Management of rare movement diseases in different world regions.

To evaluate the management of rare movement disorders (RMD) at the international level and identify care needs to be addressed, the Rare Movement Disorders Study Group of the International Parkinson and Movement Disorders Society (MDS) has conducted an exploratory survey. We sent an online survey to experts in Africa, Asia, Oceania and American continents following the classification of the MDS Regional Sections: Africa, Asia and Oceania (A&O), and Pan-America. We did not include Europe as the European Reference Network for Rare Neurological Diseases recently performed a similar care needs survey across European countries. We obtained responses from experts from 20 African, 26 A&O and 19 Pan-American countries. According to the respondents, only 55% of African countries had movement disorders experts, while these were present in 96% of A&O and 91% of Pan-American. Access to care for patients with RMD was stated difficult in 70% of African, 54% of A&O, and 65% of Pan-American countries. Africa was the region with greatest difficulties in accessing diagnostic tests. However, in Pan-America and A&O, large inequalities were observed between countries with quite variable access to therapeutic options such as deep brain stimulation. The survey results reflect wide variability in the management of RMD and provide evidence that a worldwide care-focused network is highly warranted. Scientific and medical organisations should raise awareness of deficits in managing RMD and care disparities among regions. The goals should be to facilitate the training of professionals, establish improvement strategies, and increase support and budgeting for these diseases.

COVID-19 and Integrated Multidisciplinary Care Model in Parkinson's Disease: Literature Review & Future Perspectives.

Clinical diversity and multi-systemic manifestations of Parkinson's disease (PD) necessitate the involvement of several healthcare professionals from different disciplines for optimal care. Clinical guidelines recommend that all persons with PD should have access to a broad range of medical and allied health professionals to implement an efficient and effective multidisciplinary care model. This is well supported by growing evidence showing the benefits of multidisciplinary interventions on improving quality of life and disease progression in PD. However, a "multidisciplinary" approach requires gathering healthcare professionals from different disciplines into an integrative platform for collaborative teamwork. With the Coronavirus Disease 2019 (COVID-19) pandemic, implementation of such a multidisciplinary care model has become increasingly challenging due to social distancing mandates, isolation and quarantine, clinics cancellation, among others. To address this problem, multidisciplinary teams are developing innovate virtual platforms to maintain care of people with PD. In the present review, we cover aspects on how SARS-CoV-2 has affected people with PD, their caregivers, and care team members. We also review current evidence on the importance of maintaining patient-centered care in the era of social distancing, and how can we utilize telehealth and innovative virtual platforms for multidisciplinary care in PD.

Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson's Disease.

Background: Treating medication-refractory freezing of gait (FoG) in Parkinson's disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS). Methods: In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when "on" PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate. Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both "on" and "off" medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit. Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

Lower Urinary Tract and Gastrointestinal Dysfunction Are Common in Early Parkinson's Disease.

PURPOSE: Autonomic dysfunction is a common nonmotor feature and early manifestation of Parkinsons disease (PD). Autonomic dysfunction in PD is associated with a worse prognosis. We sought to characterize autonomic dysfunction and identify associated factors in patients with early PD. METHODS: An observational, cross-sectional, descriptive, and analytical study was conducted to evaluate patients with early PD from the Parkinsons Progression Markers Initiative. We utilized the Scales for Outcomes in Parkinsons Disease-Autonomic dysfunction questionnaire to determine the prevalence and frequencies of autonomic symptomatology. The cohort was grouped into high and low dysautonomic scores. A regression model identified variables that independently explained dysautonomic scores in our early PD cohort. RESULTS: 414 PD patients had a mean age of 61.1 (SD 9.7) years at diagnosis and mean disease duration of 6.7 (SD 6.6) months. Among all patients, 43.7% (181/414) had high dysautonomic scores. Urinary and gastrointestinal symptoms were the most prevalent and frequently reported dysautonomic symptoms. Patients with fatigue (beta = 4.28, p < 0.001), probable rapid eye movement sleep behavior disorder (beta = 2.71, p < 0.001), excessive daytime sleepiness (beta = 1.88,p=0.039), impulsivity and compulsivity (beta = 2.42, p < 0.001), and increasing age (beta = 1.05, p < 0.001) were more likely to have high dysautonomic scores. CONCLUSION: Lower urinary tract and gastrointestinal symptoms are prevalent and frequent in early PD patients. Fatigue, sleep disorders, impulsivity and compulsivity, and age are predictors of autonomic dysfunction. Autonomic symptoms predominated in this group of early PD patients in the disease course and were associated with more severe disease.

Review of Hereditary and Acquired Rare Choreas.

Background: Movement disorders are often a prominent part of the phenotype of many neurologic rare diseases. In order to promote awareness and diagnosis of these rare diseases, the International Parkinson's and Movement Disorders Society Rare Movement Disorders Study Group provides updates on rare movement disorders. Methods: In this narrative review, we discuss the differential diagnosis of the rare disorders that can cause chorea. Results: Although the most common causes of chorea are hereditary, it is critical to identify acquired or symptomatic choreas since these are potentially treatable conditions. Disorders of metabolism and mitochondrial cytopathies can also be associated with chorea. Discussion: The present review discusses clues to the diagnosis of chorea of various etiologies. Authors propose algorithms to help the clinician in the diagnosis of these rare disorders.

