This cross-sectional cohort study provides the first large-scale data on disease manifestation, progression, and modifying factors, with relevance for counseling of HSP families and planning of future cross-sectional and natural history studies. Later age of onset, specific complicating features, and the SPG11 genotype are strongly associated with more severe disease. Future interventional studies will require stratification for modifiers of disease progression identified in this study. Prospective longitudinal studies will verify progression rates calculated in this baseline analysis.

Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391-397, 2016.

No abstract

Cerebellar ataxia is associated with an implicit motor learning dysfunction, specifically, a miscalibration of internal models relating motor commands to state changes of the body. Explicit cognitive strategies could compensate for deficits in implicit calibration. Surprisingly, however, patients with cerebellar ataxia use insufficient strategies compared to healthy controls. We report a candidate physiological phenomenon of disrupted strategy use in cerebellar ataxia, reflected in an interaction of implicit and explicit learning effects on cortical beta oscillations. We recorded electroencephalography in patients with cerebellar ataxia (n=18), age-matched healthy controls (n=19), and young, healthy individuals (n=34) during a visuomotor rotation paradigm in which an aiming strategy was either explicitly instructed, or had to be discovered through learning. In young, healthy individuals, learning a strategy, but not implicit learning from sensory prediction error alone, decreased the post-movement beta rebound. Disrupted learning from sensory prediction error in patients, on the other hand, unmasked effects of explicit and implicit control that are normally balanced. Specifically, the post-movement beta rebound increased during strategy use when implicit learning was disrupted, i.e., in patients, but not controls. We conclude that a network disturbance due to cerebellar degeneration surfaces in imbalanced cortical beta oscillations normally involved in strategy learning.