Displaying all 15 publications

  1. Wo SW, Ong LC, Low WY, Lai PSM
    Epilepsy Res, 2017 10;136:35-45.
    PMID: 28753498 DOI: 10.1016/j.eplepsyres.2017.07.009
    PURPOSE: To systematically examine published literature which assessed the prevalence of academic difficulties in children with epilepsy (CWE) of normal intelligence, and its associating factors.

    METHODS: A search was conducted on five databases for articles published in English from 1980 till March 2015. Included were studies who recruited children (aged 5-18 years), with a diagnosis or newly/recurrent epilepsy, an intelligent quotient (IQ) of ≥70 or attending regular school, with or without a control group, which measured academic achievement using a standardised objective measure, and published in English. Excluded were children with learning difficulties, intellectual disabilities (IQ<70) and other comorbidities such as attention deficits hyperactive disorder or autism. Two pairs of reviewers extracted the data, and met to resolve any differences from the data extraction process.

    RESULTS: Twenty studies were included. The majority of the studies assessed "low achievement" whist only two studies used the IQ-achievement discrepancy definition of "underachievement". Fourteen studies (70%) reported that CWE had significantly lower academic achievement scores compared to healthy controls, children with asthma or reported norms. The remaining six studies (30%) did not report any differences. CWE had stable academic achievement scores over time (2-4 years), even among those whose seizure frequency improved. Higher parental education and children with higher IQ, and had better attention or had a positive attitude towards epilepsy, were associated with higher academic achievement score. Older children were found to have lower academic achievement score.

    CONCLUSIONS: In CWE of normal intelligence, the majority of published literature found that academic achievement was lower than controls or reported norms. The high percentages of low achievement in CWE, especially in the older age group, and the stability of scores even as seizure frequency improved, highlights the need for early screening of learning problems, and continued surveillance.

  2. Mohd-Tahir NA, Li SC
    Epilepsy Res, 2018 01;139:113-122.
    PMID: 29220742 DOI: 10.1016/j.eplepsyres.2017.11.007
    AIM: This study conducted a systematic review evaluating the effectiveness of newer antiepileptic drugs (AEDs) (namely, lamotrigine, levetiracetam, topiramate, vigabatrin, zonisamide, oxcarbazepine, perampanel, gabapentin, and stiripentol) as add-on for treatment of focal epilepsy in children.

    METHODS: Articles were retrieved from EMBASE, Medline and Cochrane Library from inception to January 2016. Treatment outcomes were analysed based on responder, seizure-free, withdrawal and adverse event rates. Quality of each study was also assessed.

    RESULTS: Twelve articles fulfilled the inclusion criteria. Heterogeneity and quality of the included studies were considered acceptable. Overall, newer AEDs as adjunct therapy in children with inadequate control of focal seizure showed a trend of better seizure outcomes. The pooled ORs for responder, seizure-free and withdrawal rates were 2.15 (95%CI:1.72, 2.69), 1.99 (95%CI:0.72, 5.48) and 0.69 (95%CI:1.13, 2.39) respectively. Adverse events of newer AEDs were comparatively higher than placebo (OR:1.64, 95%CI:1.13, 2.39).

    CONCLUSION: In our updated review, newer AEDs as adjunct therapy for focal epilepsy in children have trends of better effectiveness compared to placebo. Newer AEDs are associated with statistically more children with >50% seizure reduction, and a trend of better seizure freedom. Their tolerability would also be considered acceptable with the observed low withdrawal rate. However, the relative lack of well-conducted RCTs evaluating their effectiveness against other active AED treatment in children would not facilitate evidence-based practice. This highlights the knowledge gap and the need for more well-conducted RCTs against active treatments to ascertain the long term effectiveness and the role of newer AEDs in managing epilepsy in children.

