P3C243: When Vomiting Is All in Your Head: Area Postrema Syndrome as a First Manifestation of Pediatric NMOSD

Introduction: Vomiting can also be a sign of diseases of the central nervous system (CNS). Neuromyelitis optica spectrum disorder (NMOSD) is a rare, severe acquired demyelinating syndrome of the CNS that often manifests with optic neuritis, longitudinally extensive transverse myelitis, and other demyelinating syndromes. Area postrema syndrome (APS), characterized by demyelination of the dorsal medulla and causing intractable nausea, vomiting, and hiccups, is considered a core clinical characteristic of NMOSD.

Case Description: A 14-year-old female presented to the ED with nine days of nausea and vomiting not responsive to ondansetron and famotidine. Lipase was mildly elevated; other labs were normal. She was discharged but returned the following day with persistent symptoms. Urinalysis, comprehensive metabolic panel and abdominal x-ray were normal, and she was discharged with a diagnosis of viral gastroenteritis. Symptoms persisted and she was admitted to the hospital four days later. She was treated for three days with aprepitant, cyproheptadine and intravenous fluids. She was discharged with a referral to a gastroenterologist. Subsequently, she developed double vision, lower extremity paresthesias, constipation, and gait difficulty—prompting a fourth ED visit. She had lost 8 Kg.

Neurologic exam revealed bilateral end-gaze horizontal nystagmus. MRI of the brain and orbits with contrast demonstrated bilateral optic neuritis and a T2 hyperintense lesion involving the dorsal cervicomedullary junction consistent with APS. MRI of the cervical and thoracic spine revealed changes suggestive of longitudinally extensive transverse myelitis. Routine cerebrospinal fluid chemistries and meningitis/encephalitis panels were negative.

She was treated empirically with daily IV methylprednisolone with significant improvement. After discharge, the patient's anti-AQP4 IgG titers resulted at 1:10,000; anti-MOG IgG titers were negative. On retrospective review of systems, the patient revealed that she also suffered from intractable hiccups but was not asked by previous providers about the presence of hiccups accompanying her intractable nausea and vomiting.

Discussion: Pediatric NMOSD is estimated to account for 3-5% of all NMOSD cases. It is estimated that APS is the initial manifestation of NMOSD in up to 12% of patients. Shared features of patients first presenting with APS include several weeks of symptoms, significant weight loss, extensive negative GI workup, poor response to antiemetics, and rapid response to immunotherapy. Additionally, hiccups are present in most patients and are often intractable.

Conclusion: Clues that nausea and vomiting may be caused by APS include negative GI workup, poor response to antiemetics, rapid response to immunotherapy, intractable hiccups, chronic course of symptoms, and the presence of other neurologic signs or symptoms. In these contexts, physicians should maintain a high index of suspicion for APS, as timely recognition can allow for initiation of chronic immunomodulatory therapy and delay accrual of attack-related disability.