Concomitant Viral and Bacterial Encephalitis after Temozolomide for Glioblastoma

Following resection of a left temporal lobe glioblastoma, a 59-year-old man received radiation therapy with concurrent and adjuvant temozolomide (TMZ).During this time, he was maintained on dexamethasone 4mg daily.His disease remained stable clinically and radiographically on this therapy.(Figure 1) Four months after radiation therapy, he presented with a oneweek history of confusion, hallucinations and fever.A brain computed tomogram scan showed a resection site abscess for which he underwent surgical drainage.Samples obtained at surgery for bacterial culture demonstrated gram positive cocci.A complete blood count revealed mild lymphopenia with a serum lymphocyte count between 600 and 1,000 x 10 6 /L, and mildly elevated absolute neutrophil count between 7 and 15 x 10 9 /L.Broad-spectrum antibiotic therapy was therefore initiated early for suspected bacterial infection in an immunocompromised patient.However, the patient did not improve clinically and remained stuporous with a best post-operative Glasgow Coma Scale (GCS) never exceeding 7.An electroencephalogram performed three days after surgery showed bilateral anterior temporal periodic lateralizing epileptiform discharges (PLEDs).At that time a brain magnetic resonance imaging (MRI) demonstrated new bilateral temporal, orbito-frontal, and thalamic hyperintensities on T2-weighted sequences (Figure 2).These findings were suspicious for acute Herpes Simplex virus (HSV) encephalitis, and thus acyclovir was added to his antibiotic regimen.Cerebrospinal fluid (CSF) analysis was positive for herpes simplex virus type 1 by polymerase chain reaction (PCR).Given a high pre-test probability and the known high sensitivity and specificity of CSF PCR analysis for viral meningoencephalitis, the result was concluded as confirmative for HSV-1 encephaitis. 1 Despite early broad-spectrum anti-bacterial therapy and immediate initiation of acyclovir following the brain MRI that was suspicious for herpes encephalitis, the patient failed to improve clinically.Follow-up MRI performed three weeks later demonstrated hemorrhagic necrosis of the right anterior temporal lobe and progressive and extensive edema involving adjacent cortex.(Figure 3) Although the patient survived, his functional status was significantly impaired, and no further anticancer therapy was administered.The patient was transferred to palliative care.Temozolomide is myelosuppressive and causes lymphopenia, with selective CD4+ T-lymphocyte suppression in addition to diminished peripheral CD8+ T-cell and B-cell populations.

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