Neurophysiological Correlates of Gait in the Human Basal Ganglia and the PPN Region in Parkinson's Disease.

This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson's disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1-8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD. Clinical Trial Registration: Clinicaltrials.gov identifier; NCT02318927.

Factores asociados con deterioro cognitivo en una cohorte mexicana multicéntrica de Parkinson: estudio transversal comparativo.

INTRODUCTION: Cognitive impairment is common in Parkinson's disease and represents a risk for dementia. Identifying associated factors will help implement early interventions and study its progression. OBJECTIVE: To identify factors associated with cognitive impairment. METHOD: Cross-sectional study of 306 subjects with Parkinson's disease who were assessed for 12 months. Demographics and clinical variables were analyzed as explanatory variables, and cognitive impairment as outcome variable. Significant variables were used to construct a cognitive impairment predictive model. RESULTS: Cognitive impairment was reported in 43.8%. Female gender (p = 0.001, odds ratio [OR] = 1.77), age at diagnosis (p < 0.001, mean deviation [MD] = 5.7), level of education (p < 0.001, MD = -2.9), disease duration (p = 0.003, MD = 1.7), MDS-UPDRS part III score (p < 0.001, MD = 9.7), presence of anxiety (p = 0.007, OR = 2.11), hallucinations (p = 0.029, OR = 2.27) and freezing of gait (p = 0.048, OR = 1.91) were predictors for cognitive impairment. The use of type B monoamine oxidase inhibitors was associated with less cognitive impairment (p = 0.001). CONCLUSIONS: Predictive factors that were consistent with those previously reported were identified. Prospective studies are required in order to clarify the effect of type B monoamine oxidase inhibitors on cognition.

INTRODUCCIÓN: El deterioro cognitivo en Parkinson es común y representa un riesgo para demencia. Identificar los factores asociados ayudará a implementar intervenciones tempranas y estudiar la progresión del deterioro cognitivo. OBJETIVO: Identificar factores asociados con deterioro cognitivo. MÉTODO: Estudio transversal de 306 sujetos con Parkinson evaluados durante los últimos 12 meses. Se estudiaron variables demográficas y clínicas como explicativas y el deterioro cognitivo como desenlace. Las variables significativas se utilizaron para construir un modelo predictor de deterioro cognitivo. RESULTADOS: El 43.8 % reportó deterioro cognitivo. El sexo femenino (p = 0.001, RM = 1.77), edad al diagnóstico (p < 0.001, desviación media [DM] 5.7), escolaridad (p < 0.001, DM −2.9), duración de enfermedad (p = 0.003, DM 1.7), puntuación en MDS-UPDRS parte III (p < 0.001, DM 9.7), presencia de ansiedad (p = 0.007, RM = 2.11), de alucinaciones (p = 0.029, RM = 2.27) y congelamientos de la marcha (p = 0.048, RM = 1.91) fueron predictores para deterioro cognitivo. El uso de inhibidores ­monoamina-oxidasa tipo B se asoció con menor deterioro cognitivo (p = 0.001). CONCLUSIONES: Se identificaron factores predictores consistentes con lo reportado previamente. Se requieren estudios prospectivos para aclarar el efecto de los inhibidores monoamina-oxidasa tipo B en la cognición.

Square Biphasic Pulse Deep Brain Stimulation for Parkinson's Disease: The BiP-PD Study.

BACKGROUND: Conventional Parkinson's disease (PD) deep brain stimulation (DBS) utilizes a pulse with an active phase and a passive charge-balancing phase. A pulse-shaping strategy that eliminates the passive phase may be a promising approach to addressing movement disorders. OBJECTIVES: The current study assessed the safety and tolerability of square biphasic pulse shaping (sqBIP) DBS for use in PD. METHODS: This small pilot safety and tolerability study compared sqBiP versus conventional DBS. Nine were enrolled. The safety and tolerability were assessed over a 3-h period on sqBiP. Friedman's test compared blinded assessments at baseline, washout, and 30 min, 1 h, 2 h, and 3 h post sqBIP. RESULTS: Biphasic pulses were safe and well tolerated by all participants. SqBiP performed as well as conventional DBS without significant differences in motor scores nor accelerometer or gait measures. CONCLUSION: Biphasic pulses were well-tolerated and provided similar benefit to conventional DBS. Further studies should address effectiveness of sqBIP in select PD patients.

Changes in Midline Tremor and Gait Following Deep Brain Stimulation for Essential Tremor.

