1,238 results match your criteria CADASIL Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy


A Novel NOTCH3 Gene Mutation in a Polish CADASIL Family.

J Stroke Cerebrovasc Dis 2018 Dec 10. Epub 2018 Dec 10.

Department of Neurology, Pomeranian Medical University, Szczecin, Poland. Electronic address:

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetically determined disease of the cerebral vessels, characterized by recurrent ischemic strokes, dementia, and degeneration of the cerebral white matter. The condition is caused by a mutation in the NOTCH3 gene, whose product plays a great role in the development and physiology of the cardiovascular system. Magnetic resonance imaging reveals multiple hyperintensive lesions of the white matter in the T2-weighted images also in asymptomatic carriers of CADASIL and can be detected even 10-15 years prior to clinical signs. Read More

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.040DOI Listing
December 2018

Comparison of brain magnetic resonance imaging between myotonic dystrophy type 1 and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

PLoS One 2018 6;13(12):e0208620. Epub 2018 Dec 6.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Anterior temporal lobe hyperintensities detected by brain MRI are a recognized imaging hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Because similar findings may be present in patients with myotonic dystrophy type 1 (DM1), the brain MRI in these two diseases is often misinterpreted. We compared the MRI findings between the two entities to examine whether they display distinctive characteristics. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208620PLOS
December 2018
6 Reads

Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era.

J Neurol Neurosurg Psychiatry 2018 Nov 22. Epub 2018 Nov 22.

Department of Neuroinflammation, UCL Institute of Neurology, London, UK.

Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. Read More

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http://dx.doi.org/10.1136/jnnp-2018-319481DOI Listing
November 2018
12 Reads

MRI Lesion Load of Cerebral Small Vessel Disease and Cognitive Impairment in Patients With CADASIL.

Front Neurol 2018 16;9:862. Epub 2018 Oct 16.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the best known and the most common monogenic small vessel disease (SVD). Cognitive impairment is an inevitable feature of CADASIL. Total SVD score and global cortical atrophy (GCA) scale were found to be good predictors of poor cognitive performance in community-dwelling adults. Read More

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http://dx.doi.org/10.3389/fneur.2018.00862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232772PMC
October 2018
1 Read

3T MRI study discloses high intrafamilial variability in CADASIL due to a novel NOTCH3 mutation.

J Clin Neurosci 2018 Dec 24;58:25-29. Epub 2018 Oct 24.

Department of Neuroradiology, Montreal Neurological Institute and Hospital, McGill University, 3801 rue University, Montreal H3A2B4, QC, Canada. Electronic address:

In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger gene sequencing in a proband with suspected but not confirmed CADASIL and her apparently asymptomatic father. The 35-year-old proband presented with migraine with visual aura. Brain MRI showed diffuse leukoencephalopathy, suggesting CADASIL. Read More

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http://dx.doi.org/10.1016/j.jocn.2018.10.080DOI Listing
December 2018
3 Reads

Peak width of skeletonized mean diffusivity (PSMD) as marker of widespread white matter tissue damage in multiple sclerosis.

Mult Scler Relat Disord 2018 Nov 13;27:294-297. Epub 2018 Nov 13.

Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. Electronic address:

Background: Peak width of skeletonized mean diffusivity (PSMD) is a novel and fully automated, MRI biomarker, which has shown clinical relevance in cerebral small vessel diseases (SVD). We aimed here to assess PSMD levels across the brain of patients with multiple sclerosis (MS), in comparison to normal controls (NC) and patients with CADASIL, a genetically defined form of severe SVD.

Methods: We assessed PSMD in relapsing-remitting (RR) MS patients (n = 47) in comparison to age-matched CADASIL patients (n = 25) and NC (n = 28). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22110348183049
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http://dx.doi.org/10.1016/j.msard.2018.11.011DOI Listing
November 2018
8 Reads

Event-Related Potential Correlates of Recognition Memory in Asymptomatic Individuals with CADASIL.

Brain Res 2018 Nov 13. Epub 2018 Nov 13.

Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Neuroscience Group, University of Antioquia, Medellin, Colombia. Electronic address:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder and is caused by mutations of the NOTCH3 gene. Cognitive decline in CADASIL is characterized by early impairments of attention, memory, and executive functions. Studying asymptomatic individuals with CADASIL offers a unique genetic model to understand preclinical vascular cognitive impairment and dementia. Read More

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http://dx.doi.org/10.1016/j.brainres.2018.11.016DOI Listing
November 2018
3 Reads

Nuclear abnormalities in vascular myocytes in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Neuropathology 2018 Dec 6;38(6):601-608. Epub 2018 Nov 6.

Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a stroke and dementia syndrome with degeneration and loss of vascular smooth muscle cells (VSMCs). The disease is due to mutations in NOTCH3 playing an important role in VSMC differentiation, proliferation and apoptosis. Searching for a possible cause of VSMC dysfunction in CADASIL, we investigated morphology and proliferative activity the affected myocytes. Read More

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http://doi.wiley.com/10.1111/neup.12519
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http://dx.doi.org/10.1111/neup.12519DOI Listing
December 2018
5 Reads

Autophagy-lysosomal defect in human CADASIL vascular smooth muscle cells.

Eur J Cell Biol 2018 Nov 22;97(8):557-567. Epub 2018 Oct 22.

Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Huddinge, Sweden. Electronic address:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial progressive degenerative disorder and is caused by mutations in NOTCH3 gene. Previous study reported that mutant NOTCH3 is more prone to form aggregates than wild-type NOTCH3 and the mutant aggregates are resistant to degradation. We hypothesized that aggregation or accumulation of NOTCH3 could be due to impaired lysosomal-autophagy machinery in VSMC. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01719335183008
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http://dx.doi.org/10.1016/j.ejcb.2018.10.001DOI Listing
November 2018
12 Reads

Role of NOTCH3 Mutations in the Cerebral Small Vessel Disease Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Stroke 2018 Nov;49(11):2793-2800

From the Department of Neurobiology, Care Sciences, and Society (K.C., H.K.), Karolinska Institutet Stockholm, Sweden.

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http://dx.doi.org/10.1161/STROKEAHA.118.021560DOI Listing
November 2018

Dysfunctional effort-based decision-making underlies apathy in genetic cerebral small vessel disease.

Brain 2018 Nov;141(11):3193-3210

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Apathy is a syndrome of reduced motivation that commonly occurs in patients with cerebral small vessel disease, including those with the early onset form, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The cognitive mechanisms underlying apathy are poorly understood and treatment options are limited. We hypothesized that disrupted effort-based decision-making, the cognitive process by which potential rewards and the effort cost required to obtain them is integrated to drive behaviour, might underlie the apathetic syndrome. Read More

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https://academic.oup.com/brain/advance-article/doi/10.1093/b
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http://dx.doi.org/10.1093/brain/awy257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202575PMC
November 2018
9 Reads
9.200 Impact Factor

Clinical Outcomes of CADASIL-Associated NOTCH3 Mutations in 451,424 European Ancestry Community Volunteers.

Transl Stroke Res 2018 Oct 18. Epub 2018 Oct 18.

Epidemiology and Public Health, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter, EX2 5DW, UK.

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http://dx.doi.org/10.1007/s12975-018-0671-6DOI Listing
October 2018

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

J Neurol 2018 Dec 11;265(12):2934-2943. Epub 2018 Oct 11.

Neurology Unit, Department of Neuroscience and Sensory Organs, Maggiore Policlinico Hospital Foundation IRCCS Ca' Granda, Milan, Italy.

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. Read More

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http://link.springer.com/10.1007/s00415-018-9072-8
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http://dx.doi.org/10.1007/s00415-018-9072-8DOI Listing
December 2018
3 Reads
3.380 Impact Factor

Detrimental effects of intracerebral haemorrhage on patients with CADASIL harbouring NOTCH3 R544C mutation.

