Study protocol for LOMCAD Trial: Effect of lomerizine hydrochloride to prevent recurrence of cerebral ischemic events in CADASIL patients.

Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride.

Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL.

Methods: We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke.

Effect of Lomerizine Hydrochloride on Preventing Strokes in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow.

A Nationwide Survey and Multicenter Registry-Based Database of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy in Japan.

Objectives: Clinical characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) include migraine, recurrent stroke, white matter lesions, and vascular dementia. CADASIL is one of the most common hereditary cerebral small vessel diseases. Clinical presentation of CADASIL varies and a racial gap may exist between the Asian and Caucasian populations.

Clinical and Genetic Aspects of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in , is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. MRI imaging shows cerebral white matter (WM) hyperintensity, particularly in the external capsule and temporal pole. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL.

Genotype-phenotype correlations and effect of mutation location in Japanese CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by NOTCH3, and characterized by recurrent cerebral ischemic events without vascular risk factors, mood disturbance, and dementia. MRI testing shows cerebral white matter hyperintensities, especially in the external capsule and temporal pole. Typical mutations are cysteine-related missense ones located in one of 34 EGF-like repeats (EGFr) in the NOTCH3 receptor.

The CADASIL Scale-J, A Modified Scale to Prioritize Access to Genetic Testing for Japanese CADASIL-Suspected Patients.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is definitely diagnosed by genetic testing. Such testing involves the analysis of exons 2-24 of NOTCH3, which encode the epidermal growth factor-like repeat domain, where CADASIL mutations are localized. We previously reported clinical diagnostic criteria for screening CADASIL-suspected Japanese patients prior to genetic testing.

RNF213-related susceptibility of Japanese CADASIL patients to intracranial arterial stenosis.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by NOTCH3, primarily affects small cerebral arteries; however, stenosis of major intracranial arteries has occasionally been reported. Recent studies identified a close association between the c.14576G>A (p.

New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan.

Purpose: Definite diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy (CADASIL) is mostly done by identification of NOTCH3 mutations. We aimed to develop criteria for selecting patients suspected for CADASIL to undergo genetic testing.

Subjects And Methods: All subjects were Japanese.

Simultaneous impairment of intracranial and peripheral artery vasoreactivity in CADASIL patients.

Background: Reduced cerebrovascular reactivity (CVR) is an important step in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The present study utilized quantitative single photon emission computed tomography (SPECT) with the autoradiographic (ARG) method and reactive hyperemia peripheral arterial tonometry (RH-PAT) to assess vasoreactivity in intracranial arteries and in peripheral arteries in patients with CADASIL.

Methods: Quantitative SPECT studies were conducted in eight patients with CADASIL, while RH-PAT analysis was conducted in eight CADASIL patients and in eight age-matched normal subjects.

Transendocytosis is impaired in CADASIL-mutant NOTCH3.

Mutations in the human NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), but the pathogenesis of CADASIL has remained unclear. Recently, endocytosis of the Notch ectodermal domain into ligand-expressing cells, called transendocytosis, has come to be considered critical for Notch activation. We hypothesized that the mutant NOTCH3 protein, particularly the ectodermal domain of NOTCH3 (N3ECD), may be refractory to degradation on the cell surface due to impaired transendocytosis.