Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study.

BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

Modulation of inhibitory systems to enhance motor rehabilitation: insights for the use of noninvasive brain stimulation

Motor impairment following stroke is a leading cause of disability in adults. Despite advances in motor rehabilitation techniques, many adult stroke survivors never approach full functional recovery. Intriguingly, children exhibit better rehabilitation outcomes when compared to adults suffering from comparable brain injuries, yet the reasons for this remain unclear. A common explanation is that neuroplasticity in adults is substantially limited following stroke, thus constraining the brain's ability to reorganize in response to neurological insult. This explanation, however, does not suffice for there is much evidence suggesting that neuroplasticity in adults is not limited following stroke. We hypothesize that diminished functional recovery in adults is in part due to inhibitory neuronal interactions, such as transcallosal inhibition, that serve to optimize motor performance as the brain matures. Following stroke, these inhibitory interactions pose rigid barriers to recovery by inhibiting activity in the affected regions and hindering recruitment of compensatory pathways. In contrast, children exhibit better rehabilitation outcomes in part because they have not fully developed the inhibitory interactions that impede functional recovery in adults. We suggest that noninvasive brain stimulation can be used in the context of motor rehabilitation following stroke to reduce the effects of existing inhibitory connections, effectively returning the brain to a state that is more amenable to rehabilitation. We conclude by discussing further research to explore this hypothesis and its implications