J Neurol Neurosurg Psychiatry 2018 Oct 11. Epub 2018 Oct 11.

Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.

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http://jnnp.bmj.com/lookup/doi/10.1136/jnnp-2018-319268
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http://dx.doi.org/10.1136/jnnp-2018-319268DOI Listing
October 2018
1 Read
6.810 Impact Factor

CADASIL affecting a black African man.

Neurol Genet 2018 Oct 19;4(5):e270. Epub 2018 Sep 19.

Department of Neurology, Tygerberg Academic Hospital, University of Stellenbosch, Cape Town, South Africa.

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http://dx.doi.org/10.1212/NXG.0000000000000270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167179PMC
October 2018
7 Reads

Correction: The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant.

Genet Med 2018 Sep 20. Epub 2018 Sep 20.

CADASIL Research Group, Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the Article have been modified accordingly. Read More

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http://dx.doi.org/10.1038/s41436-018-0306-zDOI Listing
September 2018

A Japanese CADASIL patient with homozygous NOTCH3 p.Arg544Cys mutation confirmed pathologically.

J Neurol Sci 2018 Nov 29;394:38-40. Epub 2018 Aug 29.

Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S0022510X183035
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http://dx.doi.org/10.1016/j.jns.2018.08.029DOI Listing
November 2018
7 Reads

Cerebral Autosomal Dominant Arteriopathy (CADASIL) with cardiac involvement (ANOCA) and subcortical leukencephalopathy.

J Cardiovasc Comput Tomogr 2018 Aug 31. Epub 2018 Aug 31.

Department of Radiology, Innsbruck Medical University, Austria. Electronic address:

We report a rare case of a CADASIL-syndrome with cardiac involvement presenting as ANOCA (angina in the absence of obstructive coronary artery disease). Our case highlights the added value of non-invasive fractional flow reserve (FFR) over coronary CT angiography (CTA), and recommends CTA as useful indication in CADASIL patients for screening of occult coronary artery disease (CAD). Read More

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http://dx.doi.org/10.1016/j.jcct.2018.08.005DOI Listing

Peripheral neuropathy in a case with CADASIL: a case report.

BMC Neurol 2018 Aug 31;18(1):134. Epub 2018 Aug 31.

Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8520, Japan.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized clinically by central nervous system dysfunctions. It is unclear whether CADASIL is involved in peripheral neuropathy.

Case Presentation: A 67-year-old Japanese man with stepwise progression of sensory and motor neuropathy was admitted to our hospital. Read More

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http://dx.doi.org/10.1186/s12883-018-1131-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117928PMC
August 2018
1 Read

RVCL-S and CADASIL display distinct impaired vascular function.

Neurology 2018 Sep 3;91(10):e956-e963. Epub 2018 Aug 3.

From the Departments of Neurology (I.d.B., A.H.S., R.Z., I.v.d.S., A.M.J.M.v.d.M., M.D.F., G.M.T.), Human Genetics (A.M.J.M.v.d.M.), and Internal Medicine (E.J.P.d.K.), Leiden University Medical Center, Leiden, the Netherlands; and Center for Clinical Pharmacology (L.B., J.N.d.H.), University Hospitals Leuven and Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium.

Objective: We aimed to evaluate the role of endothelial-dependent and endothelial-independent vascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), both cerebral small vessel diseases are considered models for stroke, vascular dementia, and migraine.

Methods: RVCL-S (n = 18) and CADASIL (n = 23) participants with and mutations, respectively, were compared with controls matched for age, body mass index, and sex (n = 26). Endothelial function was evaluated by flow-mediated vasodilatation, and endothelial-independent vascular reactivity (i. Read More

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http://dx.doi.org/10.1212/WNL.0000000000006119DOI Listing
September 2018
2 Reads

Increased PKR level in human CADASIL brains.

Virchows Arch 2018 Dec 2;473(6):771-774. Epub 2018 Aug 2.

INSERM U942, Paris, France.

