Long-term Antiepileptic Drugs Research Articles

Anticonvulsants impacting bone metabolism: interim results from a cross-sectional study

Background. Despite a wide range of antiepileptic drugs (AEDs) with an improved pharmacological profile, patients often experience a variety of side effects during long-trem anticonvulsant therapy, among which are osteoporotic disorders. Currently, the mechanisms of AED effect on bone metabolism remain poorly understood, which creates certain difficulties in prevention and treatment of AED-induced osteoporosis.Objective: to study bone mineral density and laboratory parameters of bone metabolism in patients with epilepsy and longterm AED administration.Material and methods. A cross-sectional study included two comparison groups: 100 adult patients with epilepsy receiving AEDs for more than 12 months and 58 healthy volunteers without taking AEDs. All participants underwent general clinical examination, computed tomography (CT) densitometry at three time points (L1, L2 and femoral neck) and laboratory tests of mineral metabolism.Results. According to CT-densitometry results, a decrease in bone mineral density was detected in the majority of participants from both study groups. While assessing an impact of osteoporosis risk factors on bone tissue in epileptic patients, low motor activity and duration of AED therapy were the most significant, which was associated with lower bone mineral density indices. The study of laboratory mineral metabolism indicators revealed significant inter-group differences in indicators such as ionized calcium, 25-hydroxy-calciferol, free thyroxine and prolactin (p(U)=0.044, p(U)=0.040, p(U)=0.001, p(U)=0.003, respectively).Conclusion. The intermediate study results showed that long-term anticonvulsant use negatively affected bone metabolism in patients suffering from epilepsy. The data obtained point at need for further in-depth study of AED therapy effect on mineral metabolism.

Serum Level of 25-Hydroxyvitamin D in Children with Epilepsy Receiving Long-Term Antiepileptic Treatment

Background: Long-term treatment with antiepileptic drugs (AED) requires monitoring of potential side effects, one of them is the decreasing in serum vitamin D level. Low serum vitamin D level is also a global health problem in healthy children. There are conflicting results regarding the low serum vitamin D level in epileptic children due to treatment with AED. Purpose: This study aimed to compare serum vitamin D level between healthy children and children with epilepsy receiving long-term AED treatment in Soetomo General Hospital. Methods: This was a cross-sectional study conducted in the pediatric neurology clinic of Soetomo general academic hospital from August 2018 to July 2019. Subjects are children ages 2-18 years with epilepsy receiving AED treatment for over 6 months (n=22), with healthy children as control (n=22). Peripheral serum 25-hydroxyvitamin D level were measured using enzyme-linked fluorescence assay (ELFA) method. The differences of those groups were analyzed by comparing the mean of 25-hydroxyvitamin D level of both groups using Anova and T-test (95% CI). Results: Low serum vitamin D level were identified in 27% children with epilepsy and 13% healthy children. The mean of serum 25-hydroxyvitamin D level in children with epilepsy and healthy children was 21.5 ng/ml (SD 8.41) and 34.3 ng/ml (SD 10.09), respectively. There was a significant difference between groups (p<0.05). Conclusion: Children with epilepsy receiving long-term AED treatment have lower level of serum 25-hydroxyvitamin D than healthy children.

Prevalence and Risk Factors of Low Vitamin D Level in Adults with Epilepsy: A Cross-sectional Study at a Single Tertiary Neurological Center in Thailand

