Hiccups, nausea, and vomiting: water channels under attack!

Abstract

In March, 2009, a previously healthy 15-year-old girl was referred to us with a 2-week history of intractable hiccups, nausea, and vomiting. Her symptoms had started suddenly after waking. Physical examination was normal. Laboratory tests showed a high amylase concentration (125 U/L), without signs of infection, or liver, kidney, electrolyte, thyroid, or haematological abnormalities. Because of the high amylase measurement, MRI of the abdomen was done, but no abnormalities were detected. However, MRI of the head showed a single hyperintense lesion in the medulla including the area postrema (fi gure A). Visual evoked potentials (VEP) were within the normal range. Cerebrospinal fl uid showed a normal cell count with no biochemical abnormalities. Additional blood tests were done for antibodies to aquaporin-4 (anti-AQP4). During the 3-week wait for the test results, the patient developed internuclear ophthalmoplegia. Anti-AQP4 was detected in a cell-based assay with AQP4-transfected HEK293 cells adapted from Waters and colleagues. Repeat MRI of the head showed enlargement of the lesion in the medulla oblongata (fi gure B) and a second hyperintense lesion in the right thalamus. Spinal-cord MRI and repeated VEP were normal. A diagnosis of neuromyelitis optica spectrum disorder was made. We started our patient on 1000 mg methylprednisolone intravenously for 5 days. After the fi rst day of treatment, internuclear ophthalmoplegia disappeared, and after 5 days, she had stopped vomiting. When last seen in February, 2010, she was well. Neuromyelitis optica is an infl ammatory disease that aff ects the spinal cord and optic nerves. It typically spares the brain and follows a relapsing course. Neuromyelitis optica can be distinguished from multiple sclerosis by a combination of clinical, neuroimaging, and cerebrospinal fl uid investigations. In 2004, antibodies to AQP4, a protein that forms water channels in the brain, were identifi ed. These antibodies are thought to have an important causal role in neuromyelitis optica. Therefore, identifi cation of anti-AQP4 helps to confi rm a diagnosis of neuromyelitis optica and distinguishes it from multiple sclerosis. Intractable hiccups and nausea can be a unique symptom of relapsing neuromyelitis optica and are associated with a high prevalence of medulla lesions. This location corresponds to a site of high AQP4 expression. There are several treatment approaches for neuromyelitis optica. For initial treatment of acute exacerbations, current treatment is intravenous methylprednisolone. If this treatment is unsuccessful, plasmapheresis is a second-line option. Daily oral prednisone, generally in combination with azathioprine, mitoxantrone, mycophenolate mofetil, or rituximab, can be used for long-term therapy.