Combination Of Antiepileptic Drugs Research Articles

Assessment of adherence to carbamazepine using plasma and saliva samples, a study from Jordan

BackgroundThe measurement of carbamazepine levels in a biological sample is required to guide dosing, and prevent toxicity, and can be useful to assess medication adherence. AimThe primary aim of the presented study is to analyze carbamazepine levels in saliva and plasma samples of outpatients and to assess adherence to carbamazepine using saliva and plasma levels. MethodsAdults who used carbamazepine for at least one month were recruited from the outpatient clinic department of Princess Basma Hospital, a public hospital in Irbid. Saliva and blood samples (1 ml) were collected simultaneously from subjects, and using a microanalytical method with high-performance liquid chromatography coupled with an ultraviolet detector, the level of carbamazepine (in micrograms per milliliter) was ascertained. Analysis of adherence to carbamazepine was carried out using plasma and saliva levels. ResultsA total of 69 consecutive patients attending the neurology clinic were recruited, of whom 85.5% had epilepsy. Approximately one-third (34.8%) used carbamazepine as monotherapy, whereas the remainder used a combination of antiepileptic drugs to control seizures. Overall, about two-thirds (71.9%) of the studied samples were non-adherent in either plasma or saliva samples. By referring to the plasma sample carbamazepine concentration, 75.4% of the respondents were adherents, 15.9% had under-adherence, and 8.7% had over-adherence. A total of 85.9% of the responders were adherent using the carbamazepine level in saliva samples. Plasma and saliva carbamazepine levels were linearly correlated to one another. Polypharmacy was commonly utilized with the patients, as 42% of the patients used two medications, with a range of 1–7 drugs used concomitantly. The predictor associated with higher plasma and saliva carbamazepine levels, as determined by multiple linear regression analysis, was the occurrence of seizures less than once a month, as compared to seizures with higher frequencies. ConclusionSaliva carbamazepine levels show the potential to be used as an alternative matrix to assess medication adherence, with a considerable correlation with the plasma carbamazepine level. Healthcare professionals can address routine care non-adherence through such measures.

The modern approaches to the diagnostics and treatment of Lennox–Gastaut syndrome (literature review)

Despite significant advances made in epileptology, treatment-resistant epilepsy accounts for approximately 30 % of all forms of this disease. Such diseases include, among others, Lennox–Gastaut syndrome – a classic developmental and epileptic encephalopathy with onset in childhood, characterized by resistance to therapy, severe course and poor prognosis. For patients in this category, the search for new effective antiepileptic drugs remains highly relevant, especially in cases where numerous combinations of antiepileptic drugs do not produce an effect, surgical treatment is impossible, and alternative methods (vagus nerve stimulation and ketogenic diet) are ineffective. The authors present a review of the literature on the modern definition and diagnostic criteria of Lennox–Gastaut syndrome, diagnostic methods and treatment of this form of epilepsy, which has a severe course and a generally unfavorable prognosis.

Retracted: The Effectiveness and Safety of Hormonal Combinations of Antiepileptic Drugs in the Treatment of Epileptic Electrical Continuity in Children during Sleep: A Meta-Analysis

Retracted: The Effectiveness and Safety of Hormonal Combinations of Antiepileptic Drugs in the Treatment of Epileptic Electrical Continuity in Children during Sleep: A Meta-Analysis

Study on the reversal of epileptic drug resistance by tetramethylpyrazine in combination with carbamazepine through modulation of P-Glycoprotein expression in rat brain microvessel endothelial cell.

