial analysis. Voice recordings were transformed into Mel spectrograms. Three 2D CNN architectures (ResNet-50, VGG-16, and a custom model) were trained to classify PD vs. controls. Facial videos were processed using a compact 3D-CNN and an inflated 3D (I3D) model to extract spatiotemporal features linked to hypomimia. A late fusion strategy combined audio and video predictions via weighted linear integration. Models were evaluated using leave-one-out cross-validation across pronunciation tasks, reporting precision, recall, F1-score, accuracy, and AUC. All networks were trained with binary cross-entropy, Adam optimizer, early stopping, and a learning rate of 1 \times 10^{-5} over 25 epochs. Results: Audio-based classification using Mel spectrograms showed that VGG-16 outperformed ResNet-50 and a baseline CNN, achieving an average AUC of 69.72%, with peak performance (73.55%) during vowel articulation. For video analysis, a custom 3D-CNN surpassed both a 2D ResNet-50 and an inflated 3D (I3D) model, effectively capturing spatiotemporal facial patterns linked to hypomimia. Multimodal fusion of VGG-16 (audio) and 3D-CNN (video) improved diagnostic accuracy across tasks, with the highest AUC (85.39%) observed for phonemes at fusion weight λ = 0.5. This approach demonstrates the complementary value of combining speech and facial cues. Discussion: The multimodal approach effectively integrates facial and vocal biomarkers. Phoneme-based facial cues via 3D-CNN yielded superior performance (AUC = 82.59%), likely due to expressive dynamics from plosive articulations. Vowel-based audio features processed via VGG-16 achieved an AUC of 73%, benefiting from stable acoustic phases. Fusion enhanced classification across all tasks, supporting the hypothesis that synchronized motor and speech signals offer complementary diagnostic value. Complementary studies have focused on audio-only representations, achieving high accuracy but overlooking facial-vocal interplay. Our synchronized dataset contributes a valuable resource for integrated modeling. Correlations between jaw motion and respiratory control support multimodal analysis. Compared to prior fusion methods, our approach captures richer temporal dynamics and articulatory complexity. Conclusions:The proposed framework improves PD classification by combining deep audio and visual embeddings, with phoneme articulation as the most informative task. Convex fusion outperformed unimodal models, with highest gains for phonemes (AUC = 85.39 at λ = 0.5), reinforcing the clinical relevance of synchronized motor-speech impairments. Future work will explore end-to-end models capable of learning fusion weights and temporal dependencies directly from raw inputs. Expanding the dataset to include spontaneous and emotionally expressive speech, as well as broader phonetic coverage, will enhance ecological validity. Longitudinal studies will track disease progression and therapy response, enabling personalized diagnostic tools and early intervention.
Derechos de autor 2025 William Omar Contreras López, Brayan Valenzuela, John Archila, John Arévalo, Fabio Martíınez https://creativecommons.org/licenses/by/4.0
Connectome Analysis of the Nucleus Accumbens: Refining Radiosurgical Targeting for Addictive Disorders
Introduction: Addictions pose a major global health and socioeconomic challenge. Treatment strategies include pharmacological interventions, deep brain stimulation, and ablative procedures. Stereotactic radiosurgery (SRS) has emerged as a noninvasive, precise option for addiction management. nderstanding the anatomy and connectivity of the nucleus accumbens (NAc) is key to refining radiosurgical targets and improving outcomes. Method: Diffusion tensor imaging from 3T and 1.5T MRI scanners was obtained in five healthy subjects using T1 and T2 sequences. Images were fused with autosegmentation of the NAc, ventral tegmental area (VTA), amygdala, hippocampus, hypothalamus, and periventricular gray (PVG). The insula, medial/lateral orbitofrontal cortex, and dorsolateral prefrontal cortex were manually drawn. Connectivity to the NAc was visually assessed with fractional anisotropy thresholds (20–10). The five densest fiber tracts guided target selection, aligned to the anterior–posterior commissure, and transferred to Gamma Plan for radiosurgical planning. Results: The strongest connections were between the medial orbitofrontal cortex (mOFC), hypothalamus, VTA, PVG, and amygdala with the NAc. The mOFC–NAc and hippocampus–NAc tracts were the most and least robust, respectively. Derived stereotactic coordinates supported connectome-based targeting, proposing a 90 Gy dose to the NAc shell and aligning the 20 Gy isodose for neuromodulation. The right and left NAc received > 20 Gy in 75.2% and 55.6% of their volumes, while the optic apparatus received ≤ 5.4 Gy (Dmax). Discussion: The NAc, within the ventral striatum, integrates limbic, cognitive, and motor inputs regulating reward and motivation. Its shell and core subregions differ functionally, with the shell showing dense dopaminergic input from the VTA and high sensitivity to reinforcement stimuli. Chronic substance exposure induces neuroplastic changes underlying compulsive behaviors, making the NAc shell a rational neurosurgical target. DBS, radiofrequency ablation, and SRS have yielded variable but promising results in refractory opioid and alcohol dependence. Advances in diffusion imaging now enable precise mapping of NAc connectivity and subregion-specific targeting. High-dose (up to 90 Gy) LINAC-based radiosurgery has shown safety and potential for radiomodulation, highlighting the therapeutic promise of anatomically informed, connectivity-guided interventions. Conclusions: Addiction remains a pervasive disorder with high relapse rates despite medical and behavioral therapies. Radiosurgery, a time-tested and safe functional technique, may offer a new treatment alternative. Connectivity-based SRS using commercial planning software allows visualization and autosegmentation of key NAc connections, supporting patient-specific, circuit-informed targeting in addiction neuromodulation.
Derechos de autor 2025 William Omar Contreras López, José Chang, Richard Gonzalo Párraga, Jorge Torres Monterrosa, Larissa Merlos Salazar https://creativecommons.org/licenses/by/4.0
Simultaneous Bilateral Implantation of DBS Electrodes for Parkinson´s Disease using a Frameless Customized Platform: First Report in Latin America
Introduction: Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) has been historically performed with frame-based stereotaxy. However, extended operative time and patient discomfort motivated the evaluation of frameless technology, achieving accurate electrode placement like conventional techniques. We report the first case in Latin America of bilateral DBS implantation for Parkinson's Disease using a frameless platform. Clinical description: A 64-year-old female with a 5-year evolution of Parkinson’s disease presented left-sided onset hemibody and mixed-phenotype tremor. The patient experienced motor fluctuations, and morning akinesia despite optimized pharmacological therapy including levodopa-carbidopa-entacapone, rotigotine, and mirtazapine, with partial tremor control. Non-motor symptoms include anxiety, insomnia, and depression. The levodopa Challenge Test (LCT) demonstrated a 53% improvement in Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III), confirming dopaminergic responsiveness. Based on persistent tremor, motor complications, absence of psychiatric conditions or cognitive impairment, the patient was considered for a bilateral subthalamic nucleus (STN) DBS. Discussion: Simultaneous bilateral DBS using a customized frameless platform proved to be feasible and safe. The simultaneous bilateral DBS strategy reduces operation time in both half arcs strategy. In this procedure, the operative time was 120 minutes, which is comparable with dual-arc technique (136.4 ± 20.93 minutes). Moreover, the surgical time is significantly reduced, and this technology is even more advanced than semi-frame systems, since it does not require either a CT scan or an MRI with the stereotactic frame on the day of surgery. StarFix planning and guidance system provides an accurate position of electrodes by integrating patient-specific cranial geometry into a customized platform. Its precision is comparable with other frameless systems and its accuracy is related with the increasing experience of the surgical team. Conclusions:This frameless platform demonstrated feasibility, accuracy, and operative DBS efficiency. This first case highlights the potential of frameless systems to expand access to DBS therapy in Latin America. Further studies with larger cohorts of patients and long-term follow-up are needed to confirm the benefit of these approaches.
