Autosomal Dominant Cerebral Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Type 1 (CADASIL)

Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy type 1 is usually called CADASIL type 1. It is a rare, inherited disease that damages the tiny blood vessels (small arteries) in the brain. Because blood flow is reduced, small strokes and long-term white-matter damage slowly build up over many years. This can cause migraine attacks, repeated “small strokes,” changes in thinking, and finally dementia in some people. JCN+1

Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy type 1, usually called CADASIL, is a rare inherited disease that damages the small blood vessels in the brain. It is caused by a mutation in the NOTCH3 gene and is passed in an autosomal dominant pattern, which means a child has a 50% chance of inheriting it if one parent is affected. Over time, the walls of small brain arteries become thick and abnormal, reducing blood flow and leading to tiny strokes (subcortical infarcts) and white-matter damage (leukoencephalopathy). People with CADASIL often develop migraine with aura, repeated strokes or transient ischemic attacks, mood problems, and progressive thinking and memory difficulties. There is no cure yet, so treatment focuses on reducing stroke risk, treating symptoms, and supporting quality of life. MedlinePlus+2NCBI+2

CADASIL type 1 is caused by a harmful change (mutation) in a gene called NOTCH3. This gene gives instructions to make a protein on the surface of smooth muscle cells in blood vessel walls. When the gene is damaged, the protein changes shape and builds up abnormally around the small arteries in the brain. Over time, these arteries become thick, stiff, and narrow, which reduces blood flow and leads to tiny deep strokes and white-matter damage. Orpha+2MedlinePlus+2

The disease is autosomal dominant, which means that a person only needs one copy of the altered gene from either mother or father to develop the condition. Often, many members of the same family across several generations are affected. However, sometimes a new mutation happens in one person, even when no one else in the family has the disease. NCBI+1

People with CADASIL type 1 usually start with migraine (often with aura) in early or mid-adult life, then may have transient ischemic attacks (TIAs) or small strokes, and later develop problems with memory, thinking, mood, walking, and balance. Brain MRI scans show typical changes: white-matter hyperintensities, lacunar (small deep) infarcts, and sometimes tiny micro-bleeds. PMC+2National Organization for Rare Disorders+2

Other names and classification

This condition has many different names in the medical literature. Common other names include:

• CADASIL

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

• Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 (CASIL)

• Hereditary multi-infarct dementia / hereditary multi-infarct type dementia

• Familial vascular leukoencephalopathy

• CADASIL1, CADASIL type 1, CADASIL syndrome MedlinePlus+2MalaCards+2

These names all describe the same basic problem: inherited (familial) disease of brain arteries, causing many small deep strokes and white-matter damage. The long official name “cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy type 1” is used in genetic databases, but doctors usually just say “CADASIL.” MalaCards+1

Types / subgroups

1. Classic CADASIL type 1 with NOTCH3 cysteine-changing mutations – This is the most common form. Mutations change a cysteine amino acid in certain repeats in the NOTCH3 protein and are strongly linked with typical MRI and clinical features. Orpha+1

2. Atypical CADASIL type 1 with cysteine-sparing NOTCH3 mutations – Some people have NOTCH3 variants that do not change cysteine. They may have a similar clinical picture but slightly different MRI patterns (for example, less involvement of the anterior temporal lobe). PLOS+1

3. Early-onset severe phenotype – In some families, symptoms such as strokes and dementia appear earlier and progress faster. This may be linked to certain “stronger” NOTCH3 mutations and other risk factors like smoking or high blood pressure. JCN+1

4. Late-onset mild phenotype – In other families, symptoms are milder or appear later in life. These people may have fewer strokes and slower decline, even though they still carry a NOTCH3 mutation. Cervco+1

5. CADASIL-like small-vessel diseases (related but distinct) – There are other genetic small-vessel diseases such as CARASIL (autosomal recessive, HTRA1 gene), CADASIL type 2 (heterozygous HTRA1), and CARASAL (CTSA gene). They can look similar on MRI, but they are considered separate conditions from CADASIL type 1. Nature+2PMC+2

Causes

1. NOTCH3 gene mutation (main cause)
   The true root cause of CADASIL type 1 is a harmful mutation in one copy of the NOTCH3 gene. This mutation leads to abnormal NOTCH3 protein on smooth muscle cells in small arteries of the brain, causing the vessels to become diseased and narrow. Without this gene change, a person does not develop CADASIL type 1. Orpha+2SSRN+2

2. Autosomal dominant inheritance from an affected parent
   Most patients inherit the NOTCH3 mutation from a mother or father who also carries it. Because the pattern is autosomal dominant, each child of an affected person has a 50% chance to inherit the mutation and the disease. NCBI+1

3. New (de novo) NOTCH3 mutation
   In a small number of cases, the mutation appears for the first time in a person, due to a random change in the egg or sperm. This is called a de novo mutation. This person can then pass the mutation to future children. NCBI+1

4. Accumulation of abnormal NOTCH3 protein in vessel walls
   The mutant NOTCH3 protein builds up around smooth muscle cells as tiny deposits called granular osmiophilic material (GOM). These deposits disturb the structure and function of the vessel wall, eventually causing loss of smooth muscle cells and thickening of the artery. SSRN+1

5. Chronic small-vessel ischemia (low blood flow)
   Because the small arteries become narrowed and stiff, the brain’s deep white matter receives less blood and oxygen over many years. This chronic low-grade ischemia leads to white-matter damage (leukoencephalopathy) and small deep strokes (lacunar infarcts). PMC+2Frontiers+2

6. High blood pressure (worsening factor)
   CADASIL type 1 is not caused by high blood pressure, but uncontrolled hypertension adds extra stress on already diseased small arteries. This increases the risk of strokes and speeds up brain damage. AHA Journals+1

7. Smoking and tobacco exposure
   Smoking damages blood vessels and promotes clot formation. In a person with CADASIL, smoking further worsens the small-vessel disease, increasing the risk of strokes and earlier disability. AHA Journals+1

