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]

• Epilepsy

  Less common signs include reversible acute encephalopathy (accompanied by headache, confusion, and seizures), epilepsy and subclinical peripheral neuropathy. [orpha.net]

  In the brain, the resulting blood vessel damage (arteriopathy) can cause migraines, often with visual sensations or auras, or recurrent seizures (epilepsy). [ghr.nlm.nih.gov]

  Cognitive deficits were seen in 59%, migraine in 38%, psychiatric symptoms in 30% and epilepsy in 10%. [patient.info]

  Coauthor(s) Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine Selim R Benbadis, MD is a member of the [emedicine.medscape.com]

  Most patients develop seizures (epilepsy) late in the illness that are easy to control. Life expectancy is reduced, though patients can live into their second or third decades. [cadasil.weebly.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]

  More Clinical News View All >> Insomnia Severity High in Patients with Post COVID-19 Related Fatigue October 27, 2022 10:00 AM By Connor Iapoce Neera Dahl, MD, Identifies how to Diagnose Autosomal Dominant Polycystic Kidney Disease October 26, 2022 10 [hcplive.com]

• Unconsciousness

  Later, he wrote: ‘I was struck down by an acute inflammatory illness … and reduced to a state of extreme weakness, lying at one stage unconscious for some hours’ (Ruskin, 1906 ). [doi.org]

• Surgical Procedure

  This form of skin infection is difficult to treat with antibiotics alone and typically requires a surgical procedure to remove the involved sweat glands in order to stop the skin inflammation. [livingnaturally.com]

• Vomiting

  Decline in memory and thinking skills (cognitive deterioration) Seizures Vision problems Slow movements and tremors (parkinsonism) Psychiatric problems such as mood disturbances (apathy and depression) Numbness or weakness Rapid onset of vertigo, nausea/vomiting [ninds.nih.gov]

  […] 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]

• Nausea

  […] dementia Decline in memory and thinking skills (cognitive deterioration) Seizures Vision problems Slow movements and tremors (parkinsonism) Psychiatric problems such as mood disturbances (apathy and depression) Numbness or weakness Rapid onset of vertigo, nausea [ninds.nih.gov]

  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]

• Myopathy

  Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes: a distinctive clinical syndrome. Ann. Neurol. 16, 481–488 (1984). 3 Mudd, S.H., Levy, H.L. & Skovby, F. [doi.org]

  […] 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 [rarediseases.info.nih.gov]

  MELAS(mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, MIM 540000) ：繰り返す嘔吐，頭痛，痙攣，脳卒中様発作を特徴とするミトコンドリア病の一病型である． [jhsnet.org]

  We have previously described a patient with CADASIL caused by a R133C mutation in the NOTCH3 gene and with a concomitant myopathy caused by a 5650G>A mutation in the MTTA gene in mitochondrial DNA (mtDNA) [4]. [wikigenes.org]

  Salih Myopathy Peter Hackman, Marco Savarese, Virginie Carmignac, Bjarne Udd, and Mustafa A Salih. Initial Posting: January 12, 2012; Last Update: April 11, 2019. [ncbi.nlm.nih.gov]

• Psychiatric Symptoms

  Cognitive deficits were seen in 59%, migraine in 38%, psychiatric symptoms in 30% and epilepsy in 10%. [patient.info]

  Predominant clinical features include migraine with aura (atypical or isolated), strokes, memory loss, and multiple psychiatric symptoms including dementia. [clinicaltrials.gov]

  Faculty for the Psychiatry of Old Age ( 2006 ) Atypical Antipyschotics and Behavioural and Psychiatric Symptoms of Dementia: Prescribing Update for Old Age Psychiatrists. Royal College of Psychiatrists ( http://www.rcpsych.ac.uk/PDF/BPSD.pdf ). [apt.rcpsych.org]

  Neurological signs of the disease, such as migraine, transient ischemic attacks, lacunar infarcts, cognitive declines and dementia, are often comorbid with psychiatric symptoms (1,3). [dusunenadamdergisi.org]

• Psychiatric Manifestation

  Psychiatric disorders At least 20 to 40% of patients with CADASIL exhibit psychiatric disorders. In a report of 454 patients, 106 (24%) had mood disorders 75. Depression is the most common manifestation - at least half of the cases. [doi.org]

• 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

  gait in association with head-motion intolerance and abnormal eye movements (acute vestibular syndrome) Currently there is no cure or effective treatment for CADASIL. [ninds.nih.gov]

  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]

• Neurologic Manifestation

  This intensive handbook is meant to give clinicians a source reference that will enable them to gain a thorough knowledge and understanding of the clinical features and management of the many neurological manifestations of stroke disorder. [books.google.de]

  The patient was a 62 years old male, presented with a past history of neurological manifestations, including gait disturbance and frequent convulsive attacks. He was diagnosed as CADASIL syndrome with Notch3 Arg133Cys mutation. [ncbi.nlm.nih.gov]

  manifestations, primarily migraines and premature onset of small vessel ischemic disease. [statpearls.com]

  manifestations such as seizures [5,6,7]. [humgenomics.biomedcentral.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]

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]

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]

The phenotypic variability in families carrying the same molecular defect as presented here makes the prediction of prognosis inconceivable. [ncbi.nlm.nih.gov]

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 [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]