Substantia nigra degeneration in spinocerebellar ataxia 2 and 7 using neuromelanin-sensitive imaging.

Objective: Spinocerebellar ataxias (SCA) are neurodegenerative diseases with widespread lesions across the central nervous system. Ataxia and spasticity are usually predominant, but patients may also present with parkinsonism. We aimed to characterize substantia nigra pars compacta (SNc) degeneration in SCA2 and 7 using neuromelanin-sensitive imaging.

Methods: Ataxic and preataxic expansion carriers with SCA2 (n=15) and SCA7 (n=15) and healthy controls (n=10) were prospectively recruited. Volume and signal-to-noise ratio (SNR) values of the SNc were extracted from neuromelanin-sensitive images. ROC curves were used to determine the metrics that best differentiated SCA participants. Correlations between imaging measurements, clinical variables, and plasma neurofilaments light chain (NfL) levels were investigated.

Results: SCA2 participants had lower SNR values in the SNc than controls (110.2 ± 1.3 versus 113.2 ± 1.4; p < 0.001) and those with SCA7 (112.5 ± 2.1; p < 0.01). SNR in SCA7 participants and controls did not differ. In ataxic patients, SNc volumes were lower in SCA2 (0.13 ± 0.04; p = 0.06) and SCA7 (0.10 ± 0.03, p = 0.02) patients compared to controls (0.17 ± 0.04). Signal decrease was detected at the preataxic stage in SCA2, but not in SCA7. SCA2 participants showed prominent involvement of the associative and limbic nigral territories. SNR discriminated ataxic and preataxic SCA2 participants from controls (AUC ≥0.94). SNc volume differentiated ataxic SCA7 participants from controls (AUC = 1), but not preataxic ones. In SCA7, correlations were observed between SNc volume and time to onset, CAG repeats, clinical severity scores, and NfL.

Conclusions: Neuromelanin-sensitive imaging provides biomarkers of nigral degeneration in SCAs, detectable from the preataxic stage in SCA2, which could potentially serve as outcome measures in clinical trials.