BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a

BackgroundThe European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) is a prospective international registry investigating the natural history of Friedreich ataxia (FRDA). We report one-and two-year longitudinal data to delineate potential outcomes for clinical trials. MethodsWe enrolled genetically confirmed FRDA patients from eleven European study sites. Patients were seen on an annual basis at three visits. Our primary endpoint was the Scale for the Assessment and Rating of Ataxia (SARA). Secondary outcomes were the Inventory of Non-Ataxia Signs (INAS), the Spinocerebellar Ataxia Functional Index (SCAFI), phonemic verbal fluency (PVF) and the quality of life measures activities of daily living (ADL) and EQ-5D-3L index. Disease progression was analyzed with linear mixed effect models. This study is registered with ClinicalTrials.gov, number NCT02069509. Patients with more than 353 GAA repeats on the shorter allele had a higher SARA progression rate (by 0·09 [0·02] per additional 100 repeats). Annual worsening for INAS was 0·10 (0·03), for SCAFI -0·04 (0·01), for ADL 0·93 (0·06) and for EQ-5D-3L -0·02 (0·004). PVF performance improved by 0·99 [0·14] words per year. 548 or 184 patients would be needed to detect a 50% reduction in SARA progression at 80% power in a one-year or two-year clinical trial, respectively. InterpretationThe EFACTS longitudinal analysis provides suitable outcome measures and sample size calculation for upcoming clinical trial designs in FRDA.

BackgroundThe European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) is a prospective international registry investigating the natural history of Friedreich ataxia (FRDA). Based on our 1 year and 2 year data we aimed to delineate potential outcomes for clinical trials. MethodsWe enrolled patients with genetically confirmed FRDA from 11 European study sites. Patients were seen on an yearly basis at three visits. Our primary endpoint was the Scale for the Assessment and Rating of Ataxia (SARA). Secondary outcomes were the Inventory of Non-Ataxia Signs (INAS), the Spinocerebellar Ataxia Functional Index (SCAFI), phonemic verbal fluency (PVF), and the quality of life measures activities of daily living (ADL) and EQ-5D-3L index. Disease progression was analysed with linear mixed effect models.This study is registered with ClinicalTrials.gov, number NCT02069509. Findings 605 FRDA patients were enrolled between 15-Sep-2010 and 21-Nov-2013. 546 patients (90%) contributed data with at least one follow-up visit. Annual progression rate for SARA was 0•77 points (SE 0•06) in the overall cohort. Deterioration in SARA was associated with a lower age of onset (by -0•02 [0•01] points per year) and a lower SARA baseline score (-0•07 [0•01] per baseline-point). Patients with more than 353 GAA repeats on the shorter allele had a higher SARA progression rate (by 0•09 [0•02] per additional 100 repeats).Annual worsening for INAS was 0•10 (0•03), for SCAFI -0•04 (0•01), for ADL 0•93 (0•06) and for EQ-5D-3L -0•02 (0•004). PVF performance improved by 0•99 [0•14] words per year. 548 or 184 patients would be needed to detect a 50% reduction in SARA progression at 80% power in a one-year or two-year clinical trial, respectively. InterpretationThe EFACTS longitudinal analysis provides suitable outcome measures and sample size calculation for upcoming clinical trial designs in FRDA.

The role of the cerebellum in cognition, both in healthy subjects and in patients with cerebellar diseases, is debated. Neuropsychological studies in spinocerebellar ataxia type 1 (SCA1) and type 2 (SCA2) demonstrated impairments in executive functions, verbal memory, and visuospatial performances, but prospective evaluations are not available. Our aims were to assess progression of cognitive and psychiatric functions in patients with SCA1 and SCA2 in a longitudinal study. We evaluated at baseline 20 patients with SCA1, 22 patients with SCA2 and 17 matched controls. Two subgroups of patients (9 SCA1, 11 SCA2) were re-evaluated after 2 years. We tested cognitive functions (Mini Mental State Examination, digit span, Corsi span, verbal memory, attentional matrices, modified Wisconsin Card Sorting Test, Raven Progressive Matrices, Benton test, phonemic and semantic fluency), psychiatric status (Scales for Assessment of Negative and Positive Symptoms, Hamilton Depression and Anxiety Scales), neurological conditions (Scale for Assessment and Rating of Ataxia), and functional abilities (Unified Huntington Disease Rating Scale–part IV). At baseline, SCA1 and SCA2 patients had significant deficits compared to controls, mainly in executive functions (phonemic and semantic fluencies, attentional matrices); SCA2 showed further impairment in visuospatial and visuoperceptive tests (Raven matrices, Benton test, Corsi span). Both SCA groups had higher depression and negative symptoms, particularly apathy, compared to controls. After 2 years, motor and functional disability worsened, while only attentive performances deteriorated in SCA2. This longitudinal study showed dissociation in progression of motor disability and cognitive impairment, suggesting that in SCA1 and SCA2 motor and cognitive functions might be involved with different progression rates.

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