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.

Sex Differences in Dystonia.

Background: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms.

Objectives: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences.

Blood-Based Proteomics for Adult-Onset Focal Dystonias.

Objectives: The adult-onset focal dystonias are characterized by over-active muscles leading to abnormal movements. For most cases, the etiology and pathogenesis remain unknown. In the current study, unbiased proteomics methods were used to identify potential changes in blood plasma proteins.

Exploration of potential immune mechanisms in cervical dystonia.

Background: Although there are many possible causes for cervical dystonia (CD), a specific etiology cannot be identified in most cases. Prior studies have suggested a relationship between autoimmune disease and some cases of CD, pointing to possible immunological mechanisms.

Objective: The goal was to explore the potential role of multiple different immunological mechanisms in CD.

An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm.

Background: Blepharospasm is treated with botulinum toxin, but obtaining satisfactory results is sometimes challenging.

Objective: The aim is to conduct an exploratory trial of oral dipraglurant for blepharospasm.

Methods: This study was an exploratory, phase 2a, randomized, double-blind, placebo-controlled trial of 15 participants who were assigned to receive a placebo or dipraglurant (50 or 100 mg) and assessed over 2 days, 1 and 2 hours following dosing.

An Empirical Comparison of Commonly Used Universal Rating Scales for Dystonia.

Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia.

Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia.

Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants.

Demographics and Clinical Characteristics Associated with the Spread of New-Onset Laryngeal Dystonia.

Objectives: Adult-onset idiopathic laryngeal dystonia (LD) can be associated with the risk of spread to muscles in the body. Subjects with extralaryngeal onset of dystonia have exhibited spread to the larynx. Previous studies analyze the spread of other dystonias but emphasis has not been placed on LD.

Thyroid disease in cervical dystonia.

There are many possible etiologies for cervical dystonia (CD), but a cause cannot be identified in most cases. Most recent attention has focused on genetic causes, although a few prior studies have highlighted autoimmune mechanisms instead. Because autoimmune disorders frequently co-exist, the current study evaluated the hypothesis that autoimmune disorders might be more common in CD than neurological controls.

Diagnosis and classification of blepharospasm: Recommendations based on empirical evidence.

Background: Blepharospasm is one of the most common subtypes of dystonia, and often spreads to other body regions. Despite published guidelines, the approach to diagnosis and classification of affected body regions varies among clinicians.

Objective: To delineate the clinical features used by movement disorder specialists in the diagnosis and classification of blepharospasm according to body regions affected, and to develop recommendations for a more consistent approach.

Current Guidelines for Classifying and Diagnosing Cervical Dystonia: Empirical Evidence and Recommendations.

Background: The dystonias are phenotypically and etiologically heterogenous disorders. Many proposals and a consensus recommendation have been provided for the diagnosis and classification of the dystonias, but these recommendations serve only as general guidelines. Current diagnosis and classification may still depend on clinical judgment causing different opinions.

Diagnostic criteria for blepharospasm: A multicenter international study.

Background: There are no widely accepted criteria to aid the physician in diagnosing BSP.

Objective: To validate recently proposed diagnostic criteria for blepharospasm in a larger and geographically diverse population and to develop a screening system for blepharospasm.

Methods: Video-recordings from 211 blepharospasm patients and 166 healthy/disease controls were examined by 8 raters.

A Multi-center Genome-wide Association Study of Cervical Dystonia.

Background: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility.

Objective: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach.

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon.

A metabolomic study of cervical dystonia.

Introduction: Cervical dystonia is the most common of the adult-onset focal dystonias. Most cases are idiopathic. The current view is that cervical dystonia may be caused by some combination of genetic and environmental factors.

Soft Material-Enabled, Active Wireless, Thin-Film Bioelectronics for Quantitative Diagnostics of Cervical Dystonia.

Recent advances in flexible materials, nanomanufacturing, and system integration have provided a great opportunity to develop wearable flexible hybrid electronics for human healthcare, diagnostics, and therapeutics. However, existing medical devices still rely on rigid electronics with many wires and separate components, which hinders wireless, comfortable, continuous monitoring of health-related human motions. Here, we introduce advanced materials and system integration technologies that enable a soft, active wireless, thin-film bioelectronics.

Soft Nanomembrane Sensors and Flexible Hybrid Bioelectronics for Wireless Quantification of Blepharospasm.

Blepharospasm (BL) is characterized by involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle. The gold standard for clinical evaluation of BL involves visual inspection for manual rating scales. This approach is highly subjective and error prone.

The course of awake breathing disturbances across the lifespan in Rett syndrome.

Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, is associated with a peculiar breathing disturbance exclusively during wakefulness that is distressing, and can even prompt emergency resuscitation. Through the RTT Natural History Study, we characterized cross sectional and longitudinal characteristics of awake breathing abnormalities in RTT and identified associated clinical features. Participants were recruited from 2006 to 2015, and cumulative lifetime prevalence of breathing dysfunction was determined using the Kaplan-Meier estimator.

The Role of Estrogens in Pancreatic Islet Physiopathology.

In rodent models of insulin-deficient diabetes, 17β-estradiol (E2) protects pancreatic insulin-producing β-cells against oxidative stress, amyloid polypeptide toxicity, gluco-lipotoxicity, and apoptosis. Three estrogen receptors (ERs)-ERα, ERβ, and the G protein-coupled ER (GPER)-have been identified in rodent and human β-cells. This chapter describes recent advances in our understanding of the role of ERs in islet β-cell function, nutrient homeostasis, survival from pro-apoptotic stimuli, and proliferation.