Cerebral autosomal dominant arteriolopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is the most common form of hereditary small vessel disease (SVD) of the brain. Neuronal apoptosis has been demonstrated in the cortex of patients. Whether it is associated with an activation of the pro-apoptotic protein PKR pathway is unknown. Read More

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http://dx.doi.org/10.1007/s00428-018-2425-yDOI Listing
December 2018
9 Reads

Focal Epilepsy Secondary to Juxtacortical Lesions in Cerebral Autosomal Dominant Arteriopathy with Subacute Infarcts and Leukoencephalopathy.

Can J Neurol Sci 2018 07;45(4):462-463

1Department of Clinical Neurological Sciences,Western University,London,Ontario,Canada.

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http://dx.doi.org/10.1017/cjn.2018.29DOI Listing

Different Types of White Matter Hyperintensities in CADASIL.

Front Neurol 2018 10;9:526. Epub 2018 Jul 10.

UMR-S 1161 INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

In CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), white matter hyperintensities (WMH) are considered to result from hypoperfusion. We hypothesized that in fact the burden of WMH results from the combination of several regional populations of WMH with different mechanisms and clinical consequences. To identify regional WMH populations, we used a 4-step approach. Read More

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http://dx.doi.org/10.3389/fneur.2018.00526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048276PMC
July 2018
2 Reads

The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant.

Genet Med 2018 Jul 22. Epub 2018 Jul 22.

CADASIL Research Group, Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Purpose: CADASIL is a small-vessel disease caused by a cysteine-altering pathogenic variant in one of the 34 epidermal growth factor-like repeat (EGFr) domains of the NOTCH3 protein. We recently found that pathogenic variant in EGFr domains 7-34 have an unexpectedly high frequency in the general population (1:300). We hypothesized that EGFr 7-34 pathogenic variant more frequently cause a much milder phenotype, thereby explaining an important part of CADASIL disease variability. Read More

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http://dx.doi.org/10.1038/s41436-018-0088-3DOI Listing

Hemiplegic Migraine as the Initial Presentation of Biopsy Positive Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Cureus 2018 May 15;10(5):e2631. Epub 2018 May 15.

Medicine, Atlantic Health System.

The diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in adults can be challenging. Initially, this disease can mimic embolic cerebral infarction, multiple sclerosis, and other neurological diseases on imaging studies. CADASIL is the most common hereditary cerebral angiopathy which is inherited in an autosomal dominant fashion. Read More

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http://dx.doi.org/10.7759/cureus.2631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044483PMC

Notch3 immunotherapy improves cerebrovascular responses in CADASIL mice.

Ann Neurol 2018 Aug 25;84(2):246-259. Epub 2018 Aug 25.

Genetics and Pathogenesis of Cerebrovascular Diseases, Inserm, Paris Diderot University, Paris, France.

Objective: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), caused by dominant mutations in the NOTCH3 receptor, is the most aggressive small vessel disease of the brain. A key feature of its pathogenesis is accumulation of the extracellular domain of NOTCH3 receptor (Notch3 ) in small vessels, with formation of characteristic extracellular deposits termed granular osmiophilic material (GOM). Here, we investigated the therapeutic potential of a mouse monoclonal antibody (5E1) that specifically recognizes Notch3 . Read More

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http://dx.doi.org/10.1002/ana.25284DOI Listing
August 2018
8 Reads

Altered dynamics of neurovascular coupling in CADASIL.

Ann Clin Transl Neurol 2018 Jul 21;5(7):788-802. Epub 2018 May 21.

Sorbonne Paris Cité Inserm UMR1161 Université Denis Diderot Paris VII Paris France.

Background And Objective: Neurovascular coupling is the complex biological process that underlies use-dependent increases in blood flow in response to neural activation. Neurovascular coupling was investigated at the early stage of CADASIL, a genetic paradigm of ischemic small vessel disease.

