National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

CADASIL

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Other Names:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; Dementia, hereditary multi-infarct type; Familial vascular leukoencephalopathy; Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; Dementia, hereditary multi-infarct type; Familial vascular leukoencephalopathy; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy; CASIL See More
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This disease is grouped under:
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy) is an inherited disease of the blood vessels that occurs when the thickening of blood vessel walls blocks the flow of blood to the brain. The disease primarily affects the small blood vessels in the white matter of the brain. CADASIL is characterized by migraine headaches and multiple strokes, which progresses to dementia. Other symptoms include white matter lesions throughout the brain, cognitive deterioration, seizures, vision problems, and psychiatric problems such as severe depression and changes in behavior and personality. Individuals may also be at higher risk of heart attack. Symptoms and disease onset vary widely, with signs typically appearing in the mid-30s. Some individuals may not show signs of the disease until later in life.[1]

CADASIL is caused by a variant (or mutation) in a gene called NOTCH3.  Inheritance is autosomal dominant.[1][2] There is no cure yet. Treatment is only supportive and depends on the symptoms.[1][3] Most people with CADASIL become bed-ridden and develop dementia over time.  Life expectancy is also reduced in people with CADASIL due, especially, to lung and heart diseases. Because people who smoke or have high arterial pressure or have other vascular risk factors, control of any vascular risk factors is an important part of CADASIL management.[3][4][5]
Last updated: 6/4/2018
The most common  signs and symptoms of CADASIL are  caused by damage to small blood vessels, especially those within the brain and include: stroke,  cognitive impairment,  migraine with aura, and  psychiatric disturbances. These symptoms are:[6] 
  • Recurrent ischemic strokes (transient ischemic attack/stroke) in adulthood that may lead to severe disability such as an inability to walk and urinary incontinence. The average age at onset for stroke-like episodes is 46 years. Transient ischemic attacks and stroke are reported in approximately 85% of symptomatic individuals 
  • Progressive cognitive decline with dementia developing in about 75% of affected people including significant difficulty with reasoning and memory
  • Migraine, usually with aura, as the first symptom in the third decade of life
  • Psychiatric problems such as mood disturbances (apathy and depression), presenting in about 30% of people with CADASIL 
  • Seizures with epilepsy is present in 10% of affected people and usually presents at middle age
  • Diffuse white matter lesions and subcortical infarcts on neuroimaging.
Less common signs and symptoms may include:[5] 
  • Other psychiatric issues such as gambling, a seizure lasting 30 minutes or longer, or a cluster of shorter seizures for 30 minutes or more with little or no recovery between episodes (recurrent status epilecticus), psychosis, and bipolar disease
  • Slow movements and tremors (parkisionism)
  • Memory loss (amnesia)
  • Dysfunction of one or more peripheral nerves, typically causing numbness or weakness (neuropathy)
  • Muscular weakness due to a muscular disease (myopathy)
  • Confusion, fever and coma (CADASIL coma)
  • Acute vestibular syndrome ( rapid onset (over seconds to hours) of vertigo, nausea/vomiting, and abnormal gait in association with head-motion intolerance and abnormal eye movements, lasting days to weeks)
  • Spinal cord involvement.


