Harrison C. Walker

Introduction: Restless legs syndrome (RLS) is a lifelong disorder characterized by recurrent, uncomfortable sensations and irresistible urges to move the legs that peak in the evening. Spinal cord stimulation (SCS) is a longstanding neuromodulation treatment for chronic neuropathic pain with emerging evidence of potential effectiveness toward RLS through a potential shared pathophysiology of central sensitization. Methods: A retrospective review of our institution’s electronic health record system was performed to identify patients who received SCS for chronic pain with a concomitant RLS diagnosis. Patients who had a diagnosis of RLS in their chart were secondarily confirmed to have RLS using the Cambridge-Hopkins RLS Questionnaire via telephone. The International Restless Leg Syndrome (IRLSS) Study Group Rating Scale and multiple Patient-Recorded Outcomes Measurements System (NIH PROMIS) of sleep data were obtained via telephone with patients recalling their symptoms pre- and post-SCS implantation. Results: A group of 11 patients with an existing SCS system implanted for chronic pain and comorbid RLS confirmed on the Cambridge-Hopkins questionnaire were identified. The IRLS summed score showed a statistically significant (p = 0.0343) improvement with a large effect size (r = 0.64) indicating that overall symptom severity measured by the IRLS scale decreased significantly with SCS. There was also a significant (p = 0.0223) reduction with a large effect size (r = 0.69) in the summed NIH PROMIS sleep-related impairment scores, suggesting that SCS had a substantial positive impact on sleep-related impairments. Contrary to this, insignificant (p = 0.778) changes were observed in the summed NIH PROMIS sleep disturbance scores with a small effect size (r = 0.09). Conclusion: SCS has been shown to be an effective, novel treatment for chronic pain but also has positive effects on medication refractory RLS. While this small, retrospective study is limited by recall bias, it provides further evidence of SCS serendipitously improving RLS symptoms. Future prospective research evaluating the effects of SCS on RLS symptoms, pathophysiology, and sleep is needed to further evaluate this phenomenon.

Background: Essential and Parkinsonian tremors are common movement disorders that impair quality of life. Two incisionless ablative techniques for refractory disease are Gamma Knife radiosurgery (GKRS) and MR-guided focused ultrasound (MRgFUS); both are frame-based, and GKRS treatment times may extend to several hours. We examined a non-invasive, frameless, linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) technique using a virtual cone method for thalamotomy. Methods: In this prospective, single-centre, open-label trial, 40 patients with medically refractory tremor (35 essential tremor, 4 tremor-dominant Parkinson's disease, 1 mixed) underwent unilateral LINAC virtual-cone thalamotomy with thermoplastic-mask immobilisation. The primary outcome was contralateral tremor improvement on the Fahn-Tolosa-Marin (FTM) scale at 3, 6, and ≥12 months. Secondary outcomes were safety (CTCAE), satisfaction, and quality of life. Wilcoxon signed-rank tests compared pre- versus post-treatment scores; linear mixed-effects models assessed change over time. This trial is registered with ClinicalTrials.gov, NCT03305588. Findings: At a median follow-up of 31·7 months, 38 of 40 patients (95%) achieved ≥10% contralateral FTM improvement by 6 months (p<0·001). Mean contralateral FTM reduction was 54·6% (SD 36·0) in the intention-to-treat cohort and 60·7% (24·6) among responders. Five patients (12·5%) had serious neurological adverse events (dysarthria, focal hemiparesis), typically at 6 months, generally improving with corticosteroids or bevacizumab; one died of unrelated causes. Transient paraesthesia was the most common minor event. Interpretation: Frameless, coneless, LINAC-based thalamotomy may be an effective alternative to frame-based SRS or FUS for medically refractory tremor, with comparable risk and short, mask-based treatment. Larger randomised or comparative studies with blinded assessment are warranted.

Background: Both neuromodulation and physical therapy have been shown to mitigate motor and non-motor symptoms of Parkinson’s disease. To date, no studies have examined the integration of transcutaneous auricular vagus nerve stimulation (taVNS) with physical therapy approaches for improving Parkinsonian symptoms. The purpose of this study was to investigate the safety, tolerability, and feasibility of combining taVNS with physical therapy to enhance the therapeutic benefits of exercise as medicine in a clinical setting. Methods: Participants were randomly assigned to receive active or sham bilateral taVNS in combination with PT for 12 visits over 6 weeks. Safety, tolerability, and feasibility outcomes were primary. Secondly, exploratory analyses of changes in cardiovascular and motor function over time were also performed. Results: Overall, taVNS was safe and well-tolerated prior to PT. Cardiovascular analyses suggest that active taVNS may augment HR response to exercise compared to sham. For motor outcomes, both groups showed significant overall improvements; however, no significant between-group differences were found. Conclusions: The preliminary results obtained in this pilot trial confirm that taVNS combined with physical therapy for individuals with PD is safe and feasible. The exploratory cardiovascular and motor findings support the need for larger, adequately powered clinical trials investigating the integration of taVNS into PT and exercise methods for improving PD symptomology. Trial registration: ClinicalTrials.gov NCT05871151.

