Unraveling the threads of stability: A review of the neurophysiology of postural control in Parkinson's disease.

Postural instability is a detrimental and often treatment-refractory symptom of Parkinson's disease. While many existing studies quantify the biomechanical deficits among various postural domains (static, anticipatory, and reactive) in this population, less is known regarding the neural network dysfunctions underlying these phenomena. This review will summarize current studies on the cortical and subcortical neural activities during postural responses in healthy subjects and those with Parkinson's disease. We will also review the effects of current therapies, including neuromodulation and feedback-based wearable devices, on postural instability symptoms. With recent advances in implantable devices that allow chronic, ambulatory neural data collection from patients with Parkinson's disease, combined with sensors that can quantify biomechanical measurements of postural responses, future work using these devices will enable better understanding of the neural mechanisms of postural control. Bridging this knowledge gap will be the critical first step towards developing novel neuromodulatory interventions to enhance the treatment of postural instability in Parkinson's disease.

Focused Ultrasound for Treatment of Movement Disorders: A Review of Non-Food and Drug Administration Approved Indications.

INTRODUCTION: MRI-guided focused ultrasound (FUS) is an incisionless thermo-ablative procedure that may be used to treat medication-refractory movement disorders, with a growing number of potential anatomic targets and clinical applications. As of this article's publication, the only US Food and Drug Administration (FDA)-approved uses of FUS for movement disorders are thalamotomy for essential tremor (ET) and tremor-dominant Parkinson's Disease (PD), and pallidotomy for other cardinal symptoms of PD. We present a state-of-the-art review on all non-FDA approved indications of FUS for movement disorders, beyond the most well-described indications of ET and PD. Our objective was to summarize the safety and efficacy of FUS in this setting and provide a roadmap for future directions of FUS for movement disorders. METHODS: A state-of-the-art review was conducted on use of FUS for non-FDA approved movement disorders. All movement disorders excluding FDA-approved uses for ET and PD were included. RESULTS: A total of 25 studies on 172 patients were included. In patients with tremor plus dystonia syndromes (n = 6), ventralis intermediate nucleus of the thalamus (VIM)-FUS gave >50% tremor reduction, with no improvement in dystonia and worsened dystonia in 2/6 patients. Ventral-oralis complex (VO)-FUS gave >50% improvement for focal hand dystonia (n = 6) and 100% return to musical performance in musician's dystonia (n = 6). In patients with multiple sclerosis (MS) and tremor (n = 3), improvement in tremor was seen in 2 patients with a favorable skull density ratio; no MS disease change was noted after VIM-FUS. In patients with tremor and comorbid ataxia syndromes (n = 3), none were found to have worsened ataxia after VIM-FUS; all had clinically significant tremor improvement. Subthalamic nucleus (STN)-FUS for PD (n = 49) gave approximately 50% improvement in PD motor symptoms, with dystonia and mild dyskinesias as possible adverse effects. Cerebellothalamic tract (CTT-FUS) for ET (n = 42) gave 55-90% tremor improvement, with gait dysfunction as a rare persistent adverse effect. Pallidothalamic tract (PTT-FUS) for PD (n = 50) gave approximately 50% improvement in motor symptoms, with mild speech dysfunction as a possible adverse effect. CONCLUSION: VIM-FUS appeared safe and effective for heterogenous tremor etiologies, and VO-FUS appeared most effective for isolated segmental dystonia. STN-FUS was effective for PD symptom reduction; postoperative dystonia and mild on-medication dyskinesias required medical management. Tractography-based targeting with CTT-FUS for ET and PTT-FUS for PD demonstrated promising early results. Larger prospective trials with long-term follow-up are needed to the evaluate the safety and efficacy non-FDA approved indications for FUS.

Human upper extremity motor cortex activity shows distinct oscillatory signatures for stereotyped arm and leg movements.