Last updated: 6/4/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Amaurosis fugax 0100576
Aphasia
Difficulty finding words
Losing words
Loss of words
[ more ] 		0002381
Coma 0001259
Confusion
Disorientation
Easily confused
Mental disorientation
[ more ] 		0001289
Dementia
Dementia, progressive
Progressive dementia
[ more ] 		0000726
Depressivity
Depression
0000716
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase
[ more ] 		0003236
Fever 0001945
Hemiplegia
Paralysis on one side of body
0002301
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches
[ more ] 		0002076
Retinal arteriolar tortuosity 0001136
Sensory neuropathy
Damage to nerves that sense feeling
0000763
30%-79% of people have these symptoms
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Cerebral ischemia
Disruption of blood oxygen supply to brain
0002637
Cranial nerve paralysis 0006824
EEG abnormality 0002353
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Impaired pain sensation
Decreased pain sensation
0007328
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory
[ more ] 		0002354
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
5%-29% of people have these symptoms
Abnormality of extrapyramidal motor function 0002071
Atherosclerosis
Narrowing and hardening of arteries
0002621
Hypertension 0000822
Hypoglycemia
Low blood sugar
0001943
Peripheral neuropathy 0009830
Recurrent pneumonia 0006532
Seizure 0001250
Sensorineural hearing impairment 0000407
Subcutaneous hemorrhage
Bleeding below the skin
0001933
Subdural hemorrhage 0100309
Varicose veins 0002619
Visual loss
Loss of vision
Vision loss
[ more ] 		0000572
1%-4% of people have these symptoms
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Percent of people who have these symptoms is not available through HPO
Abnormal electroretinogram 0000512
Abnormality of the skin 0000951
Abnormality of visual evoked potentials 0000649
Adult onset
Symptoms begin in adulthood
0003581
Autosomal dominant inheritance 0000006
Leukoencephalopathy 0002352
Nonarteritic anterior ischemic optic neuropathy 0007634
Pseudobulbar paralysis 0007024
Recurrent subcortical infarcts 0007236
Stroke 0001297
Subcortical dementia 0007123
Urinary incontinence
Loss of bladder control
0000020
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Last updated: 7/1/2020
CADASIL is caused by a variant (mutation) in the NOTCH3 gene. The NOTCH3 gene gives the body instructions to make the Notch3 receptor protein, needed for normal function and survival of vascular smooth muscle cells. Mutations in NOTCH3 cause the body to make an abnormal protein, thus impairing the function and survival of vascular smooth muscle cells and causing these cells to self-destruct. The loss of vascular smooth muscle cells in the brain causes blood vessel damage that leads to the characteristic features of CADASIL.[2]
Last updated: 6/4/2018
CADASIL is inherited in an autosomal dominant manner. This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause CADASIL. In most cases, an affected person inherits the mutated gene from an affected parent. In rare cases, CADASIL may result from having a new mutation in the gene, in which case it is not inherited from a parent.[2]

When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated copy of the gene.[2]
Last updated: 6/4/2018

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
There is no cure or effective treatment for CADASIL yet. While antiplatelet treatment is often used, it is also not proven to be useful and some professionals do not recommend using these because microbleeds in the brain may occur in people with CADASIL, and, for this reason, the safety of antiplatelet drugs in this disease is still unknown.[5][6] 

Migraine should be treated both symptomatically and prophylactically (with preventative methods), depending on the frequency of symptoms. Some medication that have shown some efficacy in some studies, but have not being proven may include acetazolamide, and sodium valproate for the migraine, and acetylcholinesterase inhibitor for cognitive decline.[5]

When hypertension, diabetes or hypercholesterolemia (high cholesterol) are also present, they should be treated. Supportive care, including practical help, emotional support, and counseling, is useful for affected people and their families.[5][6]

Yearly follow up by a neurologist with expertise in CADASIL is recommended from the time of diagnosis, as well as other specialists as needed.[6]

Smoking, angiography, anticoagulants and thrombolytic therapy are all to be avoided by those with CADASIL as they increase the risk of strokes and/or brain bleeding.[5]

Last updated: 6/4/2018

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.
Symptoms of CADASIL usually progress slowly. By age 65, most people have severe cognitive problems and dementia. Some people lose the ability to walk, and most become completely dependent on the care of others due to multiple strokes.[1] Life expectancy in people with CADASIL is reduced, mainly because of lung or heart problems.[4][5]
Last updated: 6/4/2018

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Binswanger disease, primary angiitis of the central nervous system and multiple sclerosis as well as other genetic disorders such as CARASIL, MELAS syndrome, Fabry disease and small-vessel diseases associated with COL4A1 mutations (e.g. familial porencephaly) (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to CADASIL. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss CADASIL. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Both my grandfather and my uncle died from strokes caused by CADASIL and MS. My father was tested and does not have it. What are the chances that it may have passed him and I will have it? See answer

  • I was diagnosed with multiple sclerosis (MS) after a spinal tap and MRI. My neurologist ordered genetic testing of NOTCH3, which was positive for CADASIL. Is it possible to have MS and CADASIL? Also, would CADASIL cause lesions on the brain? See answer

  • My mother and her identical twin sister have CADASIL. While some of my cousins have the condition, I do not. Am I at risk to inherit this condition?  See answer


  1. NINDS CADASIL Information Page. National Institute of Neurological Disorders and Stroke (NINDS). 2017; http://www.ninds.nih.gov/disorders/cadasil/CADASIL.htm.
  2. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genetics Home Reference (GHR). May 2013; http://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy.
  3. Behrouz R. CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy). Medscape Reference. 2017; http://emedicine.medscape.com/article/1423170.
  4. CADASIL. Orphanet. 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=136.
  5. Donato ID, Bianchi S, Stefano N & cols. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects. BMC Medicine. February 24, 2017; 15:41:https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0778-8#Sec14.
  6. Rutten J & Lesnik Oberstein SAJ. CADASIL. GeneReviews. 2016; http://www.ncbi.nlm.nih.gov/books/NBK1500/.