POLG2-Linked Mitochondrial Disease: Functional Insights from New Mutation Carriers and Review of the Literature.

Different pathogenic variants in the DNA polymerase-gamma2 (POLG2) gene cause a rare, clinically heterogeneous mitochondrial disease. We detected a novel POLG2 variant (c.1270 T > C, p.

In Vivo Investigation of Glucose Metabolism in Idiopathic and PRKN-Related Parkinson's Disease.

Background: Alterations in mitochondrial dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). Mitochondrial energy production is linked to glucose metabolism, and diabetes is associated with PD. However, studies investigating glucose metabolism in vivo in genetically stratified PD patients and controls have yet to be performed.

Time estimation and arousal responses in dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response.

Quantitative susceptibility mapping reveals alterations of dentate nuclei in common types of degenerative cerebellar ataxias.

The cerebellar nuclei are a brain region with high iron content. Surprisingly, little is known about iron content in the cerebellar nuclei and its possible contribution to pathology in cerebellar ataxias, with the only exception of Friedreich's ataxia. In the present exploratory cross-sectional study, quantitative susceptibility mapping was used to investigate volume, iron concentration and total iron content of the dentate nuclei in common types of hereditary and non-hereditary degenerative ataxias.

Altered homodimer formation and increased iron accumulation in VAC14-related disease: Case report and review of the literature.

Background: Pathogenic variants in the VAC14 component of PIKFYVE complex (VAC14) gene have been identified as a cause of a childhood-onset complex dystonia with striato-nigral degeneration. VAC14 is a scaffold protein relevant for the regulation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P) and is known to form homodimers.

Methods: Whole exome sequencing was performed in a 32-year-old patient with adolescence-onset complex dystonia and his unaffected mother.

Predictive coding and adaptive behavior in patients with genetically determined cerebellar ataxia--A neurophysiology study.

Genetically determined cerebellar ataxias (CA) are a heterogeneous group of disorders with progressive decline of cerebellar functions. The cerebellum influences internal forward models that play a role in cognitive control, but whether these processes are dysfunctional in CA is unclear. Here, we examined sensory predictive coding processes and response adaptation in CA and healthy controls (HC) using behavioral tests with concomitant EEG recordings.

Temporal discrimination threshold and blink reflex recovery cycle in cervical dystonia - two sides of the same coin?

Introduction: Elevated temporal discrimination thresholds (TDT) have been found in cervical dystonia (CD) and unaffected first-degree relatives, indicating autosomal dominant inheritance with reduced penetrance, serving as an endophenotype and being indicative of abnormal inhibitory processing within the brainstem-basal ganglia circuits. The blink reflex R2 recovery cycle (BRRC) is also a measure of excitability of brainstem-basal ganglia circuits, and inconsistent findings are reported in CD. The aim was to investigate TDT and BRRC in CD and evaluate its reliability as an endophenotype.

Spinocerebellar Ataxia Type 28-Phenotypic and Molecular Characterization of a Family with Heterozygous and Compound-Heterozygous Mutations in AFG3L2.

While heterozygous mutations in the AFG3L2 gene have been linked to spinocerebellar ataxia 28 (SCA28), homozygous mutations in the same gene can cause spastic ataxia 5 (SPAX5). AFG3L2 encodes a mitochondrial ATP-dependent metalloprotease. We here report a SCA28 patient with biallelic AFG3L2 variants and his heterozygous mother.

Role of ANO3 mutations in dystonia: A large-scale mutational screening study.

Background: The role of ANO3 variants as a monogenic cause of dystonia is still under debate because of its relatively high frequency also in controls.

Objective: To screen >1000 patients with movement disorders for rare ANO3 variants.

Methods: We searched for rare ANO3 variants in 729 dystonia and 294 Parkinson's disease (PD) patients using a gene panel.

Utility and implications of exome sequencing in early-onset Parkinson's disease.

Background: Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD.

Methods: We searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes.

Boys in a famous choir: Singing and ticcing.

This informal observational study on the tic prevalence in 40 young singers was carried out during a public concert of Bach's Christmas Oratorio. Tics were highly prevalent (present in 35% = 14 boys). Given the possibility of an overrepresentation of perioral tics in this group of highly achieving young vocal artists, one might speculate that there is a relationship between the ability of the motor system to produce a surplus of movements (tics) and high performance (exquisite singing).

Alcohol improves cerebellar learning deficit in myoclonus-dystonia: A clinical and electrophysiological investigation.

Objective: To characterize neurophysiological subcortical abnormalities in myoclonus-dystonia and their modulation by alcohol administration.

Methods: Cerebellar associative learning and basal ganglia-brainstem interaction were investigated in 17 myoclonus-dystonia patients with epsilon-sarcoglycan (SGCE) gene mutation and 21 age- and sex-matched healthy controls by means of classical eyeblink conditioning and blink reflex recovery cycle before and after alcohol intake resulting in a breath alcohol concentration of 0.08% (0.

Facial twitches in ADCY5-associated disease - Myokymia or myoclonus? An electromyography study.

Objective: A clinical feature in patients with ADCY5 gene mutations are perioral muscle twitches initially described as facial myokymia.

Methods: Five patients with ADCY5-associated disease with facial twitches and truncal jerks underwent electrophysiological investigations of the orbicularis oris and trapezius muscles to delineate neurophysiological characteristics of these phenomena.

Results: Electromyography (EMG) recordings showed a complex electrophysiological pattern with brief bursts of less than 100 ms and longer bursts with a duration of 100-300 ms up to several seconds in keeping with myoclonus and chorea, respectively, as key findings.

[On the fast track to diagnosis : Recommendations for patients without a diagnosis].

Background: Patients, who have spent many years without a proper diagnosis present an extraordinary problem to health care providers and to the healthcare system as a whole. A long 'diagnostic journey' increases the risk of disease chronification, as well as the number of therapy attempts, which could lead to iatrogenic impairment. New resources and specialized health care departments are being developed to help and support this patient group.

Qualitative Characteristics of Depression in Parkinson's Patients and Controls.

Background: Depression is common in Parkinson's disease (PD); in light of typical PD pathology it may differ phenomenologically from depression in the general population.

Objective: To assess depressive symptoms in PD patients and control groups and compare symptom profiles.

Methods: After postal screening of 10,000 citizens of Lübeck, 642 participants were examined and the Beck Depression Inventory (BDI) was sufficiently answered by 477 subjects.

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.

Frequency of the D620N mutation in VPS35 in Parkinson disease.

Objective: To evaluate the frequency and clinical spectrum of the recently identified p.D620N mutation in the VPS35 gene in Parkinson disease (PD) in an international sample.

Design: Genetic analysis by DNA sequencing and detailed clinical and neuropsychiatric assessment as well as neuroimaging in mutation carriers.