title: "Non-classical" paraneoplastic neurological syndromes associated with well-characterized antineuronal antibodies as compared to "classical" syndromes - More frequent than expected.
abstract: OBJECTIVE
  Paraneoplastic neurological syndromes (PNSs) are rare disorders in association with cancer and sub-divided into "classical" and "non-classical" syndromes according to a 2004 consensus paper proposed by a panel of PNS experts. "Classical" PNSs are regarded to account for the vast majority of cases. However, systematic reports on clinical PNS manifestations are rare. Therefore, we analyzed the spectrum of PNS in our clinic.
  
  
  METHODS
  We retrospectively investigated medical records from consecutive patients diagnosed with definite PNS and serological evidence of well-characterized onconeural antibodies (anti-Hu, Yo, Ri, CV2/CRMP5, Ma1, Ma2, and amphiphysin) analyzed between 1991 and 2014 in our clinic.
  
  
  RESULTS
  Of the 50 patients identified with onconeural antibody-positive PNS, 28 patients (56.0%) had "classical" PNS, and 22 (44.0%) "non-classical" PNS. Subacute cerebellar degeneration was the most frequent "classical" syndrome, brainstem encephalitis and subacute sensorimotor neuronopathy the most frequent "non-classical" syndromes. Anti-Hu antibodies were most frequent in both groups. 86.1% of patients developed neurological symptoms before the cancer was known. No differences between "classical" and "non-classical" syndromes were detected with respect to age, tumor entities and median time to diagnosis. However, whereas most patients with "classical" syndromes were females, there was no gender predominance in patients with "non-classical" PNS and the latter had significantly more frequent peripheral neurological syndromes.
  
  
  CONCLUSIONS
  The so-called "non-classical" PNSs in association with well-characterized onconeural antibodies were more common in our patient population than expected. Therefore, in neurological disorders of unclear etiology with a subacute onset and atypical presentation further diagnostic work-up including investigation of onconeural antibodies is necessary.
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany. Electronic address: benjamin.berger@uniklinik-freiburg.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Berger
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bischler
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Rick
authors.initials: R
authors.lastname: Dersch
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hottenrott
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany; Ravo Diagnostika GmbH, Oltmannsstrasse 5, D-79100 Freiburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rauer
authors.affiliation: University Hospital Freiburg, Department of Neurology and Neurophysiology, Breisacher Strasse 64, D-79106 Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000097:blood*; D001933:Brain Stem / Q000276:immunology; D002526:Cerebellar Diseases / Q000276:immunology; D051959:ELAV Proteins / Q000276:immunology; D004660:Encephalitis / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000276:immunology; D020361:Paraneoplastic Syndromes, Nervous System / Q000145:classification / Q000209:etiology* / Q000276:immunology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D000912:Antibodies, Neoplasm; D051959:ELAV Proteins
keywords: PNS; Paraneoplastic antibodies; Paraneoplastic neurological syndromes; Well-characterized onconeural antibodies; “Classical” PNS; “Non-classical” PNS