Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
Also known as: CADASIL, Hereditary multi-infarct dementia, NOTCH3-related CADASIL
CADASIL is a hereditary stroke disorder caused by mutations in the NOTCH3 gene. It leads to thickening of blood vessel walls, reducing blood flow to the brain and causing a variety of neurological symptoms, including migraine with aura, recurrent stroke, cognitive decline, and psychiatric disturbances. The condition typically manifests in adulthood and progresses over time.
CADASIL is like having tiny problems in the pipes that bring blood to your brain. These problems can cause headaches, make it hard to think clearly, and sometimes cause strokes. It's something you can get from your parents, and doctors can help manage the symptoms.
Signs & Symptoms
- Migraine with aura
- Recurrent stroke or transient ischemic attacks (TIAs)
- Cognitive decline leading to dementia
- Psychiatric disturbances (depression, apathy, psychosis)
- Seizures
- White matter lesions on brain MRI
- Muscle weakness
- Dysarthria (difficulty speaking)
- Dysphagia (difficulty swallowing)
Treatment Options
Symptomatic treatment for migraine
MODERATELY EFFECTIVEAntiplatelet agents (e.g., aspirin, clopidogrel)
MODERATELY EFFECTIVEAntihypertensive medications
MODERATELY EFFECTIVEPhysical therapy
SUPPORTIVEOccupational therapy
SUPPORTIVESpeech therapy
SUPPORTIVEPsychiatric support and medications for mood disorders
MODERATELY EFFECTIVEDiagnosis
- Clinical evaluation
- Brain MRI (magnetic resonance imaging) showing characteristic white matter lesions
- Genetic testing for NOTCH3 mutations
- Skin biopsy with granular osmiophilic material (GOM) deposition in blood vessels
History
CADASIL was first described in 1977 by Marie-Germaine Bousser and colleagues in a French family. The genetic basis of the disease, mutations in the NOTCH3 gene, was identified in 1996 by Elisabeth Tournier-Lasserve's group.
Recent Breakthroughs
Novel therapeutic targets identified in CADASIL pathogenesis
Research has identified potential therapeutic targets by elucidating the role of specific inflammatory pathways and vascular remodeling processes in CADASIL. These findings may lead to the development of targeted therapies to slow disease progression.
Improved MRI techniques for early CADASIL diagnosis
Advanced MRI techniques, such as diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM), are being used to detect subtle changes in brain microstructure in early stages of CADASIL, potentially improving diagnostic accuracy and enabling earlier intervention.