title: Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL.
abstract: A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.
authors.affiliation: Institute of Neuropathology, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. hagel@uke.uni-hamburg.de
authors.forename: C
authors.initials: C
authors.lastname: Hagel
authors.forename: C
authors.initials: C
authors.lastname: Groden
authors.forename: R
authors.initials: R
authors.lastname: Niemeyer
authors.forename: D
authors.initials: D
authors.lastname: Stavrou
authors.forename: H J
authors.initials: HJ
authors.lastname: Colmant
mesh_terms: D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D002648:Child; D015161:Dementia, Multi-Infarct / Q000473:pathology*; D015140:Dementia, Vascular / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D014057:Tomography, X-Ray Computed
chemical_list: D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface