No abstract

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.

BackgroundGuillain-Barre syndrome (GBS) is characterized by acute onset and progressive course, and is usually associated with a good prognosis. However, there are forms of poor prognosis, needing ventilatory support and major deficits at discharge. With this study we try to identify the factors associated with a worse outcome.Methods106 cases of GBS admitted in our hospital between years 2000–2010 were reviewed. Epidemiological, clinical, therapeutical and evolutionary data were collected.ResultsAt admission 45% had severe deficits, percentage which improves throughout the evolution of the illness, with full recovery or minor deficits in the 87% of patients at the first year review. Ages greater than 55 years, severity at admission (p < 0.001), injured cranial nerves (p = 0.008) and the needing of ventilator support (p = 0.003) were associated with greater sequels at the discharge and at the posterior reviews in the following months. 17% required mechanical ventilation (MV). Values < 250 L/min in the Peak Flow-test are associated with an increased likelihood of requiring MV (p < 0.001).ConclusionsOlder age, severe deficits at onset, injured cranial nerves, requiring MV, and axonal lesion patterns in the NCS were demonstrated as poor prognostic factors. Peak Flow-test is a useful predictive factor of respiratory failure by its easy management.

This study demonstrated an acceptable safety profile of deferiprone at 20mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20mg/kg/day may reduce disease progression, whereas higher doses appear to worsen ataxia.

No abstract

No abstract

MicroRNAs (miRNAs) are noncoding RNAs that contribute to gene expression modulation by regulating important cellular pathways. In this study, we used small RNA sequencing to identify a series of circulating miRNAs in blood samples taken from Friedreich's ataxia patients. We were thus able to develop a miRNA biomarker signature to differentiate Friedreich's ataxia (FRDA) patients from healthy people. Most research on FDRA has focused on understanding the role of frataxin in the mitochondria, and a whole molecular view of pathological pathways underlying FRDA therefore remains to be elucidated. We found seven differentially expressed miRNAs, and we propose that these miRNAs represent key mechanisms in the modulation of several signalling pathways that regulate the physiopathology of FRDA. If this is the case, miRNAs can be used to characterize phenotypic variation in FRDA and stratify patients' risk of cardiomyopathy. In this study, we identify miR-323-3p as a candidate marker for phenotypic differentiation in FRDA patients suffering from cardiomyopathy. We propose the use of dynamic miRNAs as biomarkers for phenotypic characterization and prognosis of FRDA.Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia in people of European descent, affecting around 2-5 people in every 100,000 (Orphanet reports). This rare, childhood-onset disease is characterized by a progressive loss of sensory neurons in the dorsal root ganglia (DRG) and posterior columns. This loss of neurons is followed by degeneration of corticospinal and spinocerebellar tracts of the spinal cord, culminating in gait and limb ataxia, loss of tendon reflexes and dysarthria 1, 2 . The cerebellar dentate nucleus is also affected 3 . Other non-neurological features of FRDA are scoliosis, diabetes and cardiac symptoms [4][5][6] . Hypertrophic cardiomyopathy, which is found in two thirds of FRDA patients at the time of diagnosis, is the primary cause of death in these patients 7,8 . FRDA is most often caused by a homozygous GAA repeat expansion mutation (typically between 600 and 1200 repeats) in the first intron of the frataxin gene (FXN), which is found on chromosome 9q21.11 and encodes the protein frataxin 2, 9 . The elevated number of GAA repeats and resulting blockage effects on the RNAPII transcription machinery ("sticky DNA", hairpin structures, parallel duplex structures, R-loops, etc.; reviewed in ref. 10) have been proposed as causes of decreased expression of the mitochondrial protein frataxin 11 . The frataxin

Our results seem to indicate some uncertain benefit on the neurological and heart functions of this triple therapy in FRDA.