Neuromyelitis optica unique area postrema lesions: Nausea, vomiting, and pathogenic implications
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In neuromyelitis optica spectrum disorder, persistent nausea and vomiting due to area postrema involvement is a well-described 'area postrema syndrome' and should prompt neurologic evaluation in appropriate contexts.
“In neuromyelitis optica spectrum disorder, persistent nausea and vomiting due to area postrema involvement is a well-described ‘area postrema syndrome’ and should prompt neurologic evaluation in appropriate contexts (Popescu et al., 2011).”
From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as Popescu et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 39 · Cited by 296
Research works printed but not linked: 34
- Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neu- romyelitis optica. Neurology 2006;66:1485-1489.
- Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis op- tica. Lancet Neurol 2007;6:805-815.
- Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Luc- chinetti CF, Weinshenker BG. Brain abnormalities in neu- romyelitis optica. Arch Neurol 2006;63:390 -396.
- Pittock SJ, Weinshenker BG, Lucchinetti CF, Winger- chuk DM, Corboy JR, Lennon VA. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expres- sion. Arch Neurol 2006;63:964 -968.
- Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 2002;125:1450 -1461.
- Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106 -2112.
- Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005;202:473- 477.
- Roemer SF, Parisi JE, Lennon VA, et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuro- myelitis optica from multiple sclerosis. Brain 2007;130: 1194 -1205.
- Apiwattanakul M, Popescu BF, Matiello M, et al. Intracta- ble vomiting as the initial presentation of NMO. Ann Neurol 2010;68:757-761.
- Misu T, Fujihara K, Nakashima I, Sato S, Itoyama Y. In- tractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica. Neurology 2005;65:1479 -1482.
- Takahashi T, Miyazawa I, Misu T, et al. Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations. J Neurol Neuro- surg Psychiatry 2008;79:1075-1078.
- Duvernoy HM, Risold PY. The circumventricular organs: an atlas of comparative anatomy and vascularization. Brain Res Rev 2007;56:119 -147.
- Gross PM. Morphology and physiology of capillary sys- tems in subregions of the subfornical organ and area pos- trema. Can J Physiol Pharmacol 1991;69:1010 -1025.
- Price CJ, Hoyda TD, Ferguson AV. The area postrema: a brain monitor and integrator of systemic autonomic state. Neuroscientist 2008;14:182-194.
- Frigeri A, Gropper MA, Turck CW, Verkman AS. Immuno- localization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes. Proc Natl Acad Sci USA 1995;92:4328 -4331.
- Sharma R, Fischer MT, Bauer J, et al. Inflammation in- duced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demy- elination. Acta Neuropathol 2010;120:223-236.
- Broadwell RD, Sofroniew MV. Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the cen- tral nervous system. Exp Neurol 1993;120:245-263.
- Quan N, Mhlanga JD, Whiteside MB, McCoy AN, Kris- tensson K, Herkenham M. Chronic overexpression of pro- inflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei. J Comp Neurol 1999;414:114 -130.
- Hiyama TY, Matsuda S, Fujikawa A, et al. Autoimmunity to the sodium-level sensor in the brain causes essential hy- pernatremia. Neuron 2010;66:508 -522.
- Hinson SR, Roemer SF, Lucchinetti CF, et al. Aquaporin- 4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med 2008;205:2473-2481.
- Lassmann H. Experimental models of neuromyelitis op- tica. Rinsho Shinkeigaku 2009;49:900 -901.
- Misu T, Fujihara K, Kakita A, et al. Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain 2007;130:1224 -1234.
- Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic po- tential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 2007;69:2221-2231.
- Nicchia GP, Frigeri A, Liuzzi GM, Svelto M. Inhibition of aquaporin-4 expression in astrocytes by RNAi determines alteration in cell morphology, growth, and water transport and induces changes in ischemia-related genes. Faseb J 2003;17:1508 -1510.
- Tang H, Brimijoin S. Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody. J Neuroimmunol 2001; 115:53-63.
- Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol 2007;28: 138 -145.
- Goehler LE, Erisir A, Gaykema RP. Neural-immune inter- face in the rat area postrema. Neuroscience 2006;140: 1415-1434.
- Konsman JP, Kelley K, Dantzer R. Temporal and spatial relationships between lipopolysaccharide-induced expres- sion of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain. Neuroscience 1999;89:535-548.
- Gotow T, Hashimoto PH. Fine structure of the ependyma and intercellular junctions in the area postrema of the rat. Cell Tissue Res 1979;201:207-225.
- Takahashi T, Fujihara K, Nakashima I, et al. Anti- aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007;130:1235- 1243.
- Berger UV, Hediger MA. Distribution of the glutamate transporters GLAST and GLT-1 in rat circumventricular organs, meninges, and dorsal root ganglia. J Comp Neurol 2000;421:385-399.
- Viegas S, Weir A, Esiri M, et al. Symptomatic, radiological and pathological involvement of the hypothalamus in neu- romyelitis optica. J Neurol Neurosurg Psychiatry 2009;80: 679 -682.
- Poppe AY, Lapierre Y, Melancon D, et al. Neuromyelitis optica with hypothalamic involvement. Mult Scler 2005; 11:617-621.
- Sellner J, Hemmer B, Muhlau M. The clinical spectrum and immunobiology of parainfectious neuromyelitis op- tica (Devic) syndromes. J Autoimmun 2010;34:371- 379.
- Authors
- Popescu, B. F. G., Lennon, V. A., Parisi, J. E., Howe, C. L., Weigand, S. D., Cabrera-Gómez, J. A., Newell, K., Mandler, R. N., Pittock, S. J., Weinshenker, B. G., & Lucchinetti, C. F.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lucchinetti, C.F.
- ORCID
- Venue
- Neurology
- Published
- 2011-04-05
- Volume
- 76
- Issue
- 14
- Pages
- 1229-1237
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3068006
- OpenAlex
- W2091440939
- Cited by
- 296
- References
- 39
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 12 · 2023: 11 · 2022: 18 · 2021: 19 · 2020: 19 · 2019: 20 · 2018: 20 · 2017: 30 · 2016: 21 · 2015: 21 · 2014: 26 · 2013: 32 · 2012: 16
- FWCI
- 19.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society
- Multiple Sclerosis Society
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01-NS049577-01A2, R01NS049577)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- neuromyelitis optica, area postrema, fourth ventricle floor, nausea and vomiting, hiccups, brainstem lesions, neuropathology, complement deposition, astroglial reaction, microglial activation, eosinophils, multiple sclerosis, optic neuritis, transverse myelitis
- MeSH terms
- Adolescent, Adult, Aged, Humans, Middle Aged, Nausea, Neuromyelitis Optica, Retrospective Studies, Vomiting, Area Postrema, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
