title: Principal component analysis of cerebellar shape on MRI separates SCA types 2 and 6 into two archetypal modes of degeneration.
abstract: Although "cerebellar ataxia" is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes.
authors.affiliation: Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD, 21287, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jung
authors.forename: Soo I
authors.initials: SI
authors.lastname: Choi
authors.forename: Annie X
authors.initials: AX
authors.lastname: Du
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cuzzocreo
authors.forename: Zhuo Z
authors.initials: ZZ
authors.lastname: Geng
authors.forename: Howard S
authors.initials: HS
authors.lastname: Ying
authors.forename: Susan L
authors.initials: SL
authors.lastname: Perlman
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Prince
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Ying
mesh_terms: D000328:Adult; D017668:Age of Onset; D001284:Atrophy / Q000473:pathology; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D020754:Spinocerebellar Ataxias / Q000473:pathology* / Q000503:physiopathology