eprintid: 19367
rev_number: 18
eprint_status: archive
userid: 1589
dir: disk0/00/01/93/67
datestamp: 2015-12-09 07:43:06
lastmod: 2024-03-10 04:24:47
status_changed: 2015-12-09 07:43:06
type: article
metadata_visibility: show
creators_name: Jarius, Sven
creators_name: Kleffner, Ilka
creators_name: Dörr, Jan M.
creators_name: Sastre-Garriga, Jaume
creators_name: Illes, Zsolt
creators_name: Eggenberger, Eric
creators_name: Chalk, Colin
creators_name: Ringelstein, Marius
creators_name: Aktas, Orhan
creators_name: Montalban, Xavier
creators_name: Fechner, Kai
creators_name: Stöcker, Winfried
creators_name: Ringelstein, Erich B.
creators_name: Paul, Friedemann
creators_name: Wildemann, Brigitte
title: Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study
subjects: ddc-610
divisions: i-911100
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.  
date: 2014
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 453610374
own_urn: urn:nbn:de:bsz:16-heidok-193672
language: eng
bibsort: JARIUSSVENCLINICALPA2014
full_text_status: public
publication: Journal of neuroinflammation
volume: 11
number: 46
place_of_pub: London
pagerange: 1-11
issn: 1742-2094
citation:   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  (2014) Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study.  Journal of neuroinflammation, 11 (46).  pp. 1-11.  ISSN 1742-2094     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19367/1/12974_2013_Article_1119.pdf