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Bone Mineral Changes in Epilepsy Patients During Initial Years of Antiepileptic Drug Therapy

Shiek Ahmad B, O'Brien TJ, Gorelik A, Hill KD, Wark JD

J Clin Densitom, 2016 Oct;19(4):450-456.
PMID: 27553750 DOI: 10.1016/j.jocd.2016.07.008

Antiepileptic drug (AED) therapy is associated with decreased bone mineral density; however, the time course for this development is unclear. The aim of this study was to evaluate bone mineral changes during the initial years of AED therapy in AED-naive, newly diagnosed epilepsy patients compared with non-AED users. In 49 epilepsy patients newly started on AEDs and in 53 non-AED users of both genders, bone mineral density (BMD) and bone mineral content were measured using dual-energy X-ray absorptiometry at baseline (within the first year of therapy) and at least 1 yr later. Bone changes between the 2 assessments, adjusted for age, height, and weight, were calculated as the annual rate of change. The median duration of AED therapy was 3.5 mo at baseline and 27.6 mo at follow-up. No overall difference was found in mean BMD and bone mineral content measures between user and nonuser cohorts in both cross-sectional baseline and the annual rate of change (p > 0.05). However, users on carbamazepine monotherapy (n = 11) had an increased annual rate of total hip (-2.1% vs -0.8%, p = 0.020) and femoral neck BMD loss (-2.1% vs -0.6%, p = 0.032) compared to nonusers. They also had a marginally higher rate of femoral neck BMD loss (-2.1%, p = 0.049) compared with valproate (-0.1%, n = 13) and levetiracetam users (+0.6%, n = 13). During the initial years of AED treatment for epilepsy, no difference was found in bone measures between AED users as a group and nonuser cohorts. However, the data suggested that carbamazepine monotherapy was associated with increased bone loss at the hip regions, compared to users of levetiracetam or valproate and nonusers. Larger studies of longer duration are warranted to better delineate the bone effects of specific AEDs, with further consideration of the role of early dual-energy X-ray absorptiometry scanning and careful AED selection in potentially minimizing the impact on bone health in these patients.

Matched MeSH terms: Epilepsy/drug therapy*
Bone loss with antiepileptic drug therapy: a twin and sibling study

Shiek Ahmad B, Petty SJ, Gorelik A, O'Brien TJ, Hill KD, Christie JJ, et al.

Osteoporos Int, 2017 Sep;28(9):2591-2600.
PMID: 28589417 DOI: 10.1007/s00198-017-4098-9

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility.
INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use.
METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated.
RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031).
CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Matched MeSH terms: Epilepsy/drug therapy*
Prevalence and factors of verbal learning and memory dysfunction in patients with epilepsy - A single centre study

Subramaniam SR, Khoo CS, Raymond AA, Che Din N, Syed Zakaria SZ, Tan HJ

J Clin Neurosci, 2020 Mar;73:31-36.
PMID: 32094071 DOI: 10.1016/j.jocn.2020.02.003

The objective of this study is to determine prevalence and factors leading to verbal learning and memory dysfunction among patients with epilepsy. A total of 211 subjects were recruited. Their verbal memory was assessed by Rey's Auditory Verbal Learning Test (RAVLT). This test was further subdivided into four major spheres for analysis, namely the verbal learning, interference list, immediate memory and delayed memory. All data collected were analyzed using Statistical Package for Social Sciences. Among the 211 patients, 55% (n = 116) had focal seizures and the remaining 45% (n = 95) had generalized seizures. Prevalence of verbal learning and memory impairment was high at 39.97% overall, and found most commonly in patients with focal impaired awareness seizures. Verbal learning and immediate memory dysfunction were significantly lower in focal impaired awareness group compared to others. Age more than 50 years, exposure to three or more antiepileptic drugs and use of carbamazepine more than 1000 mg a day were the predictors in poor verbal memory outcome. No statistical difference was observed in the mean RAVLT scores among the gender and hand dominance groups. Between patients with and without electroencephalogram changes as well as brain magnetic resonance imaging changes, the mean RAVLT scores showed no statistically significant difference. Verbal learning and memory impairment is prevalent among the epilepsy patients. The consequences of the memory impairment can be as debilitating as the seizure control. RAVLT is a reliable and practical test in the clinical setting.

