MRI-based Annual Cerebellar Volume Atrophy Rate as a Biomarker of Disease Progression in Patients with Cerebellar Degeneration

Abstract

Background: The rate of disease progression differs among patients with degenerative cerebellar ataxia. Purpose: We determined the annual cerebellar volume atrophy rate with magnetic resonance imaging (MRI) and disease progression in ataxia with the International Cooperative Ataxia Rating Scale (ICARS) according to the subtype of cerebellar degeneration using longitudinal follow-up data. Methods: We examined 50 patients consisting of 22 cases of spinocerebellar ataxia (SCA), 17 cases of multiple system atrophy (MSA), and 11 cases of cortical cerebellar ataxia (CCA). In all patients, at least two sets of evaluations including MRI and ICARS scoring were performed. A total of 146 sets of evaluations was obtained with the longest follow-up period being 77 months. The cerebellar volume of all patients (ml) was divided by each cranial AP diameter (mm) to correct for the individual head size differences as a volume index (Vdx). The annual atrophy volume in Vdx and the annual progression in the ICARS were calculated in each patients. Results: The annual atrophy rates for each subtype were: SCA: 0.027 ± 0.020 ml/mm, MSA: 0.039 ± 0.026 ml/mm, and CCA: 0.019 ± 0.016 ml/mm. There was a significant difference among subtypes (p = 0.049). The ICARS scores (annual progression) were 4.79 ± 3.86, 8.82 ± 3.93, and 2.31 ± 1.96 for SCA, MSA, and CCA, respectively (p = 0.002).The progression in ICARS per decrease in Vdx of 0.01 ml/mm in MSA, SCA and CCA was measured as 5.9 points,1.8 points and 1.4 points, respectively. Conclusions: The annual atrophy rate and ICARS score (annual progression) were significantly different among subtypes of cerebellar degeneration. MRI-based cerebellar volume measurements can be used as an imaging biomarker for disease progression.

Stratification of disease progression in a broad spectrum of degenerative cerebellar ataxias with a clustering method using MRI-based atrophy rates of brain structures

“…We demonstrated that the cerebellar volume obtained from MRI correlates well with the International Cooperative Ataxia Rating Scale (ICARS) score in a broad spectrum of degenerative cerebellar ataxias [22]. We also confirmed that the annual atrophy rate of the cerebellar volume and the annual progression of the ICARS score were significantly different among subtypes of cerebellar degeneration [23]. However, categorizing individual symptom progression only by the atrophy rate of the cerebellum is not feasible.…”

“…However, MRI-based cerebellar volume measurements have never been established as a stratification tool to categorize disease progression. Recently, we demonstrated that the annual atrophy rate of the cerebellar volume and the annual progression of the ICARS score are significantly different among subtypes of cerebellar degeneration, but categorizing individual symptom progression only with the atrophy rate of the cerebellum is not feasible [ 22 , 23 ]. Our current study demonstrated that cluster analysis based on the annual atrophy rates of the corpus callosum and cerebellum successfully categorized the difference in disease progression in a broad spectrum of degenerative cerebellar ataxias.…”

“…1a ), and we measured the total area (mm 2 ). Cerebellar volume was measured as described elsewhere [ 22 , 23 ]. Briefly, the cerebellum was defined as the area lateral to the line connecting the anterior lobe of the cerebellum and cerebellar flocculus.…”