We present a Turkish family with CADASIL, in which 12 individuals in four generations were affected showing the typical clinical features of recurrent strokes. [ncbi.nlm.nih.gov]

Presentation is usually with recurrent transient ischemic attacks (TIAs) or strokes in multiple vascular territories. Presenile dementia and migraines develop in the third-to-fourth decades of life. [radiopaedia.org]

We present a short review of the literature on the clinical presentation of patients with CADASIL and provide recommendations for the detection and diagnosis of similar cases. [functionalneurology.com]

This can positively diagnose CADASIL, though a negative result on this test does not necessarily mean that the disease is not present. [web.archive.org]

• Disability

  Overview Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant genetic disease that induces recurrent subcortical ischemic strokes and ultimately leads to severe disability and death [medlink.com]

  Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). [ncbi.nlm.nih.gov]

  Migraine headaches are an early symptom of this condition, which progresses to strokes and mini-strokes, depression, apathy, motor disability and excutive dysfunction (an inability to plan and organize everyday activities.) [corleycadasil.btck.co.uk]

  Please enable JS and disable any ad blocker [lequotidiendumedecin.fr]

• Asymptomatic

  Brain MRI of elderly asymptomatic and paucisymptomatic individuals with a NOTCH3 mutation compared to MRI in classical cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [raredr.com]

  The exams in 2a and 2b are from asymptomatic patients with depression. Note temporal lobe lesions even in asymptomatic patients (2b). [commons.wikimedia.org]

  All symptomatic subjects had prominent signal abnormalities on MRI with hyperintense lesions on T2-weighted images in the subcortical white-matter and basal ganglia which were also present in 19 asymptomatic subjects. [ncbi.nlm.nih.gov]

  However, no randomised and controlled trials have explored this topic.21–23 Lastly, the diagnosis may be confirmed in a patient's asymptomatic family members by means of a genetic study. [elsevier.es]

• Progressive Dementia

  Subcortical ischaemic events occur in 84% with progressive or stepwise subcortical dementia and pseudobulbar palsy in 31%. [ 8 ] Migraine with aura occurs in 22% and mood disorders with severe depressive episodes in 20%. [patient.info]

  Mellies JK, Baumer T, Muller JA, Tournier-Lasserve E, Chabriat H, Knobloch O, et al. (1998) SPECT study of a German CADASIL family: a phenotype with migraine and progressive dementia only. Neurology 50:1715–1721 PubMed Google Scholar 11. [doi.org]

  Clinically, CADASIL is associated with progressive dementia, mood disorders, migraine, and recurrent subcortical cerebral infarctions. [emedicine.medscape.com]

  But we now know that patients with Cadasil often have the kind of severe headaches this patient described, as well as strokes and an early and relentlessly progressive dementia associated with often significant personality changes. [nytimes.com]

• Fatigue

  […] mini-strokes); This a progressively debilitating disease; The progress, severity and specific symptoms are variable from person to person and can include migraines, headaches, small strokes, strokes, gait problems, mood disorder, anxiety, depression, apathy, fatigue [rarediseaseday.org]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019 [patientslikeme.com]

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• Vomiting

  […] 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 [rarediseases.info.nih.gov]

  These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding. [livingnaturally.com]

  The other individual (PN 3) had visual, sensory, and aphasic aura followed by unilateral headache, photophobia, phonophobia, and vomiting, with attacks clustering in the first 3 years of adolescence. [jamanetwork.com]

• Nausea

  Some of the symptoms can be somewhat pedestrian like numbness or tingling and dizziness or nausea to more serious warnings like severe migraine headaches and even strokes. [theexaminernews.com]

  […] 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 [rarediseases.info.nih.gov]

  Common accompanying features were seizures (n = 10), fever (n = 4), hallucinations (n = 13), nausea and/or vomiting (n = 9) and meningism (n = 2) (Table 3). [journals.plos.org]

• Dysphagia

  This burden is increased by cognitive deficits and other manifestations, such as dysphagia and incontinence, which are both frequent and a source of further complications. [academic.oup.com]