Methods: Functional hyperemia and evoked potentials during 20- and 40-sec visual and motor stimulations were monitored simultaneously using arterial spin labeling-functional magnetic resonance imaging (ASL-fMRI) and electroencephalography. Read More

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http://dx.doi.org/10.1002/acn3.574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043774PMC
July 2018
9 Reads

Why Are Only Some Subcortical Ischemic Lesions on Diffusion Magnetic Resonance Imaging Associated With Stroke Symptoms in Small Vessel Disease?

Stroke 2018 Aug;49(8):1920-1923

From the Department of Neurology, APHP, Lariboisière Hospital, Paris, France (O.O., H.C., E.J.).

Background and Purpose- In cerebral small vessel diseases, small subcortical ischemic lesions (SSIL) on diffusion imaging are responsible for stroke manifestations but can also be occasionally observed in the absence of overt neurological symptoms. We aimed to determine, in a large cohort of young patients with CADASIL (Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic condition leading to SSIL in young patients, the characteristics of SSIL and of surrounding cerebral tissue associated with the presence of stroke symptoms. Methods- Among a cohort of 323 genetically confirmed CADASIL patients who were systematically evaluated every 18 months clinically and with magnetic resonance imaging, we studied all visible SSIL and documented ischemic stroke events with available magnetic resonance imaging data. Read More

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http://dx.doi.org/10.1161/STROKEAHA.118.021342DOI Listing

Genetic diagnosis of CADASIL in three Hong Kong Chinese patients: A novel mutation within the intracellular domain of NOTCH3.

J Clin Neurosci 2018 Oct 3;56:95-100. Epub 2018 Jul 3.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region. Electronic address:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset hereditary stroke syndrome characterized by recurrent stroke and progressive cognitive impairment caused by NOTCH3 mutations. We report here the clinical and molecular findings of three unrelated Hong Kong Chinese families with CADASIL syndrome. Sanger sequencing of genomic DNA revealed a novel heterozygous variant NM_000435. Read More

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http://dx.doi.org/10.1016/j.jocn.2018.06.050DOI Listing
October 2018
2 Reads

Redistribution of Mature Smooth Muscle Markers in Brain Arteries in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

Transl Stroke Res 2018 Jun 22. Epub 2018 Jun 22.

Department of Neurology, University of Michigan, Ann Arbor, MI, 48109-5622, USA.

Vascular smooth muscle cells (SMCs) undergo a series of dramatic changes in CADASIL, the most common inherited cause of vascular dementia and stroke. NOTCH3 protein accumulates and aggregates early in CADASIL, followed by loss of mature SMCs from the media of brain arteries and marked intimal proliferation. Similar intimal thickening is seen in peripheral arterial disease, which features pathological intimal cells including proliferative, dedifferentiated, smooth muscle-like cells deficient in SMC markers. Read More

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http://dx.doi.org/10.1007/s12975-018-0643-xDOI Listing
June 2018
8 Reads

Serum Neurofilament Light Chain Levels Are Related to Small Vessel Disease Burden.

J Stroke 2018 May 31;20(2):228-238. Epub 2018 May 31.

Stroke Center and Department of Neurology, University Hospital Basel, Basel, Switzerland.

Background And Purpose: Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment.

Methods: Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Read More

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http://dx.doi.org/10.5853/jos.2017.02565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007291PMC
May 2018
2 Reads

Updates on Prevention of Hemorrhagic and Lacunar Strokes.

J Stroke 2018 May 31;20(2):167-179. Epub 2018 May 31.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Intracerebral hemorrhage (ICH) and lacunar infarction (LI) are the major acute clinical manifestations of cerebral small vessel diseases (cSVDs). Hypertensive small vessel disease, cerebral amyloid angiopathy, and hereditary causes, such as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), constitute the three common cSVD categories. Diagnosing the underlying vascular pathology in these patients is important because the risk and types of recurrent strokes show significant differences. Read More

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http://dx.doi.org/10.5853/jos.2018.00787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007298PMC
May 2018
20 Reads

Acute Simultaneous Multiple Diffusion-Weighted MRI Abnormalities in a Patient With CADASIL.

