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Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge

Yeap LL, Lim KS, Lo YL, Bakar MZ, Tan CT

Epileptic Disord, 2014 Sep;16(3):375-9.
PMID: 25167568 DOI: 10.1684/epd.2014.0671

Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.

Matched MeSH terms: Anticonvulsants/adverse effects*; Anticonvulsants/pharmacokinetics; Anticonvulsants/therapeutic use
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: Anticonvulsants/administration & dosage; Anticonvulsants/pharmacokinetics*; Anticonvulsants/therapeutic use
The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label

Wang YH, Chen CB, Tassaneeyakul W, Saito Y, Aihara M, Choon SE, et al.

Clin. Pharmacol. Ther., 2019 01;105(1):112-120.
PMID: 29569740 DOI: 10.1002/cpt.1071

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

Matched MeSH terms: Anticonvulsants/adverse effects
Fulltext Lamotrigine as an add-on therapy in intractable paediatric epilepsy--the Kuala Lumpur Hospital experience

Vigneswari G, Sofiah A, Hussain IHMI

Med J Malaysia, 2001 Sep;56(3):359-64.
PMID: 11732083

An observational study of all children with intractable epilepsy at the Paediatric Institute prescribed Lamotrigine as an add-on therapy between January 1994 and November 1998 was conducted. A total of 30 children were recruited. Three had adverse effects to the drug and it was withdrawn. Of the remaining 27, there were 20 boys and 7 girls, ranging from 2 to 17 years. Fifteen children had generalised epilepsy, 6 had partial epilepsy, 2 had West syndrome and 4 had Lennox Gastaut syndrome. Six children (20%) became seizure free, and 14 (54%) had a greater than 50% reduction in seizure frequency. However 7 children (23%) did not respond and 3 experienced a deterioration in seizure severity. Nine children were noted to have an improvement in alertness and behaviour. Our small series suggests that Lamotrigine is useful as add-on therapy in childhood intractable epilepsy.

Matched MeSH terms: Anticonvulsants/therapeutic use*
Fulltext Mixed-mode oscillations in pyramidal neurons under antiepileptic drug conditions

V-Ghaffari B, Kouhnavard M, Elbasiouny SM

PLoS One, 2017;12(6):e0178244.
PMID: 28591171 DOI: 10.1371/journal.pone.0178244

Subthreshold oscillations in combination with large-amplitude oscillations generate mixed-mode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductance-based models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under antiepileptic drug conditions (i.e., when persistent sodium current is inhibited). We investigated not only the mathematical properties of MMOs in these neurons, but also the electrophysiological mechanisms that shape spike clustering. Our results show that pyramidal neurons can display two types of MMOs and the magnitude of the slow potassium current determines whether MMOs of type I or type II would emerge. Our results also indicate that slow potassium currents with large time constant have significant impact on generating the MMOs, as opposed to fast inward currents. Our results provide complete characterization of the subthreshold activities in MMOs in pyramidal neurons and provide explanation to experimental studies that showed MMOs of type I or type II in pyramidal neurons under antiepileptic drug conditions.

Matched MeSH terms: Anticonvulsants/pharmacology*
Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings

Tsai JJ, Wu T, Leung H, Desudchit T, Tiamkao S, Lim KS, et al.

Acta Neurol. Scand., 2018 Apr;137(4):378-391.
PMID: 29214650 DOI: 10.1111/ane.12879

Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

Matched MeSH terms: Anticonvulsants/therapeutic use*
Fulltext An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

Then, Sue-Mian, Azman Ali Raymond

Neuroscience Research Notes, 2019;2(2):1-17.
MyJurnal

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainlyon the type of seizure. However, the useof AEDs mayalso lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens-Johnsonsyndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discoveredthat the HLA-B*15:02 allele was strongly associatedwith carbamazepine(CBZ)-induced SJS/TEN amongHan Chinese and this ledto the discovery of other HLAallelesand cytochrome P450 (CYP) genes that were significantly associatedwith various AED-inducedcADRsacross variouspopulations. This mini-reviewis an update on the latest findings ofthe involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamotrigine(LTG) in different case-control studies around the world. From our review, we found that CBZ-and PHT-induced cADRsweremore commonly reportedthan the other AEDs.Therefore,there were morerobust pharmacogenetics studies related to these AEDs. OXC-and LTG-induced cADRswereless commonly reported,and somore studies are needed to validate the reported association of the newer reported HLA alleles with theseAEDs. It is also importantto considerthe allelic frequency within a given population before concludingthe use of thesealleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research pointto a combination of alleles as a better pharmacogenetic marker comparedto the use of a single gene as a genetic marker for AED-induced cADR.

Matched MeSH terms: Anticonvulsants
In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing

Teo SY, Yew MY, Lee SY, Rathbone MJ, Gan SN, Coombes AGA

J Pharm Sci, 2017 01;106(1):377-384.
PMID: 27522920 DOI: 10.1016/j.xphs.2016.06.028

Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 μg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 μg/mL. An in vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 μg/mL phenytoin concentration resulted in 75%-82% "scratch closure" after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.