8. High cholesterol and other lipid problems
   Elevated LDL cholesterol and other lipid disorders may speed up atherosclerosis and further impair blood flow in already fragile small arteries, adding to stroke risk. AHA Journals+1

9. Diabetes and high blood sugar
   Long-term high blood sugar damages small vessels and nerves. In people with CADASIL, diabetes may worsen small-vessel injury and lead to more frequent or severe strokes and cognitive decline. AHA Journals+1

10. Obesity and sedentary lifestyle
    Being overweight and not exercising increase many vascular risk factors, including hypertension, dyslipidemia, and insulin resistance. These factors together can worsen brain vessel health in CADASIL. AHA Journals+1

11. Oral contraceptive pills and estrogen therapy (possible trigger)
    Some hormonal therapies can slightly increase the risk of blood clots and stroke. In a patient with CADASIL, this may contribute to stroke events, especially if other risk factors like smoking are present. AHA Journals+1

12. Heavy alcohol use
    Excess alcohol can raise blood pressure, damage the liver, and affect clotting. These changes may increase the chance of hemorrhagic or ischemic stroke in someone with CADASIL. AHA Journals+1

13. Illicit drug use (for example, cocaine)
    Some illegal drugs cause sudden severe rises in blood pressure and direct vessel spasm. This can trigger acute strokes on top of the chronic small-vessel disease of CADASIL. AHA Journals+1

14. Sleep apnea and poor sleep
    Obstructive sleep apnea causes repeated drops in oxygen and surges in blood pressure at night. Over time, this can harm blood vessels and may worsen the ischemic brain damage seen in CADASIL. AHA Journals+1

15. Chronic stress and depression
    Persistent stress and depressive illness can increase stress hormones, blood pressure, and unhealthy habits such as smoking. This indirect pathway may accelerate vascular damage in CADASIL patients. ARUP Consult+1

16. Additional small-vessel disease genes (rare double hits)
    Rarely, a person may carry a NOTCH3 mutation plus another variant in a different small-vessel gene such as HTRA1. This can produce a more complex or severe phenotype, as reported in some recent case studies. Nature+2PMC+2

17. Aging of blood vessels
    With age, everyone’s arteries become stiffer and less responsive. In CADASIL, this normal aging adds on top of the genetic vessel damage, further increasing the risk of strokes and cognitive decline in later life. JCN+1

18. Recurrent small strokes themselves
    Each small infarct kills a tiny area of brain tissue. Over time, many small strokes add up to significant brain damage, causing stepwise worsening of movement, balance, and thinking. This becomes a self-reinforcing cycle. JCN+2JCN+2

19. Poor control of general vascular risk factors
    Failure to treat high blood pressure, high cholesterol, diabetes, and smoking does not cause the gene mutation but does strongly influence how fast the disease progresses and how many strokes occur. AHA Journals+1

20. Lack of awareness and delayed diagnosis
    When the disease is not recognized early, people may not receive advice on avoiding triggers and controlling risk factors. This delay can allow more preventable brain damage to occur. GSConline Press+1

Symptoms

1. Migraine headaches, often with aura
   Many people with CADASIL type 1 first notice recurrent migraine attacks, often starting in their 20s–40s. The aura may include flashing lights, zigzag lines, or temporary vision loss before the headache. These migraines are a very typical early sign of the disease. National Organization for Rare Disorders+2Cervco+2

2. Transient ischemic attacks (TIAs)
   A TIA is a “mini-stroke” where symptoms such as weakness, numbness, or speech problems appear suddenly but go away within 24 hours. In CADASIL, TIAs often happen repeatedly and are a warning that small strokes may follow. JCN+1

3. Lacunar (small deep) strokes
   Over time, many patients develop small deep strokes in the white matter, basal ganglia, or brainstem. These strokes may cause sudden weakness, clumsiness, or speech difficulty. The MRI shows small holes or dark areas called lacunes in these regions. PMC+2Cureus+2

4. Progressive problems with thinking and memory
   As white-matter damage increases, people may have trouble with attention, planning, decision making, and short-term memory. This often develops slowly over years and can lead to subcortical vascular dementia in advanced stages. JCN+2ARUP Consult+2

5. Changes in mood and behavior
   Depression, apathy (loss of motivation), irritability, and anxiety are very common. Some people may have sudden mood swings or even episodes of mania or psychosis. These changes are due to both psychological reaction and direct brain damage in mood-related circuits. Cervco+1

6. Difficulty walking and keeping balance
   Damage to the deep white matter and connections to the cerebellum can cause unsteady gait, poor balance, and frequent falls. People may walk with short steps, a wide base, or need a cane over time. JCN+2ACEN+2

7. Weakness or numbness on one side of the body
   Small strokes or TIAs can cause weakness, clumsiness, or numbness in an arm, leg, or one side of the face. Sometimes the symptoms are mild but still interfere with daily tasks like writing, buttoning clothes, or climbing stairs. Cureus+1

8. Speech and language problems
   Some people have trouble finding words, speaking clearly, or understanding complex sentences, especially after strokes. Speech may become slow, slurred, or hesitant, which can be very frustrating. History of Medicine Journal+1

9. Vision disturbances
   Visual aura during migraine is common, but strokes can also affect vision. People may see blurred areas, lose part of their visual field, or have double vision, depending on which brain area is affected. National Organization for Rare Disorders+1

10. Seizures (epileptic fits)
    A smaller group of patients develop seizures. These may involve brief staring spells, jerking movements, or loss of consciousness. Seizures usually happen in people with more advanced brain damage. NCBI+1

11. Urinary urgency or incontinence
    As white-matter pathways controlling bladder function are damaged, some people feel a strong, sudden need to urinate or may have accidents, especially later in the disease. JCN+1

12. Fatigue and reduced stamina
    Many patients report feeling unusually tired, both physically and mentally. They may need more rest and feel worn out after tasks that used to be easy. This may be due to brain damage, mood changes, and repeated strokes. Cervco+1

