The latest medical research on Epilepsy

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about epilepsy gathered by our medical AI research bot.

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Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy.

Epilepsia

Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity.

Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected.

The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9 μg/ml).

Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy.

Yield and risk associated with prolonged presurgical video-EEG monitoring: a systematic review

Epileptic Disorders

Presurgical long-term video-EEG monitoring (LT-VEEG) is an important part of the presurgical evaluation in patients with focal epilepsy. Multiple seizures need to be recorded, often in limited time and with the need to taper anti-seizure medication (ASM). The aim of this study was to systematically study the yield – in terms of success – and risks associated with presurgical LT-VEEG, and to identify all previously reported contributing variables.

A systematic review of the databases of PubMed Medline, Embase, Cochrane Central, and the Cochrane Database of Systematic Reviews were searched following the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline. Publications about presurgical LT-VEEG reporting on variables contributing to yield and risk were included. Study characteristics of all included studies were extracted following a standardized template. Within these articles, studies presenting multivariable analyses of factors contributing to the risk of adverse events or the success of LT-VEEG were identified.

We found 36 articles reporting on LT-VEEG, including 4,703 presurgical patients, both children and adults. Presurgical LT-VEEG monitoring led to an average yield of 85%. Adverse events occurred with an averaged total event rate of 17%, but the type of included events was variable among studies. Factors reported to independently contribute to successful LT-VEEG were: baseline seizure frequency, a shorter interval from the most recent seizure, extratemporal lobe epilepsy, and no requirement for ASM reduction. Factors independently contributing to the occurrence of adverse events were: ASM tapering, a history of status epilepticus, a history of focal to bilateral tonic-clonic seizures, psychiatric comorbidity, and ASM taper rate.

This study reveals that the data on factors contributing to yield and risk of adverse events is significant and variable, and often reported with inadequate statistics. Future research is warranted to develop guidelines for ASM withdrawal during presurgical video-EEG monitoring, taking predefined factors for success and risks of adverse events into account.

Differentiation of subclinical and clinical electrographic events in long-term EEG recordings.

Epilepsia

With the advent of ultra-long-term recordings for monitoring of epilepsies, the interpretation of results of isolated EEG recordings covering only selected brain regions attracts considerable interest. In this context, the question arises whether detected ictal EEG patterns correspond to clinically manifest seizures or rather to purely electrographic events, i.e. subclinical events.

The analysis of EEG patterns from 268 clinical seizures and 252 subclinical electrographic events from 50 patients undergoing video-EEG monitoring. Features extracted included predominant frequency band, duration, association with rhythmic muscle artifacts, spatial extent and propagation patterns. Classification using logistic regression was performed based on data from the whole dataset of 10-20-EEG recordings and from a subset of two temporal electrode contacts.

Correct separation of clinically manifest and purely electrographic events based on 10-20-EEG recordings was possible in up to 83.8% of events, depending on the combination features included. Correct classification based on two-channel recordings was only slightly inferior, achieving 78.6% accuracy 74.4 and 74.8%, respectively, of events could be correctly classified when using duration alone with either electrode set, but classification accuracies were lower for some subgroups of seizures, particularly focal aware seizures and epileptic arousals.

A correct classification of subclinical vs. clinical EEG events was possible in 74-83% of events based on full EEG recordings, and in 74-78% when considering only a subset of 2 electrodes, matching the channel number available from new implantable diagnostic devices. This is a promising outcome suggesting that ultra-long-term low-channel EEG recordings may provide sufficient information for objective seizure diaries. Intra-individual optimization using high numbers of ictal events may further improve separation, provided that supervised learning with external validation is feasible.

Economic aspects of treating seizure clusters.

Epilepsia

Seizure clusters may initiate a chain of events that have economic as well as clinical consequences. The potential economic consequences of seizure...

Introduction to use of an acute seizure action plan for seizure clusters and guidance for implementation.

Epilepsia

It is important for patients with epilepsy and their caregivers, including care partners, to understand the patient's seizure clusters and what to ...

Recognizing seizure clusters in the community: The path to uniformity and individualization in nomenclature and definition.

Epilepsia

Seizure emergencies experienced by patients with epilepsy include status epilepticus and seizure clusters. Although an accepted definition of statu...

Incidence and risk factors of post-traumatic epilepsy following pediatric traumatic brain injury: a systematic review and meta-analysis.

Epilepsia

Post-traumatic epilepsy (PTE) is a well-known chronic complication following traumatic brain injury (TBI). Despite some evidence that age at the ti...

International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) incl. Febrile Infection-Related Epilepsy Syndrome (FIRES): Statements and Supporting Evidence.

Epilepsia

To develop consensus-based recommendations for the management of adult and paediatric patients with NORSE/FIRES based on best evidence and experience.

The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater or equal to 7, and inappropriate if the median score was less than or equal to 3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey.

Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article.

This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.

An epilepsy curriculum for primary health care providers: a report from the Education Council of the International League Against Epilepsy

Epileptic Disorders

Primary health care providers are directly responsible for the care of people with epilepsy. However, their education about epilepsy might be inadequate or lacking. Our objective was to develop an evidence-based and consensus-driven educational curriculum for the management of epilepsy within the primary healthcare setting.

