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  1. Haerian BS, Baum L
    Seizure, 2013 Jan;22(1):53-8.
    PMID: 23140995 DOI: 10.1016/j.seizure.2012.10.007
    PURPOSE: The gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes the GABRγ2 protein, which has been implicated in susceptibility to epilepsy. Several studies have examined a possible link between the exonic GABRG2 rs211037 locus and susceptibility to febrile seizure (FS) and idiopathic generalized epilepsy (IGE), however results have been inconclusive. We therefore performed a systematic review and meta-analysis to examine whether this polymorphism is associated with FS or IGE.
    METHODS: Eight studies comprising 1871 epilepsy patients and 1387 controls, which evaluated association of the GABRG2 rs211037 polymorphism with susceptibility to epilepsy, were included in this meta-analysis. Meta-analysis was carried out separately for FS and IGE.
    RESULTS: Meta-analysis showed a significant association between this polymorphism and susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30-0.73, p=0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42-0.83, p=0.003) and dominant (OR 0.54, 95% CI 0.39-0.75, p=0.0002) genetic models, influenced by two studies with small sample size. Neither allele nor genotype association was observed with IGE.
    CONCLUSION: This study showed significant association of GABRG2 rs211037 with susceptibility to FS, caused by two studies with small sample sizes, however the possibility of false positive results due to the effect of significant studies for FS cannot be excluded. Future studies with larger sample sizes of these patients are suggested to verify the results.
  2. Salih MR, Bahari MB, Shafie AA, Hassali MA, Al-lela OQ, Abd AY, et al.
    Seizure, 2012 Dec;21(10):764-9.
    PMID: 22939458 DOI: 10.1016/j.seizure.2012.08.005
    Aims of this study were to estimate the first-year medical care costs of newly diagnosed children with structural-metabolic epilepsy and to determine the cost-driving factors in the selected population.
  3. 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.
  4. 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.
  5. Neni SW, Latif AZ, Wong SY, Lua PL
    Seizure, 2010 Jun;19(5):280-90.
    PMID: 20466567 DOI: 10.1016/j.seizure.2010.04.006
    This study was carried out to gauge the preliminary insight regarding epilepsy among the rural society. The purposes of this study were: (1) to determine general level of awareness, knowledge and attitudes (AKA) towards epilepsy among rural communities, (2) to compare the AKA level based on socio-demographic characteristics and (3) to investigate rural cohort's perception of the best epilepsy treatment, preference for epilepsy information delivery and preference for mode of transportation to seek medical treatment. This prospective, cross sectional study included a sample of 615 rural residents enrolled via cluster sampling in East Coast region of Peninsular Malaysia (mean age=41.6+/-18.02, female=56.6%, married=65.5%, Malay=94.0%, monthly income < or = RM 500=56.9%). The Total AKA level was generally low (2.66+/-0.7). Gender-wise no significant difference was shown regarding AKA level (p>0.05). However, respondents with higher education significantly possessed better attitudes and higher Total AKA level compared to those with lower education level (p<0.001). Employed respondents reported significantly more favourable attitudes than unemployed respondents (p=0.011). Additionally, higher income rural cohorts possessed both significantly better attitudes and better AKA. These rural communities perceived modern medicine as the best epilepsy treatment (56.60%), preferred to obtain direct epilepsy-related information from health personnel (60.4%) and chose to use their own car to seek medical treatment in hospital (76.30%). The outcomes of this preliminary study signified the need to devise a dedicated epilepsy education program for implementation among rural residents. Increased AKA level in the society could enhance the people's acceptance, reduce stigmatisation and improve health-related quality of life (HRQoL) for epilepsy patients and their family.
  6. 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.
  7. Ab Rahman AF
    Seizure, 2005 Dec;14(8):593-6.
    PMID: 16246597
    University students represent a better-educated group of society and it is important that they possess the correct knowledge and attitude towards healthcare issues. The aim of this study was to determine the current level of awareness and knowledge of epilepsy among students at a public university in Malaysia.
  8. Tamijani SM, Karimi B, Amini E, Golpich M, Dargahi L, Ali RA, et al.
    Seizure, 2015 Sep;31:155-64.
    PMID: 26362394 DOI: 10.1016/j.seizure.2015.07.021
    Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here.
  9. Lai ST, Tan WY, Wo MC, Lim KS, Ahmad SB, Tan CT
    Seizure, 2019 Oct;71:132-139.
    PMID: 31325820 DOI: 10.1016/j.seizure.2019.07.008
    PURPOSE: The literature on caregiver burden tends to focus on children and teenagers with epilepsy and less on adults. As caregiving is a dynamic, complex process across the trajectories, this study aims to examine the factors associated with caregiving burden in those caring for adults with epilepsy.

