**Background:** Patients with persistent hiccups (lasting >48 hours) or intractable hiccups (>2 months) are often referred to gastrointestinal services. The etiology is broad and can involve many organ systems. Neuromyelitis optica spectrum disorder (NMOSD) is a rare, serious autoimmune condition characterized by demyelination and axonal damage, typically involving the optic nerve or spinal cord. Area postrema syndrome, a subtype of NMOSD, occurs when lesions are present in the dorsal medulla and can cause nausea, vomiting, and hiccups. Up to 30% of NMOSD patients present with typical brainstem lesion symptoms. Early diagnosis and treatment are important for improved outcomes.
**Methods:** This is a case report of an 18-year-old male who presented to the emergency department with an 8-day history of nausea, emesis, and intermittent hiccups. He was admitted to the gastroenterology service. Workup included laboratory tests (comprehensive metabolic panel, lipase, C-reactive protein, erythrocyte sedimentation rate, complete blood count, urinalysis, urine toxicology, streptococcal A antigen, monospot, COVID-19 PCR), abdominal imaging (CT scan, abdominal radiograph, complete abdominal ultrasound, upper gastrointestinal radiography series), and esophagogastroduodenoscopy with biopsy. Due to worsening hiccups refractory to medical therapy (metoclopramide, cyproheptadine, baclofen), a Pediatric Neurology consult was obtained, leading to a detailed neurological exam and brain/spine MRI. Subsequent workup included autoantibody testing and cerebrospinal fluid analysis.
**Key Results:** Laboratory findings on admission showed hypokalemia of 3.1 mEq/L and hypochloremia of 94 mEq/L, with otherwise normal comprehensive metabolic panel, lipase, C-reactive protein, and erythrocyte sedimentation rate. Complete blood count showed monocytosis of 14.8%. Urinalysis showed 1+ ketones, 1+ bilirubin, and 4+ urobilinogen. All infectious and viral tests were negative. Esophagogastroduodenoscopy revealed severe distal esophagitis, and biopsy showed acute ulcerative esophagitis with negative infectious/viral testing. Despite treatment with high-dose intravenous proton-pump inhibitor and sucralfate, the patient's intermittent hiccups became persistent over three days. Neurological exam revealed ankle contractures, clonus, and diffuse hyperreflexia. Brain MRI showed a 5.5 mm enhancing lesion in the dorsal medulla. Autoantibody testing and cerebrospinal fluid analysis confirmed the diagnosis of NMOSD. The patient was started on high-dose intravenous steroids with rapid improvement in symptoms and was discharged on oral steroids, proton-pump inhibitor, and close neurology and gastroenterology follow-up.
**Clinical Implications:** This case highlights that severe esophagitis found on endoscopy may be a consequence of prolonged nausea, emesis, and hiccups rather than the cause. When hiccups and gastrointestinal symptoms do not respond to standard therapy, clinicians should have a low threshold to consider central nervous system causes, including NMOSD. Early diagnosis and treatment of NMOSD are critical to prevent relapses and improve outcomes. The presence of neurological signs such as ankle contractures, clonus, and hyperreflexia should prompt further neurological evaluation and imaging.