Background: Epilepsy has a wide-ranging impact on the quality of life in patients of all age groups. Reduced levels of active vitamin D contribute to various bone diseases and may influence seizure control. Nevertheless, the risk factors for low vitamin D levels in patients with epilepsy remain inconclusive and are not well-established. The limited number of studies in Thailand may not be sufficient to provide guideline recommendations for screening vitamin D levels in adults with epilepsy. Objective: To evaluate the prevalence and risk factors of low vitamin D levels in Thai adults with epilepsy taking long-term antiepileptic drugs. To provide supporting recommendations for screening vitamin D levels in patients with epilepsy for early diagnosis and appropriate vitamin supplementation. Materials and Methods: The present study was a cross-sectional study conducted on 87 adults with epilepsy aged 18 to 76 years who were followed up at the Neurological Institute of Thailand between March and October 2023. Patients with comorbidities affecting vitamin D metabolism were excluded from the study. Baseline demographic data, epilepsy-related information, and anti-seizure medication information were analyzed. Blood tests for vitamin D for 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, and albumin were performed. Results: The prevalence of low vitamin D levels was 85%, including deficiency at 37% and insufficiency at 48%, with the mean (±SD) of serum 25(OH)D being 21.9±7.60 ng/mL. Multivariate analyses revealed that female was significantly associated with low vitamin D levels, adjusted OR 4.97 (95% CI 1.23 to 20.05). There was no significant association among epilepsy-related information, anti-seizure medications, and low vitamin D levels. Conclusion: The prevalence of low vitamin D levels in the present study was significantly higher than that observed in the previous studies, which is consistent with the findings of the recent studies in many countries. The authors strongly recommend screening for vitamin D levels in Thai adults with epilepsy, particularly in females. Early diagnosis and management of this condition are beneficial for patients with epilepsy and can help mitigate the various complications resulting from low vitamin D levels. Keywords: Epilepsy; Low vitamin D level; Vitamin D deficiency; Vitamin D insufficiency; Antiseizure medications; Prevalence; Risk factors

Arachidonic acid modulates the cellular energetics of human pluripotent stem cells and protects the embryoid bodies from embryotoxicity effects in vitro

Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos. As early embryogenesis depends on AA, we investigated the embryo protective effects of AA against the embryotoxic drug VA in this study. The effects of AA on the proliferation and cell cycle parameters of PSCs were studied. In particular, the potential of AA to abrogate VA-induced embryotoxicity in vitro was evaluated using ROS detection and antioxidant assays. In response to AA, we observed modulation in cell proliferation of induced pluripotent stem cells (iPSCs) and pluripotent NTERA-2 embryonal carcinoma (EC) cells. The present study substantiates the cytoprotective effects of AA against VA. These results imply that AA plays a critical role in the proliferation and differentiation of iPSCs and EC cells and protects the EBs from cytotoxic damage, thereby ensuring normal embryogenesis. Thus, the bioactive lipid AA may be explored for supplementation to benefit pregnant women treated with long-term anti-epileptic drugs to prevent in-utero fetal growth malformations.

Prognosticators of bone health in pediatrics with epilepsy using anti-epileptic drugs

Introduction: Epilepsy is a common and long-lasting neurological disorder in children who require long-term treatment with Antiepileptic drugs (AED). Such long-term AED use may have negative effects on bone causing bone loss and osteoporosis, necessitating frequent monitoring. Data on the effect of AED on bone health in children is scarce compared to adults and hence this study was undertaken. Aim: To compare and quantify the effects of sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) on bone health in children using specific bone biomarkers such as vitamin D, calcium, phosphorus, ALP, osteocalcin (OCN), and beta serum cross laps (CTx). Materials and methods: A prospective interventional study was carried out in Rajarajeswari Medical College and Hospital, Bangalore, between October 2019 to March 2022. A total of 79 confirmed cases of epilepsy within the age group of 1-18 years, receiving treatment with sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) monotherapy for a period of minimum one month were enrolled. Serum samples of calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALP), Vitamin D were analyzed at the time of initiation of study and these levels were considered as baseline levels.

Assessment of asymmetric dimethylarginine and homocysteine in epileptic children receiving antiepileptic drugs

BackgroundEpilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children.MethodsThis study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children.ResultsLow-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001).ConclusionsLong-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs.ImpactThe long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation.A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.

Factors Influencing the Withdrawal of Antiepileptic Drugs in Adult Patients with Symptomatic Seizures Secondary to Neuronal Surface Antibodies-Associated Autoimmune Encephalitis