Authors:
Brian J Sweeney

Headache 2018 May;58(5):744-745

Department of Neurology, Cork University Hospital, Wilton, Cork, Ireland.

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http://dx.doi.org/10.1111/head.13322DOI Listing

Stem Cell Factor in Combination with Granulocyte Colony-Stimulating Factor reduces Cerebral Capillary Thrombosis in a Mouse Model of CADASIL.

Cell Transplant 2018 Apr 5;27(4):637-647. Epub 2018 Jun 5.

1 Department of Neurosurgery, State University of New York, Upstate Medical University, Syracuse, New York, NY, USA.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 mutation-induced vascular smooth muscle cell (VSMC) degeneration, leading to ischemic stroke and vascular dementia. Our previous study has demonstrated that repeated treatment with a combination of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces VSMC degeneration and cerebral endothelial cell (EC) damage and improves cognitive function in a mouse model of CADASIL (TgNotch3R90C). This study aimed to determine whether cerebral thrombosis occurs in TgNotch3R90C mice and whether repeated SCF+G-CSF treatment reduces cerebral thrombosis in TgNotch3R90C mice. Read More

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http://dx.doi.org/10.1177/0963689718766460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041883PMC
April 2018
10 Reads

Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer's disease.

Acta Neuropathol Commun 2018 Jun 4;6(1):46. Epub 2018 Jun 4.

Department of Pathology, Amsterdam Neuroscience, VU University Medical Center, PO Box 7057, 1007, MB, Amsterdam, The Netherlands.

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) deposits as plaques in the parenchyma and in the walls of cortical and leptomeningeal blood vessels of the brain called cerebral amyloid angiopathy (CAA). It is suggested that CAA type-1, which refers to amyloid deposition in both capillaries and larger vessels, adds to the symptomatic manifestation of AD and correlates with disease severity. Currently, CAA cannot be diagnosed pre-mortem and disease mechanisms involved in CAA are elusive. Read More

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http://dx.doi.org/10.1186/s40478-018-0540-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985582PMC
June 2018
6 Reads

Stroke, cerebrovascular diseases and vascular cognitive impairment in Africa.

Brain Res Bull 2018 May 25. Epub 2018 May 25.

Institute of Neuroscience, Newcastle University, Campus for Ageing & Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom. Electronic address:

With increased numbers of older people a higher burden of neurological disorders worldwide is predicted. Stroke and other cerebrovascular diseases do not necessarily present with different phenotypes in Africa but their incidence is rising in tandem with the demographic change in the population. Age remains the strongest irreversible risk factor for stroke and cognitive impairment. Read More

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http://dx.doi.org/10.1016/j.brainresbull.2018.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252289PMC
May 2018
5 Reads

OCT-Angiography reveals reduced vessel density in the deep retinal plexus of CADASIL patients.

Sci Rep 2018 May 25;8(1):8148. Epub 2018 May 25.

Department of Ophthalmology, University of Muenster Medical Center, Muenster, Germany.

Optical coherence tomography angiography (OCT-A) represents the most recent tool in ophthalmic imaging. It allows for a non-invasive, depth-selective and quantitative visualization of blood flow in central retinal vessels and it has an enormous diagnostic potential not only in ophthalmology but also with regards to neurologic and systemic diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular small-vessel disease caused by Notch3 mutations and represents the most common form of hereditary stroke disorder. Read More

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http://dx.doi.org/10.1038/s41598-018-26475-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970147PMC

Notch3 protein expression in skin fibroblasts from CADASIL patients.

J Neurol Sci 2018 Jul 19;390:121-128. Epub 2018 Apr 19.

Institute of Neurological Sciences, National Research Council, Mangone, CS, Italy; Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council, Rende, CS, Italy.

