Seven Strategies to Integrate Equity within Translational Research in Neurology.

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.

A pilot study for testing a low-cost 3D design with an inertial sensor for the quantitative assessment of finger tapping in patients with Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders worldwide. Current identification and monitoring of its motor symptoms depends on the clinical expertise. Repetitive finger tapping is one of the most common clinical maneuvers to assess for bradykinesia. Despite the increasing use of technology aids to quantitatively characterize the motor symptoms of PD, there is still a relative lack of clinical evidence to support their widespread use, particularly in low-resource settings. In this pilot study, we used a low-cost design prototype coupled with an inertial sensor is coupled to quantify the frequency of the finger tapping movements in four participants with PD. Repetitive finger tapping was performed using both hands before and after taking levodopa as part of their clinical treatment. The proposed 3D design allowed repetitive movements to be performed without issues. The maximum frequency of finger tapping was in the range of 0.1 to 4.3 Hz. Levodopa was associated with variable changes in the maximum frequency of finger tapping. This pilot study shows the feasibility for low-cost technology to quantitatively characterize repetitive movements in people living with PD.Clinical relevance- In this pilot study, a low-cost inertial sensor coupled to a design prototype was feasible to characterize the frequency of repetitive finger tapping movements in four participants with PD. This method could be used to quantitatively identify and monitor bradykinesia in people living with PD.

Deep Brain Stimulation for Refractory Status Dystonicus in Children: Multicenter Case Series and Systematic Review.

OBJECTIVE: We sought to better understand the workflow, outcomes, and complications of deep brain stimulation (DBS) for pediatric status dystonicus (SD). We present a systematic review, alongside a multicenter case series of pediatric patients with SD treated with DBS. METHODS: We collected individual data regarding treatment, stimulation parameters, and dystonia severity for a multicenter case series (n = 8) and all previously published cases (n = 77). Data for case series were used to create probabilistic voxelwise maps of stimulated tissue associated with dystonia improvement. RESULTS: In our institutional series, DBS was implanted a mean of 25 days after SD onset. Programming began a mean of 1.6 days after surgery. All 8 patients in our case series and 73 of 74 reported patients in the systematic review had resolution of their SD with DBS, most within 2 to 4 weeks of surgery. Mean follow-up for patients in the case series was 16 months. DBS target for all patients in the case series and 68 of 77 in our systematic review was the globus pallidus pars interna (GPi). In our case series, stimulation of the posterior-ventrolateral GPi was associated with improved dystonia. Mean dystonia improvement was 32% and 51% in our institutional series and systematic review, respectively. Mortality was 4% in the review, which is lower than reported for treatment with pharmacotherapy alone (10-12.5%). INTERPRETATION: DBS is a feasible intervention with potential to reverse refractory pediatric SD and improve survival. More work is needed to increase awareness of DBS in this setting, so that it can be implemented in a timely manner. ANN NEUROL 2023.

A systematic review of the potential consequences of abnormal serum levels of vitamin B6 in people living with Parkinson's disease.

The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.

Monitoring gait at home with radio waves in Parkinson's disease: A marker of severity, progression, and medication response.

Parkinson's disease (PD) is the fastest-growing neurological disease in the world. A key challenge in PD is tracking disease severity, progression, and medication response. Existing methods are semisubjective and require visiting the clinic. In this work, we demonstrate an effective approach for assessing PD severity, progression, and medication response at home, in an objective manner. We used a radio device located in the background of the home. The device detected and analyzed the radio waves that bounce off people's bodies and inferred their movements and gait speed. We continuously monitored 50 participants, with and without PD, in their homes for up to 1 year. We collected over 200,000 gait speed measurements. Cross-sectional analysis of the data shows that at-home gait speed strongly correlates with gold-standard PD assessments, as evaluated by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III subscore and total score. At-home gait speed also provides a more sensitive marker for tracking disease progression over time than the widely used MDS-UPDRS. Further, the monitored gait speed was able to capture symptom fluctuations in response to medications and their impact on patients' daily functioning. Our study shows the feasibility of continuous, objective, sensitive, and passive assessment of PD at home and hence has the potential of improving clinical care and drug clinical trials.

Virtual Adaptation of an International Exchange Program in Medical Education.

Medical education has drastically transformed during the COVID-19 pandemic. Measures such as adopting telemedicine visits, minimizing the number of trainees on service, discontinuing external rotations, and converting in-person to online didactics have been broadly and swiftly implemented. While these innovations have promoted greater interconnectivity amongst institutions and made continuing medical education possible, international exchange programs in medical education are still largely disrupted. In response to the changing guidelines and restrictions necessitated by the COVID-19 pandemic, the authors used Kern's six-step approach to design and implement a virtual curriculum to replace the in-person activities of the 2020-2021 Neurology Peru-Rochester exchange program (NeuroPro). Twenty-seven trainees participated in this virtual adaptation. The average daily attendance was ≥85% and the program was rated 9/10 on average in a feedback survey (63% response rate). The median percentage of correct answers during the pre-test was 64% and it increased to 79% during the post-test (P = 0.003). Virtual adaptation of international exchange programs in medical education is feasible to safely continue international collaborative efforts to promote symbiotic building of local expertise and cross-cultural exchange during the ongoing COVID-19 pandemic and beyond.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. OBJECTIVES: To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. METHODS: Randomized, double-blinded, double-crossover trial. RESULTS: In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided amplitude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P = 0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected). CONCLUSIONS: Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.

