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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Jarius
authors.forename: Ilka
authors.initials: I
authors.lastname: Kleffner
authors.forename: Jan M
authors.initials: JM
authors.lastname: Dörr
authors.forename: Jaume
authors.initials: J
authors.lastname: Sastre-Garriga
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
authors.forename: Eric
authors.initials: E
authors.lastname: Eggenberger
authors.forename: Colin
authors.initials: C
authors.lastname: Chalk
authors.forename: Marius
authors.initials: M
authors.lastname: Ringelstein
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Kai
authors.initials: K
authors.lastname: Fechner
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.forename: Erich B
authors.initials: EB
authors.lastname: Ringelstein
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D003072:Cognition Disorders / Q000209:etiology; D003240:Connective Tissue Diseases / Q000097:blood; D006311:Hearing Disorders / Q000209:etiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007391:International Cooperation; D007958:Leukocyte Count; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood; D012698:Serologic Tests; D055955:Susac Syndrome / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D014786:Vision Disorders / Q000209:etiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; C087589:anti-endothelial cell antibody