Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke

Kilarski, Laura L.; Rutten-Jacobs, Loes C.A.; Bevan, Steve; Rj, Baker; Hassan, Ahamad; Hughes, D.A.; Markus, Hugh S.; Study, UK Young Lacunar Stroke Dna

doi:10.1371/journal.pone.0136352

Cited by 41 publications

(35 citation statements)

References 36 publications

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“…However, such study design, which has never been applied in previous studies, would require huge funding support. Moreover, the results of recent studies screening systematically patients with stroke for monogenic diseases did not find higher disease frequencies, 27 supporting the idea that the use of more narrow selection criteria is more favorable for identifying an higher number of positive patients.…”

Section: 2mentioning

confidence: 80%

Clinical Pregenetic Screening for Stroke Monogenic Diseases

Bersano

Markus

Quaglini

et al. 2016

Stroke

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Background and Purpose— Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease Methods— We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. Results— In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. Conclusions— In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.

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Section: 2mentioning

confidence: 80%

Clinical Pregenetic Screening for Stroke Monogenic Diseases

Bersano

Markus

Quaglini

et al. 2016

Stroke

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“…There have been some previous attempts of identifying specific clinical and neuroradiological features distinguishing NOTCH3 positive from negative patients. These studies, showed that several MRI characteristics, such as temporal lobe lesions, external capsule lacunes, severe WMHs as well as the family history, were more frequent in positive patients [9,[18][19][20][21][22]. Some specific algorithms supporting the identification of clinically suspected CADASIL have been proposed so far but the reliability is still debated since in most cases they were elaborated from heterogeneous and retrospectively collected populations [12][13][14][15][16][17][18][19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

The role of clinical and neuroimaging features in the diagnosis of CADASIL

Bersano¹,

Bedini²,

Markus³

et al. 2018

J Neurol

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Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. Methods: Patients with lacunar stroke or TIA, were included in the present study. For each patient demographic and clinical data were collected.MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. Results: 128 patients (mean age 56.3±12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of all these factors together with familial history for stroke result in a higher positive predictive value and specificity. Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.

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“…Genetic testing should be considered only when lacunes are present in a young patient with extensive WMHs in the absence of sufficient conventional vascular risk factors. 105 The presence of migraine, cognitive impairment, and a positive family history are additional features of CADASIL, the commonest monogenic disorder that causes cerebral small vessel disease. 106 CADASIL can be diagnosed on the basis of testing for mutations in the NOTCH3 gene.…”

Section: Suggestions and Considerations For Investigations In Patientmentioning

confidence: 99%

Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Smith¹,

Saposnik²,

Biessels³

et al. 2017

Stroke

302

297

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Abstract-Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians. (Stroke. 2017;48:e44-e71.

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Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke

Cited by 41 publications

References 36 publications

Clinical Pregenetic Screening for Stroke Monogenic Diseases

Clinical Pregenetic Screening for Stroke Monogenic Diseases

The role of clinical and neuroimaging features in the diagnosis of CADASIL

Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

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