Combining inertial sensors and optical flow to assess finger movements: Pilot study for telehealth applications.

Parkinson's disease is the fastest growing neurological disorder worldwide. Traditionally, diagnosis and monitoring of its motor manifestations depend on examination of the speed, amplitude, and frequency of movement by trained providers. Despite the use of validated scales, clinical examination of movement is semi-quantitative, relatively subjective and it has become a major challenge during the ongoing pandemic. Using digital and technology-based tools during synchronous telehealth can overcome these barriers but it requires access to powerful computers and high-speed internet. In resource-limited settings without consistent access to trained providers, computers and internet, there is a need to develop accessible tools for telehealth application. We simulated a controlled asynchronous telehealth environment to develop and pre-test optical flow and inertial sensors (accelerometer and gyroscope) to assess sequences of 10 repetitive finger-tapping movements performed at a cued frequency of 1 Hz. In 42 sequences obtained from 7 healthy volunteers, we found positive correlations between the frequencies estimated by all modalities (ρ=0.63-0.93, P<0.01). Test-retest experiments showed median coefficients of variation of 7.04% for optical flow, 7.78% for accelerometer and 11.79% for gyroscope measures. This pilot study shows that combining optical flow and inertial sensors is a potential telehealth approach to accurately measure the frequency of repetitive finger movements.Clinical relevance- This pilot study presents a comparative analysis between inertial sensors and optical flow to characterize repetitive finger-tapping movements in healthy volunteers. These methods are feasible for the objective evaluation of bradykinesia as part of telehealth applications.

Approach to the Patient with Gait Disturbance.

The assessment of patients presenting with disorders of gait can be a daunting task for neurologists given the broad potential localization and differential diagnosis. However, gait disorders are extremely common in outpatient neurology, and all neurologists should be comfortable with the assessment, triage, and management of patients presenting with difficulty walking. Here, we aim to present a manageable framework for neurologists to approach the assessment of patients presenting with gait dysfunction. We suggest a chief complaint-based phenomenological characterization of gait, using components of the neurological history and examination to guide testing and treatment. We present the framework to mirror the outpatient visit with the patient, highlighting (1) important features of the gait history, including the most common gait-related chief complaints and common secondary (medical) causes of gait dysfunction; (2) gait physiology and a systematic approach to the gait examination allowing appropriate characterization of gait phenomenology; (3) an algorithmic approach to ancillary testing for patients with gait dysfunction based on historical and examination features; and (4) definitive and supportive therapies for the management of patients presenting with common neurological disorders of gait.

Neurophysiological biomarkers to optimize deep brain stimulation in movement disorders.

Intraoperative neurophysiological information could increase accuracy of surgical deep brain stimulation (DBS) lead placement. Subsequently, DBS therapy could be optimized by specifically targeting pathological activity. In Parkinson's disease, local field potentials (LFPs) excessively synchronized in the beta band (13-35 Hz) correlate with akinetic-rigid symptoms and their response to DBS therapy, particularly low beta band suppression (13-20 Hz) and high frequency gamma facilitation (35-250 Hz). In dystonia, LFPs abnormally synchronize in the theta/alpha (4-13 Hz), beta and gamma (60-90 Hz) bands. Phasic dystonic symptoms and their response to DBS correlate with changes in theta/alpha synchronization. In essential tremor, LFPs excessively synchronize in the theta/alpha and beta bands. Adaptive DBS systems will individualize pathological characteristics of neurophysiological signals to automatically deliver therapeutic DBS pulses of specific spatial and temporal parameters.

Digital Technology in Movement Disorders: Updates, Applications, and Challenges.

PURPOSE OF REVIEW: Digital technology affords the opportunity to provide objective, frequent, and sensitive assessment of disease outside of the clinic environment. This article reviews recent literature on the application of digital technology in movement disorders, with a focus on Parkinson's disease (PD) and Huntington's disease. RECENT FINDINGS: Recent research has demonstrated the ability for digital technology to discriminate between individuals with and without PD, identify those at high risk for PD, quantify specific motor features, predict clinical events in PD, inform clinical management, and generate novel insights. Digital technology has enormous potential to transform clinical research and care in movement disorders. However, more work is needed to better validate existing digital measures, including in new populations, and to develop new more holistic digital measures that move beyond motor features.