PurposeThis retrospective study aimed to investigate the relationship between clinical characteristics, seizure outcomes, and the potential factors influencing the withdrawal of antiepileptic drugs (AEDs) in adult patients with symptomatic seizures secondary to neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE).Patients and MethodsEighty-one patients (age ≥18 years) diagnosed with NSAb-associated AE were included in this retrospective study. After at least 1 year of follow-up, clinical details, magnetic resonance imaging (MRI) findings, electroencephalography (EEG) data, cerebrospinal fluid parameters, and the therapeutic outcomes were analyzed. Patients who needed long-term AEDs to control seizures were divided into two groups (withdrawal ≤1 year and withdrawal >1 year). Multivariable logistic regression analysis was performed to identify the risk factors affecting the AEDs’ withdrawal in patients with seizures secondary to NSAb-associated AE.ResultsDuring the 12-month follow-up after AEDs’ withdrawal, 28 (44.4%) patients among the 63 patients who needed long-term AEDs stopped AEDs within 1 year, while 35 (55.6%) patients continued AEDs treatment. Multivariable logistic regression analysis showed that delayed immunotherapy, status epilepticus (SE), and elevated intrathecal Immunoglobulin G synthesis rate of 24 hours (24-h intrathecal IgG) were independent risk factors for delayed withdrawal in patients with seizure secondary to NSAb-associated AE (odds ratios: 1.129, 6.497, 3.415, P<0.05). The receiver operating characteristics (ROC) curve analysis showed that the area under the curve (AUC) of delayed immunotherapy, SE, and elevated 24-h intrathecal IgG was 0.816 (95% CI=0.711–0.921, P<0.001).ConclusionDelayed immunotherapy, status epilepticus and elevated 24-hour intrathecal IgG synthesis rate are the factors that may influence the decision to delay AEDs’ withdrawal.

Management of Post-traumatic Seizures and Epilepsy

Post-traumatic seizures and epilepsy are major complication of traumatic brain injury. Early and late and seizures have different implications for prognosis and management. Early seizures, which occur within one week of the trauma, are acute symptomatic events. On the other hand, presence of late seizures indicate epilepsy. Patients with early seizures are treated with anti-epileptic drugs(AEDs)within weeks to avoid status epilepticus, which may increase cerebral blood flow and increase intracranial pressure. Because prophylactic administration of AEDs reduces the incidence of early seizures but not late seizures, it is recommended to limit it to one week. A long-term AED administration is recommended for patients with late seizures, because late seizures represent epilepsy. AED should be selected according to the considerations of age and comorbidity that apply to other individuals with new-onset epilepsy. Since epileptic seizures often cause serious accidents, such as traffic accidents, drowning, burns, falls and others, lifestyle guidance for patients and their families is important.

Epilepsy and psychosis– where are we now?

IntroductionEpilepsy has long been considered a risk factor for psychosis, and studies estimate that up to 80% of patients with epilepsy will experience a psychotic episode at some point in the course of their disease. However, data on the treatment of psychotic disorders in epilepsy is limited and the management of these problems is still founded on individual clinical experience.ObjectivesTo assess evidence pertaining psychosis related to epilepsy, especially its risks factors and treatment approaches available.MethodsBibliographic research was made through the PubMed/NCBI database. No time limit was specified on the search. Pertinent manuscripts were individually reviewed for additional relevant citations.ResultsRecent literature shows a prevalence in psychotic disorders of 5.6%, and up to 7% in patients with epilepsy. So far, mechanisms of psychosis in epileptic patients remain unknown. Risk factors are earlier age of epilepsy onset, more frequent seizures, longer duration of epilepsy, high number of relatives with epilepsy and long-term antiepileptic drugs therapy. Psychiatric manifestations may include both positive and negative symptoms, including auditory hallucinations, paranoid delusions, and disorganized thought and/or behaviour. Poor adherence to treatment with oral antipsychotics occurs in more than 40% of patients; long-acting injectable medication should be considered, bearing in mind interactions with anti-epileptic medication and possibility of increased side effects.ConclusionsOur findings emphasize the importance of early recognition and management of psychosis in epileptic patients. Unfortunately, there is lack of evidence for the use of antipsychotic medication in epileptic patients, since available studies pertain to populations with primary psychiatric disorders.

The effects of antiepileptic drugs on bone health: A systematic review

PurposeEpilepsy may be treated with antiepileptic drugs (AEDs), which have been reported to decrease bone mineral density (BMD). Current data is conflicting and variable, and little is known with regard to how duration of AED use or specific AEDs, such as CYP-450 enzyme-inducing (EIAEDs) versus non-enzyme inducing (NEIAEDs) drugs affect BMD. We sought to systematically review BMD changes due to AED use to identify trends in reporting. MethodsA literature search via Medline (PubMed), EMBASE, and Cochrane databases was performed. Peer-reviewed articles were identified that reported on BMD measurements in conjunction with AEDs. ResultsTwenty-six studies met inclusion criteria. Long-term therapy was shown across multiple, well-controlled studies to have the most significant BMD loss. Carbamazepine had the most frequent reporting of unfavorable effects on bone health and Lamotrigine seemed to show the most bone-protective qualities. Serum biochemical markers of bone turnover did not significantly correlate with measured BMD changes. ConclusionThe present study provides evidence that long-term AED therapy is the most significant risk factor for BMD loss. Furthermore, there was little compelling evidence to support that EIAEDs, as a class, were more harmful to bone than NEIAEDs, which has been previously suggested in multiple studies. Early clinical concern for significant loss of BMD may not be warranted as lower BMD was less likely to be observed during the initial years of AED therapy. Furthermore, serum markers of bone turnover are not clinically reliable in assessing BMD changes in patients taking AEDs.