    METHOD: This is a cross-sectional, survey-based study in which participants responded to questionnairesregarding perceived burden (ZBI), quality of life (IEQoL), psychological distress (DASS-21), family functioning (FAD) and perceived social support (MSPSS). Additional measures include socio-demographics and clinical characteristics of the care-recipient.

    RESULTS: A total of 111 caregivers participated, of whom 72.1% were females, 55% parents, 59.5% Chinese, 51.4% unemployed and 46.0% with tertiary education.Approximately half (42.3%) reported mild-to-moderate levels of burden (mean ZBI score 29.93, SD 16.09).Furthermore, multiple regression analysisidentified10 predictors of caregiver burden, namely family functioning, weekly caregiving hours, number of caregivers per family, attitude towards epilepsy, family support, caregivers' gender, personal income and as well as care-recipients' age of onset, seizure frequency and ADL dependency (F(10, 85) = 11.37, p 

  10. Kong AN, Fong CY, Ng CC, Mohamed AR, Khoo TB, Ng RL, et al.
    Seizure, 2020 Jul;79:103-111.
    PMID: 32464532 DOI: 10.1016/j.seizure.2020.05.009
    PURPOSE: Children with epilepsy (CWE) are at risk of vitamin D deficiency. Single nucleotide polymorphisms (SNPs) affecting the vitamin D pathway are potentially important risk factors for serum 25-hydroxyvitamin D [25(OH)D] concentration. The aims of our study were to evaluate the association of vitamin d-related SNPs to serum 25(OH)D concentrations in Malaysian CWE.

    METHODS: Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.

    RESULTS: 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.

    CONCLUSIONS: Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.

  11. Thuy Le MA, Fong SL, Lim KS, Gunadharma S, Sejahtera DP, Visudtibhan A, et al.
    Seizure, 2019 Jul;69:51-56.
    PMID: 30974407 DOI: 10.1016/j.seizure.2019.04.002
    PURPOSE: This survey was performed to determine the availability of epilepsy surgery, and understand the limiting factors to epilepsy surgery in ASEAN countries with total of 640 million population.

    METHOD: A cross-sectional survey was completed by national representatives in all ASEAN countries (Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam).

    RESULTS: Overall facilities for initial epilepsy pre-surgical evaluation are available in most countries, but further non-invasive and invasive investigations are limited. Three countries (Brunei, Cambodia, and East Timor) have no epilepsy center, and 2 countries (Laos, Myanmar) have level 2 centers doing tumor surgery only. Level-3 epilepsy centers are available in 6 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand, Vietnam); only 5 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand) has at least one level-4 epilepsy care facility. Indonesia with 261 million population only has one level 3 and another level 4 center. The costs of presurgical evaluation and brain surgery vary within and among the countries. The main barriers towards epilepsy surgery in ASEAN include lack of expertise, funding and facilities.

    CONCLUSIONS: Epilepsy surgery is underutilized in ASEAN with low number of level 3 centers, and limited availability of advanced presurgical evaluation. Lack of expertise, facilities and funding may be the key factors contributing to the underutilization.

  12. Khor SB, Lim KS, Fong SL, Ho JH, Koh MY, Tan CT
    Seizure, 2021 May;88:56-59.
    PMID: 33812309 DOI: 10.1016/j.seizure.2021.03.024
    BACKGROUND: The standardized mortality ratio (SMR) of epilepsy in Asia ranges from 2.5 to 5.1. However, there are no such published data in Malaysia to date. Understanding the mortality rate and related factors will allow us to better assess and monitor the health status of PWE, thereby, preventing premature deaths among PWE. Hence, this study aimed to determine the mortality rate of adults with epilepsy (PWE) at the University Malaya Medical Centre (UMMC), a tertiary hospital in Malaysia.