Interhemispheric interactions between the right angular gyrus and the left motor cortex: a transcranial magnetic stimulation study.

The interconnection of the angular gyrus of right posterior parietal cortex (PPC) and the left motor cortex (LM1) is essential for goal-directed hand movements. Previous work with transcranial magnetic stimulation (TMS) showed that right PPC stimulation increases LM1 excitability, but right PPC followed by left PPC-LM1 stimulation (LPPC-LM1) inhibits LM1 corticospinal output compared with LPPC-LM1 alone. It is not clear if right PPC-mediated inhibition of LPPC-LM1 is due to inhibition of left PPC or to combined effects of right and left PPC stimulation on LM1 excitability. We used paired-pulse TMS to study the extent to which combined right and left PPC stimulation, targeting the angular gyri, influences LM1 excitability. We tested 16 healthy subjects in five paired-pulsed TMS experiments using MRI-guided neuronavigation to target the angular gyri within PPC. We tested the effects of different right angular gyrus (RAG) and LM1 stimulation intensities on the influence of RAG on LM1 and on influence of left angular gyrus (LAG) on LM1 (LAG-LM1). We then tested the effects of RAG and LAG stimulation on LM1 short-interval intracortical facilitation (SICF), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). The results revealed that RAG facilitated LM1, inhibited SICF, and inhibited LAG-LM1. Combined RAG-LAG stimulation did not affect SICI but increased LICI. These experiments suggest that RAG-mediated inhibition of LAG-LM1 is related to inhibition of early indirect (I)-wave activity and enhancement of GABAB receptor-mediated inhibition in LM1. The influence of RAG on LM1 likely involves ipsilateral connections from LAG to LM1 and heterotopic connections from RAG to LM1.NEW & NOTEWORTHY Goal-directed hand movements rely on the right and left angular gyri (RAG and LAG) and motor cortex (M1), yet how these brain areas functionally interact is unclear. Here, we show that RAG stimulation facilitated right hand motor output from the left M1 but inhibited indirect (I)-waves in M1. Combined RAG and LAG stimulation increased GABAB, but not GABAA, receptor-mediated inhibition in left M1. These findings highlight unique brain interactions between the RAG and left M1.

Motor blocks during bilateral stepping in Parkinson's disease and effects of dopaminergic medication.

INTRODUCTION: Freezing of gait (FOG) is a complex symptom in Parkinson's disease (PD) that manifests during walking as limited forward progression despite the intention to walk. It is unclear if lower limb motor blocks (LLMB) that occur independently from FOG are related to overground FOG and the effects of dopaminergic medications. METHODS: Nineteen patients with PD were tested on two separate days in the dopaminergic medication "on" and "off" states. The patients completed a series of freezing-provoking tasks while videotaped. Raters assessed videos for FOG presence using Movement Disorders Society Unified Parkinson's Disease Rating Scale item 3.11 score greater than or equal to 1 and FOG severity using the standardized FOG score. Whilst seated in a virtual environment, patients and 20 healthy controls stepped in right-left sequence on foot pedals. Frequency and percent time in LLMB were assessed for accurate classification of FOG presence and correlation to the FOG score. RESULTS: Frequency and percent time spent in LLMB predicted the presence of FOG in both medication states. Percent time spent in LLMB correlated with FOG severity in both medication states. LLMB frequency predicted FOG severity in the "off" state only. CONCLUSIONS: LLMB during bilateral stepping in a virtual environment predicted the presence and severity of FOG in PD in both "on" and "off" medication states. These findings support the use of this non-walking paradigm to detect and assess FOG in PD patients unable or unsafe to walk.

A Distinct EEG Marker of Celiac Disease-Related Cortical Myoclonus.

BACKGROUND: Celiac disease is associated with motor cortex hyperexcitability and neurological manifestations including cortical myoclonus. Electroencephalography abnormalities have been described, but no distinct pattern has been reported. METHODS: We describe the neurophysiological characteristics of 3 patients with celiac-associated cortical myoclonus using electroencephalography, magnetoencephalography, and transcranial magnetic stimulation. RESULTS: Electroencephalography in all cases demonstrated lateralized low-amplitude, electropositive beta-frequency polyspike activity over the central head region, corresponding to motor cortex contralateral to the myoclonic limb. Jerk-locked back-averaging demonstrated a preceding cortical potential; magnetoencephalography source localization revealed a cortical generator in the posterior wall of the precentral gyrus for the back-averaged potential and oscillatory abnormality. In 1 patient, cerebellar inhibition of the motor cortex was physiologically normal. CONCLUSIONS: Central head oscillatory, low-amplitude, electropositive electroencephalography polyspike activity may be a distinct marker of celiac-related cortical myoclonus and is consistent with celiac-related motor cortex hyperexcitability, which may not necessarily result from cerebellar disinhibition. © 2020 International Parkinson and Movement Disorder Society.