Autosomal dominant migraine with MRI white‐matter abnormalities mapping to the CADASIL locus

Chabriat, Hugues; Tournier-Lasserve, E.; Vahedi, Katayoun; Leys, D.; Joutel, Anne; Nibbio, A; Escaillas, J. P.; Iba-Zizen, M. T.; Bracard, Serge; Tehindrazanarivelo, Alain Djacoba; Gastaut, J. L.; Bousser, Marie Germaine

doi:10.1212/wnl.45.6.1086

Cited by 143 publications

(48 citation statements)

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“…[105][106][107] One CADASIL family has been described with typical FHM attacks, 108 and another family, linked to the CADASIL locus, with migraine and CADASIL-like white matter lesions on magnetic resonance imaging. 109 All these observations contributed to the clinical spectrum of migraine-FHM-CADASIL. Further study of this intriguing relation is needed.…”

Section: Cadasil: Clinical But No Genetic Overlap With Migrainementioning

confidence: 93%

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Terwindt

Ophoff²,

Haan

et al. 1998

Eur J Hum Genet

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Clinical and genetic heterogeneity as well as influence of environmental factors have hampered identification of the genetic factors which are involved in episodic diseases such as migraine, episodic ataxia and epilepsy. The study of rare, but clearly genetically determined subtypes, may help to unravel the pathogenesis of the more common forms. Recently, different types of mutation in the brain-specific P/Q type calcium channel α 1A subunit gene (CACNA1A) on chromosome 19p13 were shown to be involved in three human disorders: familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), and chronic spinocerebellar ataxia type 6 (SCA6). In addition, evidence is accumulating that the same gene is also involved in the common forms of migraine with and without aura. In the tottering and leaner mouse, which are characterised by epilepsy and ataxia, similar mutations were identified in the mouse homologue of the calcium channel α 1A subunit gene. These findings add to the growing list of episodic (and now also chronic) neurological disorders, which are caused by inherited abnormalities of voltage-dependent ion channels. The findings in migraine illustrate that rare, but monogenic variants of a disorder, may be successfully used to identify candidate genes for the more common, but genetically more complex, forms.

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Section: Cadasil: Clinical But No Genetic Overlap With Migrainementioning

confidence: 93%

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Terwindt

Ophoff²,

Haan

et al. 1998

Eur J Hum Genet

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“…However, more than 50% of individuals may exhibit atypical, hemiplegic or prolonged auras 43 , and even rarer presentations, with meningism, mental confusion, fever and coma 55 . The frequency of attacks varies between affected individuals, from less than one to several attacks a month 56 . In addition to the therapeutic and prophylactic measures in the primary migraine, patients with CA-DASIL may show benefit with the prophylactic use of acetazolamide 57,58 .…”

Section: Migrainementioning

confidence: 99%

CADASIL: pathogenesis, clinical and radiological findings and treatment

André

2010

Arq. Neuro-Psiquiatr.

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of ischemic strokes and a most important model for the study of subcortical vascular dementia. This unrelentlessly progressive disease affects many hundreds of families all over the world but is not well studied in Brazil. This manuscript reviews pathogenetic, clinical, radiological and therapeutic features of CADASIL. The causal mutations are now very well known, but the same can not be said about its intimate pathogenetic mechanisms. The variable clinical presentation should lead physicians to actively pursue the diagnosis in many settings and to more thouroughly investigate family history in first degree relatives. A rational approach to genetic testing is however needed. Treatment of CADASIL is still largely empiric. Highquality therapeutic studies involving medications and cognitive interventions are strongly needed in CADASIL. Key words: CADASIL, etiology, genetics, diagnosis, therapeutics.cADAsIL: patogênese, achados clínicos e radiológicos e tratamento resumo CADASIL é a causa genética mais freqüente de infartos cerebrais e constitui modelo importante de estudo de demências vasculares subcorticais. De natureza inexoravelmente progressiva, afeta milhares de pessoas em todo o mundo. Sua importância é pouco reconhecida entre nós, o que nos levou à presente revisão dos principais aspectos patogenéticos, clínicos, neuroradiológicos e terapêuticos da doença. As mutações causais são hoje bem conhecidas, mas os mecanismos patogenéticos íntimos ainda permanecem misteriosos. A apresentação clínica variável deve fazer com que os médicos considerem o diagnóstico em vários contextos clínicos e investiguem de forma mais extensa que o usual a história familial deparentes de primeiro grau. Além disso, uma abordagem racional é necessária para reduzir custos e aumentar a eficiência do diagnóstico genético. O tratamento atual de pacientes com CADASIL é basicamente empírico. Estudos clínicos sobre medicamentos e intervenções cognitivas de alto nível metodológico constituem uma necessidade urgente.

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“…The resulting blood flow restriction leads to characteristic ischaemic changes, white matter loss and lacunar infarcts 14. White matter changes observed via magnetic resonance imaging (MRI) are a characteristic feature of CADASIL that have been utilized as an indication of the disease 15, 16…”

Section: Introductionmentioning

confidence: 99%

Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGFβ expression

Panahi

Mesri

Samuelsson

et al. 2018

J Cellular Molecular Medi

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Cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial fatal progressive degenerative disorder. One of the pathological hallmarks of CADASIL is a dramatic reduction of vascular smooth muscle cells (VSMCs) in cerebral arteries. Using VSMCs from the vasculature of the human umbilical cord, placenta and cerebrum of CADASIL patients, we found that CADASIL VSMCs had a lower proliferation rate compared to control VSMCs. Exposure of control VSMCs and endothelial cells (ECs) to media derived from CADASIL VSMCs lowered the proliferation rate of all cells examined. By quantitative RT‐PCR analysis, we observed increased Transforming growth factor‐β (TGFβ) gene expression in CADASIL VSMCs. Adding TGFβ‐neutralizing antibody restored the proliferation rate of CADASIL VSMCs. We assessed proliferation differences in the presence or absence of TGFβ‐neutralizing antibody in ECs co‐cultured with VSMCs. ECs co‐cultured with CADASIL VSMCs exhibited a lower proliferation rate than those co‐cultured with control VSMCs, and neutralization of TGFβ normalized the proliferation rate of ECs co‐cultured with CADASIL VSMCs. We suggest that increased TGFβ expression in CADASIL VSMCs is involved in the reduced VSMC proliferation in CADASIL and may play a role in situ in altered proliferation of neighbouring cells in the vasculature.

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Autosomal dominant migraine with MRI white‐matter abnormalities mapping to the CADASIL locus

Cited by 143 publications

References 0 publications

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

CADASIL: pathogenesis, clinical and radiological findings and treatment

Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGFβ expression

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