Management of bone metabolism in epilepsy.

Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.

Availability, affordability, and quality of essential antiepileptic drugs in Lao PDR.

ObjectiveEpilepsy is a chronic condition treatable by cost‐effective antiepileptic drugs (AEDs), but limited access to treatment was documented. The availability and affordability of good quality of AEDs play a significant role in access to good health care. This study aimed to assess the availability, affordability, and quality of long‐term AEDs in Lao PDR.MethodA cross‐sectional study was performed in both public and private drug supply chains in urban and rural areas in Lao PDR. Data on AEDs availability and price were obtained through drug suppliers. Affordability was estimated as the number of day wages the lowest‐paid government employee must work to purchase a monthly treatment. Samples of AEDs were collected, and the quality of AEDs was assessed through Medicine Quality Assessment Reporting Guidelines.ResultsOut of 237 outlets visited, only 50 outlets (21.1% [95% CI 16.1‐26.8]) had at least one AED available. The availability was significantly different between urban (24.9%) and rural areas (10.0%), P = .017. Phenobarbital 100 mg was the most available (14.3%); followed by sodium valproate 200 mg (9.7%), phenytoin 100 mg (9.7%), and carbamazepine 200 mg (8.9%). In provincial/district hospitals and health centers, AEDs were provided free of charge. In other healthcare facilities, phenytoin 100 mg and phenobarbital 100 mg showed the best affordability (1.0 and 1.2 day wages, respectively) compared to carbamazepine 200 mg (2.3 days) and other AEDs. No sample was identified as counterfeit, but 15.0% [95% CI 7.1‐26.6] of samples were classified as of poor quality.SignificanceWe quantified and qualified the various factors contributing to the high treatment gap in Lao PDR, adding to diagnostic issues (not assessed here). Availability remains very low and phenobarbital which is the most available and affordable AED was the worst in terms of quality. A drug policy addressing epilepsy treatment gap would reduce these barriers.

Relationship between APO-A, APO-B, and C-reactive Protein with Depression in Epileptic Patients

Background: Epilepsy is one of the oldest neurological disease requiring long-term treat­ment. Long-term use of certain anti-epileptic drugs (AED) will strongly induce cytochrome-P450 (CYP) enzyme resulting increase of homo­cysteine associated with risk of cerebrovascular disease and depression. The purpose of this study was to determine relationship between serum level of ApoA, ApoB, and C-Reactive Protein (CRP) with depression in epileptic patients receiving AED therapy. Subjects and Method: Respondents of this cross-sectional study were epileptic outpatients in neurology clinic Dr. Moewardi Hospital, Surakarta receiving AED therapy and met inclusion and exclusion criteria. Depression condition was evaluated by Hamilton Depress­ion Rating Scale (HDRS). Serum level of ApoA, ApoB, and CRP of each respondent were mea­sured from vein blood. Data were analyzed by a multiple linear regression. Results: There were 51 epileptic patients with proportional ratio between men and women (1.2:1) with age range from 18 to 59 years old. The average length of AED 92.67 months (Mean= 92.67; SD= 91.58). Average of HDRS score was 8.49. Meanwhile, average of ApoA level was 86.14 mg/dL, average of ApoB level was 47.57 mg/dL, and average of CRP level was 0.18 mg/dL. Serum level of ApoA, ApoB, and CRP increased depression (HDRS score) in epileptic patients. Conclusion: There was a statistically signi­fi­cant relationship between serum level of ApoA, ApoB, and CRP with depressive condi­tion of epileptic patients receiving long-term AED treatment. Keywords: ApoA, ApoB, C-Reactive Protein, depression, epilepsy

Differences in knowledge about epilepsy and antiepileptic drugs among pharmacy-dispensing workers in Cambodia and in Lao PDR

