A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13

Hervé, Dominique; Chabriat, Hugues; Rigal, Mélanie; Dalloz, Marie-Amélie; Marchini, Aida Kawkabani; Lepeleire, Jean De; Fontaine, Bertrand; Groote, Chantal Ceuterick‐de; Alili, Nassira; Miné, Manuèle; Delaforge, Audrey; Bousser, Marie‐Germaine; Guichard, Jean‐Pierre; Martin, Jean‐Jacques; Gray, Françoise; Tournier‐Lasserve, Elisabeth

doi:10.1212/wnl.0b013e3182768954

Cited by 26 publications

(26 citation statements)

References 9 publications

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“…Other familial forms of vascular dementia include an autosomal dominant type of Swedish dementia not linked to CADASIL; and PADMAL, an autosomal dominant ‘subcortical angiopathic encephalopathy’ primarily affecting the pons, for which the causal gene is not known . A novel hereditary vascular leukoencephalopathy mapping to chromosome 20q13 (possibly related to CARASAL, see above) has been reported . Neuropathologic details of one case have been provided: this examination showed a combination of severe AD changes including CAA, and microvascular changes that (though not illustrated) appear to represent severe AS or lipohyalinosis.…”

Section: Hereditary (Cerebral) Microangiopathiesmentioning

confidence: 99%

Review: Vascular dementia: clinicopathologic and genetic considerations

Vinters

Zarow

Borys

et al. 2018

Neuropathology Appl Neurobio

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The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer's disease (AD). Not surprisingly, heterogeneous forms of CVD may coexist with AD changes in the ‘ageing brain’. These include angiopathies (affecting both large and small arteries) that result from ‘classical’ risk factors (hypertension, smoking and diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked to AD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimic AD – though the vascular abnormalities are usually detectable by neuroimaging. More subtle effects of CVD may include neuroinflammation and biochemical ‘lesions’ that have no reliable morphologic correlate and thus escape the attention of even an experienced Neuropathologist. The pathogenesis of hippocampal injury resembling ischaemic change – commonly seen in the brains of geriatric subjects – remains controversial. In recent years, genetically determined forms of microangiopathy (e.g. CADASIL, CARASIL, Trex1‐related microangiopathies, CARASAL, familial forms of cerebral amyloid angiopathy or CAA) have provided interesting cellular and molecular clues to the pathogenesis of sporadic microvascular disease such as arteriolosclerosis and AD‐related CAA.

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Section: Hereditary (Cerebral) Microangiopathiesmentioning

confidence: 99%

Review: Vascular dementia: clinicopathologic and genetic considerations

Vinters

Zarow

Borys

et al. 2018

Neuropathology Appl Neurobio

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“…These changes caused the leukoencephalopathy to become virtually diffuse. Hervé et al reported a French family with autosomal-dominant vascular leukoencephalopathy with an MRI pattern similar to that in CARASAL [101,102]. Neuropathological findings included a diffuse white matter-and myelin pallor, asymmetric fibrous thickening in small arterioles or astroglyosis.…”

Section: Cathepsin A–related Arteriopathy With Strokes and Leukoenmentioning

confidence: 97%

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome

Giau

Bagyinszky

Youn

et al. 2019

IJMS

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Cerebral small vessel diseases (SVD) have been causally correlated with ischemic strokes, leading to cognitive decline and vascular dementia. Neuroimaging and molecular genetic tests could improve diagnostic accuracy in patients with potential SVD. Several types of monogenic, hereditary cerebral SVD have been identified: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), hereditary diffuse leukoencephalopathy with spheroids (HDLS), COL4A1/2-related disorders, and Fabry disease. These disorders can be distinguished based on their genetics, pathological and imaging findings, clinical manifestation, and diagnosis. Genetic studies of sporadic cerebral SVD have demonstrated a high degree of heritability, particularly among patients with young-onset stroke. Common genetic variants in monogenic disease may contribute to pathological progress in several cerebral SVD subtypes, revealing distinct genetic mechanisms in different subtype of SVD. Hence, genetic molecular analysis should be used as the final gold standard of diagnosis. The purpose of this review was to summarize the recent discoveries made surrounding the genetics of cerebral SVD and their clinical significance, to provide new insights into the pathogenesis of cerebral SVD, and to highlight the possible convergence of disease mechanisms in monogenic and sporadic cerebral SVD.

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“…First, the recent identification of distinct monogenic forms of SVDs has revealed that the distribution of WMHs may differ substantially among different hereditary SVDs. For instance, early extensive WMHs in the anterior temporal lobe are highly characteristic of CADASIL, whereas WMHs are mild or absent in this region in both cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) [7,61] and pontine autosomal-dominant microangiopathy with leukoencephalopathy (PADMAL) [6,62]. In contrast with other ischaemic hereditary SVDs, the severity of WMHs in CARASAL has been reported to be disproportionately extensive compared with lacunar infarcts, which are very rare [7,61].…”

Section: Heterogeneity Of Wmhsmentioning

confidence: 99%

“…For instance, early extensive WMHs in the anterior temporal lobe are highly characteristic of CADASIL, whereas WMHs are mild or absent in this region in both cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) [7,61] and pontine autosomal-dominant microangiopathy with leukoencephalopathy (PADMAL) [6,62]. In contrast with other ischaemic hereditary SVDs, the severity of WMHs in CARASAL has been reported to be disproportionately extensive compared with lacunar infarcts, which are very rare [7,61]. Second, longitudinal analyses of WMHs in elderly community-dwelling volunteers have shown that early, confluent WMHs, but not punctate WMHs, are actually progressive during follow-up [14].…”

Section: Heterogeneity Of Wmhsmentioning

confidence: 99%

Pathogenesis of white matter changes in cerebral small vessel diseases: beyond vessel-intrinsic mechanisms

2017

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Cerebral small vessel diseases (SVDs) are a leading cause of age and hypertension-related stroke and dementia. The salient features of SVDs visible on conventional brain magnetic resonance images include white matter hyperintensities (WMHs) on T2-weighted images, small infarcts, macrohemorrhages, dilated perivascular spaces, microbleeds and brain atrophy. Among these, WMHs are the most common and often the earliest brain tissue changes. Moreover, over the past two decades, large population- and patient-based studies have established the clinical importance of WMHs, notably with respect to cognitive and motor disturbances. Here, we seek to provide a new and critical look at the pathogenesis of SVD-associated white matter (WM) changes. We first review our current knowledge of WM biology in the healthy brain, and then consider the main clinical and pathological features of WM changes in SVDs. The most widely held view is that SVD-associated WM lesions are caused by chronic hypoperfusion, impaired cerebrovascular reactivity (CVR) or blood-brain barrier (BBB) leakage. Here, we assess the arguments for and against each of these mechanisms based on population, patient and experimental model studies, and further discuss other potential mechanisms. Specifically, building on two recent seminal studies that have uncovered an anatomical and functional relationship between oligodendrocyte progenitor cells and blood vessels, we elaborate on how small vessel changes might compromise myelin remodelling and cause WM degeneration. Finally, we propose new directions for future studies on this hot research topic.

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A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13

Cited by 26 publications

References 9 publications

Review: Vascular dementia: clinicopathologic and genetic considerations

Review: Vascular dementia: clinicopathologic and genetic considerations

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome

Pathogenesis of white matter changes in cerebral small vessel diseases: beyond vessel-intrinsic mechanisms

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