The clinical spectrum of Caspr2 antibody-associated disease.
Neurology. 2016-07-01; 87(5): 521-528
DOI: 10.1212/wnl.0000000000002917
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van Sonderen A(1), Ariño H(1), Petit-Pedrol M(1), Leypoldt F(1), Körtvélyessy P(1), Wandinger KP(1), Lancaster E(1), Wirtz PW(1), Schreurs MW(1), Sillevis Smitt PA(1), Graus F(1), Dalmau J(1), Titulaer MJ(2).
Author information:
(1)From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology
(M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology
(A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department
of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona;
Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology,
Hospital Clinic (J.D.), Institut d’Investigació Biomèdica August Pi i Sunyer
(IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical
Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.),
University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.),
University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical
Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department
of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology
(E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of
Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA),
Barcelona, Spain.
(2)From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology
(M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology
(A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department
of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona;
Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology,
Hospital Clinic (J.D.), Institut d’Investigació Biomèdica August Pi i Sunyer
(IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical
Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.),
University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.),
University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical
Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department
of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology
(E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of
Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA),
Barcelona, Spain. .
Comment in
Neurology. 2017 Jan 17;88(3):333.
Neurology. 2017 Jan 17;88(3):333-334.
OBJECTIVE: To report a large cohort of patients with antibodies against
contactin-associated protein-like 2 (Caspr2) and provide the clinical spectrum of
this disorder.
METHODS: Serum and CSF samples were assessed at 2 neuroimmunology centers in
Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were
confirmed with 2 independent techniques, including brain immunohistochemistry and
cell-based assay. Clinical information was obtained by the authors or provided by
treating physicians after patients’ informed consent.
RESULTS: Median age at symptom onset was 66 years. Of 38 patients, 34 were male.
Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent
syndromes included limbic encephalitis (42%) and Morvan syndrome (29%).
Seventy-seven percent of the patients had ≥3 of the following symptoms:
encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral
nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or
weight loss. A tumor, mostly thymoma, occurred in 19% of the patients.
Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had
immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients
and 25% had clinical relapses.
CONCLUSIONS: Caspr2 antibodies associate with a treatable disorder that
predominantly affects elderly men. The resulting syndrome may vary among patients
but it usually includes a set of well-established symptoms. Recognition of this
spectrum of symptoms and consideration of the protracted clinical course are
important for early diagnosis of this disorder. Prompt immunotherapy and tumor
therapy (if needed) often result in improvement.
© 2016 American Academy of Neurology.