Abstract
BACKGROUND: Negative-pressure hydrocephalus is characterized by neurological deterioration with ventriculomegaly but negative intracranial pressure (ICP), clinically indistinguishable from acute hydrocephalus with elevated ICP. Subatmospheric CSF drainage, neck wrapping, endoscopic third ventriculostomy (ETV), and shunt placement are treatment methods. Medical therapy remains elusive. The authors describe a patient with refractory negative-pressure hydrocephalus who failed conventional therapies but responded robustly to theophylline. OBSERVATIONS: A 30-year-old man with traumatic brain injury underwent decompressive hemicraniectomy, cranioplasty, and ventriculoperitoneal shunt placement. He was later rehospitalized for acute hydrocephalus and shunt infection. Surgical revision was complicated by intraventricular hemorrhage with worsening hydrocephalus. An external ventricular drain was inserted, demonstrating negative ICP. Treatment for more than 3 months with subzero drainage, two ETVs, and ventriculopleural shunt placement was unsuccessful. Theophylline was initiated and the ventriculomegaly improved drastically on imaging with increased ICP. He developed status epilepticus, managed medically, with resolution within 5 days. He was discharged with return to his neurological baseline. LESSONS: Theophylline, a methylxanthine derivate used for obstructive pulmonary disease, can raise ICP in intracranial hypotension. The authors present the first successful case of theophylline for the treatment of refractory acute negative-pressure hydrocephalus. Further studies are warranted to explore the safety and efficacy of theophylline for negative-pressure hydrocephalus. https://thejns.org/doi/10.3171/CASE2554.