Antiepileptic Drug Polytherapy Research Articles

Folic acid supplementation in women of childbearing age with epilepsy: No association with type or number of antiepileptic drugs.

For over two decades, a daily folic acid (FA) supplementation has been recommended for women of childbearing age with epilepsy. This recommendation is based on evidence that FA administration before conception and during pregnancy can decrease the risk of fetal malformations in the general population, improve cognitive development, and reduce the risk of autistic traits in children exposed in utero to antiepileptic drugs (AEDs). The aim of this study was to evaluate FA supplementation rate in nonpregnant women of childbearing age with epilepsy and its relation to AED type and number. We retrospectively reviewed the computerized database and the medical records of all the women who had a first visit to our outpatient epilepsy clinic (Shamir-Assaf Harofeh Medical Center, Zerifin, Israel) during a 10-year period (2012-2021). Only 61 (22%) of 282 nonpregnant women of childbearing age with epilepsy treated with AEDs received FA supplementation. Ninety-two (33%) of the women were treated with AED polytherapy, and 41 (15%) received valproic acid in monotherapy or polytherapy. FA supplementation rate was higher in women aged ≤40 versus >40 (25% vs. 8.5%) (p = .004). No correlation was found between FA supplementation and AED type or number. FA supplementation rate was low and was unaffected by AED treatment. Patient and physician-targeted interventions should be implemented to increase FA prescription and patient adherence.

Cognitive impairment in epilepsy patients and its correlations

Objective Epilepsy is a severe disease in which seizures play the leading role. Striking clinical manifestations of the attacks take most of the attention of healthcare professionals. Apart from epilepsy itself, it is well known that epilepsy patients may also have psychiatric comorbidities. These disorders, such as anxiety and depression, are mostly thought to be related to epileptic seizures or antiepileptic medications. In clinical practice, cognitive impairment is another disrupted area of interest in epileptic patients. Our study aimed to detect this deterioration and its correlations with mood disorders and epileptic disease features such as seizure frequency and illness duration. Materials and methods After obtaining verbal and written consent, we enrolled 52 epilepsy patients in our study. A short demographic form indicating their gender, epileptic disease features, and medication usage information was completed for each patient. The Quick Mild Cognitive Impairment Screen (QMCI) test, the Hamilton Anxiety Rating Scale (Ham-A), and the Hospital Anxiety and Depression Scale (HADS) were applied by an experienced psychologist. Abnormal brain magnetic resonance imaging findings (e.g., encephalomalacia, large arachnoid cysts, a considerable amount of white matter gliotic lesions, neoplastic or vascular space-occupying lesions, hippocampal malformations), vitamin and electrolyte imbalances, other chronic diseases as well as thyroid dysfunction were considered as exclusion criteria since they might interfere with cognition. We excluded abnormalities to this extent because we wanted to acquire a homogenous sampling population without structural disadvantages. Thus, we could be able to determine slight changes in cognition properly. Results We found decreased cognitive scores directly proportional to lower education level, higher seizure frequency, longer disease duration, generalized tonic-clonic (GTC) type of seizure, and antiepileptic polytherapy. Also, complying with the literature, a high frequency of depression was found in our study group. Interestingly, decreased anxiety levels of the patients were statistically related to higher seizure frequency, which may indicate adaptive mechanisms to frequent seizures. Finally, a multivariate regression analysis revealed a significant negative impact of GTC type of seizure on cognition. Conclusion Epilepsy and epileptic seizures affect cognition negatively. Thus, newly diagnosed epilepsy patients should be assessed for cognitive status as soon as possible. This assessment will allow epileptologists to understand future deteriorations in their patients’ cognition. In our study, it is shown that QMCI is an effective and practical way to assess the cognitive statuses of epilepsy patients.

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.