Matched MeSH terms: Epilepsy/drug therapy
Impact of epilepsy on employment in Malaysia

Lim KS, Wo SW, Wong MH, Tan CT

Epilepsy Behav, 2013 Apr;27(1):130-4.
PMID: 23416283 DOI: 10.1016/j.yebeh.2012.12.034

Studies on the impact of epilepsy on employment have been extensively performed in European and some Asian countries but not in Southeast Asia such as Malaysia, a country with a robust economy, low unemployment rate, and minimal social security benefits for the unemployed. This study aims to determine the impact of epilepsy on employment in Malaysia.

Matched MeSH terms: Epilepsy/drug therapy
48-hour video-EEG monitoring for epilepsy presurgical evaluation is cost-effective and safe in resource-limited setting

Lim KS, Fong SL, Thuy Le MA, Ahmad Bazir S, Narayanan V, Ismail N, et al.

Epilepsy Res, 2020 05;162:106298.
PMID: 32172144 DOI: 10.1016/j.eplepsyres.2020.106298

INTRODUCTION: Video-EEG monitoring is one of the key investigations in epilepsy pre-surgical evaluation but limited by cost. This study aimed to determine the efficacy and safety of a 48-hour (3-day) video EEG monitoring, with rapid pre-monitoring antiepileptic drugs withdrawal.
MATERIAL AND METHODS: This is a retrospective study of epilepsy cases with VEM performed in University Malaya Medical Center (UMMC), Kuala Lumpur, from January 2012 till August 2016.
RESULTS: A total of 137 cases were included. The mean age was 34.5 years old (range 15-62) and 76 (55.8 %) were male. On the first 24 -h of recording (D1), 81 cases (59.1 %) had seizure occurrence, and 109 (79.6 %) by day 2 (D2). One-hundred and nine VEMs (79.6 %) were diagnostic, in guiding surgical decision or further investigations. Of these, 21 had less than 2 seizures recorded in the first 48 h but were considered as diagnostic because of concordant interictal ± ictal activities, or a diagnosis such as psychogenic non-epileptic seizure was made. Twenty-eight patients had extension of VEM for another 24-48 h, and 11 developed seizures during the extension period. Extra-temporal lobe epilepsy and seizure frequency were significant predictors for diagnostic 48 -h VEM. Three patients developed complications, including status epilepticus required anaesthetic agents (1), seizure clusters (2) with postictal psychosis or dysphasia, and all recovered subsequently.
CONCLUSIONS: 48-h video EEG monitoring is cost-effective in resource limited setting.

Matched MeSH terms: Epilepsy/drug therapy
The use of lamotrigine and other antiepileptic drugs in paediatric patients at a Malaysian hospital

Ab Rahman AF, Ibrahim MI, Ismail HI, Seng TB

Pharm World Sci, 2005 Oct;27(5):403-6.
PMID: 16341748

OBJECTIVE: (1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs).

METHOD: A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang.

MAIN OUTCOME MEASURE: Seizure frequency, cost of drug and types of AED prescribed.

RESULTS: A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00).

CONCLUSION: The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

Study site: paediatric clinic, Hospital Pulau Pinang.

Matched MeSH terms: Epilepsy/drug therapy*
Role of inflammation in epilepsy and neurobehavioral comorbidities: Implication for therapy

Paudel YN, Shaikh MF, Shah S, Kumari Y, Othman I

Eur J Pharmacol, 2018 Oct 15;837:145-155.
PMID: 30125565 DOI: 10.1016/j.ejphar.2018.08.020

