Neuromyelitis optica spectrum disorders are a group of autoimmune inflammatory diseases that affect the central nervous system (1). Neuromyelitis optica was first described by the French neurologist Eugène Devic in 1894, and for over a hundred years was believed to be a variant of multiple sclerosis. Neuromyelitis optica spectrum disorder is characterised by subacute episodes of functional neurological deficit as a consequence of focal inflammatory demyelinating lesions in the central nervous system. The disease is normally multiphasic, but monophasic courses occur. In 2005, pathogenic autoantibodies that targeted the water channel protein aquaporin-4 (AQP4) were detected in the majority of patients, which led to the condition being perceived as a separate disease entity (2). Anti-aquaportin-4-IgG binds to aquaporin-4 located in the end-feet of astrocytes at the blood-brain barrier and leads to complement activation and complement-mediated astrocyte lysis. Antibodies against aquaporin-4 are produced peripherally, and the typical distribution of lesions in the medulla and optic nerve is explained by the distribution of aquaporin-4 in the central nervous system, coupled with a physiologically weaker blood-brain barrier in some areas of the central nervous system. Only in exceptional cases, and then mainly in connection with an episode of acute exacerbation, can antibodies be detected in the cerebrospinal fluid.
The incidence of neuromyelitis optica spectrum disorder is estimated to be about 1 per 100 000 individuals, and the condition is more common in Asia and the Caribbean. The condition takes its name from the two most common clinical manifestations of the disease, transverse myelitis and optic neuritis. A more unusual onset manifestation is the so-called area postrema syndrome (3, 4). The syndrome consists of a triad of clinical symptoms: intractable hiccups, nausea and vomiting, and despite low incidence, these are still viewed as core clinical characteristics of the disorder, on a par with myelitis and optic neuritis.
Signal changes in the area postrema on MRI are not specific for neuromyelitis optica spectrum disorder. The clinical symptom of nausea, vomiting and hiccups, however, is more specific. Area postrema syndrome in anti-aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder is distinguished by acute or subacute onset nausea, vomiting and hiccups (individual or combined symptoms) with a duration of over 48 hours, and the exclusion of other aetiology. The criteria are expanded upon by Shosha et al. (4). The area postrema is located on the dorsal surface at the caudal end of the medulla oblongata and is an emetogenic centre in the brain. It is also, along with the nucleus tractus solitarius and the motor fibres of the vagus nerve, a key area for autonomic regulation of lung and heart function. The blood vessels that supply the area postrema lack a blood-brain barrier (5), and the area is thus directly exposed to substances and pathogenic antibodies in the blood circulation. In a patient series with aquaporin-4-antibody-positive patients with neuromyelitis optica spectrum disorder, area postrema syndrome was cited as the first sign of the condition in 7.1–10.3 % of patients, depending on the population group. Similarly, area postrema syndrome plays a part in a subsequent exacerbation episode in 9.4–14.5 % of patients (4).
As a rule, with neuromyelitis optica spectrum disorder, prophylactic immunotherapy is indicated to prevent new lesions. In a double-blind, randomised, placebo-controlled trial (6), rituximab, a monoclonal antibody against the cell surface marker CD20, proved very effective in preventing relapses, and is usually the first choice. Treatment with monoclonal antibody against interleukin-6-receptor, CD19, and complement factor C5 has also been approved by European and American pharmaceutical authorities. For details of the efficacy of the different therapeutic options, we refer to a recently published review (7).
The prognosis for area postrema syndrome is good as a rule, and complete recovery after starting on methylprednisolone immunotherapy is usual, which was also the case for our patient (4). Functional deficit as a consequence of optic neuritis and myelitis are often more serious, with a high risk of persistence. Typical sequelae are impaired visual field and colour vision after optic neuritis, and paraparesis with loss of sensibility and autonomous bladder and gastrointestinal disorders after myelitis. Neuromyelitis optica lesions in the area postrema are often reversible, however, and it is therefore important to make the diagnosis and commence immunomodulatory therapy to prevent myelitis and significant functional deficit. Early treatment with methylprednisolone and prompt commencement of prophylactic immunotherapy is recommended. As our case study illustrates, it is important to remember that gastrointestinal symptoms may have a central nervous aetiology.