A kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Trojano, Luigi; Ragno, Michele; Manca, Antonio; Caruso, Giuseppe

doi:10.1007/s004150050208

Cited by 29 publications

(18 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…22 In previous clinical studies of CADASIL, the focus has mostly been on the poststroke and dementia phases of the disease. 6,7,[23][24][25] Of the 2 studies mentioned, Taillia et al 7 showed results concordant with ours. Their 8 symptomatic (TIA, stroke, migraine or seizures) CADASIL patients without dementia had significantly impaired performance in Wisconsin Card Sorting Test, trail-making test, and ReyOsterreith copying.…”

Section: Discussionsupporting

confidence: 79%

“…In accordance with our study, the decline began with deterioration in tests associated with executive function, attention, and mental speed. However, the results of Trojano et al 6 differ from those of our prestroke subjects. In a 2-year follow-up study, Trojano et al 6 did not find any significant differences in cognitive performance between the controls and 5 asymptomatic CADASIL patients.…”

Section: Discussioncontrasting

confidence: 55%

“…In 1 study, no evidence was found for cognitive decline in 5 asymptomatic mutation carriers compared with controls from the same family. 6 Another study showed in 2 of 8 symptomatic, but not demented, patients a clear cognitive decline already before any major vascular event, suggesting early cognitive impairment. 7 In both studies, the pattern of cognitive decline indicated frontal lobe and subcortical involvement, but the results are somewhat contradictory with respect to how early the cognitive decline becomes manifest.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Insidious Cognitive Decline in CADASIL

Amberla

Wäljas

Tuominen

et al. 2004

Stroke

View full text Add to dashboard Cite

Background and Purpose-Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks leading to subcortical vascular dementia. The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL. Methods-Prestroke (nϭ13) and poststroke (nϭ13) mutation carriers and mutation carriers with dementia (nϭ8) were compared with healthy noncarriers from the same families using a comprehensive set of neuropsychological tests. Results-Changes in working memory and executive function were observed in the very early phase of the disease before transient ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive impairment concerned also mental speed and visuospatial ability. Finally, the subjects with dementia had multiple cognitive deficits, which engaged even verbal functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups without dementia and the controls could be reliably distinguished using 3 tests that assessed working memory/attention, executive function, and mental speed. Episodic memory was relatively well-preserved late in the disease. Conclusion-A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

See 1 more Smart Citation

Insidious Cognitive Decline in CADASIL

Amberla

Wäljas

Tuominen

et al. 2004

Stroke

View full text Add to dashboard Cite

show abstract

“…In a study done in Colombia, young individuals with typical mutation maintained their normal cognitive performance (when compared to non-carrier members of the same family) over 4 years 83 . In another Italian study, asymptomatic mutation carriers with or without visible white matter lesions on MRI showed no decline in cognitive performance over 2 years of follow-up 82 . Not infrequently, on the other hand, subtle and insidiously worsening cognitive symptoms may appear years before TIA and cerebral infarctions.…”

Section: Cognitive Decline and Dementiamentioning

confidence: 90%

“…Cognitive impairment and dementia are the second most common manifestation of CADASIL, after cerebrovascular injury 82 . The emergence of neuropsychological changes may however occur late, even in patients with well-established manifestations of the disease.…”

Section: Cognitive Decline and Dementiamentioning

confidence: 99%

CADASIL: pathogenesis, clinical and radiological findings and treatment

André

2010

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

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.

show abstract

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Wang¹

2005

Magnetic Resonance of Myelination and Myelin Disorders

View full text Add to dashboard Cite

Introduction. Fast and precise diagnostics of the disease from the large group of adult leukoencephalopathy is difficult but responsible job, because the outcome of the disease is very often determined by its name. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by the mutation of Notch 3 gene on chromosome locus 19p13. Beside the brain arterioles being the main disease targets, extracerebral small blood vessels are affected by the pathological process. Clinically present signs are recurrent ischemic strokes and vascular dementia. CADASIL in its progressive form shows a distinctive pattern of pathological changes on MRI of endocranium. The diagnosis is confirmed by the presence of granular osmiophilic material (GOM) in histopathological skin biopsies. Case reports. Two young adult patients manifested ischemic strokes of unknown etiology, cognitive deterioration, migraine and psychopathological phenomenology. MRI of endocranium pointed on CADASIL. Ultrastructural examination of skin biopsy proved the presence of GOM in the basal lamina and near smooth muscle cells of arteriole dermis leading to CADASIL diagnosis. The presence of GOM in histopathological preparation is 100% specific for CADASIL. The patients were not searched for mutation in Notch 3 gene on chromosome 19, because some other leukoencephalopathy was disregarded. Conclusion. Suggestive clinical picture, distinctive finding of endocranium MRI, the presence of GOM by ultrastructural examination of histopathological skin biopsies are sufficient to confirm CADASIL diagnosis.

show abstract

A kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Cited by 29 publications

References 22 publications

Insidious Cognitive Decline in CADASIL

Insidious Cognitive Decline in CADASIL

CADASIL: pathogenesis, clinical and radiological findings and treatment

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Contact Info

Product

Resources

About