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Seizures frequently occur as a complication of glioblastoma multiforme (GBM); however, viral meningoencephalitis is a less considered precipitant of seizure in this often-immunocompromised patient population.

A 76-year-old man with newly diagnosed right pontocerebellar GBM (WHO grade IV, IDH1 wildtype) on temozolomide, dexamethasone, and radiation therapy developed a productive cough, confusion, and respiratory distress. He was diagnosed with bilateral basilar pneumonia, COVID-19, and acute respiratory failure. His neurological assessment showed intermittent alertness with limited responsiveness. On day 3, he had worsening encephalopathy and hypoxia, necessitating intubation. Subsequent fever prompted initiation of broad-spectrum antibiotics. On day 5, left-sided mouth and arm twitching was observed prompting extended broad-spectrum antibiotics and acyclovir to cover meningoencephalitis. Continuous electroencephalogram revealed frequent seizures independently originating at F7/T3 and C4/T4. Lorazepam and levetiracetam temporarily terminated clinical/electrographic seizures. CSF analysis revealed 3 RBCs, 39 WBCs, high protein of 72, low glucose of 47. PCR results later confirmed the presence of HSV-1. Continued acute repetitive seizures prompted intensification of the antiseizure regimen to include levetiracetam, phenytoin, zonisamide, and clobazam. A midazolam drip was eventually initiated to successfully terminate the seizures and subsequently tapered off.

HSV-1 encephalitis is less frequently considered a contributor of seizure in patients with GBM and may evade early diagnosis due to GBM being presumed the etiology of seizure. Diagnosis may be particularly challenging in critically ill patients who may have a multitude of seizure threshold-lowering factors. An important clue in this case was the recognition of focal ictal activity in the temporal region, unrelated to the known tumor location. This case underscores the need to maintain a high index of suspicion for HSV-1 encephalitis as a potential precipitant of seizure in patients with GBM. Early recognition and empiric treatment with acyclovir may provide the best opportunity to improve neurological outcomes.