Vascular risk control
Aggressive blood pressure management, smoking cessation, lipid and glucose optimization. The single highest-yield intervention.
For neurologists, stroke physicians, primary care, ER, genetic counsellors
CADASIL — at clinician speed.
A focused, evidence-informed reference. Built for the moment when you are seeing a 47-year-old with a confluence of migraine, mood change, white-matter MRI findings, and a "complicated" family history — and you need to act.
The CADASIL pattern, in one minute.
Suspect when…
- Stroke or TIA before age 60, especially without classical vascular risk factors
- Migraine with aura starting in the 20s–30s
- Mood disturbance, apathy, or executive dysfunction earlier than expected
- Subcortical white-matter MRI abnormalities at any age — particularly anterior temporal poles or external capsules
- Multi-generational family history of stroke, "early dementia," or unexplained psychiatric illness
- An "atypical MS" picture without CSF or oligoclonal-band support
Confirm with…
- Brain MRI: FLAIR, T2, T1, SWI/GRE, DWI
- NOTCH3 sequencing — alone or via a small-vessel disease / stroke gene panel
- Skin biopsy with EM (GOM) and NOTCH3 immunohistochemistry, when genetics are inconclusive
- Genetic counselling — pre- and post-test
The CADASIL MRI signature.
| Feature | Sequence | Significance |
|---|---|---|
| Confluent deep + periventricular WMH | FLAIR / T2 | Earliest and most consistent finding; usually present by 30s. |
| Anterior temporal pole hyperintensities | FLAIR / T2 | Highly suggestive of CADASIL; specificity reasonable. |
| External capsule hyperintensities | FLAIR / T2 | Classic location; helpful in distinguishing from MS. |
| Lacunar infarcts (basal ganglia, thalamus, brainstem, centrum semiovale) | T1 / FLAIR | Reflect small-vessel arteriopathy; correlate with stepwise decline. |
| Cerebral microbleeds | SWI / GRE | Increase with severity; relevant to antithrombotic decisions. |
| Cortical & subcortical atrophy | T1 | Tracks disease progression and cognitive impairment. |
Distinguishing from MS
CADASIL spares the corpus callosum and U-fibers, characteristically involves the anterior temporal poles and external capsules, rarely shows enhancement, and is genetically defined. CSF studies are typically negative for oligoclonal bands.
How to order NOTCH3 testing.
Approaches
- Targeted NOTCH3 sequencing — when clinical suspicion is high.
- Small-vessel disease or stroke gene panel — increasingly preferred; covers HTRA1, COL4A1/A2, GLA, and others.
- Trio testing — useful when there is no clear family history (de novo variants are rare but described).
Practical tips
- Pair testing with genetic counselling — pre- and post-test.
- If the laboratory reports a variant of uncertain significance (VUS), reach out to a CADASIL-experienced centre and consider skin biopsy with EM.
- Document family history carefully (3-generation pedigree, age at events, cause of death where known).
- If a pathogenic variant is identified, discuss cascade testing in adult relatives — with counselling.
What good CADASIL care looks like.
Antithrombotics
Antiplatelet therapy after ischemic events is common; balance against microbleed and hemorrhage risk. Avoid long-term DAPT in most cases.
Migraine
Standard preventives and acute therapies typically appropriate. Triptans/ergots warrant caution — individualize.
Mood & cognition
Routine screening for depression and apathy. Treat aggressively. Cognitive rehabilitation has a role.
Lifestyle
Aerobic activity, Mediterranean-style nutrition, sleep apnea screening, social engagement.
Surveillance
Periodic clinical review and imaging — calibrated to severity and the patient's goals of care.
Special-caution scenarios.
- IV thrombolysis in acute stroke — review the imaging and microbleed burden carefully; coordinate with stroke specialists; consider published case-series data.
- Cerebral angiography — historically associated with CADASIL-specific complications; non-invasive imaging is preferred where feasible.
- Triptans & ergots — relative caution given the small-vessel arteriopathy.
- Perioperative hypotension — avoid if possible; brief patients and surgical teams.
- Hormonal contraception — discuss thrombotic and migraine risk individually.
Communicate the diagnosis to the system
CADASIL on the active problem list helps ER teams, anesthesiologists, and primary care make better decisions. Encourage patients to carry a wallet card or note in their EMR.
Building the network.
CADASIL Global Foundation works with academic centres, genetic counsellors, and patient advocates to make pathways clearer. We are happy to help you find or build the connections you need.
Academic centres
Connect with neurologists and neurogeneticists with CADASIL focus, including in Canada (UHN/Toronto, McGill/Montreal).
Genetic counselling
Identify counsellors with CADASIL and rare-disease experience for your patients and their families.
Research participation
Help your patients access registries, natural-history studies, and emerging therapeutic trials.