13. Cognitive slowing (“thinking more slowly”)
    Even before clear dementia, people often notice that they process information more slowly, take longer to make decisions, and struggle with multitasking. Loved ones may say the person seems “slower” or “less sharp” than before. JCN+1

14. Headache without aura and non-migraine pain
    Some patients have frequent headaches that are not classic migraines. These may be dull, pressure-type headaches linked to chronic small-vessel disease and white-matter changes. National Organization for Rare Disorders+1

15. Loss of independence and disability in later stages
    As strokes and cognitive decline accumulate, many people eventually need help with daily activities like dressing, bathing, and managing money. Some may require a wheelchair or nursing care in advanced disease. Cervco+2ARUP Consult+2

Diagnostic tests

Physical examination

1. General physical exam and vital signs
   The doctor checks blood pressure, heart rate, weight, and general health. This helps find common risk factors like high blood pressure or obesity that can worsen CADASIL and guides treatment to reduce further brain damage. AHA Journals+1

2. Detailed neurological examination
   The neurologist carefully tests strength, reflexes, sensation, eye movements, coordination, and cranial nerves. This exam looks for signs of previous small strokes or ongoing brain dysfunction, such as weakness, abnormal reflexes, or gait disturbance. JCN+1

3. Gait and balance assessment
   The patient is asked to walk, turn, stand with feet together, or perform tandem gait (heel-to-toe). Problems such as a wide-based or unsteady gait can suggest subcortical small-vessel disease like CADASIL, especially in middle-aged adults with a relevant family history. Ak Journals+1

4. Bedside mental status check
   Simple questions about time, place, recent events, and short-term memory help screen for cognitive impairment. Difficulties in these tasks may indicate subcortical vascular cognitive impairment or early dementia due to CADASIL. JCN+1

5. Eye and fundus examination
   Using an ophthalmoscope, the doctor may inspect the back of the eye for vascular changes, micro-bleeds, or other signs of small-vessel disease. While not specific for CADASIL, these findings can support the picture of widespread vascular injury. JCN+1

Manual / bedside tests

6. Mini-Mental State Examination (MMSE)
   This is a short paper-and-pencil test that measures orientation, attention, memory, language, and simple drawing. A lower score suggests cognitive impairment. In CADASIL, MMSE can track changes in thinking ability over time. JCN+1

7. Montreal Cognitive Assessment (MoCA)
   MoCA is more sensitive than MMSE for early executive and attention problems. It includes tasks like trail-making, word fluency, and delayed recall. It is useful for detecting mild cognitive impairment in CADASIL before full dementia appears. JCN+1

8. Depression and anxiety scales (for example, PHQ-9, GAD-7)
   Simple questionnaires help measure mood symptoms. Because depression and anxiety are common in CADASIL, these tools help doctors assess severity and decide on treatment such as counseling or medication. Cervco+1

9. Manual muscle strength testing
   The clinician tests each muscle group against resistance and grades strength. Subtle weakness from old small strokes can be detected, even when the patient has adapted in daily life. This helps map which brain regions may have been affected. JCN+1

10. Coordination tests (finger-to-nose, heel-to-shin, rapid alternating movements)
    These simple bedside tests look for ataxia or incoordination. Abnormal results may reflect damage to cerebellar pathways or white-matter tracts, which is common in small-vessel diseases including CADASIL. Ak Journals+1

Laboratory and pathological tests

11. Basic blood tests (CBC, electrolytes, kidney and liver function)
    These tests do not diagnose CADASIL directly, but they help rule out other causes of strokes or cognitive decline, such as anemia, infection, or metabolic problems, and ensure that the body can safely handle certain medications. ARUP Consult+1

12. Lipid profile (cholesterol and triglycerides)
    Measuring LDL, HDL, and triglycerides helps identify treatable risk factors that can worsen CADASIL. High LDL or low HDL levels may call for diet changes or medications like statins to protect blood vessels. AHA Journals+1

13. Fasting glucose and HbA1c
    These tests screen for diabetes or pre-diabetes. Because diabetes increases small-vessel damage and stroke risk, controlling blood sugar is especially important in CADASIL patients. AHA Journals+1

14. Coagulation profile (INR, aPTT, platelet count)
    Testing blood clotting helps rule out bleeding disorders or strong clotting tendencies. It is also important before starting certain medications like anticoagulants, which may be used if there are other reasons such as atrial fibrillation. AHA Journals+1

15. Genetic testing for NOTCH3 mutations
    Molecular testing of the NOTCH3 gene is the gold standard for confirming CADASIL type 1. A single pathogenic NOTCH3 variant in the right region of the gene is usually enough to make a definite diagnosis in a person with typical symptoms or MRI findings. NCBI+2Canterbury Health Laboratories+2

16. Skin biopsy with electron microscopy and immunostaining
    If genetic testing is unclear or unavailable, a small skin biopsy can be studied under an electron microscope. The presence of granular osmiophilic material (GOM) around small vessels and positive staining for NOTCH3 strongly support the diagnosis of CADASIL. NCBI+2Arkana Laboratories+2

Electrodiagnostic tests

17. Electroencephalogram (EEG)
    EEG records the electrical activity of the brain. It is especially useful in CADASIL patients who have seizures or unexplained episodes of confusion or unresponsiveness. EEG can show abnormal spikes or slowing that indicate epileptic activity or diffuse brain dysfunction. NCBI+1

18. Electrocardiogram (ECG / EKG)
    An ECG measures the heart’s electrical activity. It cannot diagnose CADASIL, but it helps find heart rhythm problems (like atrial fibrillation) that could also cause strokes. Identifying and treating these problems is important so that strokes are not wrongly blamed only on CADASIL. AHA Journals+1