Matched MeSH terms: Anticonvulsants/administration & dosage*; Anticonvulsants/pharmacology
Fulltext Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02

Teh LK, Selvaraj M, Bannur Z, Ismail MI, Rafia H, Law WC, et al.

J Pharm Pharm Sci, 2016;19(1):147-60.
PMID: 27096699 DOI: 10.18433/J38G7X

PURPOSE: The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated.
METHODS: DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers.
RESULTS: Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.

Matched MeSH terms: Anticonvulsants/adverse effects*; Anticonvulsants/chemistry
Fulltext Factors affecting adherence to antiepileptic drugs therapy in Malaysia

Tan, XC, M Makmor-Bakry, Lau, CL, Tajarudin, FW, Raymond, AA

Neurology Asia, 2015;20(3):235-241.
MyJurnal

Poor adherence to antiepileptic drug (AED) therapy can lead to various undesirable complications. Identifying the contributing factors of poor adherence is beneficial in assisting health care professionals to provide optimal interventions to control the seizures. This study aimed to identify the prevalence and factors affecting the adherence level to AED therapy in a multiracial population with epilepsy. This cross-sectional study was conducted at the neurology clinic of a tertiary care setting. Researcher-assisted questionnaire was utilised. Adherence level was assessed using validated Modified Morisky Adherence Scale-8. A total of 145 patients with epilepsy were included in this study. The prevalence of poor adherence to AED therapy was 64.1%. Poor adherence level was significantly associated with younger age (χ2 = 7.609, p = 0.022), medication adverse effects (χ2 = 5.075, p = 0.020), shorter duration of epilepsy (r = 0.180, p = 0.030) and uncertainty about the necessity for AEDs (χ2 = 11.803, p = 0.001).
Conclusion, prevalence of poor adherence to antiepileptic drugs was high and factors associated with poor adherence to AEDs were identified for a multiracial population with epilepsy.
Study site: Neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Anticonvulsants
Nanoemulsion-based Parenteral Drug Delivery System of Carbamazepine: Preparation, Characterization, Stability Evaluation and Blood-Brain Pharmacokinetics

Tan SL, Stanslas J, Basri M, Abedi Karjiban RA, Kirby BP, Sani D, et al.

Curr Drug Deliv, 2015;12(6):795-804.
PMID: 26324229

Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.

Matched MeSH terms: Anticonvulsants/administration & dosage*; Anticonvulsants/pharmacokinetics
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: Anticonvulsants/therapeutic use*
Fulltext Amlodipine-induced gingival overgrowth: a case report

Taib, H., Ali, T.B.T., Kamin, S.

Archives of Orofacial Sciences, 2007;2(1):61-64.
MyJurnal

Gingival overgrowth is frequently observed in patients taking certain drugs such as calcium channel blockers, anticonvulsants and immunosuppressant. This can have a significant effect on the quality of life as well as increasing the oral bacterial load by generating plaque retention sites. Amlodipine, a third generation calcium channel blockers has been shown to promote gingival overgrowth although in very limited cases reported. The management of gingival overgrowth seems to be directed at controlling gingival inflammation through a good oral hygiene regimen. However in severe cases, surgical excision is the most preferred method of treatment, followed by rigorous oral hygiene procedures. This case report describes the management of gingival overgrowth in a hypertensive patient taking amlodipine. Combination of surgical gingivectomy and CO2 laser treatment was used to remove the gingival overgrowth. CO2 laser surgery produced good hemostasis and less pain during the procedure and post operatively. This case report has also shown that periodontal treatment alone without a change in associated drug can yield satisfactory clinical response.

Matched MeSH terms: Anticonvulsants
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: Anticonvulsants/adverse effects
Fulltext G2677T polymorphism can predict treatment outcome of Malaysians with complex partial seizures being treated with Carbamazepine

Subenthiran S, Abdullah NR, Muniandy PK, Joseph JP, Cheong KC, Ismail Z, et al.

Genet. Mol. Res., 2013;12(4):5937-44.
PMID: 24338387 DOI: 10.4238/2013.November.26.3

Carbamazepine (CBZ) is used as the first line of treatment of complex partial seizures (CPS) in Malaysia. While this drug is known to be effective for the treatment of CPS, more than 30% of patients remain drug resistant to CBZ mono-therapy. We examined a possible relationship between patients' response to CBZ mono-therapy and the G2677T SNP of the ABCB1 gene. Three hundred and fourteen patients with CPS were recruited from the Neurology Department of the Kuala Lumpur Hospital, of whom 152 were responders and the other 162 were non-responders to CBZ mono-therapy. DNA was extracted from blood samples and real-time PCR was performed to detect the G2677T SNP of the ABCB1 gene. Results were described as genotype frequencies and compared by logistic regression analysis. Among the 152 responders, 74% had the GG genotype. However, among the 162 non-responders, 26.5% had the GT genotype and 39% had the TT genotype. There was a significant difference in genotype frequency (TT vs GG; odds ratio 4.70; 95% confidence interval, 2.70-8.20) between responders and non-responders. The presence of the T allele of the G2677T SNP appears to be a useful screening marker to determine if a patient is going to be resistant to CBZ as a single drug therapy in the treatment of CPS.

