[Pathomechanisms and treatment of CADASIL]

The pathomechanisms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are still under debate. Granular osmiophilic material (GOM), which accumulates around the basement membrane, and the extracellular domain of NOTCH3 (NECD) in the vessel are key molecules that contributes to the destruction of smooth muscle cells in CADASIL. In addition, GOM and NECD may be related to the dysfunction of cerebral small vessels in patients with CADASIL. In this review, the role of the accumulation of these abnormal proteins in the cerebral small vessels, and the pathomechanism from white matter lesions, microbleeds, and lacunar infarctions to vascular dementia are discussed. We diagnosed 63 CADASIL cases and identified 3 features that were common to Japanese cases. First, the ages of onset of clinical symptoms other than migraine were widely distributed; the age of onset of symptoms was greater than 60 years in more than 20% of the cases. Second, 65% of the Japanese CADASIL cases had stroke risk factors, such as hypertension, hyperlipidemia, or smoking. Third, in 20% of the cases, there was no family history of stroke. Therefore, new diagnostic criteria for Japanese patients with CADASIL were proposed on the basis of these clinical features in order to avoid missing cases of CADASIL. The criteria are useful for screening candidates of CADASIL, even in cases with elderly onset, stroke risk factors, and obscure family history.