Imaging tests

19. Brain MRI with T2/FLAIR and diffusion sequences
    MRI is the key imaging test. In CADASIL, MRI often shows symmetric white-matter hyperintensities in the periventricular and deep white matter, with special involvement of the anterior temporal lobes and external capsules, along with lacunar infarcts and micro-bleeds. These patterns, together with family history and symptoms, strongly suggest CADASIL. PMC+2neurology-asia.org+2

20. CT scan and vascular imaging (CT or MR angiography, carotid ultrasound)
    A CT scan may be done in emergency settings to exclude bleeding and look for strokes. CT or MR angiography and carotid ultrasound show larger arteries and help rule out other causes such as big-vessel narrowing. Even when these larger vessels look normal, the typical small-vessel MRI pattern can still point to CADASIL. AHA Journals+2r-n-j.com+2

Non-pharmacological treatments (therapies and others)

1. Blood pressure control with lifestyle changes
Careful control of blood pressure is one of the most important non-drug treatments in CADASIL, because high blood pressure increases the risk of brain strokes and speeds up damage to small vessels. Lifestyle steps include limiting salt, losing extra weight, staying physically active, managing stress, and avoiding smoking. These changes help blood vessels relax and reduce the pressure inside them, which may slow further damage to the tiny arteries affected in CADASIL. Good blood pressure control is recommended in all stroke prevention guidelines and is strongly advised for inherited small-vessel diseases like CADASIL. AHA Journals+1

2. Stopping smoking and avoiding second-hand smoke
Smoking makes blood vessels stiff, narrow, and more likely to clot. In people with CADASIL, whose vessels are already diseased, smoking can sharply increase the risk of stroke at a younger age. Stopping smoking is therefore one of the most powerful “treatments” a person can choose for themselves. When nicotine exposure stops, the blood becomes less sticky, vessel lining (endothelium) works better, and oxygen supply to the brain improves. Counseling, support programs, and nicotine-replacement products prescribed by a doctor can all help. Stroke and CADASIL experts strongly advise complete smoking cessation. AHA Journals+1

3. Healthy physical activity and physiotherapy
Regular, moderate physical activity, such as walking, cycling, or supervised exercise, helps control blood pressure, cholesterol, weight, and mood, which are all vital for people living with CADASIL. After a stroke or transient ischemic attack, physiotherapy helps patients regain strength, balance, and walking ability. Exercise also improves brain blood flow and supports the growth of new connections between brain cells (neuroplasticity). In CADASIL, where repeated small strokes cause gradual disability, long-term physiotherapy and safe exercise programs can maintain independence for longer and reduce complications such as falls and joint stiffness. AHA Journals+1

4. Occupational therapy for daily-life skills
Occupational therapy focuses on helping people manage daily activities, such as dressing, washing, cooking, working, and using devices. In CADASIL, repeated strokes and cognitive changes may make these tasks harder. An occupational therapist can suggest practical adaptations, home safety changes, and memory aids. This support reduces the risk of falls, burns, and accidents, and also lowers stress for both the patient and the family. The mechanism is not biological but functional: by adapting tasks and environments, people use their remaining abilities more efficiently and safely, which improves quality of life. NCBI+1

5. Speech and language therapy
If CADASIL causes stroke-related speech problems or difficulty swallowing, speech and language therapy becomes very important. The therapist teaches exercises to improve speech clarity, word-finding, and understanding, and may teach communication strategies such as using writing, gestures, or devices. For swallowing problems, they recommend safe food textures and special swallowing techniques to prevent choking or aspiration pneumonia. The mechanism is again functional: repeated practice strengthens the muscles and helps the brain reorganize its communication networks, supporting safer eating and clearer communication. NCBI

6. Cognitive rehabilitation and memory strategies
Many people with CADASIL develop problems with attention, planning, and memory as the disease progresses. Cognitive rehabilitation uses structured mental exercises, computer tasks, and real-life problem-solving to support the brain’s ability to compensate for damaged areas. Therapists also teach practical strategies, such as using calendars, alarms, notebooks, and simple routines. These techniques do not stop the disease but can slow functional decline, reduce frustration, and help people remain more independent in daily life. PubMed+1

7. Psychological counseling and treatment of depression/anxiety
Depression, anxiety, and personality change are common in CADASIL and can be as disabling as physical problems. Psychological counseling, such as cognitive-behavioral therapy, provides a safe space to process grief, fear about the future, and family stress. Therapy teaches coping strategies, problem-solving, and communication skills. By improving mood and reducing anxiety, counseling indirectly supports better self-care, medication adherence, and participation in rehabilitation, which all influence long-term outcomes in patients with chronic brain small-vessel disease. NCBI+1

8. Migraine trigger management and lifestyle regulation
Migraine with aura is a classic early symptom of CADASIL. Good sleep hygiene, regular meal times, hydration, stress reduction, and avoiding personal migraine triggers (such as certain foods, flashing lights, or strong smells) can reduce attack frequency. Because some migraine drugs that strongly narrow blood vessels are usually avoided in CADASIL, lifestyle regulation becomes even more important. By keeping the brain and blood vessels in a stable state, lifestyle measures may lessen migraine burden and reduce “bad days,” which supports work and social life. Stroke Manual+1

9. Family education and genetic counseling
CADASIL is inherited, so family members often worry about their own risk and that of future children. Genetic counseling explains how the NOTCH3 mutation is passed on, what testing options exist, and what results mean for life planning, pregnancy, and insurance. Education also helps relatives recognize symptoms early and seek care sooner. The mechanism is informational and preventive: by understanding the disease, families can make informed decisions and avoid unnecessary fear or guilt. MedlinePlus+1

10. Fall-prevention and home safety planning
As gait, balance, and thinking worsen, people with CADASIL are at higher risk of falls and injuries. Simple but well-planned changes, such as removing loose rugs, adding grab bars, improving lighting, and using walking aids, can greatly reduce this risk. Fall-prevention programs may also include strength and balance exercises. By lowering the chance of fractures or head injuries, these steps help preserve mobility and independence and prevent sudden serious setbacks on top of the underlying brain disease. NCBI