BACKGROUND AND OBJECTIVES: Lumbar laminectomy is routinely performed for neurogenic claudication and radicular pain from lumbosacral stenosis. Restless legs syndrome (RLS) causes nocturnal discomfort with sleep disruption and can coexist with lumbosacral radiculopathy. We evaluated whether laminectomy in patients with neurologist-diagnosed RLS and imaging-confirmed root compression is associated with RLS symptom resolution. METHODS: We performed a retrospective 1:1 propensity-matched cohort study (158 laminectomy, 158 nonoperative) with a prospectively assessed subset. The primary outcome was complete RLS resolution, defined as symptom absence and discontinuation of RLS pharmacotherapy. Secondary outcomes included International Restless Legs Scale (IRLS) scores, levodopa equivalent daily dose, Oswestry Disability Index, and pain recurrence in the surgical cohort. RESULTS: Complete RLS resolution occurred in 74% of surgical patients vs 23% of nonsurgical patients (risk ratio 3.16; P < .001). In the prospectively assessed subset, baseline IRLS was similar (25.0 ± 6.2 vs 24.0 ± 7.1), but follow-up scores were lower after laminectomy (6.0 ± 7.3 vs 17.0 ± 8.1; P < .001). A total of 78% vs 35% achieved ≥50% IRLS reduction. Levodopa equivalent daily dose decreased in surgical patients (140.0 ± 40.5 to 25.0 ± 45.8 mg/day) but increased in nonoperative patients (145.0 ± 45.7-153.0 ± 87.1 mg/day; P < .001). A total of 70% vs 24% discontinued dopaminergic therapy. Oswestry Disability Index improved more after laminectomy (mean change −13.6 ± 18.1 vs −5.9 ± 16.7; P < .001). Pain recurred in 29.1% of surgical patients. Lack of RLS resolution was associated with higher pain recurrence risk (hazard ratio 2.06; 95% CI 1.13-3.77). CONCLUSION: In patients with RLS and lumbosacral root compression, laminectomy was associated with improvements in RLS symptoms, decreased medication burden, and durability of pain relief, in addition to its conventional analgesic benefits. RLS symptom burden may represent an under-recognized dimension of outcome in spine surgery and supports routine RLS assessment when considering decompression.

The subthalamic nucleus (STN), a primary target for Parkinson’s disease (PD) neuromodulation therapies, contributes to movement dynamics but it is unknown how STN relates to specific kinematic parameters. We investigated the neuronal activity in the dorsolateral STN during a visually cued isometric grip-force task in the contralateral hand in patients with PD who were undergoing deep brain stimulation surgery. Patients applied various levels of grip force during a task that separated a sustained applied force vs periods of changing force (yank) while we recorded single unit activity with a microelectrode. We found significant force-related changes in STN unit activity, especially immediately after force onset and offset, but minimal changes during movement preparation. Significant changes in single unit activity occurred with changes in grip force (squeeze and release) as well as during sustained grip force. During sustained force, the discharge rate positively correlated with force magnitude. During a phase of the task when force changes (squeeze or release), some units’ firing rate increased, some decreased, and some had mixed responses. Units with increased firing rates during squeeze had later latencies than those with decreased rates. Most changes in firing rate followed changes in force.

Background and Purpose Both neuromodulation and physical therapy have been shown to mitigate motor and non-motor symptoms of Parkinson’s Disease. Few studies have examined the integration of noninvasive neuromodulation with physical therapy approaches for improving Parkinsonian symptoms. The purpose of this study was to investigate the safety, feasibility, and potential synergistic effects of combining transcutaneous auricular vagus nerve stimulation (taVNS) with physical therapy for enhancing the therapeutic benefits of exercise as medicine in a clinical setting. Methods This pilot study was designed as a randomized, sham-controlled clinical trial. Participants (N=20) were randomly assigned to receive active or sham-taVNS in combination with physical therapy for 12 visits over 6 weeks. We quantified safety, tolerability, and feasibility outcomes, as well as changes in cardiovascular and motor function over time. Results We observed taVNS was well tolerated without reported adverse events. Our observations further revealed taVNS administered prior to physical therapy improves cardiovascular regulation at rest and during exercise. Administering taVNS prior to exercise also led to significant and sustained improvements in motor function and balance over time. Discussion and Conclusions Combining taVNS with physical therapy was safe and tolerable. We found taVNS enhances motor improvements from physical therapy, in part, by modulating cardiovascular function during exercise. These observations support larger trials investigating the integration of taVNS into physical therapy interventions for Parkinson’s Disease. Trial Registration ClinicalTrials.gov NCT05871151.