Epilepsy is the most common neurological disorder encountered in primary care in Southeast Asia. People with epilepsy require long-term therapy management. Nonadherence to antiepileptic drugs (AEDs) has been identified as a major factor in suboptimal control of epilepsy. Pharmacies offer patients a first-line point of contact with the healthcare system. Many pharmacies operate with limited or nonqualified human resources that can lead to insufficient knowledge, inappropriate supply of medicines, and insufficient counseling. ObjectiveThe aim of this study was to evaluate the qualification and knowledge concerning epilepsy and AEDs among pharmacy-dispensing workers who sell drugs to people with epilepsy. MethodA cross-sectional qualitative study was conducted in public and private pharmacies, in both urban and rural areas of Cambodia and Lao People's Democratic Republic (Lao PDR). The knowledge was collected through a questionnaire. ResultsA total of 180 respondents from 123 outlets in the two countries were included in this study. A proportion of 40.8% (31) of respondents in Cambodia and 38.5% (40) in Lao PDR were pharmacists, followed by sellers who did not received any healthcare training with a proportion of 18.4% (14) in Cambodia compared to 20.2% (21) in Lao PDR. Head trauma was cited as the main cause of epilepsy by 72.4% (55) in Cambodia and 27.2% (28) in Lao PDR (p < 0.001). Epilepsy was considered as a contagious disease by 6.6% (5) of respondents in Cambodia compared to 18.4% (19) in Lao PDR (p = 0.03). Eighty-seven percent (66) of respondents in Cambodia knew at least one long-term AED versus 67.3% (70) in Lao PDR (p = 0.003). Phenobarbital was mentioned in more than 90.0% of cases in both countries. In overall, 15.4% (21) thought that if seizures are controlled for some months, people with epilepsy could stop taking their AEDs. Only one respondent from Lao PDR was aware of drug–drug interaction between AEDs and oral contraception. ConclusionAn educational intervention should be implemented to improve the knowledge of epilepsy and AEDs for pharmacy-dispensing workers. This could include advice for all pharmacy-dispensing workers in order to improve AED management and follow-up of therapeutic adherence.

Correlation of Vitamin D and Calcium Levels in Children in New Diagnosed Epilepsy and Minimal 6 Months After Therapy

INTRODUCTION. Children with epilepsy should take long-term anti-epileptic drugs. Long-term use of anti-epileptic drugs can reduce vitamin D levels. Low vitamin D will lead to low blood calcium levels. This study aims to analyze the relationship between vitamin D and calcium levels in newly diagnosed epileptic children and ≥6 months after therapy. METHOD. These was an analytical observational study with cross sectional research design. The vitamin D examination instrument uses the ELFA method (enzyme linked fluorescent assay) with the Vidas instrument from bioMerieux. Samples were collected during June - August 2018 from Inpatient and Outpatient Clinics. The samples were divided into new diagnosis of epilepsy group and 6 months after therapy group. Each group was measured for vitamin D and serum calcium levels. The relationship between the two parameters were analyzed using T-Test independent. RESULTS. From the 19 new diagnosis of epilepsy, there were 57.9% low vitamin D and 10.5% low calcium levels. From the 20 subjects 6 months after therapy, 70% low vitamin D and 25% low calcium levels. There were a relationship between vitamin D and calcium levels in patients with newly diagnosed and ≥6 months after therapy. DISCUSSION. Low vitamin D and low calcium levels were found more in the anti-epileptic therapy group than the new diagnosis group of epilepsy. Low vitamin D levels can be caused by the use of long-term antiepileptic drugs that will affect serum calcium levels. CONCLUSION. This study showed a significant relationship between vitamin D and serum calcium levels in patients with newly diagnosed epilepsy and 6 months after therapy. Vitamin D and calsium serum examination should be done in every patient who gets long term therapy of antiepileptic drugs. KEY WORDS. Vitamin D, calcium, epilepsy, ELFA.

