title: Cortical Superficial Siderosis in Different Types of Cerebral Small Vessel Disease.
abstract: Cortical superficial siderosis (cSS) has emerged as a clinically relevant imaging feature of cerebral amyloid angiopathy (CAA). However, it remains unknown whether cSS is also present in nonamyloid-associated small vessel disease and whether patients with cSS differ in terms of other small vessel disease imaging features.
  
  
  
  Three hundred sixty-four CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) patients, 372 population-based controls, and 100 CAA patients with cSS (fulfilling the modified Boston criteria for possible/probable CAA) were included. cSS and cerebral microbleeds were visually rated on T2*-weighted magnetic resonance imaging. White matter hyperintensities were segmented on fluid-attenauted inversion recovery images, and their spatial distribution was compared between groups using colocalization analysis. Cerebral microbleeds location was determined in an observer-independent way using an atlas in standard space.
  
  
  
  cSS was absent in CADASIL and present in only 2 population-based controls (0.5%). Cerebral microbleeds were present in 64% of CAA patients with cSS, 34% of patients with CADASIL, and 12% of population-based controls. Among patients with cerebral microbleeds, lobar location was found in 95% of CAA patients with cSS, 48% of CADASIL patients, and 69% of population-based controls. The spatial distribution of white matter hyperintensities was comparable between CAA with cSS and CADASIL as indicated by high colocalization coefficients.
  
  
  
  cSS was absent in CADASIL, whereas other small vessel disease imaging features were similar to CAA patients with cSS. Our findings suggest that cSS in combination with other small vessel disease imaging markers is highly indicative of CAA.
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Frank Arne
authors.initials: FA
authors.lastname: Wollenweber
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Ebru
authors.initials: E
authors.lastname: Baykara
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Zedde
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Benno
authors.initials: B
authors.lastname: Gesierich
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Achmüller
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Eric
authors.initials: E
authors.lastname: Jouvent
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Christian
authors.initials: C
authors.lastname: Opherk
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Linn
authors.affiliation: From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Germany (F.A.W., E.B., B.G., M.A., M.D., M.D.); Neurology Unit, Stroke Unit, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.Z.); University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, France (E.J., H.C.); Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston (A.V.); Department of Neurology, Medical University of Graz, Austria (S.R., R.S.); Klinik für Neurologie, SLK-Kliniken Heilbronn GmbH, Germany (C.O.); and Institut und Poliklinik für Neuroradiologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany (J.L.). marco.duering@med.uni-muenchen.de.
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D046589:CADASIL / Q000000981:diagnostic imaging / Q000453:epidemiology; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging* / Q000453:epidemiology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging* / Q000453:epidemiology; D059345:Cerebral Small Vessel Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D006486:Hemosiderosis / Q000000981:diagnostic imaging* / Q000453:epidemiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: CADASIL; cerebral amyloid angiopathy; cerebral small vessel diseases; intracranial hemorrhages; magnetic resonance imaging