Leg stereotypy syndrome: phenomenology and prevalence.

OBJECTIVES: To describe the phenomenology and prevalence of leg stereotypy syndrome (LSS), characterised chiefly by repetitive, rhythmical, stereotypic leg movement, especially when sitting. METHODS: We sought to characterise LSS in two groups of subjects: (1) general population (GP) group, defined as individuals accompanying patients during their visits to Baylor College of Medicine Parkinson's Disease Center and Movement Disorders Clinic who are not genetically related to the patients; and (2) movement disorders (MD) group, composed of consecutive patients with diagnoses of restless legs syndrome, Parkinson's disease, Tourette syndrome and tardive dyskinesia. RESULTS: There were 92 participants enrolled in this study; 7% of 57 individuals in the GP group and 17% of those in the MD group met the diagnostic criteria for LSS. The mean age of individuals with LSS was 44.5 (±11.9) years and mean age at onset of LSS was 17.5 (±5.7) years. In half of the individuals, the 'shaking' involved predominantly one leg. All had a positive family history of similar disorder and none had diurnal variation. The seven-item Leg Stereotypy Syndrome Questionnaire was developed as a screening tool to aid in differentiating LSS from other movement disorders. CONCLUSIONS: LSS is a common condition, occurring in up to 7% of otherwise healthy individuals, and it is even more common in patients with hyperkinetic movement disorders. Although it phenomenologically may overlap with other stereotypic disorders, we argue that it is a distinct, familial, neurological syndrome.

Botulinum Toxin for the Treatment of Tremor and Tics.

The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects.

Feasibility of regional center telehealth visits utilizing a rural research network in people with Parkinson's disease.

Background: Impaired motor and cognitive function can make travel cumbersome for People with Parkinson's disease (PwPD). Over 50% of PwPD cared for at the University of Arkansas for Medical Sciences (UAMS) Movement Disorders Clinic reside over 30 miles from Little Rock. Improving access to clinical care for PwPD is needed. Objective: To explore the feasibility of remote clinic-to-clinic telehealth research visits for evaluation of multi-modal function in PwPD. Methods: PwPD residing within 30 miles of a UAMS Regional health center were enrolled and clinic-to-clinic telehealth visits were performed. Motor and non-motor disease assessments were administered and quantified. Results were compared to participants who performed at-home telehealth visits using the same protocols during the height of the COVID pandemic. Results: Compared to the at-home telehealth visit group (n = 50), the participants from regional centers (n = 13) had similar age and disease duration, but greater disease severity with higher total Unified Parkinson's disease rating scale scores (Z = -2.218, p = 0.027) and lower Montreal Cognitive Assessment scores (Z = -3.350, p < 0.001). Regional center participants had lower incomes (Pearson's chi = 21.3, p < 0.001), higher costs to attend visits (Pearson's chi = 16.1, p = 0.003), and lived in more socioeconomically disadvantaged neighborhoods (Z = -3.120, p = 0.002). Prior research participation was lower in the regional center group (Pearson's chi = 4.5, p = 0.034) but both groups indicated interest in future research participation. Conclusions: Regional center research visits in PwPD in medically underserved areas are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

Amplitude setting and dopamine response of finger tapping and gait are related in Parkinson's disease.

Movement amplitude setting is affected early in Parkinson's disease (PD), clinically manifesting as bradykinesia. Our objective was to determine if amplitude setting of upper limb bimanual movements and bipedal gait are similarly modulated in PD. 27 PD and 24 control participants were enrolled. Participants performed a bimanual anti-phase finger tapping task wearing gloves with joint angular sensors, and an instrumented gait assessment. Participants performed normal and fast paced assessments to vary motor load. PD participants were evaluated OFF (PD-OFF) and ON (PD-ON) levodopa. PD-OFF participants had smaller tap amplitude, and greater tap amplitude variability than controls in the more affected hands (all p < 0.05). Tap amplitude and stride length (p = 0.030) were correlated in PD-OFF. Tap amplitude was also correlated with motor UPDRS (p < 0.005) and bradykinesia motor (p < 0.05) and ADL (p < 0.005) UPDRS subscores. The relative amount of improvement in tap amplitude and stride length with levodopa was correlated. In PD, upper limb and gait amplitude setting are similarly scaled with motor demand and dopamine supplementation. This suggests these automated motor functions are subserved by common functional networks.

