Repeat length in spinocerebellar ataxia type 4 (SCA4) predicts age at onset and disease severity.

Background: Recently, an exonic GGC repeat expansion (RE) was identified by long-read genome sequencing in the ZFHX3 gen, causing spinocerebellar ataxia type 4 (SCA4), a dominant form of ataxia with sensory neuropathy. However, the analysis of larger cohorts of patients remained demanding, resulting in a challenge to diagnose patients and leaving the question of anticipation in SCA4 unanswered.

Objectives: We aimed to develop a GGC repeat test for clinical SCA4 screening and to apply this test to screen two large German SCA pedigrees and samples of unrelated patients collected over the last 25 years.

Personality profiles are different in musician's dystonia and other isolated focal dystonias.

Psychological abnormalities have been reported in patients with musician's dystonia. To further differentiate these abnormalities, we evaluated personality traits in musician's dystonia and compared them to those in other isolated focal dystonias. Therefore patients with musician's dystonia (n = 101) and other isolated focal dystonias (n = 85) underwent the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI).

Neuroimaging abnormalities in individuals exhibiting Parkinson's disease risk markers.

Background: The concept of prodromal Parkinson's disease (PD) involves variable combinations of nonmotor features and subtle motor abnormalities as a result of ongoing neurodegeneration in the brain stem including substantia nigra (SN) and abnormal findings upon transcranial sonography and nuclear imaging. Except for nuclear imaging, the predictive value of risk markers for the conversion to overt PD is low.

Objective: The objective of this study was to determine whether PD risk markers are associated with changes in brain structure and to what extent cognitive changes are risk markers for PD.

Associations of specific psychiatric disorders with isolated focal dystonia, and monogenic and idiopathic Parkinson's disease.

Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood.

A Brief Nonmotor Screen Combined with Transcranial Ultrasound may Improve Diagnostic Accuracy of Parkinson's Disease.

Background: The addition of a simple nonmotor symptom (NMS) screen and transcranial sonography (TCS) to standard clinical assessment may improve the diagnostic accuracy of Parkinson's disease (PD).

Methods: Sixty-nine subjects (23 established PD group, 23 healthy controls, and 23 possible PD) were enrolled. All completed 3 "yes-no" NMS questions (score, 0-3) and had a transcranial ultrasound assessing nigral hyperechogenicity (score, 0-1).

Intertemporal choice in Parkinson's disease and restless legs syndrome.

Background: Impulse control disorders in Parkinson's disease are a potential consequence of dopaminergic therapy. Impulse control problems might be revealed by intertemporal choice tasks which entail to forgo an immediately available reward in favor of a larger but later reward. The steepness of the discounting curve can be quantified by the parameter k.

A population-based study on combined markers for early Parkinson's disease.

The prerequisite for an earlier diagnosis of Parkinson's disease (PD) are markers that are both sensitive and specific for clinically definite PD and its prediagnosic phases. Promising candidates include enlarged hyperechogenicity of the substantia nigra (SN+) on transcranial sonography (TCS) and hyposmia. However, despite good sensitivity and specificity, both markers have yet failed to yield reliable predictions.

Ultrasound-based motion analysis demonstrates bilateral arm hypokinesia during gait in heterozygous PINK1 mutation carriers.

Carriers of a single heterozygous PINK1 (PTEN-induced putative kinase 1) gene mutation provide an ideal opportunity to study the development of parkinsonian motor signs from the very beginning. Measuring tools that reliably represent mild motor symptoms could also facilitate the assessment of future neuroprotective therapies and early diagnosis of Parkinson's disease (PD). We investigated nine family members carrying a heterozygous PINK1 mutation in comparison with 25 age-matched healthy controls.

Mutations in GNAL: a novel cause of craniocervical dystonia.

Importance: Mutations in the GNAL gene have recently been shown to cause primary torsion dystonia. The GNAL-encoded protein (Gαolf) is important for dopamine D1 receptor function and odorant signal transduction. We sequenced all 12 exons of GNAL in 461 patients from Germany, Serbia, and Japan, including 318 patients with dystonia (190 with cervical dystonia), 51 with hyposmia and Parkinson disease, and 92 with tardive dyskinesia or acute dystonic reactions.

Non-motor phenotype of dopa-responsive dystonia and quality of life assessment.

Background: Dopa-responsive dystonia (DRD) is a young-onset neurometabolic disorder often presenting with a combination of parkinsonism and dystonia. The pathophysiology includes an impairment of dopaminergic and serotonergic neurotransmission. Uncontrolled reports suggest an increased frequency of neuropsychiatric abnormalities and sleep impairment.

Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?

Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients.

Altered resting state brain networks in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37) compared to healthy controls (n = 20).

Mortalin mutations are not a frequent cause of early-onset Parkinson disease.

Dysfunctional mitochondria and the mitochondrial chaperone mortalin (HSPA9, GRP75) have been implicated in the pathogenesis of Parkinson disease (PD). We screened 139 early-onset PD (EOPD) patients for mutations in mortalin revealing one missense change (p.L358P) that was absent in 279 control individuals.

Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.

Objective: A study was undertaken to identify the gene underlying DYT4 dystonia, a dominantly inherited form of spasmodic dysphonia combined with other focal or generalized dystonia and a characteristic facies and body habitus, in an Australian family.

Methods: Genome-wide linkage analysis was carried out in 14 family members followed by genome sequencing in 2 individuals. The index patient underwent a detailed neurological follow-up examination, including electrophysiological studies and magnetic resonance imaging scanning.

The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism.

The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD).

Prominent psychiatric comorbidity in the dominantly inherited movement disorder myoclonus-dystonia.

Background: Neurological and psychiatric disorders show clinical overlap suggesting a shared pathophysiological background. We evaluated myoclonus-dystonia, a monogenic movement disorder as a disease model for inherited psychopathology.

Method: We investigated 12 SGCE mutation carriers using standardized neurological and psychiatric examinations to assign DSM-IV diagnoses.

Feature analysis for Parkinson's disease detection based on transcranial sonography image.

Transcranial sonography (TCS) is a new tool for the diagnosis of Parkinson's disease (PD) according to a distinct hyperechogenic pattern in the substantia nigra (SN) region. However a procedure including rating scale of SN hyperechogenicity was required for a standard clinical setting with increased use. We applied the feature analysis method to a large TCS dataset that is relevant for clinical practice and includes the variability that is present under real conditions.

Cohort Profile: a population-based cohort to study non-motor symptoms in parkinsonism (EPIPARK).

Parkinson's disease is increasingly viewed as a complex disorder including a range of typical non-motor symptoms in addition to the cardinal motor signs. This cohort was set up in 2010 to investigate the specificity of non-motor symptoms for Parkinson's disease. For this, we included several control groups with decreasing contrast from Parkinson's disease patients.