AIMS: Familial hemiplegic migraine type 1 (FHM1) due to mutations in the CACNA1A gene is known as functional vascular disorder with cerebellar atrophy. We describe a case of a FHM1 family in which pathological changes occurred in both brain neuroimaging and skin and muscle biopsy. MATERIALS AND METHODS: In 5 of 18 affected family members, brain MRI scans revealed hyperintense changes in the cerebral white matter. In 2 of these 5 patients, skin and muscle biopsies were performed at the interictal period of the disease and examined under light and transmission electron microscopy. RESULTS: Ultrastructural examination of the biopsy samples revealed abnormal appearance of microvessels resembling oncosis. In the affected vessels, endothelial cells and myocytes/pericytes showed clear cytoplasm, distended endoplasmic reticulum, enlarged mitochondria, and numerous intracytoplasmic vesicular structures. Swollen endothelial cells often significantly narrowed vessel lumen. CONCLUSION: The morphological changes described for the first time in FHM1 suggest that the disease may not only be a functional, but also a structural vascular disorder. We suggest that the presence of these vascular abnormalities can interfere with microcirculation causing damage to the cerebral white matter, visible in MRI scans as hyperintense changes. .
AIMS: Familial hemiplegic migraine type 1 (FHM1) due to mutations in the CACNA1A gene is known as functional vascular disorder with cerebellar atrophy. We describe a case of a FHM1 family in which pathological changes occurred in both brain neuroimaging and skin and muscle biopsy. MATERIALS AND METHODS: In 5 of 18 affected family members, brain MRI scans revealed hyperintense changes in the cerebral white matter. In 2 of these 5 patients, skin and muscle biopsies were performed at the interictal period of the disease and examined under light and transmission electron microscopy. RESULTS: Ultrastructural examination of the biopsy samples revealed abnormal appearance of microvessels resembling oncosis. In the affected vessels, endothelial cells and myocytes/pericytes showed clear cytoplasm, distended endoplasmic reticulum, enlarged mitochondria, and numerous intracytoplasmic vesicular structures. Swollen endothelial cells often significantly narrowed vessel lumen. CONCLUSION: The morphological changes described for the first time in FHM1 suggest that the disease may not only be a functional, but also a structural vascular disorder. We suggest that the presence of these vascular abnormalities can interfere with microcirculation causing damage to the cerebral white matter, visible in MRI scans as hyperintense changes. .