Epilepsy is a devastating condition affecting around 70 million people worldwide. Moreover, the quality of life of people with epilepsy (PWE) is worsened by a series of comorbidities. The neurobehavioral comorbidities discussed herein share a reciprocal and complex relationship with epilepsy, which ultimately complicates the treatment process in PWE. Understanding the mechanistic pathway by which these comorbidities are associated with epilepsy might be instrumental in developing therapeutic interventions. Inflammatory cytokine signaling in the brain regulates important brain functions including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, dopaminergic transmission, the kynurenine pathway, and affects neurogenesis as well as the neural circuitry of moods. In this review, we hypothesize that the complex relationship between epilepsy and its related comorbidities (cognitive impairment, depression, anxiety, autism, and schizophrenia) can be unraveled through the inflammatory mechanism that plays a prominent role in all these individual conditions. An ample amount of evidence is available reporting the role of inflammation in epilepsy and all individual comorbid condition but their complex relationship with epilepsy has not yet been explored through the prospective of inflammatory pathway. Our review suggests that epilepsy and its neurobehavioral comorbidities are associated with elevated levels of several key inflammatory markers. This review also sheds light on the mechanistic association between epilepsy and its neurobehavioral comorbidities. Moreover, we analyzed several anti-inflammatory therapies available for epilepsy and its neurobehavioral comorbidities. We suggest, these anti-inflammatory therapies might be a possible intervention and could be a promising strategy for preventing epileptogenesis and its related neurobehavioral comorbidities.

Matched MeSH terms: Epilepsy/drug therapy
Fulltext Vitamin D deficiency and its risk factors in Malaysian children with epilepsy

Fong CY, Kong AN, Poh BK, Mohamed AR, Khoo TB, Ng RL, et al.

Epilepsia, 2016 08;57(8):1271-9.
PMID: 27378185 DOI: 10.1111/epi.13443

OBJECTIVE: Long-term use of antiepileptic drugs (AEDs) is a significant risk factor for vitamin D deficiency in children with epilepsy. The aims of our study were to evaluate the prevalence and risk factors for vitamin D deficiency among Malaysian children with epilepsy.
METHODS: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in three tertiary hospitals in Malaysia from April 2014 to April 2015. Detailed assessment of pubertal status, skin pigmentation, sunshine exposure behavior, physical activity, dietary vitamin D and calcium intake, anthropometric measurements and bone health blood tests (vitamin D, alkaline phosphatase, calcium, phosphate, and parathyroid hormone levels) were obtained on all patients. Vitamin D deficiency was defined as 25-hydroxy vitamin D [25(OH)D] levels ≤35 nmol/L and insufficiency as 25(OH)D levels of 36-50 nmol/L.
RESULTS: A total of 244 children (146 male) participated in the study. Ages ranged between 3.7 and 18.8 years (mean 12.3 years). 25(OH)D levels ranged between 7.5 and 140.9 nmol/L (mean 53.9 nmol/L). Vitamin D deficiency was identified in 55 patients (22.5%), and a further 48 (19.7%) had vitamin D insufficiency. Multivariate logistic regression analysis identified polytherapy >1 AED (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.07-4.36), age >12 years (OR 4.16, 95% CI 1.13-15.30), Indian ethnicity (OR 6.97, 95% CI 2.48-19.55), sun exposure time 30-60 min/day (OR 2.44, 95% CI 1.05-5.67), sun exposure time <30 min/day (OR 3.83, 95% CI 1.61-9.09), and female (OR 2.61, 95% CI 1.31-5.20) as statistically significant (p < 0.05) risk factors for vitamin D deficiency.
SIGNIFICANCE: Despite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency.

Matched MeSH terms: Epilepsy/drug therapy
Determinants of low bone mineral density in children with epilepsy

Fong CY, Kong AN, Noordin M, Poh BK, Ong LC, Ng CC

Eur. J. Paediatr. Neurol., 2018 Jan;22(1):155-163.
PMID: 29122496 DOI: 10.1016/j.ejpn.2017.10.007

INTRODUCTION: Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy.
METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.
RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.

