Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print May 28, 2008, doi:10.1212/01.wnl.0000314832.24682.c6)
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow Correction (v71,p1552)
Right arrow All Versions of this Article:
01.wnl.0000314832.24682.c6v1
71/2/93    most recent
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McKeon, A.
Right arrow Articles by Pittock, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McKeon, A.
Right arrow Articles by Pittock, S. J.
Related Collections
Right arrow All Immunology
Right arrow Autoimmune diseases
Right arrow Devic's syndrome
Right arrow Optic neuritis; see Neuro-ophthalmology/Optic Nerve
Right arrow Transverse myelitis
NEUROLOGY 2008;71:93-100
© 2008 American Academy of Neurology

CNS aquaporin-4 autoimmunity in children

A. McKeon, MB, MRCPI, V. A. Lennon, MD, PhD, T. Lotze, MD, S. Tenenbaum, MD, J. M. Ness, MD, PhD, M. Rensel, MD, N. L. Kuntz, MD, J. P. Fryer, MS, H. Homburger, MD, J. Hunter, MD, B. G. Weinshenker, MD, K. Krecke, MD, C. F. Lucchinetti, MD and S. J. Pittock, MD

From the Departments of Neurology (A.M., V.A.L., N.L.K., B.G.W., C.F.L., S.J.P.), Laboratory Medicine and Pathology (V.A.L., J.P.F., H.H., S.J.P.), Immunology (V.A.L.), and Radiology (K.K.), Mayo Clinic College of Medicine, Rochester, MN; Divisions of Child Neurology (T.L.) and Radiology (J.H.), Texas Children’s Hospital, Baylor College of Medicine, Houston; Department of Pediatric Neurology, National Pediatric Hospital Dr. J. P. Garrahan (S.T.), Buenos Aires, Argentina; Department of Pediatrics, University of Alabama at Birmingham and Children’s Hospital (J.M.N.); and Division of Child Neurology, The Cleveland Clinic Foundation (M.R.), OH.

Address correspondence and reprint requests to Dr. Sean Pittock, Departments of Neurology and Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905 Pittock.Sean{at}mayo.edu

Background: In adult patients, autoantibodies targeting the water channel aquaporin-4 (AQP4) are a biomarker for a spectrum of CNS inflammatory demyelinating disorders with predilection for optic nerves and spinal cord (neuromyelitis optica [NMO]). Here we describe the neurologic, serologic, and radiographic findings associated with CNS AQP4 autoimmunity in childhood.

Methods: A total of 88 consecutive seropositive children were identified through service evaluation for NMO-IgG. Sera of 75 were tested for coexisting autoantibodies. Clinical information was available for 58.

Results: Forty-two patients (73%) were non-Caucasian, and 20 (34%) had African ethnicity. Median age at symptom onset was 12 years (range 4–18). Fifty-seven (98%) had attacks of either optic neuritis (n = 48; 83%) or transverse myelitis (n = 45; 78%), or both. Twenty-six (45%) had episodic cerebral symptoms (encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups). Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas (in descending order of frequency): the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus. Additional autoantibodies were detected in 57 of 75 patients (76%), and 16 of 38 (42%) had a coexisting autoimmune disorder recorded (systemic lupus erythematosus, Sjögren syndrome, juvenile rheumatoid arthritis, Graves disease). Attacks were recurrent in 54 patients (93%; median follow-up, 12 months). Forty-three of 48 patients (90%) had residual disability: 26 (54%) visual impairment and 21 (44%) motor deficits (median Expanded Disability Status Scale 4.0 at 12 months).

Conclusions: Aquaporin-4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children.

Abbreviations: ADEM = acute disseminated encephalomyelitis; ANA = antinuclear antibodies; AQP4 = aquaporin-4; EDSS = Expanded Disability Severity Scale; EIA = enzyme immunoassay; GAD65 = glutamic acid decarboxylase; GFP = green fluorescent protein; MS = multiple sclerosis; NMO = neuromyelitis optica; NMO-IgG = neuromyelitis optica autoantibody marker; SIADH = syndrome of inappropriate antidiuretic hormone secretion; SLE = systemic lupus erythematosus; SS = Sjögren syndrome.

Supplemental data at www.neurology.org

e-Pub ahead of print on May 28, 2008, at www.neurology.org.

Disclosure: The authors disclose that, in accordance with the Bayh–Dole Act of 1980 and Mayo Foundation policy, Vanda A. Lennon, Brian G. Weinshenker, and Claudia F. Lucchinetti stand to receive royalties for commercial assays to detect aquaporin-4-specific autoantibodies. The intellectual property is licensed to a commercial entity for the development of a simple, antigen-specific assay, to be made available worldwide for patient care. The test will not be exclusive to Mayo Clinic. Until now, the authors have received less than $10,000 in royalties. Mayo Clinic offers the test as an indirect immunofluorescence assay to aid the diagnosis of neuromyelitis optica but the authors do not benefit personally from the performance of the test. The other authors report no conflicts of interest.

Received November 26, 2007. Accepted in final form March 13, 2008.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by AAN Enterprises, Inc.