Search Our Scientific Publications & Authors

J Magn Reson Imaging 2022 Jun 23. Epub 2022 Jun 23.

Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.

Background: Widespread white matter (WM) injury is a hallmark feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, controversies about the mechanism of WM tract injury exist persistently. Excessive iron accumulation, frequently reported in CADASIL patients, might cause WM tract injury. Read More

J Magn Reson Imaging 2022 Jun 22. Epub 2022 Jun 22.

Department of Neuroradiology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Neurology 2022 Jun 15. Epub 2022 Jun 15.

Département de Neurologie et Centre Neurovasculaire Translationnel, Centre de référence CERVCO, FHU NeuroVasc, Hôpital Lariboisière, AP-HP, Université de Paris, 75010 Paris, France

Background And Objective: The course and pattern of cognitive decline in ischemic cerebral small vessel disease (cSVD) remains poorly characterized. We analysed the trajectory pattern of cognitive decline from age 25 to 75 years in CADASIL.

Methods: We applied latent process mixed models to data obtained from CADASIL patients who were repeatedly scored during follow-up using 16 selected clinical scales or cognitive tests. Read More

S D Med 2022 Mar;75(3):134-137

Avera McKennan Hospital and University Health Center, Sioux Falls, South Dakota.

White matter changes on MRI can be a diagnostic puzzle as a large group of inflammatory, autoimmune, infectious, and neoplastic conditions can present in this way. An otherwise healthy 36-year-old male presented with his second episode of unilateral weakness, the first episode occurring five years previously. He did not have sensory or cerebellar symptoms with the current or previous episode. Read More

Mol Neurobiol 2022 Jun 14. Epub 2022 Jun 14.

Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, Queensland, 4059, Australia.

Monogenic forms of cerebral small vessel disease (CSVD) can be caused by both variants in nuclear DNA and mitochondrial DNA (mtDNA). Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is known to have a phenotype similar to Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy (CADASIL), and can be caused by variants in the mitochondrial genome and in several nuclear-encoded mitochondrial protein (NEMP) genes. The aim of this study was to screen for variants in the mitochondrial genome and NEMP genes in a NOTCH3-negative CADASIL cohort, to identify a potential link between mitochondrial dysfunction and CSVD pathology. Read More

Brain Pathol 2022 Jun 13:e13097. Epub 2022 Jun 13.

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We studied small vessel disease (SVD) pathology in Familial Alzheimer's disease (FAD) subjects carrying the presenilin 1 (PSEN1) p.Glu280Ala mutation in comparison to those with sporadic Alzheimer's disease (SAD) as a positive control for Alzheimer's pathology and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) bearing different NOTCH3 mutations, as positive controls for SVD pathology. Upon magnetic resonance imaging (MRI) in life, some FAD showed mild white matter hyperintensities and no further radiologic evidence of SVD. Read More

Neurology 2022 May 31. Epub 2022 May 31.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

Background And Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by a cysteine-altering mutation in one of the thirty-four epidermal growth factor-like repeat (EGFR) domains of the NOTCH3 protein. CADASIL has a variable phenotypic presentation and mutations in EGFRs 1-6 have been found correlated with greater disease severity. We examined clinical and radiological features and performed bioinformatic annotation of mutations in a large CADASIL cohort to further understand these associations. Read More

PLoS One 2022 26;17(5):e0268572. Epub 2022 May 26.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in NOTCH3, is the most common cause of hereditary cerebral small vessel disease. Whether it will involve systemic vasculopathy such as retinal vessel remains unknown. Optical coherence tomography angiography (OCT-A) is a noninvasive technique for visualising retinal blood flow. Read More

Neurology 2022 May 23. Epub 2022 May 23.

Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.

Background And Objective: CADASIL is the most common monogenic form of stroke and early onset dementia. We determined the prevalence of vascular cognitive impairment (VCI) in a cohort of CADASIL patients, and investigated which factors were associated with VCI risk, including clinical, genetic and MRI parameters.

Methods: Cognition was assessed in genetically confirmed CADASIL patients (n = 176) and healthy controls (n = 265) (mean(SD) age 50. Read More

Neurology 2022 May 23. Epub 2022 May 23.

Centre for Clinical Brain Sciences, UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK

Background: Magnetic resonance susceptibility-weighted imaging (SWI) can identify small brain blood vessels that contain deoxygenated blood due to its induced magnetic field disturbance. We observed focal clusters of possible dilated small vessels on SWI in white matter in severe small vessel disease (SVD). We assessed their prevalence, associations with SVD lesions and vascular reactivity in patients with sporadic SVD and in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Read More

Curr Mol Med 2022 ;22(4):300-311

Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy.

Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described, and new sequencing techniques such as Next-generation sequencing are available. Brain imaging is significant for the detection of these diseases. Since it is often performed at an initial stage, an MRI is a key to selecting patients for genetic testing and for interpreting nextgeneration sequencing reports. Read More

Neurology 2022 May 18. Epub 2022 May 18.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Objective: This study investigated the cutaneous small fiber pathology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and its clinical significance, i.e. the NOTCH3 deposition in cutaneous vasculatures and CNS neurodegeneration focusing on cognitive impairment. Read More

Cold Spring Harb Perspect Med 2022 May 9. Epub 2022 May 9.

Department of Ophthalmology at Harvard Medical School, Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts 02114, USA.

The Notch signaling pathway is a highly versatile and evolutionarily conserved mechanism with an important role in cell fate determination. Notch signaling plays a vital role in vascular development, regulating several fundamental processes such as angiogenesis, arterial/venous differentiation, and mural cell investment. Aberrant Notch signaling can result in severe vascular phenotypes as observed in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille syndrome. Read More

J Stroke Cerebrovasc Dis 2022 Jul 3;31(7):106541. Epub 2022 May 3.

Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small-vessel disease, which is characterized by migraine, recurrent ischemic strokes, psychiatric disorder, progressive cognitive decline, and occasionally intracerebral hemorrhage (ICH). ICH events have been reported in a high proportion of East Asian CADASIL patients with R544C mutation in exon 11 of NOTCH3; however, whether any other specific NOTCH3 mutation determines the ICH phenotype has yet to be explored.

Case Presentation: We report the case of a 60-year-old male CADASIL patient with a novel R558C mutation in exon 11 of the NOTCH3 gene, who presented with ICH in the basal ganglia and cerebellum. Read More

AJNR Am J Neuroradiol 2022 05 29;43(5):715-720. Epub 2022 Apr 29.

From the Department of Neurology (E.J.)

Background And Purpose: By studying the evolution of brain volume across the life span in male and female patients, we aimed to understand how sex, brain volume, and the epidermal growth factor repeat domain of the mutation, the 3 major determinants of disability in CADASIL, interact in driving disease evolution.

Materials And Methods: We used validated methods to model the evolution of normalized brain volume with age in male and female patients using nonparametric regression in a large, monocentric cohort with prospectively collected clinical and high-resolution MR imaging data. We used k-means clustering to test for the presence of different clinical course profiles. Read More

Open Biol 2022 04 27;12(4):220004. Epub 2022 Apr 27.

Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

Notch signalling is an evolutionarily highly conserved signalling mechanism governing differentiation and regulating homeostasis in many tissues. In this review, we discuss recent advances in our understanding of the roles that Notch signalling plays in the vasculature. We describe how Notch signalling regulates different steps during the genesis and remodelling of blood vessels (vasculogenesis and angiogenesis), including critical roles in assigning arterial and venous identities to the emerging blood vessels and regulation of their branching. Read More

Neurologia (Engl Ed) 2022 04;37(3):235-236

Estudante de Medicina, UNAERP, Ribeirão Preto, Brazil.

Clin Neurol Neurosurg 2022 06 12;217:107244. Epub 2022 Apr 12.

Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey. Electronic address:

Background And Purpose: Cerebral small vessel disease (CSVD) may present with gradual onset, chronic parkinsonism and/or dementia. In this study, we aimed to identify the prevalence and clinical characteristics of apathy, dementia and parkinsonism in a cohort of patients with CSVD and to determine the neuroimaging features in these patients.

Methods: We included all patients with CSVD, who were admitted to the stroke outpatient clinic between February 2018 and February 2019. Read More

PLoS One 2022 14;17(4):e0266974. Epub 2022 Apr 14.

Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, United States of America.

Introduction: Cerebral Small Vessel Disease (CSVD), a progressive degenerative disorder of small caliber cerebral vessels, represents a major contributor to stroke and vascular dementia incidence worldwide. We sought to conduct a systematic review of the role of retinal biomarkers in diagnosis and characterization of CSVD.

Methods: We conducted a systematic review of MEDLINE, PubMed, Scopus, the Cochrane Library Database, and Web of Science. Read More

Clin Neurol Neurosurg 2022 Apr 6;216:107239. Epub 2022 Apr 6.