  MRI shows basal ganglia and confluent white matter lesions; III: usually after 60 years, with subcortical dementia associated with pseudobulbar signs - dysarthria, dysphagia and emotional lability; and in some cases apathy, mutism and akinesia. [doi.org]

• Dysphagia

  This burden is increased by cognitive deficits and other manifestations, such as dysphagia and incontinence, which are both frequent and a source of further complications. [academic.oup.com]

  MRI shows basal ganglia and confluent white matter lesions; III: usually after 60 years, with subcortical dementia associated with pseudobulbar signs - dysarthria, dysphagia and emotional lability; and in some cases apathy, mutism and akinesia. [doi.org]

• Thrombosis

  […] and arterial thrombosis (including coronary, cerebral, retinal and lower limbs). 8-10% of all patients with venous thrombosis have antiphospholipid antibodies. [neuroweb.us]

  However, given that CADASIL is non-atherosclerotic, the role of thrombosis in causing strokes with CADASIL is in question. Thus, antiplatelet therapy may fall out of favor. [statpearls.com]

  Headache attributed to cerebral venous thrombosis (CVT) [I63.6] 6.7. Headache attributed to other intracranial vascular disorder 6.7.1. [ihs-klassifikation.de]

• Alopecia

  Although alopecia is a hallmark feature of CARASIL, HTRA1 pathogenic variants have been reported in three patients with a clinical diagnosis of CARASIL and no alopecia (Nishimoto et al. 2011. PubMed ID: 21482952; Bianchi et al. 2014. [preventiongenetics.com]

  2022 8:36 PM By Biree Andemariam, MD Current FDA-Approved Therapies for SCD Management October 26, 2022 8:33 PM By Biree Andemariam, MD IBD Patients Maintain Antibodies 6 Months Following COVID-19 Vaccination October 26, 2022 5:47 PM By Kenny Walter Alopecia [hcplive.com]

  Alopecia (a common feature in CARASIL) or prominent lesions of the skin or other organs and systems also appear to be rare 125-127. Venous insufficiency was a frequent manifestation in one oriental family 128. [doi.org]

• Premature Balding

  CARASIL ( C erebral A utosomal R ecessive A rteriopathy with S ubcortical I nfarcts and L eukoencephalopathy), predominantly reported in Japanese families, is a rare autosomal recessive SVD with a more complex phenotype that includes premature baldness [uvm.edu]

  Most common symptoms include alopecia, ischemic strokes with no hypertension, premature baldness, severe low back pain, personality changes, cognitive deficit and dementia. [preventiongenetics.com]

• Headache

  HEADACHE ATTRIBUTED TO A SUBSTANCE OR ITS WITHDRAWAL 9. HEADACHE ATTRIBUTED TO INFECTION 10. HEADACHE ATTRIBUTED TO DISORDER OF HOMOEOSTASIS 11. [ihs-klassifikation.de]

  CADASIL Migraine Aura Headache Triptans International Classification of Headache Disorders [link.springer.com]

  In her mid-thirties she developed episodic slurred speech, confusion and visual hallucinations during the headache. She later developed progressive memory impairment and gait ataxia. [neurology.org]

  since the patient has no history of headaches. [elsevier.es]

  Abstract A 17-year-old girl presented with migraine with prolonged aura and aura without headache. Neurologic examination was normal. Her mother, who did not have a history of migraine, developed right-face and -arm numbness at the age of 45. [pediatrics.aappublications.org]

• Dysarthria

  On neurological exam, he had moderate flaccid dysarthria and left-sided hemiparesis. [hindawi.com]

  Her mother had a similar progressive illness of three years duration with difficulty in walking, dysarthria, cognitive impairment, and incontinence with white matter changes in brain MRI. [neurologyindia.com]

  […] mechanism.(1) It is noteworthy that risk factors such as hypertension and diabetes mellitus are not common.(1) The age of onset is usually in the 40’s, with most patients presenting with a typical lacunar syndrome (pure motor and/or sensory stroke, dysarthria [eso-stroke.org]