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Drug treatments

1. Aspirin (antiplatelet therapy)
Aspirin is an antiplatelet drug that makes blood platelets less sticky and reduces the chance of clots forming in narrowed brain vessels. In many stroke guidelines, low-dose aspirin is used to help prevent recurrent ischemic strokes, and this approach is sometimes applied to patients with CADASIL, although direct trial data in this disease are limited. The FDA label for aspirin describes its use for secondary prevention of cardiovascular and cerebrovascular events and warns about bleeding and stomach irritation as key side effects. In CADASIL, doctors carefully balance the possible benefit for stroke prevention against the risk of bleeding in fragile brain vessels. AHA Journals+2FDA Access Data+2

2. Clopidogrel (PLAVIX) and other antiplatelet agents
Clopidogrel is another antiplatelet drug that blocks ADP-mediated platelet activation and reduces clot formation. FDA labeling for PLAVIX describes its use in preventing heart attack and stroke in high-risk patients and explains that it is a pro-drug that must be metabolized in the liver to become active, with bleeding as the main adverse effect. In CADASIL, some specialists may choose clopidogrel instead of or in combination with aspirin (dual therapy is controversial) for people with recurrent ischemic events, but evidence is extrapolated from general stroke populations, not from large CADASIL trials, so every case must be individualized. AHA Journals+2FDA Access Data+2

3. Blood pressure-lowering drugs (ACE inhibitors, ARBs, thiazide diuretics, calcium-channel blockers, beta-blockers)
For people with CADASIL and high blood pressure, medications such as ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, calcium-channel blockers, or beta-blockers are often prescribed. These drugs reduce pressure on the walls of small arteries and may slow the development of further strokes and vascular dementia, as suggested by large hypertension and stroke prevention trials in the general population. The exact drug and dose are chosen based on comorbidities, kidney function, and tolerability. Side effects depend on the class and can include cough (ACE inhibitors), dizziness or low blood pressure, electrolyte changes, and swelling. AHA Journals+1

4. Cholesterol-lowering drugs (statins)
Statins, such as atorvastatin or simvastatin, lower LDL (“bad”) cholesterol and have anti-inflammatory and plaque-stabilizing effects on blood vessels. Even though CADASIL is not caused by classic atherosclerosis, many patients also have common vascular risk factors, and guidelines often suggest statins when cholesterol is high or when there are coexisting cardiovascular risks. Statins work by blocking HMG-CoA reductase in the liver, decreasing cholesterol production. Side effects may include muscle pain, liver enzyme changes, or, rarely, muscle breakdown. The aim is to reduce overall vascular risk, not to cure the genetic vessel problem. AHA Journals+1

5. Migraine prophylaxis drugs (beta-blockers, topiramate, others)
Migraine with aura in CADASIL may be treated with preventive medications such as beta-blockers (e.g., propranolol) or anti-seizure drugs like topiramate. These drugs reduce the frequency and severity of migraine attacks by stabilizing nerve excitability and vascular responses. However, vasoconstricting drugs such as triptans and ergot derivatives are usually used with caution or avoided because of theoretical stroke risk in small-vessel disease. Side effects may include tiredness, low blood pressure (beta-blockers), or tingling and cognitive slowing (topiramate). Treatment is highly individualized. Stroke Manual+1

6. Antidepressants and mood stabilizers
Depression and mood disorders are common in CADASIL, and selective serotonin reuptake inhibitors (SSRIs) or other antidepressants may be prescribed. These medicines adjust chemical signaling between brain cells, which can improve mood, energy, sleep, and appetite. Treating depression is vital because low mood can worsen memory and participation in rehabilitation. Side effects vary and can include nausea, sexual dysfunction, and sleep changes. Occasionally, mood stabilizers or antipsychotic drugs may be used for severe mood swings or behavioral symptoms, always with careful monitoring. NCBI+1

7. Anti-seizure medicines (antiepileptic drugs)
Some people with CADASIL develop seizures due to scarred brain tissue from repeated small strokes. Standard antiepileptic drugs such as levetiracetam or lamotrigine may be used to control seizures. These medicines stabilize electrical activity in brain cells and reduce the chance of abnormal bursts that cause seizures. Side effects can include tiredness, dizziness, mood changes, or allergic skin reactions, depending on the specific drug. Good seizure control improves safety, driving eligibility (if allowed by local laws), and overall quality of life. NCBI+1

8. Cognitive enhancers (donepezil and similar drugs – off-label, limited evidence)
Donepezil is an acetylcholinesterase inhibitor approved for Alzheimer’s disease, and it increases the level of acetylcholine, a neurotransmitter involved in memory and thinking. A randomized trial in patients with CADASIL and cognitive impairment found no clear improvement in the main memory outcome but some small benefits in tests of executive function; the clinical importance was uncertain. This means that donepezil might be tried in selected patients, but expectations should be modest. Side effects include nausea, diarrhea, muscle cramps, and, rarely, slow heart rate. Use is off-label and must be carefully supervised. PubMed+2The Lancet+2

9. Diabetes and metabolic-syndrome drugs
When CADASIL patients also have diabetes or pre-diabetes, glucose-lowering medicines such as metformin or other agents may be used. Good blood sugar control reduces general vascular risk and may help protect small vessels in the brain. These drugs work through several mechanisms, including improving insulin sensitivity and reducing glucose production by the liver. Side effects vary but may include stomach upset, low blood sugar (with some drugs), or weight gain or loss depending on the class. Managing metabolic health is an important part of the whole-person treatment plan. AHA Journals+1

10. Anticoagulants (used only if there is another strong indication)
Drugs like warfarin or direct oral anticoagulants (blood thinners) are generally not recommended just for CADASIL because they may increase the risk of dangerous brain bleeding in fragile small vessels. However, if a patient has another serious condition such as atrial fibrillation or mechanical heart valve, anticoagulants may still be needed to prevent large clots. In these rare cases, doctors carefully weigh the benefits and risks and monitor very closely. This shows how complex and individualized drug treatment is in CADASIL. AHA Journals+1

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Dietary molecular supplements

(Evidence for supplements in CADASIL is limited; most data come from general brain and vascular-health research. Always discuss supplements with a doctor, especially if you take blood thinners.)