The purpose of this study was to detect the changes of P-Glycoprotein (P-GP) expression in rat brain microvessel endothelial cell line RBE4 after the action of Tetramethylpyrazine (TMP) on Carbamazepine (CBZ), so as to clarify the potential mechanism of TMP combined with CBZ against intractable epilepsy drug resistance. The RBE4 cell line was utilized for in vitro analysis. Cells were divided into control, CBZ, and CBZ-TMP group. The expression of P-GP was assessed using Western blot and reverse transcription polymerase chain reaction (RT-PCR). Intracellular concentration of CBZ was measured through high-performance liquid chromatography (HPLC). The differential expression of mRNA was evaluated by RNA sequencing. The intracellular concentration of CBZ in the CBZ-TMP group was significantly higher than that in other groups. The expression of P-GP in the CBZ group was significantly higher than that in the control group, while in the CBZ&TMP group, it was significantly lower than that in the other groups. Comparative analysis also revealed some differentially expressed genes. Compared with the CBZ group, FAM106A, SLC3A2, TENM2, etc. were upregulated most significantly in the CBZ&TMP group. ZBTB10, WDR7, STARD13, etc. were downregulated most significantly. Results suggest that TMP increases the intracellular concentration of CBZ, downregulates the expression of P-GP increased by CBZ, and modulates related cellular metabolism and signaling pathways, thus reversing the drug resistance mechanism of intractable epilepsy, providing a theoretical basis for the combination of traditional Chinese medicine and antiepileptic drugs.

A real-world pharmacovigilance study of severe cutaneous adverse reactions associated with antiepileptic drug combination therapy: data mining of FDA adverse event reporting system

ABSTRACT Background The aim of this study was to evaluate the association between antiepileptic drug combination regimens and severe cutaneous adverse reactions (SCAR). Research design and methods We gathered cases indication with epilepsy based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results Out of 128,262 reports were collected from the FAERS database, 104,278 cases were in the antiepileptic drugs group, and 23,984 cases were in the other primary suspected drugs group. A total of 20 combination regimens were associated with increased association of SCAR, top five of them were topiramate-phenytoin (ROR 57.62, 95% CI 30.93–107.34), lamotrigine-valproic acid (ROR 52.93, 95% CI 47.09–59.49), diazepam-phenobarbital (ROR 39.61, 95% CI 20.01–78.38), zonisamide-valproic acid (ROR 36.57, 95% CI 19.16–69.80), lamotrigine-diazepam (ROR 35.22, 95% CI 15.70–79.00). Conclusion The antiepileptic agent combinations may increase the incidence of SCAR and should be carefully evaluated in clinical practice. It is recommended to choose the combination regimens which have lower SCAR reporting rate for patients.

A meta analysis of key risk factors for sudden unexpected death in epilepsy

Purpose: To examine the risk factors (RFs), associated with Sudden Unexpected Death in Epilepsy (SUDEP), and the quantitative standards required to measure them Methods: The literature on RFs associated with SUDEP was systematically reviewed up to August 2020 in databases, including PubMed, the Cochrane Database and Embase. Revised Newcastle-Ottawa Scale (NOS) was performed to determine the quality of each study in this meta-analysis (MA), with a score of ≥ 3, indicating good quality. Any controversies in data extraction and quality assessment were resolved through counsel or adjudication with a third researcher. Results: An initial screening of the literature following the search strategy and manual inclusion yielded a total of 767 studies. After excluding duplicates as well as articles that did not match the topic, 112 studies remained. Twenty-nine studies were finally selected based on the inclusion and exclusion criteria. After a careful review of the full text, nine studies were included in the MA. Conclusion: The five RFs for SUDEP included age at the onset of epilepsy ≤15 years, generalized-tonic-clonic seizure, seizure frequency ≥50 seizures/year, treatment with a combination of multiple antiepileptic drugs, and history of alcohol abuse.

Focal Temporal Lobe Epilepsy, Analysis of Clinical and Anamnestic Data and Evaluation of the Effectiveness of Anti-epileptic Therapy

We studied clinical and anamnestic data and the effectiveness of anticonvulsants in 31 patients with focal temporal lobe epilepsy. Seizures in the form of isolated aura and non-motor seizures dominated at the onset of the disease (77%), which were regarded as non-epileptic paroxysms, and most patients (80%) sought medical help later than 6 months. Among non-motor seizures, it is worth noting the inhibition of behavioral reactions (22%), vegetative (42%) and mental seizures (13%). Automatisms was found in 18 (58%) patients, focal motor seizures in the form of a unilateral dystonic seizure in 9 (29%) patients, and secondary generalized seizures were noted in 19 (61%) patients. The use of modern antiepileptic drugs in combination was effective in 42%.