    METHOD: A total of 2218 PWE were recruited retrospectively into this study. Deceased cases from 2009-2018 were identified from the National Registry Department of Malaysia. Age-, gender-, and ethnic-specific SMR were calculated.

    RESULT: There was a total of 163 deaths, of which 111 (68.1%) were male. The overall case-fatality rate (CFR) was 7.3%. Male PWE had higher CFR (9.2%) compared to females (5.1%, p<0.001). The annual death rate of PWE was 867 per 100, 000 persons. The overall all-cause SMR was 1.6 (CI 95% 1.3-1.8). The SMR for younger age groups (15-19 and 20-29 years) were higher (5.4-5.5) compared to other age groups (0.4-2.5). Overall SMR for male PWE (1.8, 95% CI 1.5-2.1) was higher than females (1.2, 95% CI 0.9-1.6). However, the SMR for female PWE in the younger age groups (15-19, 20-29 and 30-39 years) was higher. SMR among the Indian PWE was the highest (1.6, 95% CI 1.2-2.0) compared to the Chinese (1.5, 95% CI 1.2-1.9) and the Malays (1.4, 95% 1.0-1.9). The CFR was higher in those with focal epilepsy (8.5% vs. 2.5-3.7% in genetic and other generalized epilepsies, p=0.003), epilepsy with structural cause (9.5% vs. 5.9% in others, p=0.005) and uncontrolled seizures (7.9% vs. 5.2% in seizure-free group, p<0.001).

    CONCLUSION: The mortality rate of PWE in Malaysia is higher than that of the general population but lower compared to other Asian countries. Specifically, the rates are higher in the younger age group, male gender, and Indian ethnicity. Those with focal epilepsy, structural causes and uncontrolled seizures have higher mortality rates.

  13. Carrizosa Moog J, Kakooza-Mwesige A, Tan CT
    Seizure, 2017 Jan;44:108-112.
    PMID: 27986419 DOI: 10.1016/j.seizure.2016.11.032
    Epilepsy is considered by the World Health Organization a public health priority with more than 50 million human beings affected by the disease. More than 80% of persons with epilepsy live in low and middle income countries and most of them in tropical areas. Several emerging, re-emerging and neglected diseases are symptomatic etiologies that jointly contribute to the enormous global burden of epilepsy. Besides the clinical strengths to reduce diagnostic and treatment gaps, other strategies in social, economic, cultural, educational and health policies are needed to prevent and treat appropriately vulnerable and affected persons with epilepsy. From the public health point of view, several of those strategies could be more effective in reducing the incidence and burden of the disease than the clinical approach of diagnosis and treatment. Special attention has to be given to stigma reduction and promotion of human rights. Several aspects mentioned in this abstract slip away the scope of the article, but it is a remainder to approach epilepsy in an inter- and transdisciplinary manner, an integral and pertinent approach needed and requested in tropical counties. The article focuses only on emergent and re-emergent etiologies of epilepsy in the tropics like malaria, HIV, neurocysticercosis, viral encephalitis and traumatic brain injury.
  14. Lim KS, Ng CC, Chan CK, Foo WS, Low JS, Tan CT
    Seizure, 2017 Feb;45:24-27.
    PMID: 27912112 DOI: 10.1016/j.seizure.2016.11.011
    PURPOSE: Ethnic variation in epilepsy classification was reported in the Epilepsy Phenome/Genome Project. This study aimed to determine the ethnic variation in the prevalence of genetic (idiopathic) generalized epilepsy (GGE) and GGE with family history in a multi-ethnic Asian population in Malaysia.

    METHOD: In this cross-sectional study, 392 patients with a clinical diagnosis of GGE were recruited in the neurology outpatient clinic, University of Malaya Medical Centre (UMMC), from January 2011 till April 2016.