Background: Essential tremor (ET) is a common movement disorder characterized by kinetic and postural tremor in the upper extremities and frequently in the midline. Persons with ET often also exhibit gait ataxia. Previous studies have observed associations between midline tremor severity and gait ataxia in persons with ET, suggesting a common pathophysiology distinct from that of upper extremity tremor. However, a causal link between midline tremor and gait impairment has not been established. Methods: We investigated tremor and gait in 24 persons with ET before and after implantation of unilateral deep brain stimulation into the ventralis intermedius nucleus of the thalamus. Results: Stimulation significantly improved tremor in the targeted upper extremity and midline. However, gait was unaffected at the cohort level. Furthermore, improvement in midline tremor was not significantly associated with gait improvement. Discussion: These findings revealed that midline tremor and gait impairment may be dissociable in persons with ET.

CAPN1 Variants as Cause of Hereditary Spastic Paraplegia Type 76.

BACKGROUND: Autosomal recessive hereditary spastic paraplegias (HSP) are a rare group of hereditary neurodegenerative disorders characterized by spasticity with or without other symptoms. SPG11 gene is the most common cause of autosomal recessive HSP. We report a case of autosomal recessive spastic paraplegia type 76 due to heterozygous variants of CAPN1 in an Argentinean subject. CASE PRESENTATION: A 38-year-old Argentinean female presented with progressive gait problems and instability of 15-year duration. Oculomotor abnormalities, ataxia, bradykinesia, cervical dystonia, and lower limb pyramidal signs were observed. Brain MRI was unremarkable. Whole-exome sequencing analysis identified two heterozygous variants in CAPN1. CONCLUSIONS: Clinicians should screen for CAPN1 mutation in a young female patient without significant family history with a spastic paraplegia syndrome associated with other symptoms.

Causes and outcomes of hospitalization in Lewy body dementia: A retrospective cohort study.

INTRODUCTION: Understanding hospitalization in Lewy body dementia (LBD) is a known knowledge gap. We aimed to identify common causes, medication profiles, complications, and outcomes of hospitalization in LBD. METHODS: A retrospective cohort study investigated details of academic medical center hospitalizations over a two-year period for patients with LBD. Data collected included demographics, home medications, pre-hospital living status, reason for admission, admission service, inpatient medications, complications, and discharge status. Non-parametric statistics assessed associations between variables and length of stay. Odds of a change in living situation based on admission variables was calculated. RESULTS: The study included 178 hospitalizations (117 individuals). Neuropsychiatric symptoms were the most common admission reason (40%), followed by falls (24%) and infection (23%). Patients were usually admitted to medicine services; neurology or psychiatric consultations occurred less than 40% of the time. Antipsychotics were administered during 38% of hospitalizations. Use of antipsychotics other than quetiapine or clozapine was associated with longer length of stay and increased odds of discharge to a higher level of care. One-third of hospitalizations resulted in transition to a higher level of care; 15% ended in hospice care or death. CONCLUSION: The most common reasons for hospitalization in LBD are potentially modifiable. Opportunities for improved care include increased involvement of neurological and psychiatric services, delirium prevention strategies, and reduced antipsychotic use. Clinicians should counsel patients and families that hospitalizations in LBD can be associated with end of life. Research is needed to identify strategies to prevent hospitalization and optimal standards for inpatient care. FUNDING: Lewy body dementia research at the University of Florida is supported by the University of Florida Dorothy Mangurian Headquarters for Lewy Body Dementia and the Raymond E. Kassar Research Fund for Lewy Body Dementia.

A randomized study of botulinum toxin versus botulinum toxin plus physical therapy for treatment of cervical dystonia.

BACKGROUND: Physical therapy (PT) for cervical dystonia is not well studied, and the underlying physiological effects are not known. METHODS: We enrolled 26 subjects comprising of 16 cervical dystonia and 10 healthy controls for normative physiological data. We randomized cervical dystonia patients who reported suboptimal benefits on botulinum toxin (BoNT) injections to BoNT alone (BoNT arm) or BoNT plus PT (PT-BoNT arm). PT-BoNT arm received manual PT on the injection day followed by six weeks of home-exercise program. Home-exercise program comprised of stretching, range-of-motion and isometric exercises. The primary outcome was change from baseline in Toronto Western spasmodic torticollis rating scale (TWSTRS) that was recorded six weeks after exercise program. TWSTRS was video evaluated by blinded raters. We probed sensorimotor plasticity with transcranial magnetic stimulation (TMS) using a paired associative stimulation (PAS) paradigm. RESULTS: TWSTRS score improved (severity 31%, p = 0.002; pain 28%, p = 0.01) and PAS plasticity decreased (p = 0.01) in PT-BoNT arm compared to BoNT arm. PAS values for PT-BoNT arm were found to approach values of healthy control values. Change in PAS measure correlated significantly with TWSTRS change (severity, r = 0.56, p = 0.04; pain, r = 0.61, p = 0.03. TWSTRS disability score only approached significance (p = 0.14) when comparing the two treatment arms. CONCLUSION: PT is a potential adjunct in patients with cervical dystonia who report suboptimal benefits with BoNT therapy. PT related benefits in cervical dystonia are likely mediated through modulation of sensorimotor plasticity.