Epilepsy in childhood: an update on management

Background: The aim of this study was to review current database for the management of childhood epilepsy, presenting and comparing the different types of treatment, focusing[1] on the ones with the best efficacy. Original articles related to the subject were obtained from SciELO, PubMed and BVS database using descriptors from “Health Sciences Descriptors”. Results: Epilepsy is characterized as a neurological disease that occurs due to abnormal neuronal discharges in the cerebral cortex. It affects 0.5% to 1% of children and is the most frequent chronic neurologic condition in childhood. Anti-epileptic drugs (AEDs) are the most used treatment for epilepsy. Non farmacological options, such as epilepsy surgery and neurostimulation therapy can be used to treat refractory or drug-resistant seizures. Conclusions: Around 70% of individuals with active epilepsy can become seizure-free and go into long-term remission shortly after starting drug treatment with antiepileptic drug in monotherapy. Randomized controlled trials comparing surgery and combinations of AEDs suggest that surgery can be more effective in stopping seizures in children.
 
 
 

Effects of antiepileptic drugs polytherapy on pregnancy outcomes in women with epilepsy: An observation study in northwest China

ObjectiveThe management of pregnant women with epilepsy (WWE) treated with antiepileptic drugs (AEDs) polytherapy poses a great challenge. The purpose of this study was to evaluate the major congenital malformations (MCMs) associated with AED polytherapy, to assess the impacts of polytherapy regimens on seizure control and breastfeeding, and to determine the potential predictors for pregnancy outcomes. MethodsThis study was based on prospectively acquired data from a registry enrolling WWE in early pregnancy from Feb 2010 to July 2019, in which 123 pregnancies in 110 WWE were exposed to 27 different AED combinations. ResultsThere were 123 pregnancies in 110 WWE analyzed in our study. The live birth rate was 86.2 % and the risk of MCMs was 10.4 %. Multivariate analysis indicated that prenatal exposure to phenobarbital (odds ratio [OR], 17.424; 95 %CI, 1.510–201.067; P = 0.022) and topiramate (OR, 9.469; 95 %CI, 1.149–62.402; P = 0.036) was associated with increased risk of MCMs. Valproate (OR, 4.441; 95 %CI, 1.165–16.934; P = 0.029), phenobarbital (OR, 13.636; 95 %CI, 2.146–86.660; P = 0.006) and topiramate (OR, 7.527; 95 %CI, 1.764–32.118; P = 0.006) were significantly correlated with adverse pregnancy outcomes. Among 67 pregnancies in four combinations over 10 patients, 15 (22.4 %) remained seizure free through pregnancy, seizure frequency increased in 17 (25.4 %), decreased in 24 (35.8 %) women, in 26 (38.8 %) remained unchanged. Only 23.6 % of mothers undertook exclusive breastfeeding. Planned pregnancy was the only independent factor significantly associated with decreased risk of adverse pregnancy outcomes (OR, 0.139; 95 % CI, 0.051–0.382; P < 0.001). Notably, no adverse pregnancy outcome was recorded in pregnancies exposed to the combination of lamotrigine plus levetiracetam. ConclusionPrenatal exposure to the combinations containing valproate, phenobarbital, or topiramate was associated with increased risk of adverse pregnant outcomes. AED-related teratogenicity may be reduced by planned pregnancy in WWE exposed to polytherapy. Our findings also suggest the combination of lamotrigine and levetiracetam seems to be most desirable to balance seizure control and fetal safety.

