Abstract
Patricio Sebastian Espinosa MD, MPH, Renato Sotelo, MD, Armand Golchin MD, Jose Valdes, PharmD, BCPP; Boca Raton Regional Hospital, Boca Raton, FL, Florida Atlantic University College of Medicine
Introduction: Glioblastoma multiforme (GBM) is a rapid growing glioma that develops from glial cells and are considered the most invasive type of glial tumors spreading to nearby brain tissue with an incidence of 3 per 100,000 adults per year, GBM accounts for 52% of all primary brain tumors, and 17% of all brain tumors. Malignant gliomas are known to release glutamate which is involved with tumor expansion and epileptogenesis. By blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors stimulated by glutamate, seizure control can be achieved. Perampanel, a noncompetitive AMPA glutamate receptor antagonist, has been shown to be effective as adjunctive treatment of patients with epilepsy. We describe the use of Perampanel, a as an effective adjunctive treatment in three patients with GBM and concomitant uncontrolled seizures. The objective of this study was to assess the efficacy of perampanel in patient’s with GBM and refractory epilepsy
Methods: Patients were seen by the neurology service between June 2015 and November 2015.Reason for consult/admitting diagnosis was recurrent seizures.•Electroencephalogram (EEG)brain wave testing was used to confirm seizure activity and foci. Glioblastoma multiforme was diagnosed using magnetic resonance imaging after treatment of seizures. Perampanel was initiated and titrated upwards at weekly intervals.
Results: Case 1: Patient is a 61 y/o caucasian female with GBM and recurrent seizures on levetiracetam 1500mg bid, oxcarbazepine 300mg bid. The patient was initiated on perampanel 4mg daily and titrated up to 6mg daily. She remained seizure free for nearly three months before passing away of non-epileptic causes.
Case 2: Patient is a 64 y/o caucasian man with GBM and epilepsia partialis continua on valproic acid 1000mg bid, levetiracetam 1500mg bid, and lacosamide 200mg bid. Patient was initiated on 2mg of perampanel daily and titrated upwards to 8mg daily. The patient has remained seizure free for 9 months since initiation of perampanel 8mg daily.
Case 3: Patient 68 y/o AA male with GBM s/p 2 surgeries and partial status epilepticus on levetiracetam 1500mg bid, valproic acid 500mg bid, carbamazepine 200mg bid. Patient was initiated on 4mg daily of perampanel and titrated up to 8mg daily. He has remained seizure free for 6 months when perampanel was initiated.
Discussion: Cells of malignant gliomas, such as GBM, secrete glutamate that causes excitotoxic cell death of surrounding neurons providing space for tumor growth. It is postulated that perampanel may aid to stop seizures in GBM and may slow the expansion of tumor growth as it’s mechanism blocks the AMPA receptor from being stimulated by glutamate.
Perampanel, indicated as an adjunctive agent in patients with partial-onset seizures and primary generalized tonic-clonic seizures, was safe and efficacious in three patients with recurrent seizures. The most common (≥5% occurrence) adverse effects are dizziness, somnolence, headache, irritability, fatigue, falls, ataxia, nausea, vertigo, and back pain
Conclusion: Perampanel is efficacious and well tolerated as an adjunctive anti-epileptic drug in patients with GBM with refractory seizures