Psychosis in adults with epilepsy and its relationship to demographic, clinical and treatment variables

ABSTRACTObjectives: Psychiatric symptoms and disorders are commonly reported with epilepsy. This study aimed to determine the prevalence of interictal psychosis (IIP) in adults with epilepsy and its risk predictors.Methods: The study included 710 patients (mean age: 36.40 years; age at onset: 13.58 years; duration of epilepsy: 22.80 years). All underwent neurological and psychiatric interviewing, electroencephalography and brain imaging.Results: IIP was reported in 20.65%, of them 50% had temporal lobe epilepsy with impaired awareness and/or to bilateral tonic clonic, 42.47% had frontal lobe epilepsy with impaired awareness and/or to bilateral tonic clonic and 7.53% had generalized tonic-clonic seizures. Compared to patients without psychosis, patients with psychosis were older at age of examination, had earlier age at onset, frequent seizures, longer duration of epilepsy and long-term antiepileptic drugs therapy and many relatives with epilepsy. Nearly 76.71% had history of postictal psychosis (PIP). The mean age of onset of IIP was 30.45 years and its mean duration was 3.84 months. Approximately 22% of patients with IIP had family history of psychosis. Patients developed IIP 10 years or more after epilepsy onset. Multivariate logistic regression analyses showed that predictors for IIP were the age at onset and duration of epilepsy, number of seizures, family history of epilepsy or psychosis, history of PIP and different types of epilepsy.Conclusion: IIP is not infrequent with chronic epilepsy regardless to its type. These findings emphasize the importance of optimizing patients’ treatment and early recognition and management of IIP.Abbreviations: IIP: interictal psychosis; PIP: post-ictal psychosis; TLE: temporal lobe epilepsy; FLE: frontal lobe epilepsy; GTC: generalized tonic clonic; AEDs: antiepileptic drugs; CBZ: carbamazepine; VPA: valproate; LEV: levetiracetam; APDs: antipsychotic drugs

Epileptic patients\u2019 willingness to receive cell-phone based medication reminder in Northwest Ethiopia

BackgroundPoor adherence compromises medication treatment effectiveness which results in suboptimal illness control. This can lead to increased use of healthcare services, reduction in patients’ quality of life and increased healthcare costs. Reminding patients of their medication intake increases their adherence. Therefore, this study aimed to assess the willingness of epileptic patients to receive cell-phone based medication reminders and its associated factors in Northwest Ethiopia.MethodsInstitution based cross sectional study was conducted in the study period scheduled from March 1 to April 30, 2018 to interview 422 study participants at University of Gondar Comprehensive and Specialized Hospital, Northwest Ethiopia. Systematic random sampling was used to select 422 epileptic patients. A structured interviewer administered questionnaire was used to collect data and analyzed by using SPSS version 21. Binary and multivariate logistic regression analysis was performed to identify the determinant factors for willingness to receive cell-phone based medication reminders. P < 0.05 at 95% confidence interval was considered statistically significant.ResultsA total of 394 (93% response rate) respondents were interviewed. The majority of respondents 262 (66.5%) owned a cellphone. Among the participants 271 (68.8%) were willing to receive reminder messages. In the multivariate regression analysis; living in urban areas (AOR = 5.63, 95% CI; 3.18–9.96), experience of forgetting things (AOR = 2.63, 95% CI; 1.44–4.80), forgetting to take Long-term Antiepileptic Drugs (AEDs) (AOR = 2.17, 95% CI; 1.06–4.43) and average monthly income ≥2000 birr (AOR = 2.43, 95% CI; 1.03–5.75) were significantly associated with willingness to receive cell-phone medication reminders. Pertaining to marital status; being married (AOR = 5.75, 95% CI; 1.11–29.70) or divorced (AOR = 5.15, 95% CI; 1.29–20.49) participants were also more willing to receive cell-phone medication reminders as compared to singles.ConclusionMost respondents have a cellphone and were willing to use it as a medication reminder. Marital status, place of residence, average monthly income, experience of forgetting things since they started AED, forget to take AED are the most notable factors that are associated with the willingness of patients to receive cell phone drug reminder messages.

Acute antiepileptic drug use in intensive care units.