Stigma and its association with health-related quality of life in adults with epilepsy

ObjectiveTo explore the presence of felt and enacted stigma in people with epilepsy (PWE), members of a self-governing epilepsy organization and to evaluate the influence of both types of stigma on health-related quality of life (HRQoL) in PWE. MethodsParticipants were 55 PWE (age range: 18–53 years), members of a non-governmental organization (further “NGO”). The sociodemographic and epilepsy-related variables were collected through structured interviews designed for the purpose of the study. Felt stigma was assessed with the Epilepsy Stigma Scale (ESS) and enacted stigma with the Questionnaire for episodes of discrimination against PWE. Quality of Life in Epilepsy Inventory (QOLIE-31) (Serbian version) was used for the evaluation of HRQoL. ResultsThe mean ESS score was 33.93 ± 14.50. Felt stigma was significantly associated with the male gender and the number of antiepileptic drugs (AEDs). Participants’ mean score on the Questionnaire for episodes of discrimination was 2.80 ± 2.78. Enacted stigma was significantly correlated with male gender and number of AEDs, as well as with older age/longer duration of the disorder. Felt stigma scores were positively correlated with enacted stigma scores (p < 0.001), but only felt stigma scores were negatively related to QOLIE-31 overall score (p = 0.01). The combination of AEDs, seizure frequency, and felt stigma best explained the HRQoL in PWE (p < 0.001). ConclusionFelt and enacted stigma are moderately related, but only felt stigma appears to be a significant predictor of the deteriorating HRQoL in this sample. Interventions targeting felt stigma should be considered a part of comprehensive epilepsy care as well as educating the wider community about epilepsy.

Felbamate add-on therapy for drug-resistant focal epilepsy.

This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs. To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy. For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 13 July 2021) on 15 July 2021. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies. We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design. Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, a third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life. We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data. Only one study reported the outcome of 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate whilst another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants. We assessed the evidence for all outcomes using GRADE and rated the evidence as very low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update. In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy, Developmental Delay and Ataxia.

Mutations in the KCNA1 gene, encoding the voltage-gated potassium channel Kv1.1, have been associated with a spectrum of neurological phenotypes, including episodic ataxia type 1 and developmental and epileptic encephalopathy. We have recently identified a de novo variant in KCNA1 in the highly conserved Pro-Val-Pro motif within the pore of the Kv1.1 channel in a girl affected by early onset epilepsy, ataxia and developmental delay. Other mutations causing severe epilepsy are located in Kv1.1 pore domain. The patient was initially treated with a combination of antiepileptic drugs with limited benefit. Finally, seizures and ataxia control were achieved with lacosamide and acetazolamide. The aim of this study was to functionally characterize Kv1.1 mutant channel to provide a genotype–phenotype correlation and discuss therapeutic options for KCNA1-related epilepsy. To this aim, we transfected HEK 293 cells with Kv1.1 or P403A cDNAs and recorded potassium currents through whole-cell patch-clamp. P403A channels showed smaller potassium currents, voltage-dependent activation shifted by +30 mV towards positive potentials and slower kinetics of activation compared with Kv1.1 wild-type. Heteromeric Kv1.1+P403A channels, resembling the condition of the heterozygous patient, confirmed a loss-of-function biophysical phenotype. Overall, the functional characterization of P403A channels correlates with the clinical symptoms of the patient and supports the observation that mutations associated with severe epileptic phenotype cluster in a highly conserved stretch of residues in Kv1.1 pore domain. This study also strengthens the beneficial effect of acetazolamide and sodium channel blockers in KCNA1 channelopathies.

The Effectiveness and Safety of Hormonal Combinations of Antiepileptic Drugs in the Treatment of Epileptic Electrical Continuity in Children during Sleep: A Meta-Analysis.

