Myotonic dystrophy (DM1) and proximal myotonic myopathy (PROMM or DM2) are two distinct muscular disorders with multisystemic involvement. Both have previously been reported to be associated with cognitive impairment and white matter lesions detected by cerebral magnetic resonance imaging (MRI). In this study, the extent of brain atrophy was investigated in vivo in ten DM1 and nine PROMM patients in comparison to age-matched healthy controls for each group. The diagnosis was confirmed by DNA analysis of all patients. As a quantitative marker, the ratio of brain parenchymal to intracranial volume, called brain parenchymal fraction (BPF), was calculated from 3-dimensional MRI data using an automated analysis technique. Compared to age-matched healthy controls (mean BPF 0.852 +/- 0.032), the BPF in DM1 patients (0.713 +/- 0.031) was highly significantly decreased (P < 0.001). In contrast, the PROMM patients (mean BPF 0.792 +/- 0.029) showed only slightly decreased BPF values (P < 0.05). BPF was not significantly correlated to any of the clinical or genetic parameters in both diseases (disease duration, motor score, educational level, and number of CTG repeats in the expanded allele). In summary, global brain atrophy was demonstrated to occur in both diseases, but was more severely manifestated in DM1 patients.