Matched MeSH terms: Epilepsy/drug therapy
Fulltext Childhood epilepsy: what parents know, believe and do

Norzila MZ, Azizi BH, Motilal R

Med J Malaysia, 1997 Mar;52(1):60-3.
PMID: 10968054

This was a descriptive study to assess parents' knowledge of epilepsy in their children at the Klinik Pakar Pediatrik in Universiti Kebangsaan Malaysia from 1.1.93-31.6.93. Factors that influence the level of knowledge were examined. Our hypothesis was that the level of knowledge was low and level of education and social factors were important. Fifty consecutive parents were interviewed during the clinic appointments. The questionnaire consisted of 25 questions which had been used in a survey on epilepsy in Australia. In order to cater for the local population the questions were modified by adding new questions pertaining to local situation. The results showed that 90% (45/50) of parents were unaware of the type of epilepsy their children were suffering from. 50% (25/50) of parents knew the underlying cause of epilepsy of which 32% (8/25) attributed it to brain disease, 8% (2/25) to birth defects and 10% (3/25) to fever. Factors such as duration of epilepsy, parental education and racial differences between Malay and other races (Chinese, Indians) did not reach any statistical significance (p > 0.05). 80% of patients (30/50) were on monotherapy. However, 90% (45/50) of parents were unaware of their children's medications. 82% of parents (31/50) knew that the anti-convulsants would only control their children's convulsions. Only 10% (8/50) of parents knew the acute management of seizures. Wrong practices such as inserting spoons (5/50) or massaging their limbs (17/50) during an acute attack were still common. 70% of parents (35/50) attended the follow-up clinics hoping that their children's epilepsy would be cured. Parents with low economic status and of children with duration of epilepsy of less than five years had been coming to the clinic regularly. (p = 0.01 and p = 0.02 respectively). In conclusion, the overall knowledge of these parents was poor. In order to improve the management of epilepsy, it is necessary to educate parents with reading materials and effective educational packages.
Study site: Paediatric clinic, Institut Pediatrik, Kuala Lumpur, Malaysia

Matched MeSH terms: Epilepsy/drug therapy*
ABCC2 rs2273697 and rs3740066 polymorphisms and resistance to antiepileptic drugs in Asia Pacific epilepsy cohorts

Sha'ari HM, Haerian BS, Baum L, Saruwatari J, Tan HJ, Rafia MH, et al.

Pharmacogenomics, 2014 Mar;15(4):459-66.
PMID: 24624913 DOI: 10.2217/pgs.13.239

To examine the relevance of ABCC2 polymorphisms to drug responsiveness in epilepsy cohorts from the Asia Pacific region.

Matched MeSH terms: Epilepsy/drug therapy*
SCN1A IVS5N+5 polymorphism and response to sodium valproate: a multicenter study

Haerian BS, Baum L, Tan HJ, Kwan P, Raymond AA, Saruwatari J, et al.

Pharmacogenomics, 2012 Oct;13(13):1477-85.
PMID: 23057548 DOI: 10.2217/pgs.12.127

Approximately 30% of epilepsy patients do not response to antiepileptic drugs (AEDs). The functional SCN1A IVS5N+5 polymorphism may play a role in response to some AEDs. The purpose of this study was to examine this hypothesis in a cohort study of Malaysian and Hong Kong Chinese epilepsy patients on sodium valproate (VPA) monotherapy and in a meta-analysis.

Matched MeSH terms: Epilepsy/drug therapy*
Fulltext Lack of association of ABCB1 haplotypes on five loci with response to treatment in epilepsy

Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.

Seizure, 2011 Sep;20(7):546-53.
PMID: 21530324 DOI: 10.1016/j.seizure.2011.04.003

Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.

Matched MeSH terms: Epilepsy/drug therapy
Association between ABCB1 polymorphism and response to sodium valproate treatment in Malaysian epilepsy patients

Haerian BS, Lim KS, Tan HJ, Mohamed EH, Tan CT, Raymond AA, et al.

Epileptic Disord, 2011 Mar;13(1):65-75.
PMID: 21388909 DOI: 10.1684/epd.2011.0419

Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.

Matched MeSH terms: Epilepsy/drug therapy*
Association of ABCB1 gene polymorphisms and their haplotypes with response to antiepileptic drugs: a systematic review and meta-analysis

Haerian BS, Lim KS, Tan CT, Raymond AA, Mohamed Z

Pharmacogenomics, 2011 May;12(5):713-25.
PMID: 21391884 DOI: 10.2217/pgs.10.212

Several studies demonstrated a link between ABCB1 gene variants and the response to treatment in epilepsy, but the results have been inconclusive. Here, we performed the first haplotype meta-analysis to examine the association of haplotypes of ABCB1 common variants with the response to treatment in epilepsy.