Derechos de autor 2025 William Omar Contreras López, Nicolás Moreno Guerra, Melissa Ibarra, Fabián Piedimonte https://creativecommons.org/licenses/by/4.0
De la adversidad al avance: Los años pioneros de la Neurocirugía Funcional Peruana ¿Qué aprendimos y hacia dónde vamos?
Introducción: La Neurocirugía Funcional (NF) en el Perú se estableció frente a significativas adversidades. Conocer la historia de sus pioneros es crucial para comprender el desarrollo de la especialidad en el país, identificar las lecciones aprendidas y trazar su futuro. Este estudio tiene como objetivos: 1) Documentar y analizar, desde la perspectiva de sus protagonistas, los desafíos, logros y factores que caracterizaron la etapa pionera de la NF en el Perú 2) Sintetizar las lecciones históricas para proponer directrices estratégicas que guíen su desarrollo futuro. Métodos: • Tipo de diseño: Estudio cualitativo, de tipo histórico-documental y de análisis de experiencia experta, mediante la técnica de entrevista semiestructurada. • Población y muestra: Población diana: neurocirujanos peruanos reconocidos como pioneros en la práctica de la NF en sus distintas sedes hospitalarias antes del año 2005. Se utilizó un muestreo intencional por criterios, reclutándose a 7 profesionales que cumplieron con los criterios de inclusión • Variables medidas: Se analizaron las siguientes dimensiones: 1) Desafíos (tecnológicos, institucionales, académicos, económicos), 2) Logros e hitos principales (primeros procedimientos, creación de servicios), 3) Factores clave de éxito, y 4) Lecciones aprendidas y perspectivas de futuro. • Recolección de datos y aspectos éticos: Se realizaron entrevistas semiestructuradas, grabadas y transcritas verbalmente para su análisis temático. El proyecto contó con la aprobación del comité de ética institucional y se obtuvo el consentimiento informado por escrito de todos los participantes, garantizando la confidencialidad y el anonimato. Resultados: Se identificaron 5 categorías principales de adversidades, siendo las más relevantes la limitada tecnología (improvisación de equipos), el escepticismo académico y la falta de apoyo institucional. Los hitos pioneros incluyeron la primera cingulotomía bilateral anterior en el año 1984 hasta la primera colocación de estereoelectroencefalografía en el año 2024; también como la fundación del primer servicio de la primera: “Unidad de Estereotaxia, Endoscopia y Neuronavegación” en Hospital Edgardo Rebagliati Martins. El análisis reveló que la perseverancia, la formación en el extranjero y el trabajo multidisciplinario fueron los factores críticos para el éxito. Las lecciones aprendidas se centran en la necesidad de una planificación estratégica continua para evitar el estancamiento. Discusión: Nuestros hallazgos coinciden con la literatura que describe el desarrollo de especialidades quirúrgicas en contextos de recursos limitados, donde la iniciativa individual y la colaboración son determinantes. La experiencia peruana es un caso paradigmático de innovación frente a la adversidad. La principal limitación del estudio es el potencial sesgo de recuerdo, inherente a las metodologías históricas. La relevancia de este trabajo radica en rescatar una memoria institucional en riesgo y ofrecer un marco de referencia para la toma de decisiones futuras en salud pública y formación de especialistas en neurociencias en el Perú. Conclusiones: La etapa pionera de la NF peruana estuvo marcada por la superación de barreras significativas, logrando hitos fundamentales gracias a la tenacidad y visión de un grupo reducido de profesionales. Las lecciones aprendidas subrayan la fragilidad de los avances médicos sin una estrategia de sostenibilidad. Se concluye que el futuro de la NF en el Perú depende de la institucionalización de los logros, la inversión en tecnología y la formación de nuevas generaciones, basándose en el legado de sus pioneros.
Derechos de autor 2025 Jason Riveros https://creativecommons.org/licenses/by/4.0
Derechos de autor 2025 Equipo Editorial https://creativecommons.org/licenses/by/4.0