Faculty Bibliography

UNLABELLED:<p>Introduction: Tremor-predominant Parkinson's disease (TPPD) generally responds favorably to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). However, traditional stereotactic targeting of the STN does not universally yield the anticipated intraoperative improvement, prompting exploration of additional targets to achieve optimal results prior to permanent implantation of electrodes. The posterior subthalamic area (PSA), including the caudal zona incerta (cZI), have been associated with tremor suppression and can be easily compared to the neighboring STN intraoperatively. METHODS:We retrospectively compared intraoperative and clinical outcomes in tremor-dominant PD patients who prospectively underwent dual trajectory microelectrode monitor targeting the STN and PSA/cZI. We compared the neurophysiology and tremor response of both the central (STN) and posterior (PSA) trajectories in 22 patients and analyzed outcomes in those who ultimately received traditional STN (16) or PSA/cZI lead implantation (12). RESULTS:While both groups achieved substantial overall motor improvement under chronic stimulation, intraoperative test stimulation through the posterior path produced more consistent tremor arrest compared with STN. These findings suggest that positioning the DBS lead further posteriorly to engage the PSA can augment tremor suppression in select cases of TPPD without compromising other parkinsonian symptom relief. CONCLUSION/CONCLUSIONS:Our results emphasize the value of intraoperative physiological feedback in trajectory selection in tremor-predominant patients and are consistent with emerging literature that PSA/cZI DBS is an effective and potentially superior target for management of tremor in PD. </p>.

The structure-function gradient along the hippocampal long axis is recognized but poorly understood. Rodent recordings mainly sample the dorsal hippocampus (posterior), while surgical recordings in epilepsy patients typically sample from the ventral hippocampus (anterior), because of greater known involvement in seizure networks. These divergent recording practices imply that the mechanisms of rodent spatial navigation may not directly apply to human episodic memory. In general, the role of the posterior hippocampus in human memory and seizure networks is under-appreciated. We survey the basic, translational, and clinical research accounting for long-axis differentiation and outline future research directions.

Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.

BACKGROUND/UNASSIGNED:Intraoperative Neural Monitoring (IONM) is mandatory for performing anterior (i.e., transthoracic) or lateral extracavitary approaches to significant anterior/anterolateral thoracic ossification of the posterior longitudinal ligament (TOPLL) (i.e. often misdiagnosed as calcified Thoracic Disc Herniations) (TDH). Notably, the remaining "posterior procedures" (i.e. laminectomy, transpedicular, and costotransversectomy) are contraindicated for treating significant anterior/anterolateral TOPLL as they result in unacceptably high frequencies of spinal cord injury (SCI) typically correlated with significant intraoperative IONM losses. METHODS/UNASSIGNED:A review of multiple studies documented that IONM (i.e. especially Tc-MEP (Transcranial Motor Evoked Potentials)) is mandatory when performing anterior transthoracic or lateral extracavitary approaches to TOPLL. This is because IONM alerts signaling the onset of SCI may likely be remediated (i.e. minized vs. limited) utilizing appropriate resuscitative maneuvers. Alternatively, extremely high frequencies of significant IONM losses occurring with "posterior procedures" carried a much higher risk of permanent/irreversible neurological injury. RESULTS/UNASSIGNED:Multiple studies documented that IONM should be used with anterior transthoracic or lateral extracavitary approaches to anterior/anterolateral TOPLL surgery, and that "posterior procedures" were largely contraindicated. In one series, significant amplitude Tc-MEP losses occurred in 73% of posterior decompressions; 39% developed Tc-MEP amplitude losses, that correlated with new SCI. In another study of 249 TOPLL patients undergoing "posterior only operations", 50 developed new significant IONM alerts (i.e. of deterioration); only 40% (20/50) were successfully resuscitated. Overall, initiating immediate resuscitative maneuvers in response to IONM occurring during various types of TOPLL surgery can avert SCI in up to 10.4%, to 40%, to 57% of cases. CONCLUSION/UNASSIGNED:IONM is mandatory for anterior/anterolateral TOPLL surgery utilizing anterior transthoracic or lateral extracavitary approaches.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Intramedullary spinal cord tumor (IMSCT) resection carries a high risk of postoperative neurological deficit because of neural tract manipulation and myelotomy. Although short-term and long-term neurological recovery represent key treatment outcomes, current prognostication methods are lacking and would benefit from further complex analysis. METHODS:From March 2009 to August 2025, all adult IMSCT resections at our institution were reviewed. Demographic, oncologic, and perioperative data were extracted from electronic medical records. This included preoperative and follow-up neurological examination data in the form of American Spinal Injury Association Impairment Scale (AIS) grading, Modified McCormick Scale (MMCS), and ambulatory status. Independent ambulation served as the primary outcome for 4 machine learning models. Each model was sequentially evaluated using area under the receiver operating characteristic curve (AUROC). RESULTS:Fifty-four patients underwent 55 surgeries for IMSCT resection. Encapsulated lesions predominated IMSCT pathology, with grade II ependymoma comprising 28 (50.9%) resections, 5 hemangioblastomas (9.1%), and 5 cavernous hemangiomas (9.1%). Gross total resection was achieved in 36 cases (65.5%), with encapsulated tumors more readily achieving gross total resection vs unencapsulated (84.6% vs 18.8%, P < .01). By 4 weeks, conversion of MMCS, but not AIS grade, significantly correlated with concurrent ambulatory conversion (P < .01 vs P = .15). At 6 months, both AIS grade conversion (P < .01) and MMCS conversion (P < .01) significantly correlated with ambulatory conversion. For predicting ambulation at latest follow-up from 4 weeks postoperatively, the comprehensive granular model achieved an AUROC of 0.833, outperforming the AIS grade (0.583), American Spinal Injury Association Motor Score (0.667), and MMCS (0.667) models. By the 6-month follow-up, the comprehensive granular model achieved strong discrimination (AUROC 1.00). CONCLUSION/CONCLUSIONS:Follow-up IMSCT data demonstrate a postoperative lability that stabilizes by 6 months into a reliably modeled outcome. By enhancing the granularity of recovery data, accurate independent ambulation modeling may improve counseling for patients with IMSCT.