P11.69.B IDH1/2wildtype gliomas grade 2 and 3 with molecular glioblastoma-like profile have a distinct course of epilepsy compared toIDH1/2wildtype glioblastomas

Abstract Background IDH1/2 wildtype (IDHwt) glioma WHO grade 2 and 3 patients with pTERT mutation and/or EGFR amplification and/or +7/−10 chromosome gain/loss have a similar overall survival time as IDHwt glioblastoma patients, and are both considered glioblastoma IDHwt according to the WHO 2021 classification. However, differences in seizure onset have been observed. This study aimed to compare the course of epilepsy in the two glioblastoma subtypes. Material and Methods We analyzed epilepsy data of an existing cohort including IDHwt histologically lower-grade glioma WHO grade 2 and 3 with molecular glioblastoma-like profile (IDHwt hLGG) and IDHwt glioblastoma patients. Primary outcome was the incidence proportion of epilepsy during the disease course. Major secondary outcomes included onset of epilepsy, number of seizure days and antiepileptic drug (AED) polytherapy. Results Out of 254 patients, 78% (50/64) IDHwt hLGG and 68% (129/190) IDHwt glioblastoma patients developed epilepsy during the disease course (p=0.121). Epilepsy onset before histopathological diagnosis occurred more frequently in IDHwt hLGG compared to IDHwt glioblastoma patients (90% versus 60%, p&amp;lt;0.001), with a significantly longer median time to diagnosis (3.5 versus 1.3 months, p&amp;lt;0.001). Median total seizure days was also longer for IDHwt hLGG patients (7.0 versus 3.0, p=0.005), and they received more often AED polytherapy (32% versus 17%, p=0.028). Conclusion Although the incidence proportion of epilepsy during the entire disease course is similar, IDHwt hLGG patients show a significantly higher incidence of epilepsy before diagnosis and a significantly longer median time between first seizure and diagnosis compared to IDHwt glioblastoma patients, indicating a distinct clinical course.

IDH1/2 wildtype gliomas grade 2 and 3 with molecular glioblastoma-like profile have a distinct course of epilepsy compared to IDH1/2 wildtype glioblastomas.

IDH1/2 wildtype (IDHwt) glioma WHO grade 2 and 3 patients with pTERT mutation and/or EGFR amplification and/or + 7/-10 chromosome gain/loss have a similar overall survival time as IDHwt glioblastoma patients, and are both considered glioblastoma IDHwt according to the WHO 2021 classification. However, differences in seizure onset have been observed. This study aimed to compare the course of epilepsy in the 2 glioblastoma subtypes. We analyzed epilepsy data of an existing cohort including IDHwt histologically lower-grade glioma WHO grade 2 and 3 with molecular glioblastoma-like profile (IDHwt hLGG) and IDHwt glioblastoma patients. Primary outcome was the incidence proportion of epilepsy during the disease course. Secondary outcomes included, among others, onset of epilepsy, number of seizure days, and antiepileptic drug (AED) polytherapy. Out of 254 patients, 78% (50/64) IDHwt hLGG and 68% (129/190) IDHwt glioblastoma patients developed epilepsy during the disease (P = .121). Epilepsy onset before histopathological diagnosis occurred more frequently in IDHwt hLGG compared to IDHwt glioblastoma patients (90% vs 60%, P < .001), with a significantly longer median time to diagnosis (3.5 vs 1.3 months, P < .001). Median total seizure days was also longer for IDHwt hLGG patients (7.0 vs 3.0, P = .005), and they received more often AED polytherapy (32% vs 17%, P = .028). Although the incidence proportion of epilepsy during the entire disease course is similar, IDHwt hLGG patients show a significantly higher incidence of epilepsy before diagnosis and a significantly longer median time between first seizure and diagnosis compared to IDHwt glioblastoma patients, indicating a distinct clinical course.

