Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study

Sven Jarius, Ilka Kleffner, Jan M Dörr, Jaume Sastre-Garriga, Zsolt Illes, Eric Eggenberger, Colin Chalk, Marius Ringelstein, Orhan Aktas, Xavier Montalban, Kai Fechner, Winfried Stöcker, Erich B Ringelstein, Friedemann Paul, Brigitte Wildemann

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Susac syndrome (SuS) is a rare disorder thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear leading to central nervous system (CNS) dysfunction, visual disturbances due to branch retinal artery occlusions (BRAO), and hearing deficits. Recently, a role for anti-endothelial cell antibodies (AECA) in SuS has been proposed.

OBJECTIVES: To report the clinical and paraclinical findings in the largest single series of patients so far and to investigate the frequency, titers, and clinical relevance of AECA in SuS.

PATIENTS AND METHODS: A total of 107 serum samples from 20 patients with definite SuS, 5 with abortive forms of SuS (all with BRAO), and 70 controls were tested for AECA by immunohistochemistry employing primate brain tissue sections.

RESULTS: IgG-AECA >1:100 were detected in 25% (5/20) of patients with definite SuS and in 4.3% (3/70) of the controls. Median titers were significantly higher in SuS (1:3200, range 1:100 to 1:17500) than in controls (1:100, range 1:10 to 1:320); IgG-AECA titers >1:320 were exclusively present in patients with SuS; three controls had very low titers (1:10). Follow-up samples (n = 4) from a seropositive SuS patient obtained over a period of 29 months remained positive at high titers. In all seropositive cases, AECA belonged to the complement-activating IgG1 subclass. All but one of the IgG-AECA-positive samples were positive also for IgA-AECA and 45% for IgM-AECA. SuS took a severe and relapsing course in most patients and was associated with bilateral visual and hearing impairment, a broad panel of neurological and neuropsychological symptoms, and brain atrophy in the majority of cases. Seropositive and seronegative patients did not differ with regard to any of the clinical or paraclinical parameters analyzed.

CONCLUSIONS: SuS took a severe and protracted course in the present cohort, resulting in significant impairment. Our finding of high-titer IgG1 and IgM AECA in some patients suggest that humoral autoimmunity targeting the microvasculature may play a role in the pathogenesis of SuS, at least in a subset of patients. Further studies are warranted to define the exact target structures of AECA in SuS.

Original languageEnglish
JournalJournal of Neuroinflammation
Volume11
Pages (from-to)46
ISSN1742-2094
DOIs
Publication statusPublished - 2014

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Susac Syndrome
Multicenter Studies
anti-endothelial cell antibody

Keywords

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies
  • Cognition Disorders
  • Connective Tissue Diseases
  • Hearing Disorders
  • Humans
  • Immunoglobulin G
  • International Cooperation
  • Leukocyte Count
  • Lupus Vasculitis, Central Nervous System
  • Middle Aged
  • Multiple Sclerosis
  • Serologic Tests
  • Susac Syndrome
  • Vision Disorders
  • Young Adult

