Hereditary cerebral small vessel diseases: A review
Department of Neurological, Neurosurgical and Behavioural Sciences, Medical School, University of Siena, Italy. Electronic address: . Journal of the neurological sciences
(Impact Factor: 2.47).
08/2012; 322(1-2):25-30. DOI: 10.1016/j.jns.2012.07.041
Cerebral microangiopathies are responsible of a great number of strokes. In the recent years advances in molecular genetics identified several monogenic conditions involving cerebral small vessels and predisposing to ischemic and/or hemorrhagic stroke and diffuse white matter disease leading to vascular dementia. Clinical features and diagnostic clues of these conditions, [cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), COL4A1-related cerebral small vessel diseases, autosomal dominant retinal vasculopathy with cerebral leukodystrophy (AD-RVLC), and Fabry's disease] are here reviewed. Albeit with variable phenotypes and with different defective genes, all these disorders produce arteriopathy and microvascular disintegration with changes in brain functions. Specific diagnostic tools are recommended, genetic analysis being the gold standard for the diagnosis.
Available from: Ubaldo Bonuccelli
- "Ophthalmological findings -telangiectasias, microaneurysms and retinal capillary obliteration starting in the macula-are common. MRI shows contrast-enhanced lesions in the white matter of the cerebrum and cerebellum . "
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ABSTRACT: Background: Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach. Scope of review: Here we review the single-gene causes of ischemic stroke, bringing the reader from the candidate gene method toward the exciting new horizons of genetic technology. Major conclusions: The aetiological diagnosis of ischemic stroke in young adults is more complex than in the elderly. The identification of a genetic cause is important to provide appropriate counseling and to start a correct therapy, when available. The advent of GWAS technology, such as for other complex pathological conditions, has contributed enormously to the understanding of many of these genetic bases. For success large, well phenotyped case cohorts are required, and international collaborations are essential. General significance: This review focuses on the main causes of genetically-based ischemic stroke in young adults, often classified as indeterminate, investigating also the recent findings of the GWAS, in order to improve diagnostic and therapeutic management.
Biochimica et Biophysica Acta - Clinical 12/2014; 349. DOI:10.1016/j.bbacli.2014.12.004
Available from: Angelica Staniloiu
- "While the diagnosis of CADASIL is established (Hervé and Chabriat, 2010; Russell, 2010; Assareh et al., 2011; Yamamoto et al., 2011; Federico et al., 2012), case descriptions with a detailed neuropsychological examination identifying areas of deficiency and preservation can enrich the understanding of this condition and provide novel insights and ideas for larger scale research. "
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ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) - is the most common genetic source of vascular dementia in adults, being caused by a mutation in NOTCH3 gene. Spontaneous de novo mutations may occur, but their frequency is largely unknown. Ischemic strokes and cognitive impairments are the most frequent manifestations, but seizures affect up to 10% of the patients. Herein, we describe a 47-year-old male scholar with a genetically confirmed diagnosis of CADASIL (Arg133Cys mutation in the NOTCH3 gene) and a seemingly negative family history of CADASIL illness, who was investigated with a comprehensive neuropsychological testing battery and neuroimaging methods. The patient demonstrated on one hand severe and accelerated deteriorations in multiple cognitive domains such as concentration, long-term memory (including the episodic-autobiographical memory domain), problem solving, cognitive flexibility and planning, affect recognition, discrimination and matching, and social cognition (theory of mind). Some of these impairments were even captured by abbreviated instruments for investigating suspicion of dementia. On the other hand the patient still possessed high crystallized (verbal) intelligence and a capacity to put forth a façade of well-preserved intellectual functioning. Although no definite conclusions can be drawn from a single case study, our findings point to the presence of additional cognitive changes in CADASIL in middle adulthood, in particular to impairments in the episodic-autobiographical memory domain and social information processing (e.g., social cognition). Whether these identified impairments are related to the patient's specific phenotype or to an ascertainment bias (e.g., a paucity of studies investigating these cognitive functions) requires elucidation by larger scale research.
Frontiers in Behavioral Neuroscience 06/2014; 8:227. DOI:10.3389/fnbeh.2014.00227 · 3.27 Impact Factor
Available from: Costantino Iadecola
- "Inflammation , in turn, aggravates the BBB breakdown and induces expression of adhesion molecules in endothelial cells, contributing to leukocyte and platelet adhesion and microvascular occlusion. phy caused by frameshift deletions in the exonuclease TREX1, and mutations of the COL4A1 gene encoding the type IV collagen alpha 1 chain (Federico et al., 2012; Gorelick et al., 2011; Lanfranconi and Markus, 2010). The ApoE 4 allele is a well-established susceptibility gene for increased cardiovascular risk and Alzheimer disease (Verghese et al., 2011). "
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ABSTRACT: Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer's disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that inextricably links the well-being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia.
Neuron 11/2013; 80(4):844-866. DOI:10.1016/j.neuron.2013.10.008 · 15.05 Impact Factor
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