Matched MeSH terms: Epilepsy/drug therapy*
Fulltext ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: a systematic review and meta-analysis

Haerian BS, Roslan H, Raymond AA, Tan CT, Lim KS, Zulkifli SZ, et al.

Seizure, 2010 Jul;19(6):339-46.
PMID: 20605481 DOI: 10.1016/j.seizure.2010.05.004

The C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at higher risk of pharmacoresistance to AEDs, but only in some studies. The hypothesis of the C-variant associated risk and resistance to antiepileptic drugs (AEDs) has been hampered by conflicting results from inadequate power in case-control studies. To assess the role of C3435T polymorphism in drug-resistance in epilepsy, a systematic review and meta-analysis was conducted.

Matched MeSH terms: Epilepsy/drug therapy*
Fulltext Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy

Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.

Seizure, 2011 Jun;20(5):387-94.
PMID: 21316268 DOI: 10.1016/j.seizure.2011.01.008

It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.

Matched MeSH terms: Epilepsy/drug therapy
SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis

Haerian BS, Baum L, Kwan P, Tan HJ, Raymond AA, Mohamed Z

Pharmacogenomics, 2013 Jul;14(10):1153-66.
PMID: 23859570 DOI: 10.2217/pgs.13.104

Aim: Approximately a third of newly diagnosed epilepsy patients do not respond to antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the genes of drug targets such as voltage-gated sodium channels may be involved in drug responsiveness. To examine this hypothesis, we compared data from two epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from published data.

Materials & methods: Genotype analysis of 39 polymorphisms located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814 polymorphisms.

Results: Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A rs17183814 polymorphisms.

Conclusion: Our comprehensive study suggests that common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in influencing response to AEDs.

Matched MeSH terms: Epilepsy/drug therapy*
Medication self-management among parents of children with epilepsy at a tertiary care center in Malaysia

Tan JW, Khoo TB, Burharudin NF, Mohamed Shah N

Epilepsy Behav, 2020 10;111:107317.
PMID: 32693382 DOI: 10.1016/j.yebeh.2020.107317

PURPOSE: Self-management is crucial in the management of chronic diseases. However, information is limited on medication self-management among parents of children with epilepsy. This study aimed to assess medication self-management among parents of children with epilepsy and its association with sociodemographic data, clinical characteristics, antiepileptic drug (AED) regimen complexity, and parent self-reported AED adherence.
METHOD: A cross-sectional survey was conducted at a tertiary care center in Malaysia from February 2019 to June 2019. Parents of children with epilepsy who were on AED for at least 3 months and aged ≤18 years old were recruited. Medication self-management was assessed using a validated Pediatric Epilepsy Medication Self-Management Questionnaire (PEMSQ). A higher total score reflects better medication self-management.
RESULTS: A total of 166 patients were recruited. The mean ± standard deviation (SD) age of patients was 8.20 ± 5.21 years, and 51.8% and 36.7% of patients have generalized seizure and focal seizure, respectively. The mean ± SD PEMSQ score was 116.2 ± 11.28 from a total score of 135. Among the four domains of PEMSQ, the barriers to treatment contributed to the lowest mean scores. Univariate analysis showed that the following were significantly associated with poorer medication self-management: differences in ethnicity, religion; higher number of medications; presence of comorbidities; inability to swallow tablets; and a more complex AED regimen. Other variables were not significant. Multivariate analysis showed that only ethnicity and presence of comorbidity remained independently significant (R2 = 0.14; F [4, 161] = 6.28; p 

Matched MeSH terms: Epilepsy/drug therapy*
Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis

Yeap LL, Lim KS, Ng CC, Hui-Ping Khor A, Lo YL

Ther Drug Monit, 2014 Feb;36(1):3-9.
PMID: 24342894 DOI: 10.1097/FTD.0000000000000024

The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.

Matched MeSH terms: Epilepsy/drug therapy*

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