Small vessel abnormalities in alternating hemiplegia of childhood: pathophysiologic implications.

BACKGROUND

The pathophysiology of alternating hemiplegia of childhood (AHC) is unclear. The authors evaluated the skin and muscle biopsies from patients with AHC for vascular abnormalities.

METHODS

Skin biopsy specimens from four patients ages 18 months, 8 years, 9 years, and 18 years and muscle biopsies from two of these patients were examined by electron microscopy and compared with healthy controls.

RESULTS

Vascular abnormalities were found in both skin and muscle. Skin biopsies showed similar abnormalities in all four patients. Vacuoles were visible in the endothelium. The most striking abnormality was the presence in the tunica media of small and unevenly shaped vascular smooth muscle cells (VSMCs) containing intracytoplasmic vacuoles and, occasionally, apoptotic nuclei, with variations according to patient age. Moreover, most VSMCs had lost junctions with neighboring cells, and some were completely isolated. In vessels from muscle biopsies, the VSMCs showed vacuoles, residual osmiophilic deposits, and myofilament loss with substitution by vacuoles.

CONCLUSIONS

The vascular abnormalities in our patients suggest a primary or secondary vascular pathophysiology to alternating hemiplegia of childhood. The vascular smooth muscle cells may be the initial target of the disease process.