  · Ischemic events are commonly subcortical and sometimes manifest as lacunar syndromes such as pure motor, pure sensory strokes or ataxic hemiparesis, sensory-motor deficit, dysarthria–clumsy hand syndrome (difficulty in speech articulation associated [medium.com]

  Fifty-four per cent of the cases had a history of pathological laughing or crying, mostly in combination with dysarthria. [academic.oup.com]

• Aphasia

  Homonymous Hemianopia (Visual loss in lateral half of both eyes) Kaleidoscopic vision (flashing shapes, patterns, floating specks of light) Sensory Aura: Involving face and arm Motor Aura: Involving arm Aphasic aura Speech Disturbances with expressive aphasia [medium.com]

  Showing of 47 | 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 [rarediseases.info.nih.gov]

  Severe aphasia, apraxia or agnosia are rare in CADASIL. Psychiatric disorders, mainly mood disturbances, appear in 20% of patients, in general as severe depressive episodes. [jneuro.com]

• Abnormal Gait

  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 [rarediseases.info.nih.gov]

• Cerebellar Sign

  There was no sensory deficit or cerebellar signs. Examination of other systems was normal. The pedigree chart is shown in [Figure - 1]. [neurologyindia.com]

  There was no motor or sensory deficit or cerebellar signs. Examination of other systems was normal. There were no abnormal reflexes. [functionalneurology.com]

Genetic testing for pathogenic mutations in the NOTCH3 gene is available for use in the diagnostic workup of individuals with a clinical history and symptoms suspicious for CADASIL syndrome. [unicare.com]

• Hypercholesterolemia

  Medications for hypertension and hypercholesterolemia are also beneficial in patients with CADASIL syndrome. [brighthub.com]

  Symptomatic treatment can be offered to patients to treat migraines and potential concomitant vascular risk factors (hypertension, hypercholesterolemia and diabetes). [orpha.net]

  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. [checkorphan.org]

  The only vascular risk factor present was moderate hypercholesterolemia (266 mg/dL [6.9 mmol/L]). [jamanetwork.com]

  Aggressive treatment of hypercholesterolemia and hypertension is reasonable, although the utility of statins and antihypertensive agents in the absence of cardiovascular risk factors is unknown. [ipfs.io]

• Amyloid Plaque

  The combination of PAS positive granular osmiophilic material in the wall of medium sized to small vessels with subcortical infarcts is characteristic of CADASIL. 7 In addition, the presence of hippocampal and neocortical amyloid plaques (some of which [jnnp.bmj.com]

  Plant GT, Revesz T, Barnard RO, Harding AE, Gautier-Smith PC (1990) Familial cerebral amyiopathy with nonneuritic amyloid plaque formation. Brain 113: 721–747 Google Scholar 35. [doi.org]

  SAP has been implicated in cognitive diseases such as Alzheimer’s as having a role in the stabilization of amyloid plaques and may have a similar role in the formation and stabilization of GOMs in CADASIL [16■■,17]. [ncbi.nlm.nih.gov]

Establishing the effects of NOTCH3 variability and exploring this with environmental factors such as smoking will help identify subsets of at-risk individuals, and promote preventative diagnosis and treatment. [mayo.edu]

Management and treatment There is no cure for CADASIL. Antiplatelet therapy is often used but it has not yet been proven as an effective treatment. [orpha.net]

Treatment was started with 40 mg, followed by a dosage increase to 80 mg after 4 weeks. Transcranial Doppler sonography measuring mean flow velocity (MFV) in the middle cerebral artery was performed at baseline and the end of the treatment period. [ncbi.nlm.nih.gov]

There is no specific treatment currently available specific to the disease, but symptomatic treatment is usually prescribed. Supportive care includes rehabilitation and counselling measures. [medium.com]

Currently there are no treatments for CADASIL but patients can receive symptomatic treatment for migraines and other symptoms that are common in patients. [raredr.com]