Feasibility of telemedicine research visits in people with Parkinson's disease residing in medically underserved areas.

Introduction: Gait, balance, and cognitive impairment make travel cumbersome for People with Parkinson's disease (PwPD). About 75% of PwPD cared for at the University of Arkansas for Medical Sciences' Movement Disorders Clinic reside in medically underserved areas (MUAs). Validated remote evaluations could help improve their access to care. Our goal was to explore the feasibility of telemedicine research visits for the evaluation of multi-modal function in PwPD in a rural state. Methods: In-home telemedicine research visits were performed in PwPD. Motor and non-motor disease features were evaluated and quantified by trained personnel, digital survey instruments for self-assessments, digital voice recordings, and scanned and digitized Archimedes spiral drawings. Participant's MUA residence was determined after evaluations were completed. Results: Twenty of the fifty PwPD enrolled resided in MUAs. The groups were well matched for disease duration, modified motor UPDRS, and Montreal Cognitive assessment scores but MUA participants were younger. Ninety-two percent were satisfied with their visit, and 61% were more likely to participate in future telemedicine research. MUA participants traveled longer distances, with higher travel costs, lower income, and education level. While 50% of MUA participants reported self-reliance for in-person visits, 85% reported self-reliance for the telemedicine visit. We rated audio-video quality highly in approximately 60% of visits in both groups. There was good correlation with prior in-person research assessments in a subset of participants. Conclusions: In-home research visits for PwPD in MUAs are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

Utility of objective gait measures in levodopa-unresponsive freezing in Parkinson's.

Levodopa-unresponsive gait freezing in Parkinson disease is debilitating. Gait kinematics, while time-consuming, can help optimize levodopa's benefit on gait stride length and stride velocity, and thereby improve freezing and falls in these patients.

Trends in Demographics of Neurology House Staff in the United States.

Background The lack of an adequate number of neurologists is a worldwide problem. As populations age, the prevalence of neurological disorders will likely increase, thereby increasing the demand for neurologists. In addition to the growing demand, inadequate diversity in the neurology healthcare workforce still exists. The purpose of this study is to examine the demographic characteristics of neurology residents and fellows. Methodology This cross-sectional study used data from the following publicly available databases: Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, and the United States Census Bureau. Trends (from 2007 to 2018) in demographic characteristics were assessed using the slope and the associated p-value of a simple linear regression model, with the year as the independent variable. All p-values of <0.05 were considered significant. Results From 2007 through 2018, the percentage of US medical school graduates in neurology residency decreased from 58% to 55% (slope = -0.25; p = 0.0004), while the percentage of international medical graduates (IMGs) decreased from 36% to 32% (slope = -0.29; p = 0.0141) and doctor of osteopathy (DO) graduates increased from 6% to 13% (slope = 0.58; p < 0.0001). Although the percentage of female neurology residents increased from 39.5% in 2007 to 43.1% in 2018 (slope = 0.03; p = 0.8659), female physicians were underrepresented in vascular neurology fellowship (34% in 2018). Collectively, the percentage of underrepresented minorities in neurology residencies was low and increased only slightly over time (from 8% in 2011 to 9% in 2018; slope = 0.17; p = 0.0788). In 2018, the proportion of underrepresented minorities was smaller in neurology fellowships (5.5% neurophysiology, 12.5% epilepsy, 10.4% neuromuscular, and 12.4% vascular) compared to the population as a whole (31.3%). Conclusions IMGs still play an important role in filling a significant portion of the neurology residencies and fellowships. DO graduates have slowly increased in neurology residencies and fellowships. Members of several racial/ethnic minority groups and women are underrepresented in neurology house staff and efforts need to be taken to increase diversity.

Resident Education During COVID-19 Pandemic: Effectiveness of Virtual Electroencephalogram Learning.