Division of Neurology, Scientific Institute for Research, Hospitalization, and Care (IRCCS) Foundation "Carlo Besta" Neurological Institute, Milan, Italy.

Background: Acute confusional state associated with migraine in adults is an infrequent entity. Around 30-60% of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients get affected by migraine attacks-the majority with aura-often as the first symptom of the disease. Acute confusional state during migraine has been rarely described in CADASIL patients and a complete neuropsychological assessment during the acute phase has never been conducted so far. Read More

Int J Mol Sci 2022 Mar 27;23(7). Epub 2022 Mar 27.

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

Cysteine oxidation states of extracellular proteins participate in functional regulation and in disease pathophysiology. In the most common inherited dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mutations in NOTCH3 that alter extracellular cysteine number have implicated NOTCH3 cysteine states as potential triggers of cerebral vascular smooth muscle cytopathology. In this report, we describe a novel property of the second EGF-like domain of NOTCH3: its capacity to alter the cysteine redox state of the NOTCH3 ectodomain. Read More

Clin Genet 2022 Jul 11;102(1):82-83. Epub 2022 Apr 11.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.

Mov Disord Clin Pract 2022 Apr 3;9(3):297-310. Epub 2022 Feb 3.

Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital-UHN, Division of Neurology University of Toronto Toronto Ontario Canada.

We selected several "imaging pearls" presented during the Movement Disorder Society (MDS) Video Challenge for this review. While the event, as implicated by its name, was video-centered, we would like to emphasize the important role of imaging in making the correct diagnosis. We divided this anthology into two parts: genetic and acquired disorders. Read More

Commun Biol 2022 04 7;5(1):331. Epub 2022 Apr 7.

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

Cerebral small vessel disease (SVD) is a prevalent disease of aging and a major contributor to stroke and dementia. The most commonly inherited SVD, CADASIL, is caused by dominantly acting cysteine-altering mutations in NOTCH3. These mutations change the number of cysteines from an even to an odd number, but the impact of these alterations on NOTCH3 protein structure remain unclear. Read More

Medicine (Baltimore) 2022 Feb;101(7):e28870

Department of Neurology, Chenzhou No.1 People's Hospital, Chenzhou, Hunan, China.

Rationale: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults, and is caused by NOTCH3 mutations. However, individual symptom types, onset, and disease severity span a wide range.

Patient Concerns: Herein, we report a case of chronic neurological symptoms including slurring of speech, recurrent weakness in both limbs and legs, and progressive memory loss. Read More

Cephalalgia 2022 Mar 18:3331024221080891. Epub 2022 Mar 18.

Department of Neurology, Neurological Institute, 46615Taipei Veterans General Hospital, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The role of the p.R544C variant, the predominant variant of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in multiple East Asian regions, in migraine is unknown.

Methods: Migraine patients (n = 2,884) (2,279F/605M, mean age 38. Read More

Stroke 2022 Jun 18;53(6):1964-1974. Epub 2022 Mar 18.

Department of Clinical Genetics (R.J.H., G.G., M.N.C., S.A.J.L.O., J.W.R.), Leiden University Medical Center, the Netherlands.

Background: To determine whether extremely mild small vessel disease (SVD) phenotypes can occur in variant carriers from Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) pedigrees using clinical, genetic, neuroimaging, and skin biopsy findings.

Methods: Individuals from CADASIL pedigrees fulfilling criteria for extremely mild -associated SVD (mSVD) were selected from the cross-sectional Dutch CADASIL cohort (n=200), enrolled between 2017 and 2020. Brain magnetic resonance imaging were quantitatively assessed for SVD imaging markers. Read More

Stroke 2022 04 3;53(4):e162-e164. Epub 2022 Mar 3.

Case Western Reserve School of Medicine (C.K., S.S.), University Hospitals Cleveland Medical Center, OH.

Ann Neurol 2022 06 31;91(6):889-890. Epub 2022 Mar 31.

Toulouse Neuroimaging Center, University of Toulouse, Inserm, University Paul Sabatier, Toulouse, France.

Front Mol Biosci 2022 9;9:812808. Epub 2022 Feb 9.

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common familial form of stroke, which is caused by mutations located in the epidermal growth factor (EGF)-like repeats of the gene. Mutations cause the NOTCH3 (N3) protein to misfold and aggregate. These aggregates will be a component of granular osmiophilic material, which when accumulated around the arteries and arterioles is believed to cause the degradation of vascular smooth muscle cells (VSMC). Read More