1. Omega-3 fatty acids (fish oil)
Omega-3 fatty acids from fish oil (EPA and DHA) may help reduce inflammation, improve blood lipid profiles, and make platelets slightly less sticky. Many studies in the general population suggest a modest benefit in cardiovascular risk and brain health, although results are mixed. For someone with CADASIL, omega-3 supplements or frequent oily fish meals may support overall vascular health, but they are not a treatment for the genetic problem itself. High doses can increase bleeding risk, especially with antiplatelet drugs, so dosing must be individualized by a clinician. AHA Journals+1

2. Folic acid and vitamin B12
Folate and vitamin B12 help control homocysteine, an amino acid linked with higher stroke and heart disease risk when levels are elevated. In people with deficiency, supplementation can correct anemia, improve nerve function, and lower homocysteine, which may support small-vessel health. For CADASIL, supplementing only makes sense if blood tests show low levels or high homocysteine. Too much supplementation without need is not helpful and may even have risks in the long term. AHA Journals

3. Vitamin D
Low vitamin D is common worldwide and has been associated with higher risk of stroke, cognitive decline, and mood problems in many observational studies. Vitamin D supports bone health, immune regulation, and possibly blood vessel function. Correcting a deficiency with appropriate doses may therefore support general health in CADASIL patients. However, very high doses can cause high calcium levels and kidney damage, so supplementation should be guided by blood tests and medical advice. AHA Journals+1

4. Antioxidant vitamins (vitamin C and vitamin E)
Oxidative stress plays a role in blood vessel damage. Vitamin C and vitamin E are antioxidants that neutralize free radicals and may help protect vessel walls in theory. Large trials in the general population, however, have not shown clear stroke-prevention benefits from routine high-dose antioxidant supplements. For CADASIL, it is generally safer to focus on a diet naturally rich in fruits, vegetables, and nuts rather than large supplement pills, unless a specific deficiency is found. AHA Journals+1

5. Coenzyme Q10
Coenzyme Q10 is involved in energy production in mitochondria and also has antioxidant properties. Some small studies suggest possible benefits in heart failure and certain mitochondrial diseases. For CADASIL, there is no direct trial evidence, but some clinicians may consider CoQ10 as an adjunct for fatigue or general vascular support. The mechanism is improved cellular energy and reduced oxidative stress. As with other supplements, potential interactions with medications should be reviewed first. AHA Journals

6. Magnesium
Magnesium plays roles in nerve signaling, muscle contraction, and blood vessel relaxation. It has been studied for migraine prevention and blood pressure control. For CADASIL patients with migraine, an adequate magnesium intake from diet or supplements may help reduce attack frequency, although evidence is modest. Too much magnesium can cause diarrhea or, in severe kidney disease, dangerous high blood levels, so dosing should be appropriate and supervised. Stroke Manual+1

7. Curcumin
Curcumin, a natural compound in turmeric, has anti-inflammatory and antioxidant effects in experimental studies. It may help reduce vascular inflammation and oxidative damage, but robust human data for stroke prevention are lacking. In CADASIL, curcumin might be used as a food ingredient rather than as high-dose capsules. Because it can affect blood clotting at high doses, patients on antiplatelet or anticoagulant drugs should be cautious. AHA Journals

8. Resveratrol
Resveratrol, found in grapes and berries, is another antioxidant studied for its potential protective effects on heart and brain. Laboratory research suggests it may improve endothelial function and reduce inflammation, but human trials are still limited. For CADASIL, resveratrol cannot be recommended as a standard treatment; at best it may be a minor supportive supplement within a balanced diet. Excessive use, especially from alcohol sources like red wine, is not safe for brain health. AHA Journals+1

9. Probiotics and gut-health support
The gut microbiome can influence inflammation and vascular health. Probiotic foods such as yogurt, kefir, and fermented vegetables may help maintain a healthier gut microbiome, which might indirectly support blood pressure and metabolic health. Evidence is still emerging. For CADASIL, focusing on a fiber-rich, varied diet that feeds beneficial gut bacteria is a sensible and low-risk approach, rather than relying on high-dose probiotic supplements. AHA Journals

10. Multivitamin in documented deficiency
Some CADASIL patients, especially those with poor appetite, swallowing difficulty, or restrictive diets, may develop multiple mild vitamin deficiencies. A standard-dose multivitamin, prescribed or approved by a doctor, can help cover basic micronutrient needs. This does not treat the genetic disease but supports general body functions, making the person more resilient to illness and rehabilitation demands. High-dose or “mega” vitamin regimens without proven need should be avoided. NCBI+1

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Immunity-supporting, regenerative and stem-cell-related drugs

(Important: there are no approved stem cell or regenerative drugs specifically for CADASIL. The items below describe research directions and general concepts.)

