Low-dose perampanel improves refractory cortical myoclonus by the dispersed and suppressed paroxysmal depolarization shifts in the sensorimotor cortex

Abstract

h i g h l i g h t sLow dose of perampanel (PER) is tolerable and effective to ameliorate refractory cortical myoclonus. PER suppresses and disperses paroxysmal depolarization shifts directly on the postsynaptic neurons. This action was reflected by temporal dispersion in giant SEPs (a potential clinical biomarker). a b s t r a c tObjective: To elucidate the effects of perampanel (PER) on refractory cortical myoclonus for dose, etiology and somatosensory-evoked potential (SEP) findings. Methods: We examined 18 epilepsy patients with seizure and cortical myoclonus. Based on data accumulated before and after PER treatment, correlations among clinical scores in myoclonus and activities of daily life (ADL); early cortical components of SEP; and PER blood concentration, were analyzed. Results: PER (mean dose: 3.2 ± 2.1 mg/day) significantly improved seizures, myoclonus and ADL and significantly decreased the amplitude of and prolonged latency of giant SEP components. The degree of P25 and N33 prolongations (23.8 ± 1.6 to 24.7 ± 1.7 ms and 32.1 ± 4.0 to 33.7 ± 3.4 ms) were significantly correlated with improved ADL score (p = 0.019 and p = 0.025) and blood PER concentration (p = 0.011 and p = 0.025), respectively. Conclusions: Low-dose PER markedly improved myoclonus and ADL in patients with refractory cortical myoclonus. Our results suggest that SEP, particularly P25 latency, can be used as a potential biomarker for assessing the objective effects of PER on intractable cortical myoclonus. Significance: In this study, PER lessened the degree of synchronized discharges in the postsynaptic neurons in the primary motor cortex.

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

“…Abnormal AMPA receptor expression on the cell surface is also known to occur in diseases involving intracellular substance accumulation. The AMPA antagonist perampanel is now recognized as a potentially efficacious drug for progressive myoclonic epilepsies (PME) [112][113][114][115][116][117][118][119][120][121][122][123], a group of rare types of epilepsy, most of which are recognized as intracellular substance storage disorders. Although each of these diseases involves increased intracellular storage of a different pathological substance, their clinical phenotypes are very similar; it is therefore reasonable to consider the existence of several similar AMPA-receptor-related endophenotypes that produce the same clinical phenotype.…”

“…gSEPs are considered to be enlarged synaptic potentials with enhanced synchronism, and are therefore similar to PDS. Oi et al [118] evaluated the effect of perampanel on gSEPs, and found that perampanel reduced gSEP amplitude. Interestingly, perampanel efficacy related to prolonged latency to the P25 and N33 components of gSEP.…”

Improvement of "Bouncy Gait" in Lance-Adams Syndrome with Perampanel

“…To our knowledge, there has been only one fully published case report [3] describing an improvement of myoclonus in LAS using perampanel (Table 1) [3,[5][6][7]. A recent electrophysiological study reported that improvement in cortical myoclonus with perampanel correlated with improvements in the parameters of giant somatosensory-evoked potentials [7].…”

The Effectiveness of Perampanel for Myoclonic Seizures in Down Syndrome with Isodicentric Chromosome 21

“…Furthermore, perampanel was newly approved as monotherapy for focal epilepsy in Japan in January 2020 [ 8 ]. Recently, the efficacy of low-dose perampanel has been reported in refractory myoclonus in epilepsy patients [ 9 , 10 ]. Perampanel has a good safety profile and is well tolerated, and therapeutic drug monitoring is considered useful since the dose correlates linearly with effect and adverse events [ 11 ].…”