Clinical, familial, and neuroimaging features of CADASIL-like patients

Nannucci, Serena; Pescini, Francesca; Bertaccini, Bruno; Bianchi, Silvia; Ciolli, Laura; Valenti, Raffaella; Dotti, M. T.; Federico, Antonio; Inzitari, Domenico; Pantoni, Leonardo

doi:10.1111/ane.12284

Cited by 14 publications

(7 citation statements)

References 31 publications

(35 reference statements)

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“…We confirmed that a family history of stroke and dementia as well as the presence of external capsule lacunes are strongly associated with a diagnosis of CADASIL. [9,11,[23][24][25]. Conversely, we found that the presence of severe WMHs, thalamic lacunes, and temporal lobe WMHs may be less useful.…”

Section: Discussionmentioning

confidence: 63%

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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Section: Discussionmentioning

confidence: 63%

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

Bersano¹,

Bedini²,

Markus³

et al. 2018

J Neurol

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“…However, due to the heterogeneity of clinical manifestation and the non-pathognomonic pattern of neuroimaging data, recognition of the disease before the genetic test is challenging. As a pregenetic screening tool, the CADASIL scale based on patients’ clinical characteristics and neuroimaging data was recently developed to narrow down the potential targets for further genetic evaluations [ 15 , 28 ]. In our study, we recruited 116 clinical suspected CADASIL patients based on this scale in Tongji Hospital.…”

Section: Discussionmentioning

confidence: 99%

“…As an inherited single-gene disorder, it is commonly assumed that the pathological changes of CADASIL are mainly due to the effects of NOTCH3 gene mutations, but not the effects of other factors, such as cerebral vascular risk factors in the CADASIL-like patients [ 6 , 28 ]. It has been reported that, compared with CADASIL-like patients, CADASIL patients had a lower percentage of vascular risk factors [ 6 , 8 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

The comparisons of phenotype and genotype between CADASIL and CADASIL-like patients and population-specific evaluation of CADASIL scale in China

Chen

et al. 2016

J Headache Pain

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BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder caused by mutations in the NOTCH3 gene. Although CADASIL scale is a widely used tool to screen clinically suspected CADASIL patients, the differential effects of this scale in various populations remain unknown.Methods92 CADASIL-like patients and 24 CADASIL patients were selected based on CADASIL scale and gene tests. The clinical, genetic and radiological characteristics were analyzed.ResultsBased on the CADASIL scale, we first screened 116 suspected CADASIL patients, and detected 20 mutations in 24 CADASIL-patients (Specificity: 20.69 %). Surprisingly, we found that transient ischemic attack/stroke, migraine, cognitive decline, psychiatric disturbances and early onset age in CADASIL scale showed no differences between the CADASIL and the CADASIL-like patients (p > 0.05). Instead, recurrent cerebral ischemic events (58.33 %, p = 0.028) and positive family histories (p < 0.05) were more frequently observed in CADASIL patients. Moreover, compared with CADASIL-like patients (21.74 %), CADASIL patients demonstrated higher percentage of temporal pole involvements (58.33 %, p = 0.001), but not the external capsule involvements (66.67 %, p = 0.602), in MRI imaging. Further, we found that vascular risk factors could occur in both CADASIL patients and CADASIL-like patients, and therefore could not be used as the markers to differentiate the two groups in our study (p > 0.05). By performing DSA analysis, we for the first time identified dysplasia of cerebral blood vessels in CADASIL patients, which were detected more frequently in CADASIL patients (41.67 %) in comparison with CADASIL-like patients (8.69 %, p <0.01).ConclusionOur data suggested that the efficacy of CADASIL scale to diagnose the disease varied with specific populations. Recurrent cerebral ischemic events, temporal pole involvements (but not the external capsule) in MRI imaging and dysplasia of cerebral blood vessels in DSA may be the new potential risk factors of the CADASIL scale suitable for Chinese patients. Gene testing by encephalopathy gene panel is expected to improve the accuracy of CADASIL differential diagnosis and increase the understanding of this disease in the future.

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“…Linkage analysis showed no distinctive haplotype attributed to the affected family members [75]. Since then, a CADASIL-like syndrome not due to NOTCH3 mutations has been described, where clinical features are largely similar to CADASIL apart from a later age of onset of stroke and a later age of onset in family members [76].…”

Section: Next Generation Sequencing and Its Impact On Svdmentioning

confidence: 96%

Monogenic causes of stroke: now and the future

Tan

Markus

2015

J Neurol

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Most stroke is multifactorial with multiple polygenic risk factors each conferring small increases in risk interacting with environmental risk factors, but it can also arise from mutations in a single gene. This review covers single-gene disorders which lead to stroke as a major phenotype, with a focus on those which cause cerebral small vessel disease (SVD), an area where there has been significant recent progress with findings that may inform us about the pathogenesis of SVD more broadly. We also discuss the impact that next generation sequencing technology (NGST) is likely to have on clinical practice in this area. The most common form of monogenic SVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, due to the mutations in the NOTCH3 gene. Several other inherited forms of SVD include cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy, collagen type IV α1 and α2 gene-related arteriopathy and FOXC1 deletion related arteriopathy. These monogenic forms of SVD, with overlapping clinical phenotypes, are beginning to provide insights into how the small arteries in the brain can be damaged and some of the mechanisms identified may also be relevant to more common sporadic SVD. Despite the discovery of these disorders, it is often challenging to clinically and radiologically distinguish between syndromes, while screening multiple genes for causative mutations that can be costly and time-consuming. The rapidly falling cost of NGST may allow quicker diagnosis of these rare causes of SVD, and can also identify previously unknown disease-causing variants.

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Clinical, familial, and neuroimaging features of CADASIL-like patients

Cited by 14 publications

References 31 publications

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

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

The comparisons of phenotype and genotype between CADASIL and CADASIL-like patients and population-specific evaluation of CADASIL scale in China

Monogenic causes of stroke: now and the future

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