Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions.

Background: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability.

Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor.

Intermediate repeat expansions of TBP and STUB1: Genetic modifier or pure digenic inheritance in spinocerebellar ataxias?

Purpose: CAG/CAA repeat expansions in TBP are responsible for spinocerebellar ataxia (SCA) type 17 (SCA17). We previously detected cosegregation of STUB1 variants causing SCA48 with intermediate alleles of TBP in 2 families. This cosegregation questions the existence of SCA48 as a monogenic disease.

Quantitative neuroimaging biomarkers in a series of 20 adult patients with POLG mutations.

Mutations in the gene encoding polymerase gamma (POLG) are a common cause of mitochondrial diseases in adults. We retrospectively analyzed volumetric and diffusion tensor imaging data from 20 adult POLG-mutated patients compared to healthy controls. We used an original clinical binary load score and electroneuromyography to evaluate disease severity.

Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis.

Background: Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, Pittsburgh compound B ([ C]PiB) can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS.

Methods: Patients with active relapsing-remitting MS (n = 20) and healthy controls (n = 8) were included in a longitudinal trial combining PET with [ C]PiB and magnetic resonance imaging.

Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.

Background: Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown.

Objective: To evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length.

Methods: The clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype-phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls.

A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity.

Objective: Diseases due to mutations of POLG gene, encoding the mitochondrial DNA polymerase, are reputed to have very diverse clinical presentations and have been proposed to cause up to 25% adult mitochondrial diseases. Our objective was the evaluation of the specificity and sensitivity of the signs encountered with POLG mutations.

Design: Forty-four patients out of 154 with sequenced POLG gene had mutations affecting either one (POLG(+/-) group) or two POLG alleles (POLG(+/+) group).

Factors influencing disease progression in autosomal dominant cerebellar ataxia and spastic paraplegia.

Objectives: To evaluate disease progression and determine validity of clinical tools for therapeutic trials.

Design: Prospective cohort study (36 months).

Setting: Referral center.

Annual change in Friedreich's ataxia evaluated by the Scale for the Assessment and Rating of Ataxia (SARA) is independent of disease severity.

Background: The objective of the study was to evaluate the sensitivity to change of the Scale for the Assessment and Rating of Ataxia (score, 0-40) in Friedreich's ataxia.

Methods: This was a follow-up study in adult patients with genetically confirmed Friedreich's ataxia evaluated at least twice (minimum interval, 6 months). Participants were outpatients at the Center for Neurogenetics of the Pitie-Salpêtrière Hospital in Paris.

Quantitative assessment of the evolution of cerebellar signs in spinocerebellar ataxias.

Background: Responsive ataxia rating scales are essential for determining outcome measures in clinical trials.

Methods: We evaluated the responsiveness over time of the composite cerebellar functional severity score, a quantitative score measuring cerebellar ataxia in 133 patients with autosomal dominant cerebellar ataxias (ADCA), which were prospectively evaluated at inclusion and after one-year of follow-up. A more responsive tool was developed, the Cerebellar Functional Severity score writing, incorporating the writing test at dominant hand to the Cerebellar Functional Severity score.

Frequency of mitochondrial defects in patients with chronic intestinal pseudo-obstruction.

Background & Aims: Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder caused by intestinal dysmotility and characterized by chronic symptoms suggesting bowel obstruction in the absence of fixed, occluding lesions. CIPO has been associated with primary defects of the mitochondrial oxidative phosphorylation pathway, although the frequency of mitochondrial disorders in patients with CIPO is unknown. This study evaluates mitochondrial function in patients with CIPO.