Introduction: Stepping and arm swing are stereotyped movements that require coordination across multiple muscle groups. It is not known whether the encoding of these stereotyped movements in the human primary motor cortex is confined to the limbs' respective somatotopy. Methods: We recorded subdural electrocorticography activities from the hand/arm area in the primary motor cortex of 6 subjects undergoing deep brain stimulation surgery for essential tremor and Parkinson's disease who performed stepping (all patients) and arm swing (n = 3 patients) tasks. Results: We show stepping-related low frequency oscillations over the arm area. Furthermore, we show that this oscillatory activity is separable, both in frequency and spatial domains, from gamma band activity changes that occur during arm swing. Discussion: Our study contributes to the growing body of evidence that lower extremity movement may be more broadly represented in the motor cortex, and suggest that it may represent a way to coordinate stereotyped movements across the upper and lower extremities.

A Systematic Review Comparing Focused Ultrasound Surgery With Radiosurgery for Essential Tremor.

BACKGROUND: Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared. OBJECTIVE: To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET. METHODS: We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence. RESULTS: Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume. CONCLUSION: Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.

Seizure outcome after resection of insular glioma: a systematic review, meta-analysis, and institutional experience.

OBJECTIVE: Gliomas arising from the insular cortex can be epileptogenic, with a significant proportion of patients having medically refractory epilepsy. The impact of surgery on seizure control for such tumors is not well established. In this study, the authors aimed to investigate seizure outcomes after resection of insular gliomas using a meta-analysis and institutional experience. METHODS: Three databases (Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) were systematically searched for published studies of seizure outcomes after insular glioma resection from database inception to March 27, 2021. In addition, data were retrospectively collected on all adults (age > 17 years) who had undergone insular glioma resection between June 1997 and June 2015 at the authors' institution. Primary outcome measures were seizure freedom rates at 1 year and the last follow-up. Secondary outcome measures consisted of persistent postoperative neurological deficit beyond 90 days, mortality, and tumor progression or recurrence. RESULTS: Eight studies reporting on 453 patients who had undergone 460 operations were included in the meta-analysis. The pooled mean age of the patients was 42 years. The pooled percentages of patients with extents of resection (EORs) ≥ 90%, 70%-89%, and < 70% were 55%, 33%, and 11%, respectively. The pooled seizure freedom rate at 1 year was 73% for Engel class IA and 78% for Engel class I. The pooled seizure freedom rate at the last follow-up was 60% for Engel class IA and 79% for Engel class I. The pooled percentage of persistent neurological deficit beyond 90 days was 3%. At the authors' institution, 109 patients had undergone resection of insular glioma. A greater EOR was the only significant independent predictor of seizure freedom after surgery (HR 0.290, p = 0.017). The optimal threshold for seizure freedom corresponded to an EOR of 81%. Patients with an EOR > 81% had a significantly higher seizure freedom rate (OR 2.16, p = 0.048). CONCLUSIONS: Maximal safe resection can be performed with minimal surgical morbidity to achieve favorable seizure freedom rates in both the short and long term. When gross-total resection is not possible, an EOR > 81% confers the greatest sensitivity and specificity for achieving seizure freedom. Systematic review registration no.: CRD42021249404 (https://www.crd.york.ac.uk/prospero/).

Improved psychotic symptoms following resection of amygdalar low-grade glioma: illustrative case.

BACKGROUND: Epilepsy-associated psychoses are poorly understood, and management is focused on treating epilepsy. Chronic, interictal psychosis that persists despite seizure control is typically treated with antipsychotics. Whether resection of a mesial temporal lobe lesion may improve interictal psychotic symptoms that persist despite seizure control remains unknown. OBSERVATIONS: In a 52-year-old man with well-controlled epilepsy and persistent comorbid psychosis, brain magnetic resonance imaging (MRI) revealed an infiltrative, intraaxial, T2 fluid-attenuated inversion recovery intense mass of the left amygdala. The patient received an amygdalectomy for oncological diagnosis and surgical treatment of a presumed low-grade glioma. Pathology was ganglioglioma, World Health Organization grade I. Postoperatively, the patient reported immediate resolution of auditory hallucinations. Patient has remained seizure-free on 2 antiepileptic drugs and no antipsychotic pharmacotherapy and reported lasting improvement in his psychotic symptoms. LESSONS: This report discusses improvement of psychosis symptoms after resection of an amygdalar glioma, independent of seizure outcome. This case supports a role of the amygdala in psychopathology and suggests that low-grade gliomas of the limbic system may represent, at minimum, partially reversible etiology of psychotic symptoms.

