A 45-year-old woman presented to the emergency department with a one-year history of headache, nausea, and vomiting, which worsened over the past month, along with recent falls. The neurological exam was normal. Brain MRI revealed acute hydrocephalus with transependymal flow and abnormal enhancement along the anterior brainstem and cervical spinal cord, raising concern for leptomeningeal disease. The patient underwent EVD placement, which resulted in improvement of her symptoms.

Laboratory testing revealed an elevated ESR (66 mm/h) and CRP (11.3 mg/dL). CSF analysis demonstrated lymphocytic pleocytosis (256 WBCs/µL), elevated protein (>600 mg/dL), elevated RBC count (39/µL), xanthochromia, and hypoglycorrhachia (32 mg/dL). CSF meningitis/encephalitis panel, fungal testing, and cytology were negative; however, CSF soluble interleukin-2 receptor level was markedly elevated (4955.6 pg/mL) and CSF ACE was also increased (9.5 U/L).

CT of the chest, abdomen, and pelvis revealed no malignancy. Whole-body PET-CT showed FDG-avid mediastinal lymphadenopathy. Biopsy of brain lesions or lymph nodes was not pursued due to high procedural risk and strong clinical suspicion for an alternative diagnosis. The patient was diagnosed with probable neurosarcoidosis and treated with high-dose intravenous methylprednisolone, leading to radiological improvement on follow-up MRI. She was transitioned to oral prednisone and remained clinically stable at follow-up.

Hydrocephalus is a rare and atypical manifestation of neurosarcoidosis that can complicate the clinical picture and delay diagnosis. Early recognition is critical, as neurosarcoidosis is a treatable condition, and timely intervention can prevent irreversible neurological damage and improve outcomes. This case underscores the importance of including neurosarcoidosis in the differential diagnosis of hydrocephalus, particularly in patients presenting with unexplained headaches and supportive imaging findings.