1. Vaccinations (influenza, pneumococcal and others)
While not “drugs for CADASIL,” routine vaccines are a very important immunity-supporting measure. Infections like influenza and pneumonia can trigger strokes, worsen disability, and lead to hospital stays in people with fragile brains and vessels. Keeping vaccinations up to date helps the immune system quickly recognize and fight these germs, reducing severe infection risk. This is a practical way to “boost” immunity safely and is recommended in most stroke and chronic-disease guidelines. AHA Journals+1

2. Mesenchymal stem-cell therapies for ischemic stroke (experimental)
Mesenchymal stem cells (MSCs) from bone marrow or other tissues are being studied in clinical trials for ischemic stroke. These cells may release growth factors and anti-inflammatory signals that help repair damaged brain tissue and support new blood vessel growth. So far, trials are small and mostly in non-CADASIL stroke patients, and no therapy is approved specifically for CADASIL. At present, MSC therapy should only be considered inside registered clinical trials, not as routine treatment. PMC+1

3. Neural stem-cell approaches (experimental)
Neural stem cells can develop into different types of brain cells and are a focus of early research into repairing white-matter damage. In theory, they could replace lost cells or support surviving cells through growth factors. In reality, many scientific and safety hurdles remain, including the risk of tumors and immune reactions. For CADASIL, neural stem-cell therapy remains a future possibility, not a current treatment. PMC+1

4. Gene-targeted therapies (pre-clinical stage)
Because CADASIL is caused by mutations in the NOTCH3 gene, research is exploring ways to silence or correct the faulty gene using gene-editing or RNA-based methods. These approaches aim to stop production of the toxic form of NOTCH3 protein that damages vessel walls. So far, work is mostly in cell and animal models. No gene therapy for CADASIL is yet available in humans, but this is one of the most promising long-term directions. JCN+1

5. Vascular-protective experimental drugs
Scientists are testing drugs that improve endothelial function, reduce oxidative stress, or change how vessel smooth muscle cells respond to injury. Examples include experimental antioxidants, anti-inflammatory agents, and drugs that affect specific signaling pathways. In CADASIL, such medicines aim to slow progression of small-vessel damage. Right now, none are approved, so they may only be used in properly monitored research studies. AHA Journals+1

6. Neuroprotective agents in stroke trials (various compounds)
Many substances have been studied as “neuroprotective” agents in acute stroke, such as NMDA-receptor blockers or free-radical scavengers. So far, most have not shown clear benefit in large human trials. Still, these research programs teach scientists about how brain cells respond to ischemia and may one day lead to therapies that help CADASIL patients during or after strokes. At present, these agents should not be used outside clinical studies. PMC+1

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Surgical and procedural options

1. Emergency decompressive surgery for large strokes (hemicraniectomy)
In rare cases, a person with CADASIL may suffer a large brain infarct that causes dangerous swelling and high pressure inside the skull. For some younger patients, surgeons may perform a decompressive hemicraniectomy, where part of the skull is temporarily removed to give the swollen brain more room. This procedure is not specific to CADASIL but is used in life-threatening strokes. It aims to prevent brain herniation and death, but survivors often have significant disability. PMC+1

2. Feeding tube placement (PEG) for severe swallowing problems
If repeated strokes cause serious swallowing difficulty, a person may be unable to eat enough or may frequently aspirate food into the lungs. In such cases, a percutaneous endoscopic gastrostomy (PEG) tube may be placed directly into the stomach through the abdominal wall. This allows safe feeding and medicine delivery. The procedure is done under endoscopic guidance and sedation. It does not treat CADASIL itself but prevents malnutrition and reduces pneumonia risk. NCBI+1

3. Ventricular shunt surgery for hydrocephalus-like complications (rare)
In rare situations, extensive white-matter changes and strokes may disturb brain fluid circulation, leading to hydrocephalus-like symptoms. Neurosurgeons may then consider placing a ventriculoperitoneal shunt to drain excess cerebrospinal fluid from the brain to the abdomen. This can improve gait and cognition in carefully selected patients. Such cases are unusual in CADASIL, and decisions require a specialist team. NCBI

4. Orthopedic surgery after major falls or fractures
Because CADASIL increases fall risk, some patients may need orthopedic surgeries such as hip fracture repair. These operations restore mobility and reduce pain after injury but do not modify the underlying brain disease. Proper pre-operative planning and post-operative rehabilitation are especially important in people with cognitive and neurological problems. NCBI+1

5. Procedures for coexisting vascular disease (only if appropriate)
If a CADASIL patient also has severe large-vessel atherosclerotic disease, such as critical carotid artery narrowing, standard procedures like carotid endarterectomy or stenting may occasionally be considered. However, these decisions are complex because CADASIL mainly affects small vessels, and the risks and benefits may differ from typical patients. A multidisciplinary stroke team must weigh all factors before recommending such surgery. AHA Journals+1

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Prevention strategies

1. Keep blood pressure in the target range with lifestyle and medicines. AHA Journals+1
2. Do not smoke and avoid second-hand smoke completely. AHA Journals+1
3. Maintain healthy cholesterol and blood sugar with diet, activity, and medicines when needed. AHA Journals
4. Exercise regularly with safe, moderate activities most days of the week. AHA Journals+1
5. Follow medical advice on antiplatelet drugs if you have had strokes or TIAs. AHA Journals+1
6. Manage migraine triggers and sleep problems to reduce stress on the brain. Stroke Manual+1
7. Keep vaccinations up to date to lower infection-related stroke triggers. AHA Journals+1
8. Attend regular follow-up visits with neurology and primary-care doctors. NCBI+1
9. Offer genetic counseling to relatives to support early recognition and planning. MedlinePlus+1
10. Avoid unnecessary medications that may increase bleeding or strongly constrict blood vessels, unless a specialist clearly advises them. AHA Journals+1

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When to see a doctor

People with CADASIL or a family history should see a doctor urgently if they notice sudden weakness, numbness, trouble speaking, vision loss, severe dizziness, or loss of balance, because these can be signs of stroke or transient ischemic attack. New or rapidly worsening migraine with aura, seizures, serious mood changes, or a big drop in memory or thinking skills should also prompt medical review. Even without sudden symptoms, regular check-ups with neurology and primary-care teams are important to adjust medications, monitor blood pressure and cholesterol, and support daily function. Anyone with a known NOTCH3 mutation or strong family history who develops early strokes or unexplained white-matter changes on MRI should be followed in a specialist clinic. MedlinePlus+2NCBI+2

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What to eat and what to avoid

Helpful foods (examples)
Focus on a Mediterranean-style pattern, which is linked with better heart and brain health:

1. Plenty of colorful fruits and vegetables every day for vitamins, minerals, and antioxidants. AHA Journals

2. Whole grains such as oats, brown rice, and whole-wheat bread to support stable blood sugar and healthy weight. AHA Journals+1