Objective A systematic evaluation of the efficacy of hormones in combination with antiepileptic drugs (AEDs) compared to AEDs alone in the treatment of children with encephalopathy related to status epilepticus during slow sleep (ESES). This study provides an evidence-based approach to the treatment of children with ESES. Materials and Methods To find all relevant studies published before March 2022, we searched PubMed, Embase, Web of Science, Clinical Trials, Cochrane Library, CNKI, and Wanfang databases. We explore the difference between AEDs combined with hormones and AEDs alone for ESES treatment. All outcome data, including Wechsler Intelligence Scale for Children, the effective rate, EEG discharges, and adverse effects rate (AER), were compared using Review Manager 5.3. Results There were 805 patients in this study's seven investigations, including 403 in the experimental group and 402 in the control group. Meta-analysis showed that after treatment, compared with the AEDs alone group, the hormone combined with AEDs. The difference in clinical improvement rate [RR = 1.25, 95% CI (1.15, 1.36), p < 0.00001], electroencephalographic (EEG) discharge improvement rate [RR = 1.31, 95% CI (1.22, 1.41), p < 0.00001], and cognitive intelligence score [SMD = 1.02, 95% CI (0.76, 1.28), p < 0.00001] was statistically significant. The differences were statistically significant in terms of 0.00001; the incidence of adverse reactions was higher in the hormone combined with AEDs group than in the AEDs group alone, and the differences were statistically significant [RR = 4.13, 95% CI (1.06, 16.13), p < 0.01], and all adverse reactions improved or disappeared after discontinuation of the drug. Conclusions The combination of hormones with AEDs for the treatment of epileptic electrical continuity in sleep has advantages over AEDs alone in terms of controlling seizures, improving EEG abnormalities, and improving cognition. The combination of hormones with AEDs has advantages over AEDs alone in controlling seizures, improving EEG abnormalities, and improving cognition and is relatively safe.

Novel Loss-of-Function Variants in CHD2 Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients.

Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic CHD2 variants. While only a few pathogenic CHD2 variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic CHD2 variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients. The seizure onset ages were from two years to six years. Patients 1 and 2 had developmental delays before epilepsy, while patient 3 had intellectual regression after the first seizure onset. The observed seizures were myoclonic, febrile, and generalized tonic-clonic, which had been controlled by different combinations of antiepileptic drugs. Two de novo (c.1809_1809+1delGGinsTT, p.? and c.3455+2_3455+3insTG, p.?) and one maternal (c.3783G>A, p.W1261*) variant were identified, which were all predicted to be pathogenic/likely pathogenic. Molecular analysis was performed in patient 1, and we detected aberrantly spliced products, proving the pathogenicity of this CHD2 variant. New cases with novel variants, along with a detailed clinical and molecular analysis, are important for a better understanding of CHD2-related epileptic encephalopathy.

Direct Oral Anticoagulants and Antiepileptic Drug Combination on Risk of Ischemic Stroke and Major Bleeding – a territory-wide review (P1-1.Virtual)

Direct Oral Anticoagulants and Antiepileptic Drug Combination on Risk of Ischemic Stroke and Major Bleeding – a territory-wide review (P1-1.Virtual)

Brivaracetam add-on therapy for drug-resistant epilepsy.