Cortico-Subthalamic Field Potentials Support Classification of the Natural Gait Cycle in Parkinson's Disease and Reveal Individualized Spectral Signatures.

The ability of humans to coordinate stereotyped, alternating movements between the two legs during bipedal walking is a complex motor behavior that requires precisely timed activities across multiple nodes of the supraspinal network. Understanding of the neural network dynamics that underlie natural walking in humans is limited. We investigated cortical and subthalamic neural activities during overground walking and evaluated spectral biomarkers to decode the gait cycle in three patients with Parkinson's disease without gait disturbances. Patients were implanted with chronic bilateral deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) and electrocorticography paddles overlaying the primary motor and somatosensory cortices. Local field potentials were recorded from these areas while the participants performed overground walking and synchronized to external gait kinematic sensors. We found that the STN displays increased low-frequency (4-12 Hz) spectral power during the period before contralateral leg swing. Furthermore, STN shows increased theta frequency (4-8 Hz) coherence with the primary motor through the initiation and early phase of contralateral leg swing. Additional analysis revealed that each patient had specific frequency bands that could detect a significant difference between left and right initial leg swing. Our findings indicate that there are alternating spectral changes between the two hemispheres in accordance with the gait cycle. In addition, we identified patient-specific, gait-related biomarkers in both the STN and cortical areas at discrete frequency bands that may be used to drive adaptive DBS to improve gait dysfunction in patients with Parkinson's disease.

Targeting Accuracy and Clinical Outcomes of Awake versus Asleep Interventional Magnetic Resonance Imaging-Guided Deep Brain Stimulation for Parkinson's Disease: The University of California, San Francisco Experience.

BACKGROUND: Interventional MRI (iMRI)-guided implantation of deep brain stimulator (DBS) leads has been developed to treat patients with Parkinson's disease (PD) without the need for awake testing. OBJECTIVE: Direct comparisons of targeting accuracy and clinical outcomes for awake stereotactic with asleep iMRI-DBS for PD are limited. METHODS: We performed a retrospective review of patients with PD who underwent awake or iMRI-guided DBS surgery targeting the subthalamic nucleus or globus pallidus interna between 2013 and 2019 at our institution. Outcome measures included Unified Parkinson's Disease Rating Scale Part III scores, levodopa equivalent daily dose, radial error between intended and actual lead locations, stimulation parameters, and complications. RESULTS: Of the 218 patients included in the study, the iMRI cohort had smaller radial errors (iMRI: 1.27 ± 0.72 mm, awake: 1.59 ± 0.96 mm, P < .01) and fewer lead passes (iMRI: 1.0 ± 0.16, awake: 1.2 ± 0.41, P < .01). Changes in Unified Parkinson's Disease Rating Scale were similar between modalities, but awake cases had a greater reduction in levodopa equivalent daily dose than iMRI cases ( P < .01), which was attributed to the greater number of awake subthalamic nucleus cases on multivariate analysis. Effective clinical contacts used for stimulation, side effect thresholds, and complication rates were similar between modalities. CONCLUSION: Although iMRI-DBS may result in more accurate lead placement for intended target compared with awake-DBS, clinical outcomes were similar between surgical approaches. Ultimately, patient preference and surgeon experience with a given DBS technique should be the main factors when determining the "best" method for DBS implantation.

Ventral Intermediate Nucleus of the Thalamus versus Posterior Subthalamic Area: Network Meta-Analysis of DBS Target Site Efficacy for Essential Tremor.