Aim: CADASIL is an inherited cerebrovascular disease caused by mutations in the NOTCH3 gene. Notch signaling is involved in a broad spectrum of function, from the cell proliferation to apoptosis. Thus far, because the molecular mechanism underlying the pathological alterations remains unclear and taking into account that fibroblasts contribute to the integrity of the vasculature, our aims was to establish whether fibroblasts, in subjects carrying different NOTCH3 mutations, show abnormalities in the protein expression. Read More

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http://dx.doi.org/10.1016/j.jns.2018.04.027DOI Listing

A Japanese Case of CADASIL with a Rare Mutation in Exon 24 of the NOTCH3 Gene.

Intern Med 2018 Oct 18;57(20):3011-3014. Epub 2018 May 18.

Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, University of Miyazaki, Japan.

A 50-year-old man with a family history of stroke and depression slowly developed brain lesions. Magnetic resonance imaging revealed hyperintense lesions in the diffuse white matter, external capsules, and temporal poles on T2-weighted imaging. A heterozygous mutation c. Read More

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http://dx.doi.org/10.2169/internalmedicine.0723-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232040PMC
October 2018

Overlapping but distinct roles for NOTCH receptors in human cardiovascular disease.

Clin Genet 2019 Jan 10;95(1):85-94. Epub 2018 Jun 10.

Centre of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.

The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. Read More

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http://dx.doi.org/10.1111/cge.13382DOI Listing
January 2019
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[Neurocognitive Disorders Other Than Alzheimer Disease: Vascular Dementia].

Authors:
Mari Yoshida

Brain Nerve 2018 May;70(5):517-531

Institute for Medical Science of Aging Aichi Medical University.

Vascular dementia involves several mechanism of pathogenesis. Cerebral small vessel diseases play a central role in vascular dementia, including sporadic cerebral small vessel diseases, cerebral autosomal-dominant or autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL or CARASIL), cerebral amyloid angiopathy, and amyloid β-related angiitis. Although these diseases have different pathomechanisms, chronic white matter hypoperfusion contributes to development of neuronal dysfunction as a common pathway in vascular dementia. Read More

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http://dx.doi.org/10.11477/mf.1416201034DOI Listing
May 2018
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Severe white matter astrocytopathy in CADASIL.

Brain Pathol 2018 Nov;28(6):832-843

Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing & Vitality, Newcastle upon Tyne, UK.

Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by strategic white matter (WM) hyperintensities on MRI. Pathological features include WM degeneration, arteriolosclerosis, lacunar infarcts, and the deposition of granular osmiophilic material. Based on the hypothesis that the gliovascular unit is compromised, we assessed the nature of astrocyte damage in the deep WM of CADASIL subjects. Read More

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http://dx.doi.org/10.1111/bpa.12621DOI Listing
November 2018
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CADASIL brain vessels show a HTRA1 loss-of-function profile.

Acta Neuropathol 2018 Jul 3;136(1):111-125. Epub 2018 May 3.

Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 17, 81377, Munich, Germany.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and a phenotypically similar recessive condition (CARASIL) have emerged as important genetic model diseases for studying the molecular pathomechanisms of cerebral small vessel disease (SVD). CADASIL, the most frequent and intensely explored monogenic SVD, is characterized by a severe pathology in the cerebral vasculature including the mutation-induced aggregation of the Notch3 extracellular domain (Notch3) and the formation of protein deposits of insufficiently determined composition in vessel walls. To identify key molecules and pathways involved in this process, we quantitatively determined the brain vessel proteome from CADASIL patient and control autopsy samples (n = 6 for each group), obtaining 95 proteins with significantly increased abundance. Read More

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http://dx.doi.org/10.1007/s00401-018-1853-8DOI Listing
July 2018
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Recognition of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Two Oligosymptomatic Sisters with Low CADASIL Scale Scores and a Venous Dysplasia: Report of a Novel Greek Family.

J Stroke Cerebrovasc Dis 2018 Sep 26;27(9):e191-e195. Epub 2018 Apr 26.

Cognitive and Movement Disorders Clinic, Eginition Hospital, 1st Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. Electronic address:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to mutations of the NOTCH3 gene is the most common cause of inherited cerebral small-vessel disease and one of the genetic causes of migraine with aura. The so-called CADASIL scale has been proposed as a clinical screening tool, and a score of 15 or higher seems useful in identifying patients with high probability of carrying NOTCH3 mutations. We studied a novel Greek family with clinical features compatible with CADASIL. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10523057183017
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.002DOI Listing
September 2018
1 Read
1.993 Impact Factor

Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel.