Isolated cranial tremors (face tremor, jaw tremor, vocal tremor, and embouchure tremor) are unusual examples of focal tremor disorders. The etiology and treatment of these troublesome and occasionally disabling conditions deserve more attention. In this review, we summarize current knowledge about these disorders and consider their etiologies and treatment approaches. We suggest changes to the current classification system of isolated cranial tremors based on shared phenomenology and treatment response.

OBJECTIVE:This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug-resistant idiopathic generalized epilepsy (IGE) with generalized tonic-clonic seizures (GTCSs). METHODS:NAUTILUS is a prospective, multicenter, single-blind, randomized sham-controlled pivotal trial. Patients were ≥12 years of age with drug-resistant IGE and ≥2 GTCSs over a 3-month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation, n = 44) or Sham (no stimulation, n = 43). The effectiveness evaluation period (EEP) began 3 months postimplant through 1 year. After a second GTCS in the EEP, patients transitioned to open-label active stimulation. The primary safety endpoint was the serious adverse device-related event (SADE) rate at 84 days postimplant. The primary effectiveness endpoint was time-to-second-GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR). RESULTS:Eighty-seven patients were implanted across 23 US centers. The SADE rate was significantly below the performance goal (6.9%, p < .0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed-effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%, p = .030). Eighteen-month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS-free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales. SIGNIFICANCE/CONCLUSIONS:NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much-needed option for drug-resistant IGE.

Precise quantification of eye-hand coordination (EHC) during pediatric dexterity tasks is limited by the lack of practical, high-resolution hand tracking methods suitable for children with brain injury or neurodegenerative disease. Traditional marker-based motion capture systems and instrumented gloves can interfere with natural grasp patterns and are often difficult to implement in clinical pediatric settings. We describe an adaptation of the Anipose markerless 3D pose estimation framework to enable synchronized three-dimensional hand kinematics and eye tracking during the Nine-Hole Peg Test (9HPT). The method integrates multi-camera video acquisition with task-specific neural network training optimized to detect fine finger movements across diverse pediatric hand sizes and grasp configurations. Camera placement and recording geometry were configured to reduce occlusion during peg manipulation and maintain multi-view visibility of hand landmarks. Model validation demonstrated low pixel error and stable three-dimensional reconstruction following confidence-based thresholding. The resulting workflow generates synchronized 2D and 3D visualizations, spatial coordinate outputs, reprojection-error metrics, and landmark confidence scores without requiring wearable sensors. This approach broadens the applicability of eye-hand coordination research within pediatric clinical populations and facilitates the development of more precise, quantitatively informed diagnostic assessments and targeted neurorehabilitation strategies for children with neurologic injury. • Markerless multi-camera 3D reconstruction of pediatric hand kinematics during the 9HPT • Integration of synchronized eye tracking and task-specific neural network training • Output of validated 3D coordinates, confidence metrics, and visualization files suitable for clinical research.

