-Associated Paroxysmal Dystonia.

Background: mutations are associated with a diverse set of distinct neurological syndromes and intermediate phenotypes that may include extra-neural features. Overall, genotype-phenotype correlations are weak. There are no consensus treatments.

Zinc gluconate for Wilson disease.

Due to financial constraints, a patient with Wilson disease required transitioning his maintenance pharmacotherapy from zinc acetate to zinc gluconate. Herein, we report the clinical and laboratory outcomes of this switch and review the relevant literature on the treatment of Wilson disease with zinc. Zinc gluconate can be a viable treatment option for patients with Wilson disease and may be associated with fewer gastrointestinal side effects than zinc acetate and, accordingly, improved long-term compliance and improved clinical outcomes.

Polymerase I as a Target for Treating Neurodegenerative Disorders.

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for the treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.

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.

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.

Variants in Blepharospasm.

Background: Genetic factors have been implicated in the pathogenesis of blepharospasm (BSP), a dystonia characterized by excessive blinking and involuntary eyelid closure. Previous research identified a co-segregating deleterious variant (GRCh38/hg38, NC_000009.12: g.

Persistent hemichoreoathetosis-hemidystonia after nonketotic hyperosmolar hyperglycemia.

Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar hyperglycemic left hemichoreoathetosis-hemidystonia that has persisted for over 1 year. The subject presented to the emergency room with dysarthria and manifested left hemichoreoathetosis-hemidystonia within 36 h of admission.

HMG-boxes, ribosomopathies and neurodegenerative disease.

The UBTF E210K neuroregression syndrome is a predominantly neurological disorder caused by recurrent dominant variants in Upstream Binding Factor, that is, essential for transcription of the ribosomal RNA genes. This unusual form of ribosomopathy is characterized by a slow decline in cognition, behavior, and sensorimotor functioning during the critical period of development. UBTF (or UBF) is a multi-HMGB-box protein that acts both as an epigenetic factor to establish "open" chromatin on the ribosomal genes and as a basal transcription factor in their RNA Polymerase I transcription.

Rescue of neuropsychiatric phenotypes in a mouse model of 16p11.2 duplication syndrome by genetic correction of an epilepsy network hub.

Neuropsychiatric disorders (NPDs) are frequently co-morbid with epilepsy, but the biological basis of shared risk remains poorly understood. The 16p11.2 duplication is a copy number variant that confers risk for diverse NPDs including autism spectrum disorder, schizophrenia, intellectual disability and epilepsy.

Behavioral and molecular effects of Ubtf knockout and knockdown in mice.

The UBTF E210K neuroregression syndrome is caused by de novo dominant mutations in UBTF (NM_014233.3:c.628G > A, p.

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.

Ribosomal DNA promoter recognition is determined in vivo by cooperation between UBTF1 and SL1 and is compromised in the UBTF-E210K neuroregression syndrome.

Transcription of the ~200 mouse and human ribosomal RNA genes (rDNA) by RNA Polymerase I (RPI/PolR1) accounts for 80% of total cellular RNA, around 35% of all nuclear RNA synthesis, and determines the cytoplasmic ribosome complement. It is therefore a major factor controlling cell growth and its misfunction has been implicated in hypertrophic and developmental disorders. Activation of each rDNA repeat requires nucleosome replacement by the architectural multi-HMGbox factor UBTF to create a 15.

Palmaris Brevis Syndrome: A Treatable Pseudodystonia.

Background: Palmaris brevis syndrome, a pseudodystonia characterized by abnormal involuntary contractions of the palmaris brevis muscle which resides in the hypothenar eminence, is believed to be due to compressive irritation of motor fibers which arise from the superficial branch of the ulnar nerve.

Case Report: Herein, we review the origins, differential diagnosis and pathophysiology of the palmaris brevis syndrome, and effective treatment of a patient with workplace modifications and injections of botulinum toxin type A.

Discussion: Prompt diagnosis of the palmaris brevis syndrome facilitates effective treatment and resolution.

A Novel Variant of ATP5MC3 Associated with Both Dystonia and Spastic Paraplegia.

Background: In a large pedigree with an unusual phenotype of spastic paraplegia or dystonia and autosomal dominant inheritance, linkage analysis previously mapped the disease to chromosome 2q24-2q31.

Objective: The aim of this study is to identify the genetic cause and molecular basis of an unusual autosomal dominant spastic paraplegia and dystonia.

Methods: Whole exome sequencing following linkage analysis was used to identify the genetic cause in a large family.

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.

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.

Urine levels of the polyglutamine ataxin-3 protein are elevated in patients with spinocerebellar ataxia type 3.

Introduction: Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients.

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion.

Background And Purpose: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.

Methods: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included.