    RESULTS: In our epilepsy cohort (n=2100), 18.7% were diagnosed to have GGE. Of those, 28.6% >(N=112) had family history of epilepsy with a mean age of seizure onset of 16.5 years old, and 42.0% had myoclonic seizures (N=47). The lifetime prevalence of epilepsy among first-degree relative of those with GGE and positive family history was 15.0%. Analysis according to ethnicity showed that Malaysian Chinese had the lowest percentage of GGE among those with epilepsy (12.3%), as compared with Indian and Malay (25.3% and 21.3%, p<0.001). In addition, 32.1% of these Indian patients with GGE had positive family history, which is more than the Malay (26.4%) and Chinese (27.5%) ethnic groups. Consanguineous marriage was noted in 5 Indian families with positive family history (9.6%).

    CONCLUSION: There was ethnic variation in the prevalence of GGE, whereby the Malaysian Chinese had the lowest percentage of GGE as compared with Indian and Malay. A substantial proportion of GGE had positive family history among the three ethnics groups.

    Study site: neurology outpatient clinic, University of Malaya Medical Centre (UMMC)
  15. Tee SK, Ong TL, Aris A, See SML, Leong HY, Khalid MKNM, et al.
    Seizure, 2019 Apr;67:78-81.
    PMID: 30947044 DOI: 10.1016/j.seizure.2019.03.012
  16. Bashiri FA, Hundallah K, Al-Baradie R, Al-Otaibi A, Ismayl O, AlMalik ME, et al.
    Seizure, 2024 Apr;117:174-182.
    PMID: 38432081 DOI: 10.1016/j.seizure.2024.02.015
    Despite the availability of international recommendations for the management of Infantile Epileptic Spasms Syndrome (IESS), there is a lack of recommendations adapted to the local context of clinical practice of pediatric neurology in the Gulf Cooperation Council (GCC) countries. By an initiative from the Saudi Pediatric Neurology Society (SPNS), a literature review was performed and an expert panel comprised of 13 pediatric neurologists from all GCC countries (Saudi Arabia, Kuwait, Bahrain, Oman, Qatar, and the United Arab Emirates) was subsequently convened to discuss all issues related to the management and diagnosis practices of IESS in the GCC. The overall aim of this consensus document was to develop practical recommendations to support the care of patients with IESS in the GCC and to reflect on how clinical management approaches compare with those adopted internationally.
  17. Zhang T, Ajamain AWH, Donnelly J, Brockington A, Jayabal J, Scott S, et al.
    Seizure, 2024 Jul 21;121:17-22.
    PMID: 39053336 DOI: 10.1016/j.seizure.2024.07.015
    PURPOSE: To document the 2-year mortality and seizure recurrence rate of a prospective cohort of patients identified with status epilepticus (SE).

    METHODS: Patients presenting to any hospital in the Auckland region between April 6 2015, and April 5 2016, with a seizure lasting 10 min or longer were identified. Follow up was at 2 years post index SE episode via telephone calls and detailed review of clinical notes.

    RESULTS: We identified 367 patients with SE over the course of one year. 335/367 (91.3 %) were successfully followed up at the 2-year mark. Two-year all-cause mortality was 50/335 (14.9 %), and 49/267 (18.4 %) when febrile SE was excluded. Two-year seizure recurrence was 197/335 (58.8 %). On univariate analyses, children (preschoolers 2 to < 5 years and children 5 to < 15 years), Asian ethnicity, SE duration <30 mins and acute (febrile) aetiology were associated with lower mortality, while older age >60 and progressive causes were associated with higher mortality on both univariate and multivariate analyses. Age < 2 years and acute aetiology were associated with lower seizure recurrence, while non convulsive status epilepticus (NCSE) with coma and a history of epilepsy were associated with higher seizure recurrence. On multivariate analyses, a history of epilepsy, as well as having both acute and remote causes were associated with higher seizure recurrence.

    CONCLUSIONS: All-cause mortality in both the paediatric and adult populations at 2 years was lower than most previous reports. Older age, SE duration ≥30 mins and progressive aetiologies were associated with the highest 2-year mortality, while febrile SE had the lowest mortality. A history of epilepsy, NCSE with coma, and having both acute and remote causes were associated with higher seizure recurrence at 2 years. Future studies should focus on functional measures of outcome and long-term quality of life.

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