J Clin Neurol.  2021 Apr;17(2):187-199. 10.3988/jcn.2021.17.2.187.

Clinical, Imaging, and Laboratory Markers of Premanifest Spinocerebellar Ataxia 1, 2, 3, and 6: A Systematic Review

  • 1Seoul National University College of Medicine, Seoul, Korea
  • 2Department of Neurology, Seoul National UniversitySeoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
  • 3Department of Neurology, Inha University Hospital, Incheon, Korea
  • 4Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea


and Purpose Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of SCA1, -2, -3, and -6, and their associations with ataxia onset.
We included studies of the premanifest carriers of SCA published between January 1998 and December 2019 identified in Scopus and PubMed by searching for terms including ‘spinocerebellar ataxia’ and several synonyms of ‘preataxic manifestation’. We systematically reviewed the results obtained in studies categorized based on clinical, imaging, and laboratory markers.
We finally performed a qualitative analysis of 48 papers. Common preataxic manifestations appearing in multiple SCA subtypes were muscle cramps, abnormal muscle reflexes, instability in gait and posture, lower Composite Cerebellar Functional Severity scores, abnormalities in video-oculography and transcranial magnetic stimulation, and gray-matter loss and volume reduction in the brainstem and cerebellar structures. Also, decreased sensory amplitudes in nerve conduction studies were observed in SCA2. Eotaxin and neurofilament lightchain levels were revealed as sensitive blood biomarkers in SCA3. Concerning potential predictive markers, hyporeflexia and abnormalities of somatosensory evoked potentials showed correlations with the time to ataxia onset in SCA2 carriers. However, no longitudinal data were found for the other SCA gene carriers.
Our results suggest that preataxic manifestations vary among SCA1, -2, -3, and -6, with some subtypes sharing specific features. Combining various markers into a standardized index for premanifest carriers may be useful for early screening and assessing the risk of disease progression in SCA carriers.


spinocerebellar ataxia; premanifest; presymptomatic; marker; systematic review
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