Serum Calcium, Vitamin D3 and Bone Specific Alkaline Phosphatase Levels in Nigerian Children Treated with Antiepileptic Drugs: A Comparative Study

Background and Aim of the Study: Studies have shown that serum 25-hydroxycholecalciferol, calcium and bone-specific alkaline phosphatase (B-ALP) are altered in children on antiepileptic drugs (AEDs), and these could result in poor bone mineralization. The study aimed to determine the serum 25-hydroxycholecalciferol, calcium, and B-ALP levels among children on AEDs attending the paediatric neurology clinic of the University of Port Harcourt Teaching Hospital (UPTH).&#x0D; Methods: This cross-sectional analytical study was carried out from January 2018 to April 2019 on 100 children on AEDs and 100 age- and gender-matched healthy controls, aged 1.5 - 17 years. Data on socio-demography, AED regimen, and clinical examination findings of the subjects, their serum 25-hydroxycholecalciferol, calcium, and B-ALP levels were obtained and entered into a proforma. Data obtained were analysed using IBM SPSS version 20. Statistical significance was set at p-value of &lt; 0.05.&#x0D; Results: The subjects had significantly lower mean serum 25-hydroxycholecalciferol and calcium and higher mean serum B-ALP levels than the controls, respectively. The mean serum 25-hydroxycholecalciferol was significantly lower in children on AED polytherapy. There was negative correlation between the duration of drug therapy and all serum biochemical indices but this was only significant for serum 25-hydroxycholecalciferol level (p = 0.027). Age significantly impacted negatively on serum 25-hydroxycholecalciferol, p = 0.036 and calcium levels, p = 0.009, but not on B-ALP (p = 0.392).&#x0D; Conclusion: Children on antiepileptic drugs in UPTH had lower mean serum 25-hydroxycholecalciferol and calcium levels but higher mean serum BALP level than healthy controls, as well as inverse relationship between duration of AED therapy and 25, hydroxycholecalciferol, calcium and B-ALP. We therefore recommend children with epilepsy on antiepileptic drugs have their serum 25-hydroxycholecalciferol, calcium and B-ALP levels monitored to enable early detection of any abnormalities.

Factors Influencing Antiepileptic Drug (AED) Nonadherence in a Tertiary Care Hospital: A Cross Sectional Study

Introduction: Epilepsy affects almost 50 to 70 million individuals’ worldwide, accounting for 0.75 percent of the worldwide illness burden. Every year, an approximate of 2.4 million individuals are afflicted with epilepsy. Due to a lack of accessibility and affordability of AEDs, up to three-quarters of patients with epilepsy in low-income nations are unable to receive the medication they require. Aim: To determine the factors influencing antiepileptic drug (AED) nonadherence in a tertiary care hospital. Methodology: According to the findings of a single center, cross-sectional investigation, we did a subgroup assessment. Patients have to be at least 18 years old to participate. The Morisky Medication Adherence Scale, which has four items, was employed to assess compliance to AEDs. To forecast parameters linked to AED nonadherence, researchers employed multivariable logistic regression assessment. Results: This subgroup evaluation includes a total of 270 patients who met the eligibility criteria. Amongst the patients, 82 (31%) did not take their medication as prescribed. AED polytherapy, medication linked negative events, and medication length beyond 3 years were three characteristics linked to poor adherence. Conclusion: Almost one third of the participants did not take their medicine as prescribed. Noncompliance may be minimized if patients’ treatments are limited to monotherapy as much as feasible and patients are taught about the length of medication and potential side effects of AEDs

Favorable Response to “Memantine” in a Child with GRIN2B Epileptic Encephalopathy

GRIN2B is a gene encoding GluN2B subunit under the family of N-methyl D-aspartate (NMDA) receptors, which is responsible for neurogenesis and cognitive processes. The role of NMDA receptor antagonists like memantine is being explored for therapies in drug-resistant epilepsies. Here, we present a case of a 20-month-old boy who presented with refractory epileptic spasms. Upon failure of multiple antiepileptic drugs, he was started on oral memantine. There was a significant reduction in average seizure episodes by ∼80%. The use of memantine along with antiepileptic drug polytherapy has proved to be beneficial in our case. Our experience with memantine and favorable outcome opens up the scope of more research into the use of NMDA receptor antagonist as a drug option for refractory epilepsies with proven genetic mutation and hence improves the overall neurodevelopmental outcome and survival chance.