BACKGROUND: Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (Vim) of the thalamus or the posterior subthalamic area (PSA) are effective treatments for essential tremor (ET). However, their relative efficacy is unknown. OBJECTIVE: Here, we present the first systematic review and network meta-analysis, examining the efficacy of Vim versus PSA DBS for treating medically refractory ET. METHODS: We included all primary studies that reported validated Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores pre-/postimplantation or on-/off-stimulation postimplantation, for patients receiving either Vim or PSA DBS. The primary outcome was FTM-TRS score reduction; the secondary outcome was percent reduction in score. We categorized all outcomes as short-term (≤12 months) or long-term (>12 months). RESULTS: For pre-/postimplantation comparisons, 19 and 11 studies met inclusion criteria for short- and long-term follow-ups, respectively. For on-/off-stimulation tremor score comparisons, 8 studies met inclusion criteria for short-term follow-up. Network meta-analysis of pre-/postimplantation tremor scores showed greater tremor reduction with PSA implantation short-term (absolute tremor reduction: PSA: -30.94 [95% confidence interval (CI): -34.93, -26.95]; Vim: -26.26 [95% CI: -33.39, -19.12]; relative tremor reduction: PSA: 63.3% [95% CI: 61.8%-64.8%]; Vim: 57.8% [95% CI: 56.5%-59.0%]). However, there was no difference in efficacy between PSA and Vim DBS when comparing tremor on-versus off-stimulation at short-term follow-up or pre- versus postimplantation tremor reduction long-term. CONCLUSION: Our systematic review highlighted both heterogeneity in scoring systems used and lack of transparency in reporting total scores, limiting direct comparison across studies. We found a modestly superior efficacy with PSA stimulation in the short term, but no difference in tremor reduction long-term.

Use of Topical Vancomycin Powder to Reduce Surgical Site Infections after Deep Brain Stimulation Surgery: UCSF Experience and Meta-Analysis.

OBJECTIVE: Surgical site infection (SSI) is the most common serious complication of deep brain stimulation (DBS) implantation surgery. Here, we report a single-surgeon experience on the efficacy of topical, intrawound vancomycin powder (VP) in reducing SSI for DBS surgery and present the first systematic review and meta-analysis examining the effect of topical vancomycin on SSI in patients after DBS surgery. METHODS: For the retrospective review, all unique patients undergoing DBS surgery at UCSF for new hardware implantation or internal pulse generator (IPG) replacement by a single surgeon from September 2013 to March 2019, with at least 1 year of follow-up data, were included. For the meta-analysis, we included all primary studies that compared SSIs with and without application of topical vancomycin in DBS surgeries. RESULTS: 368 unique patients met inclusion criteria; 195 patients received topical VP (VP group) and 173 did not (control). 99/195 patients in the VP group underwent new DBS implantation and 96/195 had IPG replacement. 71/173 patients in the control group had new DBS implantation and 102/173 had IPG replacement. There were 10 total cases of SSI: 4 patients from the VP group (3 new implants and 1 IPG replacement) and 6 patients from the control group (3 new implants and 3 IPG replacements), resulting in SSI rates of 2.1 and 3.5%, respectively (p value = 0.337). Including our retrospective analysis, 6 studies met inclusion criteria for the systematic review and meta-analysis. In the 4 studies that examined primary DBS implants, 479 total patients received topical VP and 436 did not; mean odds ratio for SSI with topical vancomycin was 0.802 (95% confidence interval [CI] 0.175-3.678). Across the 5 studies that examined IPG implantations or replacements, 606 total patients received topical VP while 1,173 patients did not; mean odds ratio for SSI with topical vancomycin was 0.492 (95% CI 0.164-1.475). In either case, topical VP application did not significantly decrease risk of SSI. CONCLUSION: Surgical infections after DBS surgery are uncommon events, with studies demonstrating mixed results on whether topical vancomycin reduces this risk. Our single-institution retrospective analysis and systematic review of prior studies both demonstrated no significant SSI rate reduction with topical VP. This is likely due to low baseline SSI rates, resulting in a small effect size for prevention. Given the cost-effectiveness, simplicity, and low risk, topical, intrawound VP remains a treatment option to further reduce risk of SSI, particularly in settings with higher baseline infection rates.

