Neuromyelitis optica unique area postrema lesions

Abstract

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 ϭ 0.02).

Relevance of Autoantibodies for the Classification and Pathogenesis of Neurological Diseases

“…This was supported by findings of patients suffering from intractable vomiting and nausea as initial symptoms of NMO (Popescu et al, 2011).…”

Area postrema syndrome as frequent feature of Bickerstaff brainstem encephalitis

“…AP syndrome should be considered in any episode of otherwise unexplained and intractable nausea, emesis or singultus, especially in combination with neurological deficits indicating brainstem dysfunction. We recommend contrast‐enhanced brain MRI, CSF analysis, neurophysiological examination in addition to anti‐ganglioside and anti‐AQP‐4‐IgG antibody testing, the latter to rule out NMO/NMOSD as a common trigger for AP syndrome 12, 13, 14, 15. Besides causal treatment, a multimodal anti‐emetic concept is crucial for the management of AP syndrome.…”

“…AP lesions in multiple sclerosis (MS)19 seem to provoke AP syndrome less frequently than comparable NMO lesions 20. This suggests additional trigger mechanisms beyond the mere localization of lesions and has led to the hypothesis that there is a causative role played by antibodies in AP syndrome 1, 14. Supporting this hypothesis, AP syndrome was described in paraneoplastic brainstem encephalitis (BE) 21.…”

Atypical presentations of neuromyelitis optica

“…Another study characterized the neuropathological features of NMO patients with intractable nausea and vomiting 20 . Forty percent of these patients exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle, and those lesions had pathological features previously reported in spinal cord pathology of NMO including loss of AQP-4 staining, preservation of myelin, and complement deposition.…”