Genetic Diversity and Expanded Phenotypes in Dystonia: Insights from Large-Scale Exome Sequencing.

Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%) and the identification of several disease-linked genes, the etiology in most patients remains elusive. Moreover, understanding the correlations between clinical manifestation and genetic variants has become increasingly complex.

The frequency and clinical impact of synonymous HTT loss-of-interruption and duplication-of-interruption variants in a diverse HD cohort.

Purpose: To determine the frequency and clinical impact of loss-of-interruption (LOI) and duplication-of-interruption modifier variants of the HTT CAG and CCG repeat in a cohort of individuals with Huntington disease (HD).

Methods: We screened symptomatic HD participants from the UBC HD Biobank and 5 research sites for sequence variants. After variant identification, we examined the clinical impact and frequency in the reduced penetrance range.

Atypical brain MRI findings in a patient with treatment responsive anti-IgLON5 disease.

Anti-IgLON5 disease is a rare autoimmune neurological condition which was relatively recently described in the literature. This syndrome encompasses a range of clinical manifestations with most cases showing unremarkable findings on brain magnetic resonance imaging (MRI). Here, we report a case of a 61-year-old female patient with unique brain MRI features that, to the best of our knowledge, has not been reported in the literature before.

A single centre prospective study of three device-assisted therapies for Parkinson's disease.

Comparative studies assessing outcomes with the three device-assisted therapies could help to individualise treatment for patients living with Parkinson's disease. We designed a single-centre non-randomised prospective observational study assessing the quality of life (QoL), motor and non-motor outcomes at 6 and 12-months in patients treated with subcutaneous apomorphine continuous 16-hours infusion (APO), levodopa-carbidopa intestinal gel (LCIG) or subthalamic nucleus deep brain stimulation (STN-DBS). In this study, 66 patients were included (13 APO; 19 LCIG; 34 STN-DBS).

Costs and Effects of School-Based Licensed Practical Nurses on Elementary Student Attendance and Chronic Absenteeism.

Despite increasing reliance on licensed practical nurses (LPNs) to provide health services in schools, we do not know whether this is a cost-effective prevention strategy against student absenteeism. Therefore, we evaluated the costs and effectiveness of an LPN-based school nursing program for improving attendance and chronic absenteeism at a large, urban school district in the southeastern USA. We first identified a matched set of 46 elementary schools (23 nurse, 23 no-nurse) by using an optimal multilevel matching algorithm based on student- and school-level characteristics.

Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review.

Objective: Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features.

Methods: This was a two-part study.

Restorative Practices: Using local evidence on costs and student outcomes to inform school district decisions about behavioral interventions.

School disciplinary practices affect student academic and life outcomes. Many schools have recently shifted towards the prevention of behavioral disorders rather than the punishment of such disorders, but disciplinary actions are still disproportionately meted out to Black students. We took advantage of a natural experiment in a large school district to investigate the costs and effects of a school-wide intervention based on the principles of restorative justice on suspensions, referrals, and three school climate constructs.

Oromandibular Dystonia: A Clinical Examination of 2,020 Cases.

The goal of this study is to better characterize the phenotypic heterogeneity of oromandibular dystonia (OMD) for the purpose of facilitating early diagnosis. First, we provide a comprehensive summary of the literature encompassing 1,121 cases. Next, we describe the clinical features of 727 OMD subjects enrolled by the Dystonia Coalition (DC), an international multicenter cohort.

Levodopa/dopa decarboxylase inhibitor associated microscopic colitis: An under-recognized drug reaction.

Background: Microscopic colitis is a form of inflammatory bowel disease characterized by profuse non-bloody watery diarrhea. Macroscopic abnormality is not present on colonoscopy, and it requires biopsy for diagnosis. Few cases have been attributed to levodopa/dopa-decarboxylase inhibitor therapy.

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease.

Introduction: In vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor.

Clinical and Demographic Characteristics of Upper Limb Dystonia.

Background: Knowledge of characteristics in upper limb dystonia remains limited, derived primarily from small, single-site studies.

Objective: The objective of this study was to characterize demographic and clinical characteristics of upper limb dystonia from the Dystonia Coalition data set, a large, international, multicenter resource.

Methods: We evaluated clinical and demographic characteristics of 367 participants with upper limb dystonia from onset, comparing across subcategories of focal (with and without dystonia spread) versus nonfocal onset.

A survey of falls in people with dystonia.

Objective: Dystonia is a chronic and sometimes progressive neurological disorder causing abnormalities in movement and function. We conducted a preliminary survey to investigate whether people with dystonia experience falls and to identify contributing factors to falls in this population.

Methods: An online survey of people with dystonia was conducted in November 2015.

The Dietary Supplement Label Database: Recent Developments and Applications.

Objective: To describe the history, key features, recent enhancements, and common applications of the Dietary Supplement Label Database (DSLD).

Background And History: Although many Americans use dietary supplements, databases of dietary supplements sold in the United States have not been widely available. The DSLD, an easily accessible public-use database was created in 2008 to provide information on dietary supplement composition for use by researchers and consumers.

Parkinsonism in PGK1 deficiency implicates the glycolytic pathway in nigrostriatal dysfunction.

Background: Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 deficiency and nigrostriatal dysfunction causing Parkinsonism has not been determined.

Objective And Methods: To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.

Internal Carotid Artery Occlusion Causing Acute Cranial Neuropathies.

A 54-year-old male with a history of left posterior parietal ischemic stroke, epilepsy, tobacco and marijuana smoking, and alcohol abuse, presented with acute left visual loss and diplopia. On examination, he had reduced left visual acuity and a left oculomotor nerve palsy. CT angiogram from aortic arch to circle of Willis identified extensive thrombus occluding the left common and internal carotid arteries, extending to the left ophthalmic artery.

24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson's disease.

Levodopa-carbidopa intestinal gel (LCIG) is effective for the control of motor fluctuations in Parkinson's disease (PD). The objective of this study is to report the reduction of dyskinesias after transitioning from 16 to 24-h/day LCIG infusion. From a cohort of 74 PD patients treated with LCIG for motor fluctuations, we identified 12 patients that were treated with 24-h per day infusion with the aim to control troublesome daytime dyskinesia.

Phenotypic insights into ADCY5-associated disease.

Background: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations.

Methods: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing.

Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series.

ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials.

Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease.

We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from patients treated in a single Australian movement disorder centre. We conducted an open-label, 12 month prospective study of treatment with LCIG in patients with advanced Parkinson's disease in a single tertiary referral hospital unit specialising in movement disorders. Patients with levodopa-responsive, advanced Parkinson's disease with motor fluctuations despite optimal pharmacological treatment were enrolled and underwent a 16 hour daily infusion of LCIG for 12 months.

24 h Levodopa-carbidopa intestinal gel may reduce falls and "unresponsive" freezing of gait in Parkinson's disease.

Objective: We report a prospective, open label study of 24 h levodopa-carbidopa intestinal gel (LCIG) as treatment for levodopa "unresponsive" freezing of gait (FOG) associated with Parkinson's disease.

Method: 5 patients with disabling FOG, documented as being levodopa "unresponsive", were commenced on continuous 24 h infusion LCIG therapy with the night-time rate at 50-80% of the daytime infusion rate. Patients underwent baseline, 3 and 6 month gait assessments, documentation of their falls frequency and completed FOG questionnaires.