Epilepsy and mortality: a retrospective cohort analysis with a nested case–control study identifying causes and risk factors from primary care and linkage-derived data

ObjectivesPeople with epilepsy (PWE) have a higher mortality rate than the general population. Epilepsy-related deaths have increased despite all-cause mortality decreasing in the general population pre-COVID-19. We hypothesised that clinical...

Relevance of NR1I2 variants on carbamazepine therapy in Mexican Mestizos with epilepsy at a tertiary-care hospital.

Aim: We evaluated the potential influence of genetic (CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug reactions and CBZ plasma concentrations in 126 MexicanMestizos (MM)with epilepsy. Subjects & methods: Patients were genotyped for 27 variants using TaqMan® assays. Results: CBZ response was associated with NR1I2 variants and lamotrigine cotreatment. CBZ-induced adverse drug reactions were related to antiepileptic polytherapy and SCN1A rs2298771/rs3812718 haplotype. CBZ plasma concentrations were influenced by NR1I2-rs2276707 and -rs3814058, and by phenytoin cotreatment. CBZ daily dose was also influenced by NR1I2-rs3814055 and EPHX1-rs1051740. Conclusion: Interindividual variability in CBZ treatment was partly explained by NR1I2, EPHX1 and SCN1A variants, as well as antiepileptic cotreatment in MMwith epilepsy.

Psychiatric comorbidity and quality of life in patients with epilepsy on anti-epileptic monotherapy and polytherapy.

Objective:The bio-psycho-social factors affecting the quality of life in patients with epilepsy can be numerous but are often overlooked. The behavioral side effects of anti-seizure medications can be one such potential factor. The aim of the study is to address the effect of the number of anti-seizure medications on the development of psychiatric comorbidity and quality of life in patients with adequate seizure control.Materials and Methods:The study recruited 100 participants with generalized tonic-clonic seizures from a tertiary care center in North India, who were seizure-free from the last 1 month. The study participants were divided into two groups based on whether they were on monotherapy or polytherapy. The two groups were matched for their socio-demographic and clinical profile. We assessed for psychiatric comorbidity in each group using Mini International Neuropsychiatric Interview. All the study participants were given Hindi translated version of quality of life in the epilepsy-31 questionnaire for objective assessment of the quality of life.Results:The patients receiving anti-epileptic polytherapy had significantly higher prevalence of psychiatric comorbidity than patients on monotherapy. Furthermore, the patients on polytherapy scored significantly less on the cognitive domain of quality of life as well as the overall quality of life domain in the epilepsy-31 questionnaire.Conclusion:The patients with epilepsy must be evaluated for psychiatric comorbidity and side effect profile of anti-seizure medications to improve the quality of life. This is particularly more important for patients who are on anti-epileptic polytherapy even if the seizure control is adequate.

The relationship between antiepileptic drug load and challenging behaviors in older adults with intellectual disability and epilepsy

Antiepileptic drugs (AEDs) may affect mood and behavior in people with epilepsy and intellectual disability. A high AED load, derived from AED polytherapy and/or high doses of AEDs, has been suggested to be a risk factor for behavioral side effects. Data were drawn from Wave 3 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA). The Behavior Problems Inventory Short Form (BPI-S) was used to assess challenging behaviors. AED load was calculated and median AED loads obtained. Non-parametric tests and binary logistic regression were performed to determine the relationship between AED load and challenging behaviors. Of participants with a reported diagnosis of epilepsy who were taking a regular AED and had completed BPI-S (n = 142), 62.7% (n = 89) exhibited challenging behaviors. Challenging behavior was found to be more prevalent in those with more severe levels of intellectual disability (p < 0.001). Aggressive/destructive behavior and stereotyped behavior were significantly more likely in participants living in residential/campus settings. For participants with a severe/profound intellectual disability, a significantly higher median AED load was found for participants exhibiting aggressive/destructive behavior and self-injurious behavior (SIB) compared to participants not exhibiting these behaviors, indicating a high AED load may contribute to some behavioral problems in this population group. However, many factors can influence behavioral outcomes, creating difficulties in determining those that are associated and the nature of the association. Careful monitoring of AED load, together with increased vigilance for breakthrough behavioral issues is essential for dealing with these complex cases. Larger studies are needed to account for the potential confounding factors.

