This disorder does not affect the Notch3 gene, and these patients do not show characteristic features of CADASIL on pathologic examination. A recent study demonstrated that hereditary multi-infarct dementia in the Swedish family reported by Sourander and Walinder was unrelated to CADASIL. Small arteries and arterioles showed medial swelling with vacuolar degeneration of smooth-muscle cells. Multiple small infarctions were seen in the basal ganglia, thalamus, and cerebral white matter at autopsy. The progressive phase of this illness was characterized by dementia, bulbar palsy with immobility, and urinary incontinence. The episodes varied considerably in frequency and severity within a family. The affected patients presented with a wide variety of transient motor, sensory, and other symptoms of vascular origin. However, their mean age at the onset was 50 years (ranging from 39 to 57 years), and their mean age at death was 60 years (ranging from 56 to 65 years). 5 described familial vascular dementia in an English family with autosomal dominant inheritance. Post-mortem studies showed multiple small cystic infarctions, localized in the central gray matter, white matter, and pons, caused by an occlusion of small intracerebral and leptomeningeal arteries. The illnesses began in early adulthood (ranging from 29 to 38 years of age) and generally lasted for 10 to 15 years. 4 They presented with pyramidal, bulbar, and cerebellar symptoms, a relapsing course, and gradually evolving severe dementia.
3 In 1977, Sourander and Walinder reported a Swedish family with multi-infarct dementia of autosomal dominant inheritance. This review summarizes the historical background, epidemiology, genetics, pathophysiology, characteristic clinical findings, neuroimaging, and treatment of this unique disorder.ĬADASIL was possibly first reported in 1955, when Van Bogaert described two sisters with rapidly progressive subcortical encephalopathy of Binswanger's type. The increasing availability of diagnostic expertise and genetic testing has lead to a gradual increase in the number of reports about patients with CADASIL. Although the exact prevalence of this disorder is not known, CADASIL has been reported worldwide in many ethnic groups. 2 The main clinical manifestations are recurrent stroke, cognitive deficits, migraines, and psychiatric disturbances. Among them, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common single-gene disorder of the cerebral small blood vessels and is caused by mutations in the Notch3 gene. Although hypertension and diabetes mellitus are known to be important risk factors for SVDs, many hereditary or idiopathic SVDs have also been identified. 1 SVDs usually manifest with lacunar infarction, intracerebral hemorrhage (ICH), and subcortical vascular dementia. At present, the incidence and prevalence of CADASIL seem to be underestimated due to limitations in clinical, neuroradiological, and genetic diagnoses of this disorder.Ĭerebral small-vessel diseases (SVDs) are a major disease burden in most developed countries. CADASIL is a prototype single-gene disorder that has evolved as a unique model for studying the mechanisms underlying cerebral SVD. The pathologic hallmark of the disease is the presence of granular osmiophilic material in the walls of affected vessels. The involvement of the anterior temporal lobe and the external capsule on brain magnetic resonance imaging was found to have high sensitivity and specificity in differentiating CADASIL from the much more common sporadic cerebral small-vessel disease (SVD). The clinical course of CADASIL is highly variable, even within families. The main clinical manifestations are recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive impairment. The exact prevalence of this disorder was unknown currently, and the number of reported CADASIL families is steadily increasing as the clinical picture and diagnostic examinations are becoming more widely known. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of the cerebral small blood vessels caused by mutations in the Notch3 gene.
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