The International League Against Epilepsy (ILAE) Education Council commissioned a task force of international experts, who met virtually at monthly intervals in 2020/2021 to develop the curriculum. The task force adopted and added to five domains from the ILAE Epileptology Curriculum after discussions on context, structure and wording of associated competencies and learning objectives. The consensus-approved curriculum was disseminated to the ILAE leadership and constituency in six different languages. An online survey was used to collate structured feedback which further refined the curriculum.

Feedback was obtained from 785 voluntary respondents who were inclusive of epilepsy specialists and primary healthcare providers. Nearly two thirds of the respondents approved the use of the curriculum to advance the competency of primary health care providers in epilepsy. The final educational curriculum comprised six domains, 26 competencies and 85 learning objectives. The six domains were: (1) ability to diagnose epilepsy and its broad subtypes; (2) ability to provide counselling to people with epilepsy over a range of issues; (3) ability to introduce treatment and follow-up to people with epilepsy; (4) competency to appropriately refer people to higher centres of care; (5) ability to manage epilepsy emergencies including status epilepticus; and (6) ability to recognize and provide basic care for psychiatric and somatic comorbidities.

The curriculum represents an advance in providing inclusive care for epilepsy within the primary health care setting and ideally should be used to facilitate future primary health care epilepsy education packages.

Long-term outcome of convulsive status epilepticus: a 10-year follow-up

Epileptic Disorders

This study aimed to determine the mortality, causes of death and factors affecting the outcome of convulsive status epilepticus (CSE) at 10 years.

This retrospective study consisted of 62 consecutive adult patients diagnosed with CSE at the Helsinki University Hospital (HUS) emergency department during 2002-2003. Patients were followed for up to 10 years or up to the time of death. Data on patient demographics, CSE characteristics, treatment, complications, and outcome from the time of CSE were collected. The Official Statistics of Finland provided the information on mortality and causes of death. Survival analysis was conducted using Cox proportional hazards regression analysis.

In-hospital mortality was 8.1%, and mortality was 25.8% at one year, 51.6% at five years and 64.5% at 10 years. Estimated standardized mortality ratio (SMR) was 5.3 and the deceased patients lost 20.9 potential years of life, on average. The leading causes of death were disorders of the brain or the circulatory system, epilepsy-related conditions or intracranial tumours. The univariable survival analysis demonstrated that age ≥65 (HR=2.8, p=0.001), Charlson Comorbidity Index (CCI)>0 (CCI=1-3: HR=3.0, p=0.009; CCI>3: HR=8.4, p<0.001), Status Epilepticus Severity Score (STESS)>4 (HR=5.3, p<0.001) and Epidemiology-Based Mortality Score (EMSE-EAC)>15 (HR=2.2, p=0.036) were risk factors and a Glasgow outcome scale (GOS) of 5 at discharge (HR=0.14, p=0.025) was a protective factor for survival. The multivariable analysis established STESS>4 (HR=5.0, p=0.002) and CCI>0 (CCI=1-3: HR=2.9, p=0.015;CCI>3: HR=6.3, p=0.006) as independent risk factors and GOS>3 (time-dependent) (GOS=4: HR=0.33, p=0.048;GOS=5: HR=0.13, p=0.019) as a protective factor for survival.

The rate of long-term mortality and number of potential years of life lost were high. Factors demonstrative of the overall situation of the patients, such as comorbidities, functional state after CSE and age, were significant predictors for long-term outcome.

Compound-heterozygous GRIN2A null variants associated with severe developmental and epileptic encephalopathy.

Epilepsia

We report on an 8-year-old girl with severe developmental and epileptic encephalopathy due to the compound heterozygous null variants p.(Gln661*) a...

Significant improvements in SEIzure interVAL (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters.

Epilepsia

Intermittent rescue therapy may be used for seizure clusters, which are clinical emergencies that may persist ≥24 h and increase risk of status epilepticus, emergency room visits, and reduced quality of life for patients with epilepsy. Beyond effectiveness for aborting seizure clusters, no data exist on how intermittent rescue therapy may impact the long-term natural course of seizure clusters. This novel analysis explores SEIzure interVAL (SEIVAL; time between seizure clusters) in patients from a long-term safety study of diazepam nasal spray (Valtoco) to assess SEIVAL changes with intermittent rescue therapy across time.

Patients were aged 6-65 years. Age- and weight-based doses of diazepam nasal spray were administered during a 12-month treatment period with an optional follow-up period. SEIVAL was evaluated in patients receiving two or more doses of diazepam nasal spray using 90-day periods.

Of 163 treated patients, 151 had one or more SEIVALs. One hundred twenty had SEIVALs in Period 1 and one or more other periods. An increase in SEIVAL was noted from Period 1 compared with all subsequent periods (p ≤ .001). A consistent cohort (n = 76) had one or more SEIVALs in each of Periods 1-4 (360 days); mean SEIVALs increased significantly (p < .01) from 12.2 days (Period 1) to 25.7 days (Period 4). Similar SEIVAL patterns occurred when repeat doses within a seizure cluster were eliminated and irrespective of age group, treatment duration, and change to concomitant medications. In adults, Quality of Life in Epilepsy scores were maintained with increased SEIVALs.

Across 12 months, increases in SEIVAL were demonstrated in patients using diazepam nasal spray for seizure cluster treatment in a phase 3 safety study. Increased time between seizure clusters may reflect a previously unrecognized beneficial effect of intermittent rescue therapy. These results generate a range of biological and behavioral hypotheses and warrant exploration of the impact of intermittent rescue therapy.