Case Presentation: An otherwise healthy 21 year old woman presented to an outside hospital with developing headache, confusion, twitching, nausea and vomiting. Workup included an unremarkable head CT with LP consistent with aseptic meningitis. Viral meningoencephalitis was suspected, she improved and was discharged. She had recurrence of intermittent frontal headaches with associated dizziness, bilateral lower extremity numbness and confusion. She presented to our health system, with a fever of 40.4°C. Repeat CT head and LP essentially unchanged with elevated protein (125 mg/dL), lymphocytic pleocytosis (259 WBC/uL), and elevated opening pressure 39cm H20 (previously 30cm H20). MRI Brain and Spine w/wo contrast obtained, and an extensive infectious, autoimmune, rheumatologic, and paraneoplastic workup was done. MRI Brain revealed leptomeningeal enhancement and restricted diffusion in the splenium of the corpus callosum. Flow cytometry from CSF resulted with atypical lymphoid population. A CT chest, abdomen, pelvis, was obtained and negative for malignancy. Given resolution of symptoms she was discharged for outpatient follow up.She was re-admitted with headache, lower extremity weakness and aphasia. Electroencephalogram (EEG) revealed potential seizure focus and she was started on levetiracetam. Ultimately given the negative non-invasive workup, a brain biopsy was considered for definitive diagnosis. She underwent a right frontal craniotomy. She was discharged in stable condition on dexamethasone taper while awaiting final pathology. Tissue pathology revealed vasculitis, predominantly subarachnoid and superficial cortex. MRA brain showed no abnormal vessel wall enhancement. Patient was treated with a 3 day course of 1,000 mg of IV methylprednisolone and discharged on oral prednisone 60 mg daily. Following initiation of systemic steroids, she has had near complete symptom resolution.
Discussion: CNS vasculitis requires a high index of suspicion given the protean nature of presentations. This was the case with our patient, whom over a 3 month time period, presented to 4 different hospital locations, was admitted 5 times, underwent 4 lumbar punctures, over 10 imaging studies of brain/spine, 3 EEGs, and had an extensive, yet unrevealing, infectious, autoimmune, rheumatologic, hypercoagulable, and paraneoplastic workup. Brain biopsy, revealed vasculitis, most likely primary angiitis of the central nervous system (PACNS). The cause of PACNS is unknown and a study investigating a population similar to our patient, suggests an annual incidence rate of 2.4 cases per 1,000,000 person-years. Given the rare nature of this illness, her relatively expedited time to diagnosis of 3 months, compared to the more common 6 months cited in the literature is likely due to multidisciplinary approach and the red herring of the atypical CSF flow cytometry.
Conclusions: This case highlights the importance of a broad differential, persistent curiosity, and a multidisciplinary approach while diagnosing rare illnesses. Following the clues led to the definitive diagnosis, which required invasive brain biopsy. Brain biopsy, though uncommon, remains a critical tool in the diagnosis of unexplained neurological presentations, or abnormal imaging findings.