This study examined alterations in gray matter (GM) and white matter (WM) in patients with cerebellar ataxias (CA) due to different causes.

CA include neurodegenerative disorders affecting motor coordination. Investigating structural brain alterations in GM and WM is essential for personalized treatment.

Twenty-eight autosomal dominant (AD) CA patients (genetic spinocerebellar ataxia and patients with an AD transmission pattern), 17 autosomal recessive (AR) CA patients (Friedreich's ataxia, CANVAS, ANO10 mutation, Oculomotor Apraxia Type 2, ARSACS, and patients with an AR without a known mutation), 29 sporadic cases of CA (16 idiopathic late-onset CA), 8 multiple system atrophy patients (MSAc) and 20 controls were included. MRI and clinical assessment were conducted. GM atrophy of whole-brain and cerebellum was estimeted. Brainstem volumes were compared between groups using Freesurfer.

CA groups showed widespread GM cerebellar atrophy compared to controls. AD and AR groups showed significant supratentorial GM atrophy compared to controls in: (i) bilateral medial temporal gyri, insula, calcarine cortex, and right orbitofrontal cortex in AR; and (ii) right inferior orbitofrontal cortex, postcentral, and superior temporal lobe gyri, left superior temporal gyrus, and cingulate cortex in AD. Moreover, MSAc showed more involvement in the medial Crus-I and II compared to AD. Concerning brainstem analysis, AD, AR, and MSAc groups exhibited reduced whole-brainstem, pons, and medulla volumes compared to controls. Moreover, AD and MSAc groups demonstrated reduced whole-brainstem and pons volumes compared to sporadic cases. AD and AR groups displayed reduced midbrain volume compared to controls, and only AD exhibited a reduction compared to sporadic cases.

Our study provides evidence of distinct structural alterations involving both GM and WM in CA patients of different etiologies, contributing to a better understanding of the underlying degenerative processes and having implications for diagnostics and future therapeutic approaches tailored to the specific CA causes.