E14. AN UNUSUAL CASE OF EPSTEIN–BARR VIRUS–ASSOCIATED CEREBRAL VASCULITIS IN AN ADULT

Abstract

Background: Cerebral vasculitis secondary to Epstein-Barr virus (EBV) is rare in adult immunocompetent patients. Methods: We report a previously healthy Myanmese gentleman who presented with unusual central nervous system manifestations who was subsequently diagnosed with Epstein-Barr virus (EBV)-associated cerebral vasculitis. Results: A 61-year-old Myanmese male living in Singapore presented acutely with fever, headache, disorientation and lethargy for 1 week. He had no known comorbidities, and no recent travel beyond Singapore. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis (total CSF white cell count of 98, 96% lymphocytes) with high protein (1.38 g/L), normal glucose (2.9 mmol/L) and negative gram stain. He was treated empirically with ceftriaxone, acyclovir, anti-tuberculous medications and intravenous steroids. CSF Cryptococcal antigen, VDRL, herpes simplex and enteroviral PCRs, fungal, mycobacterial and bacterial cultures were negative. PCR for Epstein-Barr virus (EBV) in the CSF was positive (1500 DNA copies/mL). Cytology and flow cytometry were not suggestive of lymphoma. His HIV and autoimmune screens were negative (antinuclear antibody, anti-double-stranded DNA antibody, anti-neutrophilic cytoplasmic antibody (ANCA)). Magnetic resonance imaging (MRI) of the brain showed bilateral hyperintense T2-weighted thalamic and brainstem lesions. Differentials included an infective or autoimmune encephalitis. The patient's conscious level deteriorated acutely on day two of admission, and repeat imaging revealed thalamic haemorrhage with obstructive hydrocephalus, for which urgent external ventricular drainage was done. A brain biopsy was performed and was consistent with vasculitis without evidence of granulomas, infectious organisms or malignancy. Urinalysis revealed significant proteinuria of 3.8g/day and computed tomography (CT) of the thorax showed pulmonary consolidation. The patient was treated with intravenous cyclophosphamide (CYC) 15mg/ kg body weight for presumed primary vasculitis, and glucocorticoids were continued. There was an improvement in the patient's neurological status, from a Glasgow coma scale of E4VtM3 to E4VtM6 over 30 days. Two-weekly CYC was continued, for a total of 3 doses. A kidney biopsy revealed only minimal change disease and the proteinuria and pulmonary consolidation resolved rapidly. His CSF analysis was repeated and showed a rising titre of EBV (5300 DNA copies/mL). Epstein-Barr encoding region (EBER) in situ hybridization was negative on brain tissue but was positive on inguinal lymph node biopsy samples. Due to the vasculitis possibly being secondary to chronic EBV infection, CYC was ceased and glucocorticoids were slowly tapered to 10mg oral prednisolone over 4 months. Unfortunately, the patient's course was complicated by recurrent bacterial infections and he finally succumbed to severe sepsis about 5 months after the initial presentation. Conclusion: While there are reports of EBV-associated cerebral vasculitis, these usually only occur in immunocompromised patients or children. The reasons for this patient's clinical course are not clear.