Diagnostic approach to childhood-onset cerebellar atrophy: a 10-year retrospective study of 300 patients

Abstract

Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by neuronal ceroid lipofuscinosis, ataxia telangiectasia, and late-onset GM2 gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses.

Figure 1

Clinical characteristics of patients with cerebellar atrophy in our cohort. Abbreviations: MRI, magnetic resonance imaging.

Figure 2

Neuroradiological patterns associated with cerbellar atrophy. Mild vermian atrophy is present on T1W sagittal image (a) in an 8 year old with MELAS. Note increased visualization of the interfoliate sulci of both anterior and posterior lobes. Severe vermian atrophy is seen (b) in an 11 year old with AOA2. There is widening of the interfoliate sulci, loss of vermian height and a large infravermian cistern. Mild hemispheric atrophy is present on FLAIR in a 14 year old with juvenile onset GM2 (c). The cortex is normal in signal (arrow). FLAIR axial (d) in a 6 year old with NCL demonstrates markedly increased signal intensity (arrow).

Figure 3

Supratentorial clues to a diagnosis in cerebellar atrophy cases may be present. Heterogeneous signal (arrow) is present in GM2 (a). Secondary demyelination of the posterior limb of the internal capsules (arrow) is seen on T2W axial (b) in NCL. There is also supratentorial atrophy. Severe hypomyelination is present on axial T2W image (c) in an 8 year old with H-ABC. Severe atrophy of the caudate (arrow) and putamina is present. Occipital stroke-like lesion (arrow) with cortical swelling is present on T2W image in another 8 year old with MELAS (d).

Figure 4

Approach to investigation of childhood-onset cerebellar atrophy. Abbreviations: AFP, alpha-fetoprotein; AOA1/2, ataxia with oculomotor apraxia type 1 or type 2; ARSACS, autosomal recessive spastic ataxia of Charlevoix-Saguenay; ATLD, ataxia telangiectasia-like disorder; CA, cerebellar atrophy; CBC, complete blood count; CDG, congenital disorders of glycosylation; CK, creatine kinase; CSF, cerebrospinal fluid; DD/MR, developmental delay/mental retardation; DRPLA, dentatorubral pallidoluysian atrophy; ECG, electrocardiography; EMG, electromyography; EVP, evoked potentials; HABC, hypomyelination with atrophy of the basal ganglia and cerebellum; INAD, infantile neuronal axonal dystrophy; LAHH, leukoencephalopathy with ataxia, hypodontia, and hypomyelination; LFT, liver function tests; MRI, magnetic resonance imaging; NCL, neuronal ceroid lipofuscinoses; NCV, nerve conduction velocity studies; NPC, Niemann-Pick disease type C; PEHO, progressive encephalopathy with edema, hypsarrythmia, and optic atrophy; PMD, Pelizaeus-Merzbacher disease; SCAN1, spinocerebellar ataxia, autosomal recessive with axonal neuropathy.