perampanel and Epilepsies--Myoclonic

Epileptic myoclonus or myoclonic seizures can occur in idiopathic generalized epilepsy (IGE) and progressive myoclonus epilepsy (PME). However, symptomatic myoclonus which is stimulus-sensitive and provoked by movement is typically seen in PME and Lance-Adams syndrome. Symptomatic myoclonus is not always associated with epileptiform discharges on the electroencephalogram. Therapeutic interventions such as anti-seizure medications (ASMs), the ketogenic diet and vagus nerve stimulation are not always effective. There is emerging evidence that perampanel (PER), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, may be effective for the treatment of myoclonic seizures and symptomatic myoclonus. We performed a systematic review of the literature to assess the efficacy of PER as treatment for myoclonic seizures and symptomatic myoclonus. Twenty-seven studies with a total sample size of 260 patients were included. The efficacy of PER was analysed separately for myoclonic seizures and symptomatic myoclonus. In the group with myoclonic seizures, 50% responder, 75% responder and seizure freedom rates were reported as 74.3% (101/ 136), 60.3% (82/136) and 57.4% (78/136), respectively, with a follow-up duration of 6-12 months. However, in one post-hoc analysis of data from patients with IGE, the efficacy of PER as treatment for myoclonic seizures during the double-blind phase showed no significant difference compared to placebo. The efficacy of PER for symptomatic myoclonus was reported in a total of 119 patients. Four studies (n=88 patients) reported the efficacy of PER as a decrease in myoclonus score/scale. In the remaining 31 patients, symptomatic myoclonus resolved in three patients, decreased in 21 patients and seven patients showed no improvement. We also analysed the number of patients who were already on levetiracetam (LEV) or valproic acid (VPA) at the time of PER initiation; these data were available for 153 patients. Of these, 56.8% were on LEV and 75.1% were on VPA when PER was initiated. This systematic review suggests that PER maybe effective as treatment for drug-resistant myoclonic seizures and symptomatic myoclonus. It may also be effective in patients who have already failed to respond to LEV and VPA. These findings are preliminary yet encouraging. This study has several limitations, particularly given the scarcity of high-quality randomized controlled trials and marked heterogeneity regarding the type and results of

Topics: Anticonvulsants; Epilepsies, Myoclonic; Epilepsy, Generalized; Humans; Immunoglobulin E; Levetiracetam; Myoclonic Epilepsies, Progressive; Myoclonus; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome; Valproic Acid

This study was undertaken to evaluate perampanel (PER) when used under real-world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study.. The multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic-clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation.. The Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months.. This subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad-spectrum antiseizure medication for the treatment of IGE.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Myoclonic; Epilepsy, Absence; Epilepsy, Generalized; Female; Humans; Immunoglobulin E; Male; Pyridones; Retrospective Studies; Seizures; Treatment Outcome

This study investigated the efficacy and safety of perampanel (PER) adjunctive therapy in pediatric patients with epilepsy whose seizures are pharmacoresistant to existing antiepileptic drugs.. A clinical retrospective study was conducted from 2016 to 2017 in the pediatric neurology clinic at a tertiary children's hospital. We reviewed the data obtained from 66 children whose seizures were pharmacoresistant to more than two antiepileptic drugs, and could be followed up for a minimum of 3 months after PER adjunctive therapy initiation. The efficacy was estimated by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and adverse events were also recorded.. The rate of seizure reduction of >50% was 30.3%, 37.5%, and 34.7% for all seizure types at 3, 6, and 12 months, in which 7.6%, 8.9%, and 14.3% of the patients became seizure-free at these time points, respectively. No significant differences were found between enzyme-inducing and nonenzyme-inducing antiepileptic drugs in combination with PER with regard to the responder rate. Five patients with Dravet syndrome were included in the study. Four of them (80%) exhibited 50% seizure reduction at the last visit, at which point, two patients (40.0%) were seizure-free. The retention rate was 51% at 12 months. Adverse events were documented in 25 patients (35.7%) and led to PER discontinuation in eight patients (12.1%). The most common adverse events comprised irritability, skin rash, dizziness, and somnolence; however, all were transient and successfully managed after PER dose reduction or discontinuation.. The current data support the value of adjunctive PER in child and adolescent patients with pharmacoresistant epilepsy in daily clinical practice. Perampanel was efficacious and generally well-tolerated as an add-on treatment for epilepsy.

Topics: Adolescent; Ambulatory Care Facilities; Anticonvulsants; Asian People; Child; Dizziness; Drug Resistant Epilepsy; Epilepsies, Myoclonic; Female; Follow-Up Studies; Humans; Male; Neurology; Nitriles; Outpatient Clinics, Hospital; Pediatrics; Pyridones; Retrospective Studies; Rett Syndrome; Treatment Outcome

Topics: Anticonvulsants; Down Syndrome; Epilepsies, Myoclonic; Epilepsy; Humans; Nitriles; Pyridones; Treatment Outcome

Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox-Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs.. A multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed.. Eighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1-70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent.. This is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Topics: Adult; Anticonvulsants; Epilepsies, Myoclonic; Epilepsy, Generalized; Humans; Lennox Gastaut Syndrome; Male; Nitriles; Pyridones; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

