TY - JOUR
T1 - Neuromyelitis optica unique area postrema lesions
T2 - Nausea, vomiting, and pathogenic implications
AU - Popescu, B. F.Gh
AU - Lennon, V. A.
AU - Parisi, J. E.
AU - Howe, C. L.
AU - Weigand, S. D.
AU - Cabrera-Gómez, J. A.
AU - Newell, K.
AU - Mandler, R. N.
AU - Pittock, S. J.
AU - Weinshenker, B. G.
AU - Lucchinetti, C. F.
N1 - Funding Information:
Dr. Popescu reports no disclosures. Dr. Lennon is a named investor on a patent application filed by the Mayo Foundation for Medical Education and Research that relates to the NMO antigen and its application to the diagnosis of NMO; may accrue revenue for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica; and receives research support from the NIH and the Guthy Jackson Charitable Foundation. Dr. Parisi serves on scientific advisory boards for the US Government Defense Health Board and the Subcommittee for Laboratory Services and Pathology; serves as a Section Editor for Neurology®; receives royalties from the publication of Principles & Practice of Neuropathology, 2nd ed. (Oxford University Press, 2003); and receives research support from the NIH. Dr. Howe, S.D. Weigand, and Dr. Cabrera-Gómez report no disclosures. Dr. Newell receives/has received research support from the NIH. Dr. Mandler reports no disclosures. Dr. Pittock may accrue revenue for patents re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica and aquaporin-4 autoantibody as a cancer marker; and has received research support from Alexion Pharmaceuticals, Inc. and the Guthy Jackson Charitable Foundation. Dr. Weinshenker serves on data safety monitoring boards for Novartis and Biogen Idec; serves on the editorial boards of the Canadian Journal of Neurological Sciences and the Turkish Journal of Neurology; has received research support from Genzyme Corporation and the Guthy-Jackson Charitable Foundation; and receives license royalties from RSR Ltd. for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica. Dr. Lucchinetti may accrue revenue for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica; receives royalties from the publication of Blue Books of Neurology: Multiple Sclerosis 3 (Saunders Elsevier, 2010); and receives research support from the NIH, the Guthy Jackson Charitable Foundation (PI), and the National MS Society.
Funding Information:
Study funding: Supported by the NIH (RO1-NS049577-01-A2 to C.F.L.) , the National Multiple Sclerosis Society (RG 3185-B-3 to C.F.L.) , and the Guthy Jackson Foundation (to C.F.L.).
PY - 2011/4/5
Y1 - 2011/4/5
N2 - Objective: To characterize the neuropathologic features of neuromyelitis optica (NMO) at the medullary floor of the fourth ventricle and area postrema. Aquaporin-4 (AQP4) autoimmunity targets this region, resulting in intractable nausea associated with vomiting or hiccups in NMO. Methods: This neuropathologic study was performed on archival brainstem tissue from 15 patients with NMO, 5 patients with multiple sclerosis (MS), and 8 neurologically normal subjects. Logistic regression was used to evaluate whether the presence of lesions at this level increased the odds of a patient with NMO having an episode of nausea/vomiting. Results: Six patients with NMO (40%), but no patients with MS or normal controls, exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle. These lesions were characterized by tissue rarefaction, blood vessel thickening, no obvious neuronal or axonal pathology, and preservation of myelin in the subependymal medullary tegmentum. AQP4 immunoreactivity was lost or markedly reduced in all 6 cases, with moderate to marked perivascular and parenchymal lymphocytic inflammatory infiltrates, prominent microglial activation, and in 3 cases, eosinophils. Complement deposition in astrocytes, macrophages, and/or perivascularly, and a prominent astroglial reaction were also present. The odds of nausea/vomiting being documented clinically was 16-fold greater in NMO cases with area postrema lesions (95% confidence interval 1.43-437, p = 0.02). Conclusions: These neuropathologic findings suggest the area postrema may be a selective target of the disease process in NMO, and are compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis and transverse myelitis or being the heralding symptom of NMO.
AB - Objective: To characterize the neuropathologic features of neuromyelitis optica (NMO) at the medullary floor of the fourth ventricle and area postrema. Aquaporin-4 (AQP4) autoimmunity targets this region, resulting in intractable nausea associated with vomiting or hiccups in NMO. Methods: This neuropathologic study was performed on archival brainstem tissue from 15 patients with NMO, 5 patients with multiple sclerosis (MS), and 8 neurologically normal subjects. Logistic regression was used to evaluate whether the presence of lesions at this level increased the odds of a patient with NMO having an episode of nausea/vomiting. Results: Six patients with NMO (40%), but no patients with MS or normal controls, exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle. These lesions were characterized by tissue rarefaction, blood vessel thickening, no obvious neuronal or axonal pathology, and preservation of myelin in the subependymal medullary tegmentum. AQP4 immunoreactivity was lost or markedly reduced in all 6 cases, with moderate to marked perivascular and parenchymal lymphocytic inflammatory infiltrates, prominent microglial activation, and in 3 cases, eosinophils. Complement deposition in astrocytes, macrophages, and/or perivascularly, and a prominent astroglial reaction were also present. The odds of nausea/vomiting being documented clinically was 16-fold greater in NMO cases with area postrema lesions (95% confidence interval 1.43-437, p = 0.02). Conclusions: These neuropathologic findings suggest the area postrema may be a selective target of the disease process in NMO, and are compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis and transverse myelitis or being the heralding symptom of NMO.
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UR - http://www.scopus.com/inward/citedby.url?scp=79954583376&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318214332c
DO - 10.1212/WNL.0b013e318214332c
M3 - Article
C2 - 21368286
AN - SCOPUS:79954583376
SN - 0028-3878
VL - 76
SP - 1229
EP - 1237
JO - Neurology
JF - Neurology
IS - 14
ER -