Objective To explore effectiveness of alternative methods of neurology resident electroencephalogram (EEG) learning during COVID-19 pandemic due to social distancing requirements which caused disruption of traditional in-person teaching. Methods Virtual EEG learning was instituted using Zoom platform. Residents participated in live, interactive virtual sessions for eight weeks. A pre-test and post-test were administered and a survey was performed at the end of the project. Results Based on pre-test and post-test results, there was a significant improvement on average resident test scores. On the survey, 100% agreed (81.8% strongly agreed, 18.2% agreed) that virtual EEG sessions provided a conducive learning environment with easy access while preserving effective communication with the instructor. When compared to traditional EEG reading, 100% agreed (81.8% strongly agreed and 18.2% agreed) that virtual sessions were more accessible, 72.7% agreed (54.5% strongly agreed, 18.2% agreed) that they were more interactive; 81.9% (45.5% strongly agreed, 36.4% agreed) felt more engaged and 90.9% agreed (81.8% strongly agreed, 9.1% agreed) that they were able to attend more sessions. Hundred percent residents (72.7% strongly agreed, 27.3% agreed) felt more confident in their EEG reading and all (81.8% strongly agreed and 18.2% agreed) would sign up for more virtual learning courses. Conclusions Virtual EEG education is an efficient method of resident education with improved ease of access while maintaining interactive discussion leading to increased confidence in learners. It should be considered even after resolution of the need for social distancing and its applications in other fields of learning should be further explored.

COVID-19 and stroke, a case series and review of literature.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) cases continue to increase around the World. Typical symptoms include fever and respiratory illness but a constellation of multisystem involvement including central nervous system (CNS) and peripheral nervous system (PNS) have been reported with COVID-19. Acute ischemic strokes (AIS) have also been reported as a complication. METHODOLOGY: We analyzed patient characteristics, clinical outcomes, laboratory results and imaging results of four patients with COVID-19 who had AIS. RESULTS: All four patients were =< 60 years, had hypoxemic respiratory failure secondary to pneumonia, elevated D-dimer and inflammatory markers. CONCLUSION: Ischemic strokes are known complications in patients with severe COVID-19.

Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN).

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by pathogenic sequence variants in C19orf12. Autosomal recessive inheritance has been demonstrated. We present evidence of autosomal dominant MPAN and propose a mechanism to explain these cases. METHODS: Two large families with apparently dominant MPAN were investigated; additional singleton cases of MPAN were identified. Gene sequencing and multiplex ligation-dependent probe amplification were used to characterize the causative sequence variants in C19orf12. Post-mortem brain from affected subjects was examined. RESULTS: In two multi-generation non-consanguineous families, we identified different nonsense sequence variations in C19orf12 that segregate with the MPAN phenotype. Brain pathology was similar to that of autosomal recessive MPAN. We additionally identified a preponderance of cases with single heterozygous pathogenic sequence variants, including two with de novo changes. CONCLUSIONS: We present three lines of clinical evidence to demonstrate that MPAN can manifest as a result of only one pathogenic C19orf12 sequence variant. We propose that truncated C19orf12 proteins, resulting from nonsense variants in the final exon in our autosomal dominant cohort, impair function of the normal protein produced from the non-mutated allele via a dominant negative mechanism and cause loss of function. These findings impact the clinical diagnostic evaluation and counseling.

New and emerging medical therapies in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is one of the most challenging neurodegenerative disorders to treat as it manifests with a large variety of troublesome, and often disabling, motor and non-motor symptoms. Despite limitations, such as motor and other complications, levodopa remains the most effective drug in the treatment of PD. AREAS COVERED: In this review, we focus on phase 2 and 3 studies describing new and emerging medical therapies in PD. We discuss new formulations of levodopa, medications that prolong levodopa response and ameliorate levodopa-induced dyskinesias, and innovative delivery methods that are currently being evaluated in clinical trials or are in development with the promise of better efficacy and tolerability. We also describe novel non-dopaminergic drugs that have been identified for treatment of motor and non-motor symptoms. A specific section is designated for potential disease modifying therapies. EXPERT OPINION: Alternative formulations of levodopa appear to be promising especially to help with the motor fluctuations either by providing sustained benefits with controlled released formulations or ameliorate sudden OFF by formulations such as inhaled levodopa. Several different medications affecting non-dopaminergic pathways are being evaluated which may aide levodopa. As the understanding of the disease grows further, numerous novel neuroprotective or disease modifying therapies have been suggested. This along with development of medications to treat various non-motor symptoms will help improve quality of life of patients with PD.