Prognosis The prognosis is poor with most patients eventually becoming bed-ridden and dement and requiring constant nursing care. The median age at death is 68 years. Expert reviewer(s): Dr S.A.J. [Saskia] LESNIK OBERSTEIN - Dr G.M. [orpha.net]

Read More Read Less Prognosis Prognosis Symptoms usually progress slowly. By age 65, the majority of persons with CADASIL have cognitive problems and dementia. Some will become dependent due to multiple strokes. Clinical Trials Clinical Trials [ninds.nih.gov]

Treatment and prognosis Typically the disease has a variable but progressive course leading to death between 50 to 70 years of age 2,4. [radiopaedia.org]

Prognosis Prognosis is progressive and the earliest forms of CADASIL are the most severe. Prolonged periods of stability or even transient mild improvements lasting years are common. [cadasil.weebly.com]

Prognosis Symptoms usually progress slowly. By age 65, the majority of persons with CADASIL have cognitive problems and dementia. Some will become dependent due to multiple strokes. [brainfacts.org]

Etiology CADASIL is caused by mutations in the NOTCH3 gene (>95% of cases), located to 19p13.2-p13.1, which encodes transmembrane receptor NOTCH3, mainly expressed in vascular smooth muscle cells. [orpha.net]

Insights gained from the study of CADASIL should help us better understand its etiology, as well as the options for treatment of the more common forms of microvascular disease seen in the elderly. [ncbi.nlm.nih.gov]

The original reference is provided for historical interest, and review articles are included to show recent advances in etiology and treatment. [books.google.de]

Etiology Originally, CADASIL was recognized as a heritable early-onset microvascular disease of unknown etiology. [statpearls.com]

Carrier prevalence was found to be 4.14/100000[3].An epidemiological study in Northeast England found a similar prevalence of 1.32/100000 for the disease [4]. [medium.com]

Summary Epidemiology In Europe, the prevalence of CADASIL has been estimated to range between 1/50 000- 1/25 000. [orpha.net]

Synonyms: C erebral A utosomal D ominant A rteriopathy with S ubcortical I nfarcts and L eucoencephalopathy (CADASIL), familial vascular leukoencephalopathy Epidemiology This is a rare familial form of multi-infarct dementia and other neurological problems [patient.info]

Epidemiology • Unknown prevalence – 400 families world-wide – 2/100,000 – Largely undiagnosed • Gender effect – women less severely impaired cf. to men after adjusting for age and education after 50 years of age • Presents in mid-20s to age 45 • Shortened [de.slideshare.net]

Ongoing research intends to find out the exact pathophysiology of the disease using animal models so that specific therapeutics can be developed. [medium.com]

In the open source article, the authors illustrate the significant pathophysiologic diversity that can exist in the CADASIL population in the following set of MRIs. [raredr.com]

Mutations described here cause an odd number of cysteines in the N-terminal of the EGF domain of Notch3 protein, which seems to have an important functional effect in the pathophysiology of CADASIL. [ncbi.nlm.nih.gov]

* A comprehensive source that thoroughly examines the neurological manifestations of stroke * A guide to highly studied topics, including stroke complications, syndromes, and stroke related psychiatric disorders * A better understanding of the pathophysiological [books.google.de]

Establishing the effects of NOTCH3 variability and exploring this with environmental factors such as smoking will help identify subsets of at-risk individuals, and promote preventative diagnosis and treatment. [mayo.edu]

By that time, the two main clinical trials on aspirin in primary stroke prevention—the US and British studies, published in the late 1980s—recruited only male participants. [cadasilfoundation.org]

Migraine should be treated both symptomatically and prophylactically (with preventative methods), depending on the frequency of symptoms. [checkorphan.org]

There is currently no prevention or treatment of proven efficacy for CADASIL. [mscare.org]

Treatment is usually focused on the prevention of complications. For example, anti-platelet agents such as aspirin, are given to prevent occurrence of stroke. [brighthub.com]