Proceedings of the 10th annual deep brain stimulation think tank: Advances in cutting edge technologies, artificial intelligence, neuromodulation, neuroethics, interventional psychiatry, and women in neuromodulation.

The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

Epidural Spinal Electrogram Provides Direct Spinal Recordings in Awake Human Participants.

Little is known about the electrophysiological activity of the spinal cord during voluntary movement control in humans. We present a novel method for recording electrophysiological activity from the human spinal cord using implanted epidural electrodes during naturalistic movements including overground walking. Spinal electrograms (SEGs) were recorded from epidural electrodes implanted as part of a test trial for patients with chronic pain undergoing evaluation for spinal cord stimulation. Externalized ends of the epidural leads were connected to an external amplifier to capture SEGs. Electromyographic and accelerometry data from the upper and lower extremities were collected using wireless sensors and synchronized to the SEG data. Patients were instructed to perform various arm and leg movements while SEG and kinematic data were collected. This study proves the safety and feasibility of performing epidural spinal recordings from human subjects performing movement tasks.

Long-term wireless streaming of neural recordings for circuit discovery and adaptive stimulation in individuals with Parkinson's disease.

Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.

DBS targeting for essential tremor using intersectional dentato-rubro-thalamic tractography and direct proton density visualization of the VIM: technical note on 2 cases.

OBJECTIVE: Direct visualization of the ventral intermediate nucleus (VIM) of the thalamus on standard MRI sequences remains elusive. Therefore, deep brain stimulation (DBS) surgery for essential tremor (ET) indirectly targets the VIM using atlas-derived consensus coordinates and requires awake intraoperative testing to confirm clinical benefits. The objective of this study was to evaluate the utility of proton density (PD)-weighted MRI and tractography of the intersecting dentato-rubro-thalamic tract (DRTT) for direct "intersectional" targeting of the VIM in ET. METHODS: DBS targets were selected by identifying the VIM on PD-weighted images relative to the DRTT in 2 patients with ET. Tremor reduction was confirmed with intraoperative clinical testing. Intended target coordinates based on the direct intersectional targeting technique were compared with consensus coordinates obtained with indirect targeting. Pre- and postoperative tremor scores were assessed using the Fahn-Tolosa-Marin tremor rating scale (TRS). RESULTS: Planned DBS coordinates based on direct versus indirect targeting of the VIM differed in both the anteroposterior (range 0 to 2.3) and lateral (range -0.7 to 1) directions. For 1 patient, indirect targeting-without PD-weighted visualization of the VIM and DRTT-would have likely resulted in suboptimal electrode placement within the VIM. At the 3-month follow-up, both patients demonstrated significant improvement in tremor symptoms subjectively and according to the TRS (case 1: 68%, case 2: 72%). CONCLUSIONS: Direct intersectional targeting of the VIM using PD-weighted imaging and DRTT tractography is a feasible method for DBS placement in patients with ET. These advanced targeting techniques can supplement awake intraoperative testing or be used independently in asleep cases to improve surgical efficiency and confidence.

Trends in safety and cost of deep brain stimulation for treatment of movement disorders in the United States: 2002-2014.