3. Oily fish (like salmon, sardines, mackerel) one to two times per week for natural omega-3 fats. AHA Journals+1

4. Nuts and seeds in small portions for healthy fats, fiber, and magnesium. AHA Journals

5. Olive oil as the main added fat instead of butter or ghee. AHA Journals+1

Foods and habits to limit or avoid

6. Highly salty snacks and processed foods, which raise blood pressure (such as instant noodles, chips, and salty pickles). AHA Journals+1

7. Foods rich in trans fats and very fatty processed meats, which harm blood vessels (like fast food, deep-fried items, sausages). AHA Journals

8. Sugary drinks and sweets that lead to weight gain and diabetes. AHA Journals+1

9. Excessive alcohol, which raises blood pressure and stroke risk. AHA Journals+1

10. Large “mega-dose” herbal or vitamin supplements without medical advice, especially if you take blood thinners or antiplatelet drugs, because they may change bleeding risk. FDA Access Data+1

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Frequently asked questions (FAQs)

1. Is there a cure for CADASIL?
At present, there is no cure that can remove the NOTCH3 mutation or fully reverse vessel damage. Treatment focuses on reducing stroke risk, managing symptoms such as migraine or depression, and supporting daily function with rehabilitation and social help. Research into gene therapy and regenerative medicine is ongoing, but these options are still experimental. NCBI+1

2. How is CADASIL diagnosed?
Diagnosis is based on clinical history (early strokes, migraine with aura, family pattern), MRI showing characteristic white-matter changes, and confirmation of a NOTCH3 mutation on genetic testing. Sometimes a skin biopsy is performed to show typical deposits in small vessels, but genetic testing has become the main method. MedlinePlus+1

3. What symptoms should I expect over time?
Symptoms vary widely, even within the same family. Common features include migraine with aura, recurrent strokes or TIAs, mood changes, and gradual decline in thinking and walking. Some people remain relatively stable for many years, while others develop early disability. Good risk-factor control can improve the overall course. MedlinePlus+1

4. Can children develop CADASIL symptoms?
CADASIL is often recognized in adulthood, but in rare cases symptoms can appear in adolescence or even earlier, especially in severe mutation types. Children of an affected parent have a 50% chance of inheriting the mutation. Genetic counseling helps families decide if and when testing is appropriate. MedlinePlus+1

5. Is CADASIL contagious?
No. CADASIL is a genetic disorder and cannot be passed through contact, food, or the environment. It is inherited only through genes, most often from an affected parent in an autosomal dominant pattern. MedlinePlus+1

6. Do all people with a NOTCH3 mutation get very sick?
No. There is wide variability. Some people with a mutation may have mild symptoms or be diagnosed only later in life, while others become disabled earlier. Many factors, such as blood pressure, smoking, and other medical conditions, influence the course. This is why prevention and lifestyle management are so important. JCN+1

7. Should every relative be tested?
Genetic testing is a personal decision. Some relatives want certainty to guide life planning; others prefer not to know. Genetic counseling before and after testing is strongly recommended to discuss emotional, family, and practical implications, including pregnancy and insurance issues. MedlinePlus+1

8. Can women with CADASIL have a safe pregnancy?
Many women with CADASIL have had successful pregnancies, but there may be an increased risk of stroke and high blood pressure in pregnancy. Management must involve a high-risk obstetric team and a neurologist. Pre-pregnancy counseling and careful blood pressure and migraine control during pregnancy are very important. JCN+1

9. Are triptan migraine medicines safe in CADASIL?
Because triptans can narrow blood vessels in the brain, many specialists avoid them or use them with great caution in CADASIL, preferring non-vasoconstrictive options and strong lifestyle migraine control. Decisions are individualized and should always be made by a neurologist familiar with CADASIL and stroke risk. Stroke Manual+1

10. Does aspirin guarantee I will not have another stroke?
No. Aspirin and other antiplatelet drugs can lower the risk of clot-related strokes but cannot prevent all events, especially in a genetic small-vessel disease like CADASIL. Medication is only one part of prevention; controlling blood pressure, not smoking, exercising, and following medical advice are just as important. AHA Journals+2FDA Access Data+2

11. How often should I have MRI scans?
There is no single rule. MRI is often done at diagnosis and then repeated if there are new symptoms or to monitor disease progression. The exact timing depends on clinical changes and the preferences of the neurology team. Unnecessary frequent scans are usually avoided to reduce cost and anxiety. NCBI+1

12. Can diet alone control CADASIL?
A healthy diet can greatly support blood pressure, cholesterol, and general health, which are crucial in managing CADASIL. However, diet alone cannot correct the NOTCH3 mutation or fully prevent strokes. For most people, the best approach combines diet, physical activity, medications when needed, and regular medical care. AHA Journals+1

13. Is CADASIL the same as multiple sclerosis?
No. Both conditions can cause white-matter lesions on MRI and neurological symptoms, but CADASIL is a genetic small-vessel disease, while multiple sclerosis is an inflammatory demyelinating disorder. Their MRI patterns, spinal-fluid tests, and treatments are different. Sometimes CADASIL can be mistaken for MS early on, so specialist review is important. NCBI+1

14. Will I always end up in a wheelchair or with severe dementia?
Not necessarily. While many patients develop mobility and cognitive problems over time, the severity and speed of progression vary widely. Good management of vascular risk factors, early rehabilitation, and strong social and psychological support can help many people stay active and engaged for longer. NCBI+1

15. Where can my family find reliable information and support?
Reliable information is available from genetics resources like MedlinePlus, specialist neurology clinics, national stroke foundations, and rare-disease organizations that focus on CADASIL and inherited small-vessel diseases. Patient support groups, including online communities run by reputable organizations, offer shared experiences and practical advice but should never replace medical care. MedlinePlus+2NCBI+

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: December 21, 2025.