🧠 Neurological Disorder

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Also known as: CADASIL syndrome, Hereditary multi-infarct dementia, NOTCH3-related CADASIL

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary stroke disorder caused by mutations in the NOTCH3 gene. This condition primarily affects small blood vessels in the brain, leading to recurrent strokes, cognitive decline, migraine with aura, and psychiatric disturbances. The progressive accumulation of these infarcts and white matter lesions results in significant neurological impairment.

ICD-10: I67.85 Orphanet: 154 OMIM: 125310
👥 Estimated 1-9 / 100,000 Prevalence
🔬 15 Active Trials

Imagine tiny blood vessels in your brain getting sick. CADASIL is like that. It's passed down in families and makes it hard for your brain to get enough blood. This can cause headaches, trouble thinking, and sometimes even make it hard to move or talk.

Signs & Symptoms

  • Migraine with aura
  • Recurrent ischemic strokes or transient ischemic attacks (TIAs)
  • Cognitive decline leading to dementia
  • Psychiatric disturbances (depression, apathy, psychosis)
  • Seizures
  • Subcortical infarcts and leukoencephalopathy (white matter lesions)
  • Muscle weakness
  • Dysarthria (difficulty speaking)
  • Pseudobulbar palsy

Treatment Options

MEDICATION FDA Approved

Symptomatic treatment for migraine

MODERATELY EFFECTIVE
MEDICATION FDA Approved

Antiplatelet agents (e.g., aspirin, clopidogrel)

MODERATELY EFFECTIVE
MEDICATION FDA Approved

Antihypertensive medications

MODERATELY EFFECTIVE
THERAPY

Physical therapy

SUPPORTIVE
THERAPY

Occupational therapy

SUPPORTIVE
THERAPY

Speech therapy

SUPPORTIVE
MEDICATION FDA Approved

Psychiatric support and medications for mood disorders

MODERATELY EFFECTIVE
SUPPORTIVE

Management of vascular risk factors (e.g., smoking cessation, diabetes control)

SUPPORTIVE

Diagnosis

  • Neurological examination
  • Brain MRI (magnetic resonance imaging) showing characteristic white matter lesions and subcortical infarcts
  • Genetic testing for NOTCH3 mutations
  • Skin biopsy with granular osmiophilic material (GOM) deposits around small blood vessels (less commonly used now due to genetic testing availability)

History

CADASIL was first described in the late 20th century. The NOTCH3 gene was identified as the causative gene in 1996, marking a significant breakthrough in understanding the disease's pathogenesis.

Recent Breakthroughs

2022

Advancements in MRI techniques for early CADASIL diagnosis

Improved MRI protocols, including diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM), are enhancing the ability to detect subtle changes in brain microstructure, allowing for earlier diagnosis and monitoring of disease progression.

2023

Potential therapeutic targets identified through NOTCH3 signaling pathway research

Research into the NOTCH3 signaling pathway has identified potential therapeutic targets for modulating the disease process. Studies are exploring the use of gamma-secretase inhibitors and other agents to reduce NOTCH3 accumulation and improve vascular function.