Cite this

Jarius, Sven ; Kleffner, Ilka ; Dörr, Jan M ; Sastre-Garriga, Jaume ; Illes, Zsolt ; Eggenberger, Eric ; Chalk, Colin ; Ringelstein, Marius ; Aktas, Orhan ; Montalban, Xavier ; Fechner, Kai ; Stöcker, Winfried ; Ringelstein, Erich B ; Paul, Friedemann ; Wildemann, Brigitte. / Clinical, paraclinical and serological findings in Susac syndrome : an international multicenter study. In: Journal of Neuroinflammation. 2014 ; Vol. 11. pp. 46.
@article{9827d36d0c3246c0876a141fef2e9b44,
title = "Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study",
abstract = "BACKGROUND: Susac syndrome (SuS) is a rare disorder thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear leading to central nervous system (CNS) dysfunction, visual disturbances due to branch retinal artery occlusions (BRAO), and hearing deficits. Recently, a role for anti-endothelial cell antibodies (AECA) in SuS has been proposed.OBJECTIVES: To report the clinical and paraclinical findings in the largest single series of patients so far and to investigate the frequency, titers, and clinical relevance of AECA in SuS.PATIENTS AND METHODS: A total of 107 serum samples from 20 patients with definite SuS, 5 with abortive forms of SuS (all with BRAO), and 70 controls were tested for AECA by immunohistochemistry employing primate brain tissue sections.RESULTS: IgG-AECA >1:100 were detected in 25{\%} (5/20) of patients with definite SuS and in 4.3{\%} (3/70) of the controls. Median titers were significantly higher in SuS (1:3200, range 1:100 to 1:17500) than in controls (1:100, range 1:10 to 1:320); IgG-AECA titers >1:320 were exclusively present in patients with SuS; three controls had very low titers (1:10). Follow-up samples (n = 4) from a seropositive SuS patient obtained over a period of 29 months remained positive at high titers. In all seropositive cases, AECA belonged to the complement-activating IgG1 subclass. All but one of the IgG-AECA-positive samples were positive also for IgA-AECA and 45{\%} for IgM-AECA. SuS took a severe and relapsing course in most patients and was associated with bilateral visual and hearing impairment, a broad panel of neurological and neuropsychological symptoms, and brain atrophy in the majority of cases. Seropositive and seronegative patients did not differ with regard to any of the clinical or paraclinical parameters analyzed.CONCLUSIONS: SuS took a severe and protracted course in the present cohort, resulting in significant impairment. Our finding of high-titer IgG1 and IgM AECA in some patients suggest that humoral autoimmunity targeting the microvasculature may play a role in the pathogenesis of SuS, at least in a subset of patients. Further studies are warranted to define the exact target structures of AECA in SuS.",
keywords = "Adolescent, Adult, Aged, Autoantibodies, Cognition Disorders, Connective Tissue Diseases, Hearing Disorders, Humans, Immunoglobulin G, International Cooperation, Leukocyte Count, Lupus Vasculitis, Central Nervous System, Middle Aged, Multiple Sclerosis, Serologic Tests, Susac Syndrome, Vision Disorders, Young Adult",
author = "Sven Jarius and Ilka Kleffner and D{\"o}rr, {Jan M} and Jaume Sastre-Garriga and Zsolt Illes and Eric Eggenberger and Colin Chalk and Marius Ringelstein and Orhan Aktas and Xavier Montalban and Kai Fechner and Winfried St{\"o}cker and Ringelstein, {Erich B} and Friedemann Paul and Brigitte Wildemann",
year = "2014",
doi = "10.1186/1742-2094-11-46",
language = "English",
volume = "11",
pages = "46",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
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Jarius, S, Kleffner, I, Dörr, JM, Sastre-Garriga, J, Illes, Z, Eggenberger, E, Chalk, C, Ringelstein, M, Aktas, O, Montalban, X, Fechner, K, Stöcker, W, Ringelstein, EB, Paul, F & Wildemann, B 2014, 'Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study', Journal of Neuroinflammation, vol. 11, pp. 46. https://doi.org/10.1186/1742-2094-11-46

Clinical, paraclinical and serological findings in Susac syndrome : an international multicenter study. / Jarius, Sven; Kleffner, Ilka; Dörr, Jan M; Sastre-Garriga, Jaume; Illes, Zsolt; Eggenberger, Eric; Chalk, Colin; Ringelstein, Marius; Aktas, Orhan; Montalban, Xavier; Fechner, Kai; Stöcker, Winfried; Ringelstein, Erich B; Paul, Friedemann; Wildemann, Brigitte.

In: Journal of Neuroinflammation, Vol. 11, 2014, p. 46.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Clinical, paraclinical and serological findings in Susac syndrome

