Uncontrolled nausea, hiccups may be first sign of NMOSD: Report

Area postrema syndrome in NMOSD delays diagnosis for 4 patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Neuromyelitis optica spectrum disorder (NMOSD) may begin to manifest as uncontrollable nausea, vomiting, or hiccups — a condition referred to as area postrema syndrome (APS) — as described in a report of four patients in China.

Because these symptoms can overlap with those of other diseases, their occurrence as the first sign of NMOSD increases the risk for misdiagnosis, which was the case for all four patients, according to researchers.

Knowing more about area postrema syndrome or APS can help “to improve the understanding of this disease and reduce misdiagnosis and mistreatment of patients,” the team wrote.

The report, “Clinical analysis of neuromyelitis optica spectrum disease with area postrema syndrome as the initial symptom,” was published in the European Journal of Medical Research.

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Area postrema syndrome linked to brainstem inflammation

NMOSD is an autoimmune disease characterized by inflammation in the spinal cord (transverse myelitis) and the optic nerves (optic neuritis). The optic nerves are the nerves that relay visual information from the eyes to the brain.

As such, the main symptoms of NMOSD usually include weakness in the arms and legs, and vision problems.

But the disease can also affect the brainstem, which is a stalk-like structure located at the base of the brain. When this happens, the brainstem’s area postrema can become inflamed and damaged. As a result, nausea, vomiting, and hiccups can appear suddenly and last for weeks.

While the presence of area postrema syndrome is considered a diagnostic criterion of NMOSD, it occurs rarely, in about 20% of patients. Moreover, its symptoms are commonly mistaken for other diseases.

Now, researchers in China described the cases of four NMOSD patients — three women and one man — who developed APS as first symptom of the rare disease. The four ranged in age from 23 to 62, with a mean age of 36.5.

“All of these patients were initially misdiagnosed and mismanaged,” the researchers wrote.

The first patient, a 31-year-old woman, experienced nausea and vomiting of unknown cause for more than one month. After being hospitalized in three hospitals, she was diagnosed with reflux esophagitis, or an inflammation of the esophagus caused by acid reflux, and chronic gastritis, which is an inflammation of the stomach.

However, she did not respond to appropriate treatment for nausea and vomiting. In the meantime, she also started to experience fever and delirium.

After taking antipsychotics, the woman lost consciousness for several hours and became tetraparetic, meaning she experienced muscle weakness in all four limbs. She also began having shortness of breath and bowel and bladder problems.

A 62-year-old woman was identified as the second, and oldest patient. Her symptoms were nausea, vomiting, numbness, weakness in the left limb, and dizziness. She also complained of a headache that started “1 month ago after catching a cold,” the researchers wrote.

This patient was first diagnosed with cerebral infarction, which occurs when blood stops flowing to the brain. One month later, she returned to the hospital complaining of dizziness and headache.

The third case was a 23-year-old man — the youngest patient — who had uncontrollable nausea and vomiting. He was misdiagnosed and mistreated for chronic gastritis.

These symptoms eventually worsened and he also developed limb weakness, motor coordination problems, dizziness, and headache.

The last patient, a woman, 30, initially presented with vomiting and was diagnosed with reflux esophagitis. Two months later, she reported symptoms of numbness and tetraparesis.

In all of the patients, a correct diagnosis of NMOSD was eventually achieved based on the additional findings of lesions on spinal cord or brain MRI and antibodies against aquaporin-4, the most common target of NMOSD-driving self-reactive antibodies, in body fluids.

Early identification of APS and timely therapy can prevent visual and physical disabilities, even respiratory failure, coma, and cardiac arrest.

Transverse myelitis was detected in three patients and optic neuritis in two. All four showed damaging inflammation in the dorsolateral medulla oblongata, a structure that connects the brainstem to the spinal cord.

After being correctly diagnosed with NMOSD, all four patients received intravenous (into-the-vein) methylprednisolone, an anti-inflammatory treatment. Two also were given into-the-vein immunoglobulins (IVIG), which works to neutralize the self-reactive antibodies in the blood.

The three women also received immunosuppressive treatment that included mycophenolate mofetil and low-dose rituximab.

The patients generally responded to the treatment, experiencing a reduction in disease symptoms. However, all experienced relapses either before, during, or years after treatment. In two patients, disease relapse included persistent nausea, vomiting, or hiccups, while in one, it involved double vision.

“The clinical manifestations of NMOSD are complex and diverse, and the initial symptoms, onset age, and MRI can all affect the diagnosis of the disease,” the researchers wrote.

Particularly, area postrema syndrome “can appear as an isolated clinical symptom in the early stage of the disease, often presenting as intractable nausea and vomiting,” they added.

“Early identification of APS and timely therapy can prevent visual and physical disabilities, even respiratory failure, coma, and cardiac arrest,” the team concluded.