To investigate the mechanisms by which Perampanel (PER) reduces the severity of action myoclonus, we studied on MEG signals the changes occurring in cortico-muscular coherence (CMC) and cortico-cortical connectivity in patients with progressive myoclonus epilepsies.. The subjects performed an isometric extension of the hand; CMC and cortico-cortical connectivity were assessed using autoregressive models and generalized partial-directed coherence. The contralateral (Co) sensors showing average CMC values >0.7 of the maximum (set to 1) were grouped as central (C) regions of interest (ROI), while adjacent sensors showing CMC values >0.3 were grouped as Surrounding (Sr) ROIs.. Under PER treatment, CMC decreased on Co C and Sr ROIs, but also on homologous ipsilateral (Ip) ROIs; out-degrees and betweenness centrality increased in Co ROIs and decreased in Ip ROIs. The flow from Ip to Co ROIs and from activated muscles to Ip C ROI decreased.. The improvement of myoclonus corresponded to decreased CMC and recovered leadership of the cortical regions directly involved in the motor task, with a reduced interference of ipsilateral areas.. Our study highlights on mechanisms suitable to treating myoclonus and suggests the role of a reduced local synchronization together a better control of distant synaptic effects.

Topics: Adult; Anticonvulsants; Cortical Excitability; Epilepsies, Myoclonic; Female; Humans; Male; Middle Aged; Motor Cortex; Muscle, Skeletal; Nitriles; Pyridones

Stiripentol is an orphan drug successfully used in combination with valproate and clobazam in the treatment of Dravet syndrome. Perampanel has also been added by experts. In this retrospective study, we investigated the influence of stiripentol on perampanel serum levels by using the doses and corresponding perampanel serum levels of 10 patients. The impact of stiripentol on the perampanel serum levels was significant as shown in a linear regression analysis, with perampanel serum levels increasing linearly with the stiripentol doses. We conclude that dose adjustments of stiripentol and perampanel when administered together, should be done carefully to avoid side effects or even severe intoxication. Hence, perampanel serum level monitoring seems advisable.

Topics: Adult; Anticonvulsants; Dioxolanes; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsies, Myoclonic; Female; Humans; Male; Nitriles; Pyridones

In the present study, we aimed to investigate the efficacy and tolerability of perampanel in patients with Dravet syndrome.. We retrospectively reviewed data regarding seizure frequency and adverse effects in 10 patients (four boys, six girls) with Dravet syndrome following treatment with perampanel. Perampanel treatment was considered effective when seizure frequency had been reduced by more than 50%.. The mean age of patients at perampanel introduction was 11.5 ± 2.2 years. Seizure types were as follows: generalized tonic-clonic seizure (n = 8), unilateral clonic seizure (n = 6), myoclonic seizure (n = 3), atypical absence seizure (n = 3), and focal impaired awareness seizure (n = 1). The average number of concomitant anti-epileptic drugs (AEDs) was 3 ± 0.9. The mean duration of perampanel use was 11.1 ± 3.8 months. Seizure frequency was reduced by more than 50% in five patients (50%). The efficacy of perampanel for each seizure type was as follows: generalized tonic-clonic seizure: 50% (4/8), unilateral clonic seizure: 50% (3/6), myoclonic seizure: 33% (1/3), atypical absence seizure: 33% (1/3), and focal impaired awareness seizure: 100% (1/1). The effects of perampanel in each patient occurred between 3 and 6 months following the initiation of treatment. Seizure reduction was observed beginning at perampanel doses of 0.1 ± 0.07 mg/kg/day. Adverse events were observed in seven of 10 patients. Although somnolence was noted in 50% of patients, most events were mild.. The results of this retrospective observational study indicate that perampanel treatment may be promising in some patients with Dravet syndrome. Additional studies are necessary to verify the actual efficacy of perampanel for Dravet syndrome.

Topics: Adolescent; Anticonvulsants; Child; Epilepsies, Myoclonic; Female; Humans; Male; Nitriles; Pyridones; Retrospective Studies; Treatment Outcome

Perampanel is an antiepileptic drug (AED) approved for add-on treatment of focal seizures (with or without generalization) and primary generalized tonic-clonic (GTC) seizures. Our objective was to explore the effectiveness and tolerability of adjunctive perampanel in patients with drug-resistant myoclonic seizures, after failure of other AEDs.. Retrospective, multicenter, observational study. Data were collected from individual patient clinical files and analysed using appropriate descriptive statistics and inferential analyses.. Data are reported for 31 patients with mean age 36.4 years, who had an average epilepsy duration of 18 years, previously taken an average of 5.03 AEDs, and were taking an average of 2.4 AEDs on perampanel initiation. Patients exhibited myoclonic, GTC, absence, tonic and focal seizures, and most had associated cognitive decline and/or ataxia. Median time on perampanel was 6 months, most common dose was 6 mg, and overall retention rate was 84%. The responder rate for myoclonic seizures was defined via reduction of days with myoclonic seizures per month. At 6 months, 15 (48.4%) of the 31 patients were classed as myoclonic seizure responders, 10 (32.3%) were myoclonic seizure free, and 39% saw improvements in functional ability. Of 17 patients with GTC seizures at baseline, 9 (53%) were responders at 6 months, and 8 (47.1%) were seizure free. The most frequent side effects were psychiatric disorders, instability, dizziness and irritability, and mostly resolved with dose reduction. Five patients discontinued perampanel due to side effects.. Perampanel caused clinically meaningful improvements in patients with drug-resistant myoclonic seizures. It was generally well tolerated, but psychiatric and neurological side effects sometimes required follow-up and dose reduction.

Topics: Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Myoclonic; Female; Humans; Male; Middle Aged; Nitriles; Pyridones; Retrospective Studies; Seizures; Treatment Outcome; Young Adult