Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic–clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping–derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic–clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).     

Current treatment options for familial adult myoclonus epilepsy

Familial adult myoclonus epilepsy (FAME) is a genetic condition characterized by the occurrence of cortical tremor, myoclonus, and epilepsy. To date, there is neither a curative nor a preventive treatment for FAME. Clinical management is essentially symptomatic and based on antiseizure medications (ASMs). The choice of the correct therapeutic option is limited to ASMs that have both an antiseizure and an antimyoclonic effect, such as valproate, levetiracetam, benzodiazepines, and perampanel. However, these medications control seizures well while having a limited effect on myoclonus and cortical tremor. In addition, many ASMs, including sodium channel blockers and gabapentin, are contraindicated in this condition. The ideal therapeutic option would be a precision treatment able to revert the genetic defect underlying it. Nevertheless, this does not seem to be an option that will be available soon.     

Long-term effectiveness of add-on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study

This retrospective study assessed long-term effectiveness of add-on perampanel (PER) in patients with Lennox–Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure-free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty-seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty-six patients (41.4%) were responders during a median follow-up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow-up. This study provides real-world evidence on the effectiveness of PER as adjunctive treatment in LGS patients.