Intractable nausea and vomiting can be the isolated presenting symptom of neuromyelitis optica spectrum disorder, and gastroenterologists as well as internists need to be more aware of this possibility, even though it is rare, Dr. Raffaele Iorio and his colleagues said in the March issue of Clinical Gastroenterology and Hepatology.
Neuromyelitis optica spectrum disorder is a relapsing inflammatory demyelinating disease of the CNS similar to multiple sclerosis, which progresses to optic neuritis and/or longitudinally extensive transverse myelitis. If untreated, it often results in blindness and confinement to a wheelchair. It is especially important to recognize this disorder as early as possible, so that immunosuppressant therapy can be initiated and progression to such devastating outcomes can be averted, said Dr. Iorio, of the department of laboratory medicine and pathology, Mayo Clinic, Rochester, Minn., and his associates.
Source: American Gastroenterological Association
The cause of neuromyelitis optica spectrum disorder is thought to be autoantibodies that target the astrocytic aquaporin-4 (AQP4) water channel, the principal water channel in the central nervous system. The fourth ventricular floor, which contains the chemosensitive nausea and vomiting center (the area postrema), is a particularly AQP4-enriched region of the brain.
For some patients who develop the disorder, intractable nausea and vomiting may be the only presenting symptom. "These patients commonly undergo extensive, but nonrevealing evaluations on presentation to internists and gastroenterologists, who are largely unaware of this emerging neurological entity." Consequently, many patients are subjected to unnecessary gastroscopy, biopsy, x-rays, ultrasound, CTs, and even surgery, the investigators noted.
They previously reported that a retrospective chart review identified 69 patients diagnosed at the Mayo Clinic as having neuromyelitis optica spectrum disorder. Eight of them (12%) presented with intractable nausea and vomiting as the sole initial symptom.
The researchers have since reviewed an additional 70 charts in their database and now report an additional 10 patients (14% of the 70) in whom intractable nausea and vomiting was the only presenting symptom.
Nine of these 10 patients were women. Mean age of symptom onset was 47 years (range, 26-72 years).
Nausea and vomiting were continuous rather than cyclic, and both occurred day and night. Patients did not report headache or other CNS symptoms, but three had intractable hiccups concomitant with their vomiting.
All 10 patients initially presented to a gastroenterologist or internist. Seven required immediate inpatient IV hydration. Treatment with antiemetics "yielded only partial benefit."
Inflammatory markers, including erythrocyte sedimentation rate and C-reactive protein level, were within normal limits.
A total of 6 of the 10 patients underwent extensive GI evaluation, which included abdominal CT, abdominal ultrasound, small bowel x-ray, upper gastroscopy with biopsy, pelvic and liver CT and ultrasound, gastric-emptying studies, and wireless capsule endoscopy.
One patient underwent cholecystectomy when imaging studies detected a "tiny" gallbladder polyp. Her vomiting worsened after the procedure.
A total of 5 of the 10 patients eventually underwent brain MRI. Three of them showed abnormalities in the area postrema, another showed abnormalities in the deep white matter, and the fifth patient showed no abnormalities on this exam. "With timely MRI imaging ... discrete lesions in the area postrema, the AQP4-rich emetic reflex center of the medulla," usually can be visualized, Dr. Iorio and his associates said.
The mean interval between the onset of vomiting and the development of a classic symptom of neuromyelitis optica spectrum disorder was 111 weeks.
When the disorder was finally suspected, testing revealed AQP4-IgG in serum or cerebrospinal fluid samples in all 10 patients.
During a mean follow-up of 57 months, eight patients progressed to classic neuromyelitis optica and two to neuromyelitis optica spectrum disorder.
The typical disease course included the development of optic neuritis followed by paresthesias of the lower limbs that gradually ascended to the torso. Urinary retention, constipation, and weakness of the extremities accompanied by dysesthesias and ataxia soon ensued.
Treatment with plasmapheresis and methylprednisolone generally relieved gait and sensory complaints and improved bladder and bowel function as well as the nausea and vomiting.
This study was supported by the Guthy-Jackson Charitable Foundation, the National Institutes of Health, the Mayo Foundation for Medical Education and Research, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Iorio reported no financial conflicts of interest. His associates reported holding numerous patents and having ties to Alexion Pharmaceuticals, Novartis, Biogen Idec, Genzyme Corporation, and RSR Ltd.