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Neurology. 2015 Jan 13;84(2):148-58. doi: 10.1212/WNL.0000000000001126. Epub 2014 Dec 10.

Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions.

Author information

1
From the Department of Anatomy and Cell Biology and Cameco MS Neuroscience Research Center (B.F.G.P.), University of Saskatchewan, Saskatoon, Canada; the Departments of Neurology (Y.G., J.E.P., V.A.L., S.J.P., B.G.W., S.L.C., C.F.L.), Laboratory Medicine and Pathology (M.E.J., J.E.P., V.A.L., S.J.P., G.G.), and Immunology (V.A.L.), Mayo Clinic, Rochester, MN; the Department of Neurology (D.M.W., J.C.), Mayo Clinic, Scottsdale, AZ; the Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen, Germany; the Department of Neurology (E.A.S.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (C.D.B.), Columbia University Medical Center, New York, NY; and the Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Evanston, IL.
2
From the Department of Anatomy and Cell Biology and Cameco MS Neuroscience Research Center (B.F.G.P.), University of Saskatchewan, Saskatoon, Canada; the Departments of Neurology (Y.G., J.E.P., V.A.L., S.J.P., B.G.W., S.L.C., C.F.L.), Laboratory Medicine and Pathology (M.E.J., J.E.P., V.A.L., S.J.P., G.G.), and Immunology (V.A.L.), Mayo Clinic, Rochester, MN; the Department of Neurology (D.M.W., J.C.), Mayo Clinic, Scottsdale, AZ; the Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen, Germany; the Department of Neurology (E.A.S.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (C.D.B.), Columbia University Medical Center, New York, NY; and the Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Evanston, IL. lucchinetti.claudia@mayo.edu.

Abstract

OBJECTIVE:

To assess, in a surgical biopsy cohort of active demyelinating lesions, the diagnostic utility of aquaporin-4 (AQP4) immunohistochemistry in identifying neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) and describe pathologic features that should prompt AQP4 immunohistochemical analysis and AQP4-immunoglobulin G (IgG) serologic testing.

METHODS:

This was a neuropathologic cohort study of 20 surgical biopsies (19 patients; 11 cord/9 brain), performed because of diagnostic uncertainty, interpreted as active demyelinating disease and containing 2 or more of the following additional features: tissue vacuolation, granulocytic infiltrates, or astrocyte injury.

RESULTS:

AQP4 immunoreactivity was lost in 18 biopsies and increased in 2. Immunopathologic features of the AQP4 loss cohort were myelin vacuolation (18), dystrophic astrocytes and granulocytes (17), vascular hyalinization (16), macrophages containing glial fibrillary acid protein (GFAP)-positive debris (14), and Creutzfeldt-Peters cells (0). All 14 cases with available serum tested positive for AQP4-IgG after biopsy. Diagnosis at last follow-up was NMO/NMOSD (15) and longitudinally extensive transverse myelitis (1 each relapsing and single). Immunopathologic features of the AQP4 increased cohort were macrophages containing GFAP-positive debris and granulocytes (2), myelin vacuolation (1), dystrophic astrocytes (1), Creutzfeldt-Peters cells (1), and vascular hyalinization (1). Diagnosis at last follow-up was multiple sclerosis (MS) and both tested AQP4-IgG seronegative after biopsy.

CONCLUSIONS:

AQP4 immunohistochemistry with subsequent AQP4-IgG testing has diagnostic utility in identifying cases of NMO/NMOSD. This study highlights the importance of considering NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions. AQP4-IgG testing may avert biopsy and avoid ineffective therapies if these patients are erroneously treated for MS.

PMID:
25503621
PMCID:
PMC4336081
DOI:
10.1212/WNL.0000000000001126
[Indexed for MEDLINE]
Free PMC Article

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