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[CADASIL. Clinical aspects, neuroradiology, genetics and diagnosis]
J K Mellies1, P Calabrese, H Roth
1Westfälisches Zentrum für Psychiatrie und Psychotherapie Bochum, Ruhr-Universität Bochum. joerg.k.mellies@ruhr-uni-bochum.de
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic brain disorder causing stroke and dementia. Current treatments focus on symptom management as no cure exists.
Area of Science:
- Neuroscience
- Genetics
- Vascular Biology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vasculopathy.
- It leads to subcortical dementia, lacunar infarcts, and white matter degeneration.
- Associated symptoms include migraine with aura, seizures, and affective disorders.
Purpose of the Study:
- To describe the clinical and genetic characteristics of CADASIL.
- To highlight the progressive nature and varied expression of the disease.
- To underscore the current lack of causative therapy.
Main Methods:
- Review of clinical and genetic findings in CADASIL patients.
- Analysis of neuroimaging (MRI, SPECT) findings.
- Genetic linkage studies identifying Notch3 gene mutations.
Main Results:
- CADASIL is caused by mutations in the Notch3 gene on chromosome 19p13.1.
- Complete penetrance is observed, with variable symptom onset typically in the 3rd decade.
- Early MRI reveals significant leukoencephalopathy, and SPECT shows hypoperfusion in affected individuals.
Conclusions:
- CADASIL is a significant genetic cause of stroke and dementia with a characteristic neuroimaging profile.
- The disease necessitates further research into potential therapeutic strategies.
- Understanding the genetic basis and clinical spectrum is crucial for patient management.
Abstract:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral vasculopathy progressing to subcortical dementia, caused by multiple lacunar infarcts and ischemic white matter degeneration. Migraine with aura, epileptic seizures and affective disorders are frequent additional symptoms of CADASIL. The causative mutations of the Notch3 gene are located on chromosome 19p13.1. There is complete penetrance of this disorder, although individual expression of symptoms may vary. Manifestation of CADASIL is usually in the 3rd decade, but some individuals remain asymptomatic close to the age of 60. MRI displays a marked leukoencephalopathy in affected individuals as early as in the age of 20. Frontal and subcortical hypoperfusion in demented individuals was demonstrated by SPECT-studies. The prevalence of CADASIL is still not known. To date there is no causative therapy.