Ultrastructural changes in microvessels in familial hemiplegic migraine with CACNA1A mutation

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.

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.

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.

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.
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