CADASIL — Frequently asked questions

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. It is a hereditary disease of the small blood vessels of the brain caused by mutations in the NOTCH3 gene. Read the full overview →

CADASIL is caused by certain changes in the NOTCH3 gene, which plays an important role in the cells surrounding small blood vessels. These genetic changes can affect the health and function of small arteries, particularly in the brain. More about the biology →

Yes — CADASIL is inherited in an autosomal dominant pattern. Each child of a parent with CADASIL has a 50% chance of inheriting the pathogenic NOTCH3 variant. Both males and females are affected equally. Rare de novo variants have been described.

Reported clinical prevalence is roughly 2–5 per 100,000 adults, but population genomic data suggest pathogenic NOTCH3 variants are more common — possibly approaching 1 in 300 to 1 in 400 people. The gap matters: most people who carry a variant but haven't come to clinical attention have very few symptoms, or none at all. Severe cases exist and are real, but they are a smaller share of the whole than online forums might suggest.

No. CADASIL has highly variable expression. Some people develop significant neurological symptoms relatively early, while others experience mild symptoms or remain largely unaffected until much later in life. Even people within the same family who carry the same disease-causing NOTCH3 variant can have very different experiences. A genetic diagnosis does not provide a precise prediction of an individual's future course.

The core symptoms are migraine with aura (often beginning in the 20s–30s), recurrent ischemic strokes and TIAs (typically in the 40s–60s), mood disturbance and apathy, and progressive subcortical vascular cognitive impairment. Gait disturbance is common in advanced disease. Full symptoms guide →

Migraine in CADASIL is often migraine with aura, sometimes with prolonged or atypical features (visual, sensory, language, or hemiplegic). About 30–40% of CADASIL patients experience migraine with aura — frequently as the earliest symptom.

Migraine with aura often appears in the 20s–30s. Strokes and TIAs most commonly occur between the ages of 40 and 70. Cognitive and mood changes can appear at any age, but become more prominent over time.

These are averages, not a schedule. Some people have their first stroke in their 30s. Others are diagnosed for the first time in their 70s. Some carriers in their 50s and 60s report no symptoms at all. Variability is enormous — even within the same family.

A rare but recognized complication in which a migraine attack is followed by hours to days of fever, seizures, altered consciousness, or severe migraine-like symptoms. Episodes can be alarming — patients and families are often unprepared — but they are generally reversible with supportive care in hospital. Any suspected encephalopathic episode should be evaluated in the emergency department, and it helps to tell the treating team that CADASIL is on the picture, since it changes the differential (e.g., MELAS, viral encephalitis, status migrainosus) and the management approach.

CADASIL can lead to vascular cognitive impairment, which in advanced cases meets criteria for vascular dementia. But CADASIL is fundamentally a genetic small-vessel arteriopathy — dementia is one of its later manifestations, not the disease itself.

Diagnosis combines clinical pattern recognition, brain MRI, and NOTCH3 genetic testing. Skin biopsy with electron microscopy may be used when genetic results are inconclusive. Full diagnostic pathway →

Confluent T2/FLAIR white-matter hyperintensities — particularly in the anterior temporal poles and external capsules — together with lacunar infarcts, cerebral microbleeds (on SWI/GRE), and progressive atrophy. The corpus callosum and U-fibers are typically spared.

No — and CADASIL is often misdiagnosed as MS because both can produce white-matter lesions on MRI. CADASIL is a genetic small-vessel disease defined by NOTCH3 mutations; MS is an autoimmune demyelinating disease. MRI patterns differ — CADASIL classically involves the anterior temporal poles and external capsules and spares the corpus callosum and U-fibers, and CSF studies in CADASIL are negative for oligoclonal bands.

Genetic testing is a decision, not a routine screening test. If you have symptoms suggestive of CADASIL or a relevant family history, discuss testing with a neurologist and, where available, a genetic counsellor. Predictive testing in asymptomatic adult relatives is a deeply personal choice; it can have implications for the individual and their family — including personal, family-planning, and insurance considerations. Informed discussion and pre- and post-test genetic counselling are widely recommended.

No. Migraine is common and, on its own, usually does not indicate CADASIL. CADASIL becomes more relevant to consider when migraine occurs alongside other suggestive findings — such as stroke at a younger age, unexplained white-matter changes on MRI, or a relevant family history. A healthcare professional can determine whether further evaluation is appropriate.

Not precisely. Genetics can establish or support a CADASIL diagnosis, but it cannot provide a reliable individual timeline. Age of onset, the types of symptoms, and their severity vary considerably between people — including within families who share the same variant.

GOM is an ultrastructural finding highly specific to CADASIL — abnormal deposits in the basement membrane around vascular smooth muscle cells, visible on electron microscopy of small arteries (often sampled via skin biopsy).

There is currently no treatment proven to reverse or specifically stop CADASIL. Several therapeutic strategies — including antisense oligonucleotides targeting mutant NOTCH3 — are in early-stage development. Care generally focuses on managing symptoms, addressing modifiable vascular risk factors, and applying established stroke-prevention principles where appropriate. Treatment overview →

CADASIL care is typically led by a neurologist — often a stroke specialist or neurogeneticist — in collaboration with a genetic counsellor, primary care, and mental-health and rehabilitation professionals as needed.

Managing modifiable vascular risk factors (blood pressure, smoking, lipids, glucose), regular aerobic exercise, Mediterranean-style nutrition, sleep quality, and treatment of mood symptoms are widely recommended for anyone at elevated stroke risk, including people with CADASIL. Whether these specifically alter the long-term course of CADASIL is a subject of ongoing research; individual decisions are best made with your care team.

Triptans are not absolutely contraindicated, but caution is warranted given their vasoconstrictive profile and the underlying small-vessel arteriopathy. Decisions should be individualized in consultation with a CADASIL-aware clinician.

Antiplatelet therapy (typically aspirin) is commonly used after ischemic events in CADASIL — but must be balanced against the recognized risk of intracerebral hemorrhage from microbleeds. Long-term dual antiplatelet therapy is generally avoided. Anticoagulation is reserved for clear indications. Decisions should be individualized.

Penetrance is essentially complete with age, but expressivity is highly variable. Mild variants, late onset, or earlier deaths from unrelated causes can make the disease appear to skip generations even though the genetic variant is still present.

Each child has a 50% chance of inheriting the variant. Children who do inherit it are considered at risk for CADASIL, but the age of onset, types of symptoms, and severity vary considerably — and some people who carry the variant have very few symptoms for many years. Genetic testing does not provide a precise individual prediction.

Many people with CADASIL work, raise families, and live full lives. The course of CADASIL is highly variable from person to person. Family planning decisions are personal and are best supported by informed clinical discussion and, where available, genetic counselling.

Long-term outcome in CADASIL varies considerably from person to person. Many people live independently for decades after diagnosis with good function; others have a more challenging course. Individual outcome cannot be reliably predicted from genetic testing alone. Discussing prognosis with a CADASIL-aware clinician who knows your particular situation is the most helpful starting point.

Several therapeutic strategies are in early-stage development, including antisense oligonucleotides and other gene-targeted approaches. Natural-history studies and registries are active. Patients and families can ask their neurologist or contact us for current opportunities. Research overview →