This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30% of individuals with epilepsy continue to have epileptic seizures despite treatment with an antiepileptic drug. These patients are classified as drug-resistant and require treatment with a combination of multiple antiepileptic drugs. Brivaracetam is a third-generation antiepileptic drug that is a high-affinity ligand for synaptic vesicle protein 2A. In this review we investigated the use of brivaracetam as add-on therapy for epilepsy. To evaluate the efficacy and tolerability of brivaracetam when used as add-on treatment for people with drug-resistant epilepsy. For the latest update we searched the following databases on 7 September 2021: the Cochrane Register of Studies (CRS Web); MEDLINE (Ovid) 1946 to 3 September 2021. CRS Web includes randomised controlled trials (RCTs) and quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We searched for parallel-group RCTs that recruited people of any age with drug-resistant epilepsy. We accepted studies with any level of blinding (double-blind, single-blind, or unblinded). In accordance with standard Cochrane methodological procedures, two review authors independently assessed trials for inclusion before evaluating trial quality and extracting relevant data. The primary outcome to be assessed was 50% or greater reduction in seizure frequency. Secondary outcomes were: seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse events, the proportion of participants who experienced any adverse events, and drug interactions. We used an intention-to-treat population for all primary analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs). We did not identify any new studies for this update, therefore the results and conclusions of the review are unchanged. The previous review included six studies involving a total of 2411 participants. Only one study included participants with both focal and generalised onset seizures; the other five trials included participants with focal onset seizures only. Study participants were aged 16 to 80 years. Treatment periods ranged from 7 to 16 weeks. We judged two studies to have low risk of bias and four to have unclear risk of bias. Details on the method used for allocation concealment and how blinding was maintained were insufficient in one study each. One study did not report all outcomes prespecified in the trial protocol, and there were discrepancies in reporting in a further study. Participants receiving brivaracetam add-on were more likely to experience a 50% or greater reduction in seizure frequency than those receiving placebo (RR 1.81, 95% CI 1.53 to 2.14; 6 studies; moderate-certainty evidence). Participants receiving brivaracetam were more likely to attain seizure freedom; however, the evidence is of low certainty (RR 5.89, 95% CI 2.30 to 15.13; 6 studies). The incidence of treatment withdrawal for any reason was slightly greater for participants receiving brivaracetam compared to those receiving placebo (RR 1.27, 95% CI 0.94 to 1.74; 6 studies; low-certaintyevidence). The risk of participants experiencing one or more adverse events did not differ significantly following treatment with brivaracetam compared to placebo (RR 1.08, 95% CI 1.00 to 1.17; 5 studies; moderate-certainty evidence). However, participants receiving brivaracetam did appear to be more likely to withdraw from treatment due to adverse events compared with those receiving placebo (RR 1.54, 95% CI 1.02 to 2.33; 6 studies; low-certaintyevidence). When used as add-on therapy for individuals with drug-resistant epilepsy, brivaracetam may be effective in reducing seizure frequency and may aid patients in achieving seizure freedom. However, add-on brivaracetam is probably associated with a greater proportion of treatment withdrawals due to adverse events compared with placebo. It is important to note that only one of the eligible studies included participants with generalised epilepsy. None of the included studies involved participants under the age of 16, and all studies were of short duration. Consequently, the findings of this review are mainly applicable to adult patients with drug-resistant focal epilepsy. Future research should focus on investigating the tolerability and efficacy of brivaracetam during longer-term follow-up, as well as assess the efficacy and tolerability of add-on brivaracetam in managing other types of seizures and in other age groups.

Excessive Daytime Sleepiness and Sleep Quality and their Impact on Health-Related Quality of Life in People with Epilepsy: A study from Pakistan

BackgroundEpilepsy is one of the most common but manageable neurological disorder. The relation between epilepsy, sleep, and health-related quality of life (HRQoL) in culturally distinct environment of Pakistan remains unclear. The purpose of this study was to determine prevalence and predictors of excessive daytime sleepiness (EDS), poor sleep quality (SQ), and to analyze their association with HRQoL in people with epilepsy (PWE). MethodsA study was conducted among PWE attending two tertiary care hospitals of Islamabad and Rawalpindi, Pakistan. The EDS, SQ, and HRQoL were evaluated by Urdu versions of Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Quality of Life in Epilepsy-31 (QOLIE-31). ResultsThe study included 200 PWE and 51 healthy controls with mean (SD) ages of 33.1 ± 13.9, 32.9 ± 10.9, and a disease duration of 5.01 ± 6.17, respectively. The majority of the respondents (n = 130, 65%) had poor seizure control, and most of these (n = 88, 68%) were on combination antiepileptic drug (AED) therapy. In comparison to controls, a higher number of PWE had EDS by ESS (score ≥ 11, 10% vs. 40%, p-value 0.00), and poor SQ by PSQI (score > 5, 9% vs. 71%, p-value 0.00). A multiple logistic regression analysis reveals that the factors significantly associated with EDS were: female gender; increasing age; seizure control; duration of epilepsy; and combination AED therapy. A second multiple binary logistic regression analysis suggests that factors significantly associated with poor SQ were: increasing age; female gender; poor seizure control; and combination therapy. The Hierarchical multivariate analysis suggests that poor seizure control, EDS, and poor SQ were significant predictors of low HRQoL. ConclusionThe findings suggest high prevalence of EDS and poor SQ in PWE in Pakistan. A significant negative association exists between sleep complaints and HRQoL. During routine clinical consultations, awareness about sleep hygiene practices must be provided to enhance HRQoL.