Sudden unexpected death in epilepsy: Experience of neurologists in Saudi Arabia

ImportanceSudden unexpected death in epilepsy (SUDEP) may account for up to 17% of all deaths in epilepsy. However, it is unknown if neurologists discuss this risk with patients. ObjectiveThis study aimed to examine the understanding and practices of SUDEP by neurologists in Saudi Arabia. MethodsAn electronic web-based survey was sent to 125 neurologists using the mailing list of the Saudi Neurology Society. The survey questions included respondents’ demographics, frequency of SUDEP discussion, reasons for discussing/not discussing SUDEP, and perceived patient reactions. Respondents’ knowledge of the SUDEP risk factors was examined using 12 items from the currently available literature. Logistic regression analyses were applied to examine the factors that influence the frequency of SUDEP discussions and perceived patient reactions. ParticipantsThe participants were neurologists who had completed postgraduate training, devoted >5% of their time to clinical care, and had at least one patient with epilepsy in their independent neurology clinic. ResultsA total of 60 respondents met the eligibility criteria and completed the surveys. Of them, 25% discussed SUDEP most of the time, 65% sometimes or rarely, and 10% never discussed it. Of those who discussed SUDEP with their patients, 63.3% did it if the patient was at high risk. Poor compliance with antiepileptic drugs (AEDs) was the most common patient factor highlighted (81.7%). The perceived patients’ reactions were variable, with positive reactions (motivation to comply and appreciation) being the most frequent. The majority of respondents (78.3%) had incomplete understanding of the published SUDEP risk factors, with SUDEP knowledge scores ≤2.5 (≤50% of the possible total score). The most identified risk factors were frequent generalized tonic-clonic seizures (83.3%), long duration of epilepsy (53.3%), lack of use or sub-therapeutic levels of AEDs (50%), and AED polytherapy (50%). No association was found between how often SUDEP was discussed and other factors, including training in epilepsy, ≥10 years in practice, seeing ≥100 patients, and having SUDEP cases in the past two years. It was found that patients positively reacted to discussion on SUDEP if neurologists had a good understanding of the SUDEP risk factors (χ2 = 5.773, p = 0.016). ConclusionsNeurologists in Saudi Arabia do not often discuss SUDEP with patients that have epilepsy. Moreover, when they do, they stress a more individualized approach despite having only a limited understanding of the SUDEP risk factors. Our findings suggest that more guidance should be provided to practitioners on how best to counsel their patients about SUDEP.

Gender differences in seizure recurrence and antiepileptic drug polytherapy predicting health-related quality of life of persons 1 year after diagnosis of epilepsy

PurposeThe aim of this study was to determine whether gender influences the prediction of health-related quality of life (HRQoL) in persons with newly diagnosed epilepsy (NDE). MethodsThis was a 1-year longitudinal study. Persons with NDE were assessed with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), the Hospital Anxiety Depression Scale (HADS), the Stigma Scale, and the Rosenberg Self-esteem Scale. An analysis of covariance (ANCOVA) with interaction terms was used. ResultsAmong 134 adults with NDE, there were no gender differences in the scores of the QOLIE-31 and its subscales. A multivariate linear regression analysis showed that the HADS-anxiety scores at diagnosis (p = 0.005) and seizure recurrence after diagnosis (p = 0.050) negatively predicted QOLIE-31 scores in persons with NDE. There were significant effects of the gender interaction with seizure recurrence (F = 8.745, p = 0.004, partial eta2 = 0.066) and antiepileptic drug (AED) polytherapy (F = 6.320, p = 0.013, partial eta2 = 0.049) in the adjusted model. Specifically, seizure recurrence negatively predicted the QOLIE-31 scores only in men. By contrast, AED polytherapy negatively predicted the QOLIE-31 scores only in women. ConclusionsThere are gender differences in certain epilepsy-related factors predicting HRQoL at 1 year in persons with NDE.

