Study Identifies Area Postrema Syndrome Identification Criteria in NMOSD

brain scan MRI
brain scan MRI
Investigators sought to determine how prevalent and severe intractable nausea, vomiting, or hiccups are in patients with AQP4-IgG-positive NMOSD.

According to study results published in Neurology, researchers identified the frequency and severity of area postrema syndrome (APS) symptoms in patients with neuromyelitis optica spectrum disorder (NMOSD), developed clinical criteria for recognizing APS, and discovered that immunotherapy may be useful in stopping APS attacks in the majority of patients with aquaporin-4-immunoglobulin G (AQP4-IgG)-positive NMOSD.

Study investigators searched a database of patients with AQP4-IgG-positive NMOSD from the United Kingdom, Japan, and the United States (N=430) and identified the frequency of APS in these cohorts. All patients with AQP4-IgG-positive NMOSD completed questionnaires designed to determine APS symptom status. A telephone survey of 100 patients with 157 APS symptoms was performed, querying respondents on their symptom type and onset, frequency, duration, associated symptoms, symptom severity, timing of other NMOSD core attacks, and responses to symptomatic and immunotherapy treatment.

The Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score was used to detect the severity of nausea and vomiting symptoms. A subgroup of patients with NMOSD with recent APS attacks (n=25) were used to validate the revised NMOSD PUQE scale by applying the diagnostic criteria, severity scale, and immunotherapy response.

In the 430 patients with AQP4-IgG-seropositive NMOSD from the United Kingdom, Japan, and the United States, isolated APS attacks were found to be highly prevalent, with an onset of 7.1% to 10.3% and subsequent attacks of 9.4% to 14.5% in the pooled cohort. A total of 127 (81%) nausea events occurred in the 100-patient cohort with 157 episodes of APS, which lasted for a median of 14 days (range, 2 to 365 days). In addition, approximately 72% (n=113) of events were related to vomiting, represented by a median of 5 episodes (range, 2 to 40 episodes) per day that lasted 1 to 20 minutes. Hiccups, which lasted a median of 14 days (range, 2 to 365 days) accounted for 65% (n=102) of events in the 100-patient group.

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Within 2 days of the administration of intravenous methylprednisolone or plasmapheresis immunotherapy, 88% of APS attacks completely resolved. Maintenance immunotherapy with azathioprine, mycophenolate mofetil, or rituximab also stopped APS attacks in 10 patients who initially experienced only partial symptom improvement. Data obtained from the study were used to repurpose PUQE score, with the addition that hiccups severity grade was based on the duration of symptoms.

A limitation of the study was the lack of generalizability of the findings to patients with NMOSD without AQP4-IgG positivity.

“Based on these phenotypic data, we propose an APS severity scale based on a previously validated severity scale for hyperemesis gravidarum,” the researchers concluded.


Shosha E, Dubey D, Palace J, et al. Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD. 2018;91:e1642-e1651.