Journal of epilepsy research最新文献

Background and purpose: Perampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa^® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel.

Methods: Efficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed.

Results: Most patients (82/85) received perampanel doses of 4-8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%).

Conclusions: Post hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

Background and purpose: FAME (Fycompa^® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074), a previously reported single-arm, phase IV study, showed that perampanel improved seizure control as first add-on to failed anti-seizure medication (ASM) monotherapy in 85 South Korean patients aged ≥12 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures. We present results of three post hoc analyses of FAME that further assessed the efficacy and safety of perampanel.

Methods: Patients were stratified by low- (4, 6 mg/day) versus high- (8, 10, 12 mg/day) dose maintenance perampanel, perampanel added to first- versus second-line ASM monotherapy, and concomitant background ASM monotherapy and perampanel dose. The primary endpoint was the proportion of patients with a ≥50% reduction in total seizure frequency during the 24-week maintenance period. Safety was assessed by the descriptive incidence of treatment-emergent adverse events (TEAEs).

Results: In post hoc analyses, 50% responder rates were significantly higher for low- versus high-dose maintenance perampanel (88.6% vs. 40.0%; p<0.001) and when added to first- versus second-line ASM monotherapy (83.5% vs. 33.3%; p=0.013). By concomitant background ASM and perampanel maintenance dose, 50% responder rates were 100% for perampanel 4 mg/day added to carbamazepine, oxcarbazepine, lamotrigine, or valproic acid, and 85% when added to levetiracetam. Add-on perampanel improved 75% and seizure-free responder rates, and median percent changes from baseline seizure frequency per 28 days. Perampanel was well tolerated when added to ASM monotherapy, with dizziness being the most common TEAE.

Conclusions: Post hoc analyses of FAME provide supportive data for the use of perampanel as an effective and well-tolerated first add-on treatment to a broad spectrum of ASM monotherapies in patients with FOS.

Lennox-Gastaut syndrome (LGS) is a pharmacoresistant epileptic encephalopathy. Herein reported is a case of LGS that combination therapy with levetiracetam, lamotrigine and valproate culminated in control of all seizure types and resolution of epileptic discharges in electroencephalography. This case indicates that logical combination therapy may provide seizure control and improvement of electroencephalographic pattern in patients with LGS even in cases at which epileptic surgery fails.

Acute dystonic reactions are the most prevalent extrapyramidal adverse effects associated with metoclopramide. It could be mistaken for a variety of other conditions, such as seizures, tetanus, and encephalitis, to name a few possibilities. We present a case of a 26-year-old female misdiagnosed as having an epileptic seizure who was rushed to the emergency unit with an involuntary bilateral upward deviation of the eyes, spasm, stiffness, lateral deviation of the neck, and protrusion of the tongue. Symptoms occurred 36 hours after the commencement of metoclopramide, used to treat nausea and vomiting in the referring hospital. All the laboratory work was normal. The drug was discontinued and 5 mg of intravenous biperiden was administered. The symptoms subsided in about 10 minutes with no recurrence. Metoclopramide-induced acute dystonia not only creates an anxious environment for patients but may also be life-threatening. Due to the high probability of misdiagnosis, detailed drug history and a high index of suspicion are critical in making the correct diagnosis.

Background and purpose: Oxidative stress (OS) is defined as an excessive production of reactive oxygen species that cannot be neutralized by the action of antioxidants, but also as an alteration of the cellular redox balance. The relationship between OS and epilepsy is not yet fully understood. The objective of this study was to evaluate the effect of dexamethasone on OS levels and memory in the kindling model induced by pentylenetetrazole.

Methods: The animals were divided in six groups: control group that received no treatment, vehicle group treated with vehicle, diazepam group, and groups treated with dexamethasone (1, 2 and 4 mg/kg). Treated animals received pentylenetetrazole in alternated days for 15 days. Inhibitory avoidance test was conducted in 2 hours and OS was evaluated after animal sacrifice.

Results: Regarding the treatment with dexamethasone, there was no significant difference when compared to the control groups in relation to the inhibitory avoidance test. On OS levels, there was a decrease in catalase activity levels in the hippocampus and an increase in thiobarbituric acid reactive substances and glutathione peroxidase levels in the hippocampus.

Conclusions: The anticonvulsant effect of dexametasone remains uncertain. Immunological mechanisms, with the release of cytokines and inflammatory mediators, seem to be the key to this process. The mechanisms that generate OS are probably related to the anticonvulsant effects found.

Since the first documentation of slow alpha variants in Goodwin et al., there has been a single case report with an actual electroencephalography (EEG). However, any further case has not been reported since then, and neurologists are still unfamiliar with its presence due to its scarcity. Here, we present a rare case of 3:1 subharmonic alpha variant in a hope to acquaint EEG interpretations and speculate upon its benign nature.