What Should We Do When the Kids Grow Up? Studying the Long-Term Cognitive Effects of In-Utero Anti-Seizure Medication Exposure.

Enduring Language Deficits in Children of Women With Epilepsy and the Potential Role of Intrauterine Exposure to Antiepileptic Drugs Unnikrishnan G, Jacob NS, Salim S, et al. Epilepsia. 2020;61(11):2442-2451. doi:10.1111/epi.16685Objective:Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9 to 13 years in comparison with their peers, and its relationship with intrauterine AED exposure.Methods:We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n = 144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records.Results:The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P = .001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% CI = −8.8 to −0.2, P = .04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = −13.8 to −0.8, P = .03). Intrauterine exposure to phenobarbitone (n = 61) and valproate (n = 55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n = 75) and phenytoin (n = 37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (−14.7, 95% CI = −23.1 to −6.4, P = .001) as compared to carbamazepine.Significance:Intrauterine exposure to phenobarbitone and valproate impairs language development in CWE, with effects persisting into the second decade.

Significant Association of Antiepileptic Drug Polytherapy with Decreased FT4 Levels in Epileptic Patients.

Epileptic patients have to continue anti-epileptic drugs (AED) over a long period of time which can have deleterious effects on the endocrine system including the thyroid hormones with rare check. Risk factors for the development of thyroid dysfunction are still unclear. Therefore the aim of study was to evaluate thyroid functions in epileptic patients receiving anti-epileptic drugs (AED) as monotherapy and polytherapy and to determine potential risk of low thyroid function in epileptic patients receiving treatment. This cross-sectional study included 100 epilepsy patients more than 12years of age. Serum levels of free thyroxin (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were evaluated in all subjects in addition to serum AED levels. TSH levels were found to be significantly higher in the polytherapy subgroup (p < 0.05) in comparison to the monotherapy group. 44% of the patients in the VPA monotherapy group had raised TSH levels and 41.2% of the patients on CBZ had low FT4. A significant negative correlation was observed between CBZ and FT4 (p < 0.05). Female sex and old age were additional risk factors detected for deranged thyroid function. Female patients with epilepsy, an older age and AED polytherapy were found to be associated with a higher risk of thyroid dysfunction. Thus, Thyroid function in these patients should be monitored closely. In conclusion, we observed significant changes in thyroid hormone levels in patients receiving antiepileptic treatment in both monotherapy and polytherapy. Elevated CBZ levels were significantly associated with decreased FT4 levels.

Effects of long-term antiepileptic polytherapy on bone biochemical markers in ambulatory children and adolescents and possible benefits of vitamin D supplementation: a prospective interventional study

