CADASIL

Source: Wikipedia, the free encyclopedia.
CADASIL
Other namesCADASIL syndrome
Brain MRI from patients with CADASIL showing multiple lesions.
SpecialtyNeurology, cardiology, medical genetics Edit this on Wikidata
SymptomsMigraine headaches

CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary

leukodystrophies. The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.[2][3]

The condition was identified and named by French researchers Marie-Germaine Bousser and Elisabeth Tournier-Lasserve in the 1990s.[4][5] Together with two other researchers, Hugues Chabriat and Anne Joutel, they received the 2019 Brain Prize for their research into the condition.[6]

Signs and symptoms

CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 and 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and urinary incontinence.[citation needed]

lacunar syndrome occurs in at least two-thirds of affected patients while hemispheric strokes are much less common. It is worthy of note that ischemic strokes typically occur in the absence of traditional cardiovascular risk factors. Recurrent silent strokes, with or without clinical strokes, often lead to cognitive decline and overt subcortical dementia. A case of CADASIL presenting as schizophreniform organic psychosis has been reported.[7]

Pathophysiology

The underlying pathology of CADASIL is progressive hypertrophy of the

electron microscopy.[9] Leukoencephalopathy follows. Depending on the nature and position of each mutation, a consensus significant loss of beta sheet structure of the Notch3 protein has been predicted using in silico analysis.[10]

Diagnosis

A micrograph showing punctate immunostaining (brown) with a Notch 3 antibody, as is characteristic in CADASIL.

MRIs show hypointensities on

Binswanger disease.[2][11] These white matter lesions are also seen in asymptomatic individuals with the mutated gene.[12] While MRI is not used to diagnose CADASIL, it can show the progression of white matter changes even decades before onset of symptoms.[citation needed
]

The definitive test is sequencing the whole

Notch 3 gene, which can be done from a sample of blood. However, as this is quite expensive and CADASIL is a systemic arteriopathy, evidence of the mutation can be found in small and medium-size arteries. Therefore, skin biopsies are often used for the diagnosis.[13][14]

Treatment

No specific treatment for CADASIL is available. While most treatments for CADASIL patients' symptoms – including migraine and stroke – are similar to those without CADASIL, these treatments are almost exclusively empiric, as data regarding their benefit to CADASIL patients are limited.[15] Antiplatelet agents such as aspirin, dipyridamole, or clopidogrel might help prevent strokes; however, anticoagulation may be inadvisable given the propensity for microhemorrhages.[16] Control of high blood pressure is particularly important in CADASIL patients.[15] Short-term use of atorvastatin, a statin-type cholesterol-lowering medication, has not been shown to be beneficial in CADASIL patients' cerebral hemodynamic parameters,[17] although treatment of comorbidities such as high cholesterol is recommended.[18] Stopping oral contraceptive pills may be recommended.[19] Some authors advise against the use of triptan medications for migraine treatment, given their vasoconstrictive effects,[20] although this sentiment is not universal.[18] In this regard, the advent of the "Ditans" such as Lasmiditan, lacking vasoconstrictive effect, and the "Gepants" such as Ubrogepant and Rimegepant, are attractive alternatives, albeit not yet field-tested in this condition. As with other individuals, people with CADASIL should be encouraged to quit smoking.[21]

In one small study, around 1/3 of patients with CADASIL were found to have cerebral microhemorrhages (tiny areas of old blood) on

MRI.[16]

L-arginine, a naturally occurring amino acid, has been proposed as a potential therapy for CADASIL,[22] but as of 2017 there are no clinical studies supporting its use.[19] Donepezil, normally used for Alzheimer's Disease, was shown not to improve executive functioning in CADASIL patients.[23]

Society and culture

James Whistler's Nocturne in Black and Gold – The Falling Rocket as "ask[ing] two hundred guineas for throwing a pot of paint in the public's face". This resulted in the famous libel trial that resulted in a jury's awarding Whistler one farthing damages.[24]

Recent research into the illness of philosopher Friedrich Nietzsche has suggested that his mental illness and death may have been caused by CADASIL rather than tertiary syphilis.[25] Likewise, the early death of the composer Felix Mendelssohn, at age 37, from a stroke has been potentially linked to CADASIL. His sister, Fanny Mendelssohn, was similarly affected.[26] And James Dewar, best known as vocalist for Robin Trower, died age 59 from complications of CADASIL.[27]

In the movie The Sea Inside, one of the characters is stated to have CADASIL.[28]

In the

Roderick Usher suffers from this disorder, and much of the series storyline surrounds his criminal and illicit attempts to find a cure. The limited series is based on the life's work of Edgar Allan Poe
.

See also

References

  1. S2CID 4351873
    .
  2. ^
    S2CID 44289660
    .
  3. ISBN 978-0-7216-2921-6
    .
  4. ^ "CADASIL History". www.cadasilfoundation.org. Archived from the original on 2021-05-15. Retrieved 2018-03-03.
  5. PMID 9026542
    .
  6. ^ Office, FENS. "The Brain Prize 2019: French neuroscientists honoured for outstanding research into small vessel strokes in the brain". FENS.org. Archived from the original on 2021-05-15. Retrieved 2021-03-04.
  7. PMID 25824603
    .
  8. PMID 10712431
    .
  9. S2CID 24884723
    .
  10. ^ Vlachakis D, Champeris Tsaniras S, Ioannidou K, Papageorgiou L, Baumann M, Kossida S (October 2014). "A series of Notch3 mutations in CADASIL; insights from 3D molecular modelling and evolutionary analyses". Journal of Molecular Biochemistry. 3 (3): 97–105.
  11. ISBN 978-0-07-141620-7
    .
  12. S2CID 13031278
    .
  13. S2CID 31459077
    .
  14. PMID 19363995
    .
  15. ^
    PMID 20464302
    .
  16. ^
    S2CID 22934154
    .
  17. S2CID 6502194
    .
  18. ^
    PMID 20301673
    – via PubMed.
  19. ^ a b "Questions about cadasil". www.cambridgestroke.com.
  20. ^ Sencen, Lisa. "CADASIL".
  21. ^ "CADASIL - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Archived from the original on 2021-10-27. Retrieved 2017-04-01.
  22. S2CID 42107389
    .
  23. S2CID 72564626
    .
  24. ^
    PMID 18287121
    .
  25. PMID 18575181
    .
  26. ^ "Blogger". accounts.google.com.
  27. ^ "Jimmy Dewar, singer/bassist for Robin Trower's Rock Sensation". Rock and Roll Paradise. 23 March 2019. Retrieved 2 July 2021.
  28. ^ Fisher, Christopher (14 March 2011). "CADASIL, A Vascular Brain Disorder, Is Often Misdiagnosed As Multiple Sclerosis". BMED Report. Retrieved 28 July 2021.

Further reading

Wikimedia Commons has media related to CADASIL syndrome.
  • Lesnik Oberstein SA, Boon EM, Terwindt GM (June 28, 2012). CADASIL. University of Washington, Seattle.
    PMID 20301295
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=CADASIL&oldid=1207544429"