In intensive care units (ICUs), antiepileptic drugs (AEDs) are used for manifold indications. This is the first study to assess the prevalence of acute AED use in ICUs and to identify associated clinical variables. All patients in seven adult ICUs of a German university hospital in 2016 were retrospectively evaluated. Data were extracted from the computerized critical care information system and manually reviewed. Acute AED treatments were defined as initiated during ICU treatment or ≤ 6h before ICU admission, excluding benzodiazepines and sedatives. Among 2335 patients evaluated, 8.8% received acutely started AEDs: 5.1% due to epileptic seizures, mostly acute symptomatic, and 3.7% for other indications like pain, post-hypoxic myoclonus, and singultus. Following multivariable analyses, acute AED use was independently associated with intracranial reasons for ICU admission and long durations of ICU stay, but not with increased disease severity scores or mortality. Levetiracetam was the substance most frequently used to treat epileptic seizures (88%) as was pregabalin for other conditions (49%). Among surviving patients, acute AEDs were continued beyond ICU discharge in 86% if seizure-related and in 78% if not seizure-related, even if there was no evident need for long-term AED treatment. One out of eleven ICU patients receives acute AEDs, in almost half of cases for non-seizure indications. Acute AED use is a marker for intracranial ICU indications and prolonged ICU treatments. Usually, newer-generation AEDs are employed with favourable pharmacokinetic and safety profiles. However, whenever possible, acutely started AED should be discontinued before discharge from ICU.

The measurement of both carotid intima-media thickness and epicardial adipose tissue thickness in children with epilepsy receiving antiepileptic drug therapy

ObjectiveThe aim of this study was to evaluate the carotid intima-media thickness together with the thickness of the epicardial adipose tissue in patients receiving antiepileptic drug therapy and to investigate the presence of increased cardiovascular risk in these patients. MethodsThe study included a total of 52 patients comprising 32 males and 20 females who were diagnosed as having epilepsy and who were using one or more antiepileptic drugs. The control group consisted of 34 healthy individuals comprising 16 males and 18 females. The individuals selected for the study group were requested to go to the hospital after overnight fasting. After blood sampling for serum lipid value, the carotid intima-media thickness was measured with high resolution B-mode ultrasonography and epicardial adipose tissue thickness with echocardiography in the patients and the control group subjects. ResultsThe carotid intima-media thickness was determined as 0.47 ± 0.05 mm in the patient group and 0.44 ± 0.04 mm in the control group (p = 0.028). The carotid intima-media thickness was measured as 0.45 ± 0.05 mm in patients with epilepsy taking monotherapy and 0.49 ± 0.04 mm in those taking polytherapy (p = 0.003). The epicardial adipose tissue thickness was determined as 3.42 ± 0.09 mm in the patient group and 1.72 ± 0.90 mm in the control group (p = 0.000). The epicardial adipose tissue thickness was measured as 3.16 ± 0.87 mm in patients with epilepsy taking monotherapy and 3.77 ± 0.83 mm in those taking polytherapy (p = 0.041). ConclusionsIt was determined that carotid intima-media thickness and epicardial adipose tissue thickness were significantly high in children with epilepsy taking long-term antiepileptic drugs. These results demonstrate that these patients could be at increased risk of the development of cardiovascular complications. There is a need for more extensive studies on this subject.

Side effects of long-term antiepileptic drugs on renal tubules of Indonesian children

Background Long-term treatment with antiepileptic drugs such as valproic acid (VPA) and carbamazepine (CBZ) may disrupt renal tubular function. Urinary N-acetyl-beta-D-glucosaminidase (NAG) may reflect tubular function and may be useful in detecting early-stage tubular injury. To date, no study has investigated the toxic effect of VPA and CBZ on renal tubules using urinary NAG in Indonesian children.&#x0D; Objectives To determine the toxicity of long-term VPA and/or CBZ treatment on renal tubules in children with epilepsy by measuring urinary NAG index (iNAG).&#x0D; Methods This cross-sectional study was conducted from January to March 2015 at Cipto Mangunkusumo Hospital and Anakku Clinic Pondok Pinang, Jakarta. We included children aged 3 to 16 years with epilepsy on VPA (n=36), CBZ (n=14), or VPA-CBZ combination (n=14) therapy. We measured urinary levels of creatinine and NAG. The urinary NAG reference value was obtained from age-matched healthy controls (n=30). To eliminate diurnal variations in NAG, iNAG was calculated by dividing urinary NAG by urinary creatinine. A urinary iNAG of more than two standard deviations above the mean for healthy children was considered elevated.&#x0D; Results Mean urinary iNAG values for the control, VPA, CBZ, and combination groups were 3.01, 5.9, 4.07, and 6.9 U/g, respectively. All treated groups had higher mean urinary iNAG values compared to the control group. Urinary iNAG was increased in 11/36 children on VPA, 2/14 children on CBZ, and 9/14 children on combination therapy.&#x0D; Conclusion Long-term VPA use may impair renal tubular function, as shown by the increased urinary iNAG. Combination therapy increases damage in the renal tubules.