PurposeOur aim was to investigate any adverse effects of long-term polytherapy (VPA and add-on-therapy) on bone biochemical markers in ambulatory children and adolescents with epilepsy and the possible benefits of vitamin D supplementation on the same markers. MethodsIn this prospective interventional study, the levels of 25(OH)D and the bone turnover markers of CrossLaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were determined in forty-two ambulatory children with epilepsy on polytherapy (valproic acid + one or more other from levetiracetam, topiramate, lamotrigine, or rufinamide). The same markers were assessed after a year’s supplementation of vitamin D (400 IU/d) and were compared with those of clinically healthy controls. The respective mean (±SD) ages were 11.9 ± 4.6 and 11.4 ± 4.4 yrs. ResultsThe basal mean 25(OH)D levels in the patients did not differ from controls (23.9 ± 11.5 vs 27.4 ± 13.3 ng/ml), but increased significantly after the vitamin D intake (31.1 ± 13.3 ng/ml, p < 0.01). In parallel, basal serum CTX levels were found to be significantly lower in the patients than controls (0.89 ± 0.63 vs 1.22 ± 0.58 ng/ml, p < 0.02), but not tALP. Osteoprotegerin was higher in the patients (5.7 ± 7.7 pmol/L vs 2.6 ± 1.0 pmol/L, p < 0.03), while sRANKL did not differ. After vitamin D, the CTX levels increased to comparable levels in controls (0.99 ± 0.57 ng/ml), and those of OPG decreased to levels that did not differ from controls (4.9 ± 5.1 pmol/L). The ratio of OPG/sRANKL was higher in patients than controls before treatment (0.030 ± 0.045 vs 0.009 ± 0.005, p < 0.03), but decreased (0.026 ± 0.038) to comparable values in controls later. ConclusionsThese findings imply a lower bone turnover in the young patients on long-term polytherapy (VPA and add-on-therapy), but after one year’s vitamin D intake, bone biochemical markers improved.

Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants

ObjectivePatients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments. MethodsWe recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information. ResultsWe identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI. ConclusionOur patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.

A Review on conceptual framework of Drug Side Effects and Pharmacoresistance in Epilepsy

Epileptic seizures in the form of involuntary body movements have made patients’ lives extremely difficult. There are mainly two types of seizures partial or focal seizure affect just one side of the brain and generalised seizures affect the whole brain of a person. The person suffers from neuro-sensory deregulation and consciousness loss, coupled with episodes of seizures. Different drug therapies have been used for epilepsy patients targeting neurotransmitters regulation mechanisms. The drug targets and mechanism of action in polytherapy remain ambiguous. However, 6 out of 10 patients quit antiepileptic drug (AED) therapy due to side effects like depression, aggression and psychosis. Several behavioral side effects make them socially awkward, due to which patients cease to continue drug therapies. The combined effect of AED side effects and resorting therapies lead to recurrent seizures which further disturb the neurotransmission on account of every seizure episode. The present review describes epilepsy in terms of clinical treatments and associated side effects. The study provides a novel conceptual loop of correlation between AED polytherapy, side effects and Pharmacoresistance. This review creates caution for clinicians to think intricately before prescribing drugs for epilepsy and ensure communication of side effects. The review opens research prospectives for drug targets to break the conceptual loop for the Pharmacoresistance. Further, this paper enhances the understanding of epilepsy and improves diseases condition.

A Review on conceptual framework of Drug Side Effects and Pharmacoresistance in Epilepsy

Epileptic seizures in the form of involuntary body movements have made patients’ lives extremely difficult. There are mainly two types of seizures partial or focal seizure affect just one side of the brain and generalised seizures affect the whole brain of a person. The person suffers from neuro-sensory deregulation and consciousness loss, coupled with episodes of seizures. Different drug therapies have been used for epilepsy patients targeting neurotransmitters regulation mechanisms. The drug targets and mechanism of action in polytherapy remain ambiguous. However, 6 out of 10 patients quit antiepileptic drug (AED) therapy due to side effects like depression, aggression and psychosis. Several behavioral side effects make them socially awkward, due to which patients cease to continue drug therapies. The combined effect of AED side effects and resorting therapies lead to recurrent seizures which further disturb the neurotransmission on account of every seizure episode. The present review describes epilepsy in terms of clinical treatments and associated side effects. The study provides a novel conceptual loop of correlation between AED polytherapy, side effects and Pharmacoresistance. This review creates caution for clinicians to think intricately before prescribing drugs for epilepsy and ensure communication of side effects. The review opens research prospectives for drug targets to break the conceptual loop for the Pharmacoresistance. Further, this paper enhances the understanding of epilepsy and improves diseases condition.