BACKGROUND:While genetic testing in Movement Disorders (MD) has expanded enormously, access to genetic testing and genetic counseling remains asymmetric at the global scale. Guidance on efficient testing strategies for clinicians, governments and stakeholders is crucial. OBJECTIVES/OBJECTIVE:Establish a list of genetic movement disorders considered essential as determined by a group of MD experts. METHODS:All genes associated with MD were searched using the OMIM and MDS Gene database. We collected all additional tests available at 4 different laboratories from the EuroGentest database. The results were compiled in 6 questionnaires. A genetic test was considered essential if molecular testing had a direct impact in the management of the patient, including treatment of the disease or its comorbidities, or genetic counseling of the patient and family members. Two Delphi rounds were conducted asking MD experts which specific tests they considered essential in an adult MD clinic. RESULTS:Fifty-nine disorders were considered essential to genetically identify by the MD experts. This included 25 genes associated with ataxia, 15 with parkinsonism, 14 with dystonia, eight with chorea, five with paroxysmal disorders, four with myoclonus, four with hereditary spastic paraparesis, and one with tremor. Sixteen disorders reached 100% consensus among experts: Huntington's disease, PxMD-PPRT2, Wilson's disease, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT/PARK-GCH1, Fragile-X Tremor-ataxia syndrome, PARK-GBA, PARK-LRRK2, PARK-PINK1, PARK-PRKN, PARK-SNCA, Cerebrotendinous Xanthomatosis, Ataxia-Telangiectasia, and Niemann-Pick disease type C. CONCLUSION/CONCLUSIONS:This study provides a list of genetic MD that should be molecularly tested in adult centers with a compatible phenotype according to a group of MD experts.

BackgroundFew studies have examined which patients with migraine might be responders for mind-body interventions. Thus, we examined whether certain baseline mindfulness traits and interest in physical exercise might predict response to treatment.MethodsThis is a planned exploratory analysis of a phase 2 randomized controlled study (N  =  50; 25 per arm) comparing a 6-week physical therapist (PT)-delivered biofeedback-assisted relaxation (BAR) program vs. an Enhanced Usual Care (EUC) migraine self-management program (diary tracking and emailed migraine-related educational materials). We conducted moderation analyses to determine whether the Multidimensional Assessment of Interoceptive Awareness (MAIA), Difficulties in Emotion Regulation Scale (DERS) and Physical Activity Enjoyment Scale (PACES) at baseline influenced the effect of BAR on migraine-related outcomes (Migraine-Specific Quality of Life Role Function Restrictive (MSQv2.1-RFR) and Migraine-Related Disability (MIDAS)) at 6 months.ResultsAmong the n = 40 participants (BAR = 19; EUC = 21), the majority were female (95%), non-Hispanic (77.5%) and white (67.5%). Mean (SD) age was 45.6 (11.2) years. For the MAIA Not-Worrying subscale, BAR produced the greatest improvement in 6-month MSQv2.1-RFR scores among participants with low baseline Not-Worrying scores (those who tended to worry about bodily sensations/discomfort more) (BAR = 77.1 ± 6.6 vs. EUC = 48.9 ± 5.0; p = 0.002, g = 4.75). The benefit diminished at average levels (p = 0.060, g = 2.72) and was absent at high baseline Not-Worrying (p = 0.528, g =  -0.91). For the MAIA Self-Regulation subscale, BAR was most effective among those low in baseline self-regulation (BAR = 71.7 ± 5.3 vs. EUC = 44.3 ± 7.2; p = 0.004, g = 4.27). The DERS total score showed that BAR demonstrated little benefit among participants with better baseline emotion regulation (i.e. lower DERS score; p = 0.907, g = 0.17) but was more effective as baseline emotion regulation difficulties increased, showing a moderate benefit at average levels (BAR = 69.2 ± 4.2 vs. EUC = 55.8 ± 4.0, p = 0.027, g = 3.25) and a large, significant difference at high levels (BAR = 70.6 ± 6.3 vs. EUC = 44.7 ± 5.7; p = 0.004, g = 4.22). The PACES total score indicated that BAR benefits were strongest among those with low (BAR = 76.1 ± 7.0 vs. EUC = 47.1 ± 5.3, p = 0.002, g = 4.60) to average (BAR = 71.2 ± 4.2 vs. EUC = 58.6 ± 4.0, p = 0.035, g = 3.07) enjoyment of physical activity.ConclusionsWe found subgroups of individuals with migraine who may be better responders to PT-delivered BAR, specifically those who tend to worry more about bodily sensations (lower MAIA Not-Worrying score), those with low self-regulation (lower MAIA Self-Regulation score), those with worse emotion regulation (higher DERS score) and those with lower levels of physical activity enjoyment (lower PACES score) at baseline. This may help us determine who may benefit most from BAR.Trial RegistrationClinicalTrials.gov Identifier: NCT06077812.