Background: Deep brain stimulation (DBS) elicits oscillatory local field potentials in patients with Parkinson's disease (PD) and other movement disorders. Greater knowledge about the fast dynamics of these neural responses could shed light on circuit pathophysiology and inform novel approaches to neuromodulation therapies. Objectives: To compare short‐term neuroplasticity in the globus pallidus interna (GPi) and the subthalamic nucleus (STN), the canonical functional targets for PD and dystonia. Methods: During surgery for DBS lead implantation, we delivered pairs of stimuli across various interstimulus intervals and amplitudes and recorded DBS‐evoked responses from unused contacts on the lead. After stimulus artifact removal, we contrasted the magnitude and timing of the local responses by paired pulse interval and brain target. Additionally, we compared the amplitudes of the DBS‐evoked potentials versus resting local field potentials at the same recording site. Results: In 14 patients undergoing STN DBS and 9 undergoing GPi DBS, evoked potentials in the STN exhibited greater amplitudes than those in the GPi. However, paired pulse neuroplasticity was larger in the GPi than in the STN. Otherwise, the responses at both sites exhibited similar paired pulse hastening and refractoriness, onset latencies, and frequencies measured by the first two peaks. Conclusions: Single and paired DBS pulses elicit local oscillations with larger amplitudes in the STN than in the GPi. Otherwise, the responses display similar time dynamics and short‐term neuroplasticity. These findings could inform therapeutic innovation with future DBS systems that utilize sensing technologies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective To present a novel method for removing stimulus transient that exploits the absolute refractory period of electrically excitable neural tissues. Background Electrical stimulation often generates significant signal artifacts that can obscure important physiological signals. Removal of the artifact and understanding latent information from these signals could provide objective measures of circuit engagement, potentially driving advancements in neuromodulation research and therapies. Methods We conducted intracranial physiology studies on five consecutive patients with Parkinson’s disease who underwent deep brain stimulation (DBS) surgery as part of their routine care. Monopolar stimuli (either cathodic or anodic) were delivered in pairs through the DBS electrode across a range of inter-stimulus intervals. Recordings from adjacent unused electrode contacts used broadband sampling and precise synchronization to generate a robust template for the stimulus transient during the absolute refractory period. These templates of stimulus transient were then subtracted from recordings at different intervals to extract and analyze the residual neural potentials. Results After artifact removal, the residual signals exhibited absolute and relative refractory periods with timing indicative of neural activity. Cathodic and anodic DBS pulses generated distinct patterns of local tissue activation, showing phase independence from the prior stimulus. The earliest detectable neural responses occurred at short peak latencies (ranging from 0.19 to 0.38 ms post-stimulus) and were completely or partially obscured by the stimulus artifact prior to removal. Cathodic stimuli produced stronger local tissue responses than anodic stimuli, aligning with clinical observations of lower activation thresholds for cathodic stimulation. However, cathodic and anodic pulses induced artifact patterns that were equivalent but opposite. Interpretation The proposed artifact removal technique enhances prior approaches by allowing direct measurement of local tissue responses without requirements for stimulus polarity reversal, template scaling, or specialized filters. This approach could be integrated into future neuromodulation systems to visualize stimulus-evoked neural potentials that would otherwise be obscured by stimulus artifacts.

Background: Deep brain stimulation for dystonia improves motor symptoms but variable and delayed responses challenge patient selection, targeting, and device programming. Case Report: Here we studied intracranial electrophysiology in a patient with primary dystonia and observed evoked resonant neural activity (ERNA) in the globus pallidus interna. These local stimulus-evoked potentials displayed refractory periods and paired-pulse facilitation at clinically relevant interstimulus intervals. Sensing from directional DBS contacts localized ERNA to an effective stimulation site in the ventral posterolateral portion of the pallidum. Discussion: To the best of our knowledge, this is the first observation of ERNA in the globus pallidus interna in a patient with primary dystonia. Stimulus-evoked activity could eventually guide both directional and adaptive stimulation for dystonia and other complex neuropsychiatric disorders.