Microemulsion for Simulataneous Intransal Delivery of Carbamazepine and Vitamin B6 for Treatment of Epilepsy

<p style="text-align: justify;"><strong>Background: </strong>Status epilepsy is a neurological emergency characterized by severe bouts of seizure. It has been reported that combination of antiepileptic drug with Vitamin supplements reduce the drug resistance and rapid improvement was also observed in epilepsy patients. In this study, we tried to develop novel intranasal microemulsion for simultaneous delivery of carbamazepine and Vitamin B₆ for treatment of epilepsy. <strong>Materials and Methods: </strong>For simultaneous estimation of Carbamazepine and Vitamin B₆, second derivative spectroscopy method was developed and validated. The ME containing CBZ, in lipophilic phase and Vitamin B₆ in aqueous phase was studied for physicochemical characters and ex vivo diffusion through sheep nasal mucosa. The maximal electroshock (MES)- induced seizure models was used to establish the pharmacodynamic credentials of the microemulsion. <strong>Results: </strong>The wavelength selected for Carbamazepine and Vitamin B₆ were 231 nm and 250 nm respectively. It was found that prepared microemulsion is stable with globule size of 395+12 nm. Diffusion across sheep nasal mucosa followed zero order kinetics for carbamazepine and Vitamin B₆ in the prepared microemulsion. It was found that the hind limb extension time and the recovery time were significantly different from control group (<em>p</em>&lt;0.05). The microemulsion remained stable after dilution, centrifugation and freeze thaw cycle as tested for particle size, zeta potential and percentage transmission. <strong>Conclusion:</strong> The proposed microemulsion should form the basis for treatment of epilepsy which warrants co-administration of micronutrients. <strong>Key words:</strong> Carbamazepine, Intranasal Microemulsion, Pharmacodynamic, Simultaneous Delivery, Vitamin B₆.

Symptomatic Epileptic Seizures in Patients with Brain Gliomas

Introduction. Epileptic seizures are an important problem that significantly worsens the quality of patients’ life with both newly diagnosed and recurrent brain gliomas.Review. The analysis of domestic and foreign literature showed that low-grade gliomas, this symptom occurs on average in 76%, with high-grade gliomas – in 21% of patients. Despite the maximum allowable tumor resection, it is likely that epileptic seizures persist in 18-64% of patients, and in 5% of patients they first appear in the postoperative period. From 15 to 50% of epileptic seizures in cerebral gliomas are drug-resistant. In patients undergoing chemotherapy, it is better to use new antiepileptic drugs because their cross-effects are minimal.Conclusion. There is no generally accepted algorithm for prescribing and discontinuing antiepileptic drugs in patients with symptomatic epileptic seizures with cerebral gliomas. Further research is needed to determine the optimal combination and dosage regimen of antiepileptic drugs, especially during chemotherapy.

Early infantile epileptic encephalopathy type 1 and 2: literature review and own observation

Epileptic encephalopathies and developmental encephalopathies are a group of severe disorders characterized by a delay or regression of cognitive and behavioral skills that develop as a result of resistant epileptic seizures. Because of the clinical and genetic heterogeneity of these disorders, next-generation sequencing is an important part of the examination of patients to identify the genetic etiology of the disorder and the appointment of targeted antiepileptic therapy. The article presents modern views on 1 and 2 types epileptic encephalopathies caused by pathogenic mutations of the ARX and CDKL5 genes. The main features of clinical symptoms, data of additional instrumental methods of examination and possible variations of targeted use of combinations of antiepileptic drugs in these disorders are presented. A case report of a patient with a CDKL5 gene mutation is described.