Relationship between type 1 metabotropic glutamate receptors and cerebellar ataxia

Imaging of type 1 metabotropic glutamate receptor (mGluR1) has recently become possible using positron emission tomography (PET). We aimed to examine the relationship between mGluR1 and cerebellar ataxia. Families with spinocerebellar ataxia type 19/22 (SCA19/22) and SCA6, six patients with sporadic SCA, and 26 healthy subjects underwent PET using an mGluR1 radiotracer. Volumes-of-interest were placed on the anterior and posterior lobes and vermis. The binding potential (BP_ND) was calculated to estimate mGluR1 availability. A partial volume correction was applied to the BP_ND values. The Scale for the Assessment and Rating of Ataxia (SARA) score were measured. In each patient with SCA19/22 and SCA6, the anterior lobe showed the highest decrease rates in the BP_ND values, compared with healthy subjects. In the families with SCA19/22 and SCA6, the disease durations and SARA scores were shorter and lower, respectively, in the offspring, compared with the parents. However, the offspring paradoxically showed lower BP_ND values, especially in the anterior lobe, compared with the parents. The patients with sporadic SCA showed significantly lower BP_ND values in all subregions than healthy subjects. The BP_ND values significantly correlated with the SARA scores in all participants. In conclusion, these results showed a decrease in mGluR1 availability in patients with hereditary and sporadic SCA, a correlation between mGluR1 availability and degree of cerebellar ataxia, and paradoxical findings in two families. These results suggest the potential use of mGluR1 imaging as a specific biomarker of cerebellar ataxia.