PURPOSE: Deep brain stimulation (DBS) is being increasingly utilized to treat movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. An improved understanding of national trends in safety and cost is necessary. Herein, our objectives are to (1) characterize complication, mortality, and cost profiles of patients undergoing DBS for movement disorders in the United States, (2) identify predictors of morbidity and mortality, and (3) evaluate impact of complications on cost. METHODS: DBS surgeries were extracted from the National Inpatient Sample (NIS) 2002-2014 for the clinical indications of PD, ET, and dystonia. Patient characteristics and eight complication categories (hardware malfunction, infection, neurological, other haemorrhagic, thromboembolic, cardiac, pulmonary, and renal/urinary) were reviewed. Outcomes included complications, mortality, hospitalization length, and inflation-adjusted cost. RESULTS: There were 44,866 weighted admissions (PD-73.5%, ET-22.7%, dystonia-3.8%). The number of procedures increased 2.22-fold from 2002 to 2014 (N = 2372 in 2002; N = 5260 in 2014). Inpatient cost was $22,802 ± 13,164, remaining stable from 2002 to 2014 ($24,188 ± 15,910, $20,630 ± 11,031, respectively). Four percent experienced complications (dystonia-6.0%, PD-4.4%, ET-3.1%, p < .001). In-hospital mortality was 0.2%. Cost was greater in patients with complications ($36,306 ± 29,263 vs. $22,196 ± 11,560, p < .001). Most common complications were renal/urinary (1.5%), neurological (1.1%), and pulmonary (0.7%). Thromboembolic, pulmonary, and haemorrhagic complications were associated with greatest cost. CONCLUSION: Increased DBS utilization for adult movement disorders in the United States from 2002 to 2014 was attributed to rapid adoption by teaching hospitals for PD. DBS remains a safe procedure with low overall complications and stable inpatient costs from 2002 to 2014. Complication risks vary by type of movement disorder, and although rare, multiple complications increase morbidity and cost of care.

Freezing of Gait in Parkinson's Disease: Invasive and Noninvasive Neuromodulation.

INTRODUCTION: Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life. MATERIALS AND METHODS: Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders. CONCLUSION: Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.

Brain Network Oscillations During Gait in Parkinson's Disease.

Human bipedal walking is a complex motor task that requires supraspinal control for balance and flexible coordination of timing and scaling of many muscles in different environment. Gait impairments are a hallmark of Parkinson's disease (PD), reflecting dysfunction of cortico-basal ganglia-brainstem circuits. Recent studies using implanted electrodes and surface electroencephalography have demonstrated gait-related brain oscillations in the basal ganglia and cerebral cortex. Here, we review the physiological and pathophysiological roles of (1) basal ganglia oscillations, (2) cortical oscillations, and (3) basal ganglia-cortical interactions during walking. These studies extend a novel framework for movement of disorders where specific patterns of abnormal oscillatory synchronization in the basal ganglia thalamocortical network are associated with specific signs and symptoms. Therefore, we propose that many gait dysfunctions in PD arise from derangements in brain network, and discuss potential therapies aimed at restoring gait impairments through modulation of brain network in PD.

Long-term pain outcomes in elderly patients with trigeminal neuralgia: comparison of first-time microvascular decompression and stereotactic radiosurgery.

