Intractable Cough from Seizure in a Patient with Glioblastoma Multiforme

Dear Editor:

A 58-year-old man experienced an unwitnessed seizure with brief loss of consciousness while at a business meeting. A CT scan showed a golf ball sized left frontal lobe mass. A subtotal resection yielded a diagnosis of glioblastoma multiforme. Whole brain radiotherapy and chemotherapy were administered. Seven months after diagnosis, recurrent seizures correlated with recurrence. He was treated with repeat resection and an immunotherapy regimen on clinical trial.

Eleven months after diagnosis, focal seizures and fatigue correlated with progressive disease. The immunotherapy regimen was stopped and antiangiogenesis treatment was initiated. Sixteen months after diagnosis, he was admitted for home hospice care. Seizure treatment included lacosamide (Vimpat), levetiracetam (Keppra), and phenytoin (Dilantin).

A dry mostly nonproductive cough began in the weeks preceding his death. He occasionally brought up sputum. During the final week of life, the cough was severe enough that aspiration was a concern as he grew weaker. He could not eat safely because of the cough. The cough was not particularly moist or deep, but became unrelenting. Chest auscultation revealed blowing breath sounds, but no rattle.

Opioids became ineffective on the cough. Antihistamines had no effect. The cough persisted despite declining performance status. The cough continued even when unarousable. Parenteral midazolam was initiated and cough stopped.

Coughing is a rare feature of seizures. The literature is sparse and limited primarily to case reports. The earliest case reports that we could identify were published in 1966 and linked to brain lesions. ¹ In one recent series, 0.28% of patients with epilepsy had at least one cough recorded during a seizure. ² There is a single case report of phenytoin causing cough. ³

The barking hacking cough is a source of agony for family members and other caregivers in addition to being extremely bothersome for a patient. In this case, when it persisted in an almost continuous manner despite escalating doses of opioids and usual doses of lorazepam, there was a sense of helplessness for all parties, including the health professionals. Benzodiazepines, in adequate doses, treat seizures, and seemed to be the key addition in this case to ensure comfort for patient and family.