Clin Genet 2018 Aug 8;94(2):232-238. Epub 2018 Jun 8.

Department of Neurology and Stroke Medicine, Yokohama City University, Yokohama, Japan.

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. Read More

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http://dx.doi.org/10.1111/cge.13371DOI Listing
August 2018
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The Role of in Cancer.

Oncologist 2018 Aug 5;23(8):900-911. Epub 2018 Apr 5.

Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA

The family is a highly conserved gene group that regulates cell-cell interaction, embryogenesis, and tissue commitment. This review article focuses on the third family subtype, Notch3. Regulation via Notch3 signaling was first implicated in vasculogenesis. Read More

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http://dx.doi.org/10.1634/theoncologist.2017-0677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156186PMC

[CADASIL with cysteine-sparing NOTCH3 mutation manifesting as dissociated progression between cognitive impairment and brain image findings in 3 years: A case report].

Rinsho Shinkeigaku 2018 Apr 31;58(4):235-240. Epub 2018 Mar 31.

Department of Neurology, Brain Attack Center, Ota Memorial Hospital.

A 55-year-old man with no history of stroke or migraine presented to the clinic with cognitive impairment and depression that had been experiencing for two years. Neurological examination showed bilateral pyramidal signs, and impairments in cognition and attention. Brain MRI revealed multiple lacunar lesions and microbleeds in the deep cerebral white matter, subcortical regions, and brainstem, as well as diffuse white matter hyperintensities without anterior temporal pole involvement. Read More

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https://www.jstage.jst.go.jp/article/clinicalneurol/58/4/58_
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http://dx.doi.org/10.5692/clinicalneurol.cn-001134DOI Listing
April 2018
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A novel frameshift variant in the CADASIL gene NOTCH3: pathogenic or not?

J Neurol 2018 Jun 29;265(6):1338-1342. Epub 2018 Mar 29.

Zentrum für Neurologie, Hertie-Institut für Klinische Hirnforschung, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) represents the most common monogenic cause of adult-onset ischemic stroke and vascular dementia. It is caused by heterozygous missense mutations in the NOTCH3 gene, encoding a transmembrane receptor protein on vascular smooth muscle cells. Classical CADASIL mutations affect conserved cysteine residues of the Notch3 protein. Read More

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http://dx.doi.org/10.1007/s00415-018-8844-5DOI Listing
June 2018
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Validation and Optimization of BIANCA for the Segmentation of Extensive White Matter Hyperintensities.

Neuroinformatics 2018 Apr;16(2):269-281

University Paris Diderot, Sorbonne Paris Cité, UMR-S 1161 INSERM, F-75205, Paris, France.

White matter hyperintensities (WMH) are a hallmark of small vessel diseases (SVD). Yet, no automated segmentation method is readily and widely used, especially in patients with extensive WMH where lesions are close to the cerebral cortex. BIANCA (Brain Intensity AbNormality Classification Algorithm) is a new fully automated, supervised method for WMH segmentation. Read More

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http://dx.doi.org/10.1007/s12021-018-9372-2DOI Listing

Heterozygous HTRA1 missense mutation in CADASIL-like family disease.

Braz J Med Biol Res 2018 Mar 15;51(5):e6632. Epub 2018 Mar 15.

Department of Neurology, the First Hospital of Shanxi Medical University, Taiyuan, China.

The aim of this study was to find related pathogenic genes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in (CADASIL)-like patients. The direct sequencing and high-throughput multiplex polymerase chain reaction (PCR) was performed to screen for related genes. The clinical and imaging data of a CADASIL-like patient (the pro-band) and his family members were collected. Read More

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http://dx.doi.org/10.1590/1414-431X20176632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875909PMC
March 2018
4 Reads