Matched MeSH terms: Anticonvulsants/therapeutic use*
Fulltext Linkage disequilibrium between polymorphisms of ABCB1 and ABCC2 to predict the treatment outcome of Malaysians with complex partial seizures on treatment with carbamazepine mono-therapy at the Kuala Lumpur Hospital

Subenthiran S, Abdullah NR, Joseph JP, Muniandy PK, Mok BT, Kee CC, et al.

PLoS One, 2013;8(5):e64827.
PMID: 23717663 DOI: 10.1371/journal.pone.0064827

Carbamazepine (CBZ) is used as the first line of treatment of Complex Partial Seizures (CPS) in the Epilepsy Clinic, Neurology Department of Kuala Lumpur Hospital (KLH). More than 30% of the patients remain drug resistant to CBZ mono-therapy. CBZ is transported by the P-glycoprotein (P-gp). The P-gp encoded by the ABCB1 and ABCC2 genes are expressed in drug resistant patients with epilepsy. A few studies have shown significant association between CBZ resistant epilepsy and Linkage Disequilibrium (LD) with adjacent polymorphisms of these genes. Our study is aimed at determining the correlation between patients' response to CBZ mono-therapy to Single Nucleotide Polymorphisms G2677T and C3435T of the ABCB1 gene as well as G1249A and -24C>T of the ABCC2 gene.

Matched MeSH terms: Anticonvulsants/therapeutic use*
Fulltext Lack of meaningful genotype-phenotype association in SCN1A-related infantile-onset epileptic encephalopathies

Siti Aishah Abdul Wahab, Yusnita Yakob, Khoo,Teik-Beng, Sangita Dharshini Terumalay, Vigneswari Ganesan, Teh,Chee-Ming, et al.

Neurology Asia, 2017;22(2):99-111.
MyJurnal

Background & Objective: SCN1A gene which encodes for sodium channel alpha 1 subunit has been
found to be the most common mutated gene in patients with epilepsy. This study aims to characterize the
SCN1A mutations as well as to describe genotype and phenotype association in children with SCN1Arelated
infantile-onset epileptic encephalopathies in Malaysia.

Methods: Children with infantile-onset
epileptic encephalopathy mostly suspected to have Dravet syndrome who had mutational analysis for
SCN1A gene from hospitals all over Malaysia were included in the study. Their epilepsy syndrome
diagnosis was classified into severe myoclonic epilepsy in infancy and its variants. Polymerase chain
reaction and bidirectional sequencing were used to identify SCN1A mutations.

Results: A total of 38
children with heterozygous mutations were analysed, 22 (57.9%) of which were novel mutations.
Truncated mutations were the most common mutation type (19, 50%). Other mutation types were
missense mutations (14, 36.8%), splice site mutations (4, 10.5%) and in-frame deletion (1, 2.6%). The
mean age of seizure onset was 4.7 months. Seizure following vaccination was observed in 26.3% of
the children. All of them had drug resistant epilepsy. There was no significant association between
the type of mutation with the syndromic diagnosis, age of seizure onset, tendency of the seizures to
cluster or having status epilepticus, mean age when developmental delay was observed and response
to various antiepileptic drugs.

Conclusion: This study expands the spectrum of SCN1A mutations and proves the importance of
SCN1A gene testing in diagnosing infantile-onset epileptic encephalopathies patients. Although, our
study does not support any clinically meaningful genotype-phenotype association for SCN1A-related
infantile-onset epileptic encephalopathies, the clinical characteristics of our cohort are similar to those
that have been described in previous studies.

Matched MeSH terms: Anticonvulsants
Fulltext Multiple nail gun penetrating head injury: a case report

Sim, S.K., Theophilus, S.C., Noor Azman, A.R.

International Medical Journal Malaysia, 2013;12(2):75-78.
MyJurnal

Intracranial nail gun injury is a rare subset of penetrating head injury. Here we report a case of intracranial nail gun injury in a Vietnamese patient who attempted suicide with no neurological deficit. Three nails were launched. Because the nail head acted as a brake, the launched nail could make a hole into the skull but could not entirely pass it. A rational management strategy should permit these patients to be discharged with no additional injury. Some medical and surgical management in penetrating head injury are discussed. The use of antibiotics and antiepileptic drugs and the retraction of the nail aided by the performance of a craniotomy surrounding the entry point are recommended.

Matched MeSH terms: Anticonvulsants
Changes in balance function with chronic antiepileptic drug therapy: A twin and sibling study

Shiek Ahmad B, Wark JD, Petty SJ, O'Brien TJ, Gorelik A, Sambrook PN, et al.

Epilepsia, 2015 Nov;56(11):1714-22.
PMID: 26513212 DOI: 10.1111/epi.13136

To investigate cross-sectional and longitudinal differences in static and dynamic standing balance measures and lower limb muscle strength in patients who are treated chronically with antiepileptic drugs (AEDs).

Matched MeSH terms: Anticonvulsants/administration & dosage; Anticonvulsants/adverse effects*
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: Anticonvulsants/adverse effects*

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