Background and purpose: Solitary calcified neurocysticercosis (NCC) on the computed tomography (CT) scan of brain in patients of epilepsy is common finding in endemic regions. Factors causing seizures in such cases are debatable. Immature calcification may be the causative factor for seizure recurrence. Thus, we aimed to study predictors of seizure recurrence specific to morphological characteristics on CT scan.

Methods: Patients with solitary calcified NCC on CT scan brain and active seizures were prospectively included. The protocol included clinical evaluation, contrast-enhanced CT scan of the brain, and electroencephalogram (EEG) at baseline and 9th month of 1-year follow-up in all patients. Seizure recurrence after 1 week of enrolment was recorded.

Results: One hundred twenty patients with a mean age of 23.33±12.81 years were included with a final follow-up of 109 patients and 35 patients had seizure recurrence. On univariate analysis, seizure frequency of more than 1 episode/month (45.7% vs. 25.7%, p=0.037; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.05-5.68), perilesional edema on CT head (45% vs. 10.8%, p<0.001; OR, 6.95; 95% CI, 2.58-18.7), lower density (HU) of lesion on CT head (139.85±76.54 vs. 204.67±135.9 HU p=0.009) and abnormal EEG at presentation (p<0.001; OR, 18.25; 95% CI, 2.15-155.13) were significantly associated with seizure recurrence. On multivariate analysis, presence of perilesional edema on CT head (p=0.001; OR, 6.854; 95% CI, 2.26-20.77), density of lesion on CT (HU) (p=0.036; OR, 0.995; 95% CI, 0.99-1) and abnormal EEG (p=0.029; OR, 12.125; 95% CI, 1.29-113.74) were independently associated with seizure recurrence.

Conclusions: The presence of perilesional edema, HU of calcification on CT brain, and abnormal EEG suggest an increased risk of seizure recurrence in patients of epilepsy with solitary calcified NCC.

Background and purpose: West syndrome is an epileptic encephalopathy of infancy. According to guidelines, adrenocorticotrophic hormone (ACTH) is probably effective for the short-term management of infantile spasm, but there is little uniformity in treatment due to variable response. This study has been done to evaluate the efficacy of pulse methylprednisolone as compared to ACTH in children with West syndrome.

Methods: Children between 3 months to 24 months with the diagnosis of West syndrome were included and ACTH and pulse methyl prednisolone followed by oral prednisolone were given after randomization. Total duration of treatment was 6 weeks in both groups.

Results: Total 87 children were enrolled; 12 patients lost in follow up. Finally, 43 received ACTH and 32 received pulse methylprednisolone. In pulse methylprednisolone group, 28.13% showed 50-80% response, 28.13% showed 80-99% response and 21.87% patients showed 100% response. In ACTH group, 41.86% showed 50-80% response, 25.58% showed 80-99% response and only 3 (6.97%) patients showed 100% response. Methylprednisolone treatment regimen did not cause significant or persistent adverse effects.

Conclusions: Pulse methylprednisolone followed by oral prednisolone for 6 weeks is as effective as ACTH. Thus, methylprednisolone therapy can be an important alternative to ACTH.

The use of anesthetics is inevitable to suppress seizure activity in refractory status epilepticus (RSE). Hypotension, which is a critical side effect observed when treating RSE using a higher dosage of anesthetics that enhance γ-aminobutyric acid (GABA) activity, often requires vasopressor agents. Concomitant treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, could be effective in prolonged refractory SE, while maintaining stable blood pressure owing to the blockage of catecholamine reuptake in the systemic circulation. We report two cases of patients who had RSE with hemodynamic instability treated promptly with an early combination of ketamine and low-dose midazolam. The combination treatment effectively suppressed epileptic discharge with less hemodynamic side effects; moreover, a low dose of midazolam was required when combined with ketamine therapy. The initial combination of a third-line therapy that blocks NMDA receptors with enhanced GABAergic activity could be useful in RSE. Further studies are necessary in many variable etiologies of SE.

Background and purpose: This study was aimed to describe focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients.

Methods: A total of 82 SCN1A mutation-positive patients were reviewed retrospectively (39 boys and 43 girls). Seizure type and electroencephalography (EEG) findings were investigated according to the stage, disease onset, and steady state (after age 2 years). Long-term video EEG data were used to classify the seizure type.

Results: Focal seizures at onset and the steady state were found in 54.9% (45/82) and 90% (63/70) of patients, respectively. Afebrile focal seizures were an initial seizure in about one fourth of the patients (22/82, 26.8%). Of 48 seizures captured during long-term video EEG monitoring of 30 patients, 19 seizures were classified as focal onset (39.6%). Of the 19 focal seizures, 12 were either focal motor or focal non-motor seizures, and seven were focal onset bilateral tonic-clonic seizure. Focal epileptiform discharges were more frequent than generalized epileptiform discharges at seizure onset and during the clinical course on conventional EEG (3.7% vs. 0%, 52.9% vs. 32.9%, respectively).

Conclusions: Our study provides a comprehensive description of focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. Recognizing these features as defining the clinical spectrum of Dravet syndrome may lead to earlier genetic diagnosis and tailored management.