No abstract

BackgroundThe most common spinocerebellar ataxias (SCA)—SCA1, SCA2, SCA3, and SCA6—are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset.MethodsWe combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age.ResultsFor SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (−0.105±0.005 and −0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: −0.049±0.002 and −0.090±0.009, respectively; normal: +0.013±0.005 and −0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age.ConclusionsThese estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies.ClinicalTrials.gov, numberNCT01037777 and NCT00136630 for the French patients.

Management of Freidreich's ataxia is currently focussed on symptomatic management, delivered by the multidisciplinary team. Phase II clinical trials in agents that address the abberrant silencing of the frataxin gene need to be translated into large placebo-controlled Phase III trials to help establish their therapeutic potential.

BackgroundThe natural history of clinical symptoms in the spinocerebellar ataxias (SCA)s has been well characterised. However there is little longitudinal data comparing cognitive changes in the most common SCA subtypes over time. The present study provides a preliminary longitudinal characterisation of the clinical and cognitive profiles in patients with SCA1, SCA2, SCA3, SCA6 and SCA7, with the aim of elucidating the role of the cerebellum in cognition.Methods13 patients with different SCAs all caused by CAG repeat expansion (SCA1, n = 2; SCA2, n = 2; SCA3, n = 2; SCA6, n = 4; and SCA7, n = 3) completed a comprehensive battery of cognitive and mood assessments at two time points, a mean of 7.35 years apart. All patients were evaluated clinically using the Scale for the Rating and Assessment of Ataxia (SARA) and the Inventory of Non-Ataxia Signs (INAS). Patients underwent structural MRI imaging at follow-up.ResultsClinical scale scores increased in all patients over time, most prominently in the SCA1 (SARA) and SCA3 (INAS) groups. New impairments on neuropsychological tests were most commonly observed with executive functions, speed, attention, visual memory and Theory of Mind. Results suggest possible differences in cognitive decline in SCA subtypes, with the most rapid cognitive decline observed in the SCA1 patients, and the least in the SCA6 patients, congruent with observed patterns of motor deterioration. Minimal changes in mood were observed, and MRI measures of atrophy did not correlate with cognitive decline.ConclusionAs well as increasing physical impairment, cognitive decline over time appears to be a distinct aspect of the SCA phenotype, in keeping with the cerebellar cognitive-affective syndrome. Our data suggest a trend of cognitive decline that is different for each SCA subtype, and for the majority is related to the severity of cerebellar motor impairment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0447-6) contains supplementary material, which is available to authorized users.

Patterns of infant feeding, basal prolactin concentrations, and ovarian activity were studied longitudinally in 27 breast-feeding mothers from delivery until first ovulation.Suckling frequency (61 feeds/day) and suckling duration (122 mins/day) reached peak values four weeks post partum and remained relatively constant until the introduction of supplementary food at a mean of 16 weeks post partum. There were subsequently sharp declines in both the frequency and duration of suckling, both of which correlated closely with basal prolactin concentrations. None of the 27 mothers ovulated during unsupplemented breast-feeding, but within 16 weeks of introducing supplements ovarian follicular development had returned in 20 and ovulation in 14 mothers. The mothers who ovulated within 16 weeks of giving supplements had reduced frequency and duration of suckling more quickly and weaned more abruptly than those who continued to suppress ovulation.These data suggest that the introduction of supplementary food may exert an important and hitherto unrecognised effect on the timing of first ovulation by reducing the frequency and duration of suckling episodes.