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CADASIL: a review with proposed diagnostic criteria
1Service de Neurologie, Centre Hospitalier, Argenteuil, France.
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic brain disorder affecting small vessels. Diagnosis relies on clinical, imaging, genetic, or pathological data, with no current effective treatments.
Area of Science:
- Neurology
- Genetics
- Vascular Biology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic, autosomal dominant disorder affecting small brain vessels.
- It presents with a spectrum of neurological symptoms including migraine, stroke-like episodes, psychiatric issues, and dementia, typically starting in the forties.
Purpose of the Study:
- To provide a comprehensive overview of CADASIL, including its historical context, clinical manifestations, diagnostic approaches, and genetic basis.
- To review current understanding and propose diagnostic criteria for CADASIL.
Main Methods:
- Review of existing literature and patient data on CADASIL.
- Analysis of clinical features, neuroimaging (MRI), pathological findings (including skin biopsy), and genetic data (Notch 3 gene).
Main Results:
- Over 200 patients from 30 pedigrees worldwide have been described, exhibiting variable neurological presentations and lacking classical vascular risk factors.
- MRI reveals diffuse leukoencephalopathy with subcortical infarcts; pathological findings show specific small vessel alterations.
- The Notch 3 gene mutation on chromosome 19 is identified as the genetic cause, with skin biopsy showing diagnostic ultrastructural changes.
Conclusions:
- CADASIL is a distinct genetic small vessel disease of the brain with characteristic clinical and imaging features.
- Definitive diagnosis requires genetic or pathological confirmation, and diagnostic criteria are proposed.
- The pathogenesis remains under investigation, and no effective treatments are currently available.
Abstract:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered as a new disease predominantly affecting the small vessels of the brain with an autosomal dominant transmission linked to chromosome 19. This review includes an historical perspective showing how the disease was identified from the spectrum of vascular leukoencephalopathies. More than two hundred patients have now been described, belonging to at least 30 unrelated pedigrees in Europe, America and Asia. The clinical features include four major neurological presentations associated in variable degrees during the course of the disease: migraine with or without aura, strokes or stroke-like episodes, major psychiatric symptoms and dementia. The patients are free of the classical vascular risk factors. The disease has a progressive or stepwise course with age at onset in the forties and a mean duration of 13.6 +/- 10.7 years. Death occurs in the fifties in a characteristic condition associating a pseudo-bulbar syndrome and subcortical dementia. Cerebral magnetic resonance imaging (MRI) is highly contributive to the diagnosis, showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter. Pathological data show macroscopic lesions similar to Binswanger's disease but different lesions of the small vessels including thickening of the media, characteristic PAS+ granular material and narrowing of the lumen. Skin biopsy may be a valuable diagnostic tool, showing ultrastructural alterations of skin vessels similar to those of brain vessels. The disease is highly homogeneous on a genetic basis and the identification of the gene Notch 3 on chromosome 19 has opened new avenues for research and genetic counselling. The pathogenesis of the disease has still to be elucidated. A definite diagnosis relies on genetical or pathological data. Diagnostic criteria are proposed to recognize the disease on clinical and imaging parameters. So far, no treatment has been reported to be successful for CADASIL. Copyright Lippincott-Raven Publishers