T2 - an international multicenter study

AU - Jarius, Sven

AU - Kleffner, Ilka

AU - Dörr, Jan M

AU - Sastre-Garriga, Jaume

AU - Illes, Zsolt

AU - Eggenberger, Eric

AU - Chalk, Colin

AU - Ringelstein, Marius

AU - Aktas, Orhan

AU - Montalban, Xavier

AU - Fechner, Kai

AU - Stöcker, Winfried

AU - Ringelstein, Erich B

AU - Paul, Friedemann

AU - Wildemann, Brigitte

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Susac syndrome (SuS) is a rare disorder thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear leading to central nervous system (CNS) dysfunction, visual disturbances due to branch retinal artery occlusions (BRAO), and hearing deficits. Recently, a role for anti-endothelial cell antibodies (AECA) in SuS has been proposed.OBJECTIVES: To report the clinical and paraclinical findings in the largest single series of patients so far and to investigate the frequency, titers, and clinical relevance of AECA in SuS.PATIENTS AND METHODS: A total of 107 serum samples from 20 patients with definite SuS, 5 with abortive forms of SuS (all with BRAO), and 70 controls were tested for AECA by immunohistochemistry employing primate brain tissue sections.RESULTS: IgG-AECA >1:100 were detected in 25% (5/20) of patients with definite SuS and in 4.3% (3/70) of the controls. Median titers were significantly higher in SuS (1:3200, range 1:100 to 1:17500) than in controls (1:100, range 1:10 to 1:320); IgG-AECA titers >1:320 were exclusively present in patients with SuS; three controls had very low titers (1:10). Follow-up samples (n = 4) from a seropositive SuS patient obtained over a period of 29 months remained positive at high titers. In all seropositive cases, AECA belonged to the complement-activating IgG1 subclass. All but one of the IgG-AECA-positive samples were positive also for IgA-AECA and 45% for IgM-AECA. SuS took a severe and relapsing course in most patients and was associated with bilateral visual and hearing impairment, a broad panel of neurological and neuropsychological symptoms, and brain atrophy in the majority of cases. Seropositive and seronegative patients did not differ with regard to any of the clinical or paraclinical parameters analyzed.CONCLUSIONS: SuS took a severe and protracted course in the present cohort, resulting in significant impairment. Our finding of high-titer IgG1 and IgM AECA in some patients suggest that humoral autoimmunity targeting the microvasculature may play a role in the pathogenesis of SuS, at least in a subset of patients. Further studies are warranted to define the exact target structures of AECA in SuS.

AB - BACKGROUND: Susac syndrome (SuS) is a rare disorder thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear leading to central nervous system (CNS) dysfunction, visual disturbances due to branch retinal artery occlusions (BRAO), and hearing deficits. Recently, a role for anti-endothelial cell antibodies (AECA) in SuS has been proposed.OBJECTIVES: To report the clinical and paraclinical findings in the largest single series of patients so far and to investigate the frequency, titers, and clinical relevance of AECA in SuS.PATIENTS AND METHODS: A total of 107 serum samples from 20 patients with definite SuS, 5 with abortive forms of SuS (all with BRAO), and 70 controls were tested for AECA by immunohistochemistry employing primate brain tissue sections.RESULTS: IgG-AECA >1:100 were detected in 25% (5/20) of patients with definite SuS and in 4.3% (3/70) of the controls. Median titers were significantly higher in SuS (1:3200, range 1:100 to 1:17500) than in controls (1:100, range 1:10 to 1:320); IgG-AECA titers >1:320 were exclusively present in patients with SuS; three controls had very low titers (1:10). Follow-up samples (n = 4) from a seropositive SuS patient obtained over a period of 29 months remained positive at high titers. In all seropositive cases, AECA belonged to the complement-activating IgG1 subclass. All but one of the IgG-AECA-positive samples were positive also for IgA-AECA and 45% for IgM-AECA. SuS took a severe and relapsing course in most patients and was associated with bilateral visual and hearing impairment, a broad panel of neurological and neuropsychological symptoms, and brain atrophy in the majority of cases. Seropositive and seronegative patients did not differ with regard to any of the clinical or paraclinical parameters analyzed.CONCLUSIONS: SuS took a severe and protracted course in the present cohort, resulting in significant impairment. Our finding of high-titer IgG1 and IgM AECA in some patients suggest that humoral autoimmunity targeting the microvasculature may play a role in the pathogenesis of SuS, at least in a subset of patients. Further studies are warranted to define the exact target structures of AECA in SuS.

KW - Adolescent

KW - Adult

KW - Aged

KW - Autoantibodies

KW - Cognition Disorders

KW - Connective Tissue Diseases

KW - Hearing Disorders

KW - Humans

KW - Immunoglobulin G

KW - International Cooperation

KW - Leukocyte Count

KW - Lupus Vasculitis, Central Nervous System

KW - Middle Aged

KW - Multiple Sclerosis

KW - Serologic Tests

KW - Susac Syndrome

KW - Vision Disorders

KW - Young Adult

U2 - 10.1186/1742-2094-11-46

DO - 10.1186/1742-2094-11-46

M3 - Journal article

C2 - 24606999

VL - 11

SP - 46

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

ER -