OBJECTIVE: Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD) and stereotactic radiosurgery (SRS). The use of MVD in elderly patients has been described but has yet to be prospectively compared to SRS, which is well-tolerated and noninvasive. The authors aimed to directly compare long-term pain control and adverse event rates for first-time surgical treatments for idiopathic TN in the elderly. METHODS: A prospectively collected database was reviewed for TN patients who had undergone treatment between 1997 and 2017 at a single institution. Standardized collection of preoperative demographics, surgical procedure, and postoperative outcomes was performed. Data analysis was limited to patients over the age of 65 years who had undergone a first-time procedure for the treatment of idiopathic TN with at least 1 year of follow-up. RESULTS: One hundred ninety-three patients meeting the study inclusion criteria underwent surgical procedures for TN during the study period (54 MVD, 24 MVD+Rhiz, 115 SRS). In patients in whom an artery was not compressing the trigeminal nerve during MVD, a partial sensory rhizotomy (MVD+Rhiz) was performed. Patients in the SRS cohort were older than those in the MVD and MVD+Rhiz cohorts (mean ± SD, 79.2 ± 7.8 vs 72.9 ± 5.7 and 70.9 ± 4.8 years, respectively; p < 0.0001) and had a higher mean Charlson Comorbidity Index (3.8 ± 1.1 vs 3.0 ± 0.9 and 2.9 ± 1.0, respectively; p < 0.0001). Immediate or short-term postoperative pain-free rates (Barrow Neurological Institute [BNI] pain intensity score I) were 98.1% for MVD, 95.8% for MVD+Rhiz, and 78.3% for SRS (p = 0.0008). At the last follow-up, 72.2% of MVD patients had a favorable outcome (BNI score I-IIIa) compared to 54.2% and 49.6% of MVD+Rhiz and SRS patients, respectively (p = 0.02). In total, 0 (0%) SRS, 5 (9.3%) MVD, and 1 (4.2%) MVD+Rhiz patients developed any adverse event. Multivariate Cox proportional hazards analysis demonstrated that procedure type (p = 0.001) and postprocedure sensory change (p = 0.003) were statistically significantly associated with pain control. CONCLUSIONS: In this study cohort, patients who had undergone MVD had a statistically significantly longer duration of pain freedom than those who had undergone MVD+Rhiz or SRS as their first procedure. Fewer adverse events were seen after SRS, though the MVD-associated complication rate was comparable to published rates in younger patients. Overall, the results suggest that both MVD and SRS are effective options for the elderly, despite their advanced age. Treatment choice can be tailored to a patient's unique condition and wishes.

Treatment of Post-Hypoxic Myoclonus using Pallidal Deep Brain Stimulation Placed Using Interventional MRI Methods.

Background: Post-hypoxic myoclonus (PHM) is characterized by generalized myoclonus after hypoxic brain injury. Myoclonus is often functionally impairing and refractory to medical therapies. Deep brain stimulation (DBS) has been used to treat myoclonus-dystonia, but few cases of PHM have been described. Case report: A 33-year-old woman developed severe, refractory generalized myoclonus after cardiopulmonary arrest from drowning. We performed MRI-guided asleep bilateral pallidal DBS placement, resulting in improvement in action myoclonus at one year. Discussion: Our case contributes to growing evidence for DBS for PHM. Interventional MRI guided DBS technique can be used for safe and accurate lead placement. Highlights: We report a case of a patient who developed post-hypoxic myoclonus after cardiopulmonary arrest from drowning, who later underwent deep brain stimulation to treat refractory myoclonus. This is the first case to describe asleep, interventional MRI-guided technique for implanting DBS leads in post-hypoxic myoclonus.

Comparison of Stereotactic Radiosurgery and Radiofrequency Ablation for Trigeminal Neuralgia in Multiple Sclerosis Patients.

BACKGROUND: The optimal treatment for medically refractory trigeminal neuralgia in multiple sclerosis (MS-TN) patients is unknown. OBJECTIVE: To compare treatment outcomes between stereotactic radiosurgery (SRS) and radiofrequency ablation (RFA). METHODS: We performed a retrospective study of MS-TN patients treated with SRS or RFA between 2002 and 2019. Outcomes included degree of pain relief, pain recurrence, and sensory changes, segregated based on initial treatment, final treatment following retreatment with the same modality, and crossover patients. RESULTS: Sixty surgical cases for 42 MS-TN patients were reviewed. Initial pain freedom outcomes and rates of retreatment were similar (SRS: 30%; RFA: 42%). RFA resulted in faster onset of pain freedom (RFA: <1 week; SRS: 15 weeks; p < 0.001). SRS patients with pain relief had longer intervals to pain recurrence at 2 years (p = 0.044). Final treatment outcomes favored RFA for pain freedom/off-medication outcomes (RFA: 44%; SRS: 11%; p = 0.031), though RFA resulted in more paresthesia (RFA: 81%; SRS: 39%; p = 0.012). Both provided at least 80% of adequate pain relief. Crossover patients did not have improved pain relief. CONCLUSIONS: SRS and RFA are both valid surgical options for MS-TN. Discussion with providers will need to balance patient preference with their unique treatment characteristics.