  3. Wo MC, Lim KS, Choo WY, Tan CT
    Epilepsy Res, 2015 Oct;116:67-78.
    PMID: 26354169 DOI: 10.1016/j.eplepsyres.2015.06.016
    People with epilepsy were (PWE) reported to have poorer employment rate. However, the methodologies used differ greatly from one study to another, making global comparison difficult. We aimed to determine the employment rate of PWE globally using a unified definition of employment rate and to summarize the reported positive and negative factors affecting employability in PWE, using a systematic review.
  4. Lim KS, Hills MD, Choo WY, Wong MH, Wu C, Tan CT
    Epilepsy Res, 2013 Oct;106(3):433-9.
    PMID: 23886655 DOI: 10.1016/j.eplepsyres.2013.06.014
    INTRODUCTION: There is a lack of study comparing the attitudes toward epilepsy between the teachers and general population, teachers and students, using a similar quantitative scale.
    METHODS: This study was performed in one primary and one secondary school in Kuala Lumpur, Malaysia, using the Public Attitudes Toward Epilepsy (PATE) scale.
    RESULTS: A total of 186 teachers aged 39.6±10.4 years completed the questionnaire. The mean scores in both personal and general domains of PATE scale were significantly better in the teachers, comparing to the scores in the secondary and college students reported in previous study (Lim et al., 2013; p<0.001 and <0.05, respectively). The mean scores in personal domain was significantly better in the teachers, comparing to the general population reported by Lim et al. (2012; p<0.001). This hold true when comparing teachers with general population with tertiary education, suggesting that the better attitude is specific to the job, rather than tertiary education generally. Subanalysis showed that the attitudes of teachers were significantly better than the general population and the students related to employment and social life, but were equally negative on issues directly related to education, such as placing children with epilepsy in regular classes.
    CONCLUSION: Teachers had more positive attitudes toward epilepsy as compared with the general population with tertiary education. Attitude to epilepsy may differ specific to types of work.
  5. Tan EH, Razak SA, Abdullah JM, Mohamed Yusoff AA
    Epilepsy Res, 2012 Dec;102(3):210-5.
    PMID: 22944210 DOI: 10.1016/j.eplepsyres.2012.08.004
    Generalized epilepsy with febrile seizures plus (GEFS+) comprises a group of clinically and genetically heterogeneous epilepsy syndrome. Here, we provide the first report of clinical presentation and mutational analysis of SCN1A gene in 36 Malaysian GEFS+ patients. Mutational analysis of SCN1A gene revealed twenty seven sequence variants (missense mutation and silent polymorphism also intronic polymorphism), as well as 2 novel de-novo mutations were found in our patients at coding regions, c.5197A>G (N1733D) and c.4748A>G (H1583R). Our findings provide potential genetic insights into the pathogenesis of GEFS+ in Malaysian populations concerning the SCN1A gene mutations.
  6. Wo MC, Lim KS, Choo WY, Tan CT
    Epilepsy Res, 2016 Dec;128:6-11.
    PMID: 27792885 DOI: 10.1016/j.eplepsyres.2016.10.003
    PURPOSE: People with epilepsy (PWE) are negatively prejudiced in their ability to work. This study aimed to examine demographic, clinical and psychological factors associated with employability in PWE.

    METHODS: This study recruited epilepsy patients from a neurology clinic in Malaysia. Employability was measured using employment ratio, with a ratio ≥90% (ER90) classified as high employability. Basic demographic data such as age, gender, marital status, religion, education level and household income was collected. Clinical measures consisted of age of seizure onset, seizure frequency, type of epilepsy, aura, polytherapy, nocturnal seizures and seizure control. Psychological measures included Work Self-Determination Index (WSDI), Rosenberg Self-Esteem Scale (SES), and Multidimensional Scale of Perceived Social Support (MSPSS).

    RESULTS: Of 146 PWE, 64.4% had high employability. The participants were predominantly female (52%), Chinese (50.7%), single (50%), having tertiary education (55.5%) and focal epilepsy (72.6%). Clinically, only type of epilepsy was significantly correlated to employability of PWE. Employability of PWE was associated with ability to work (indicated by education level, work performance affected by seizures, ability to travel independently and ability to cope with stress at work) and family overprotection. The high employability group was found to have lower self-perceived stigma (ESS), higher self-determined motivation (WSDI), self-esteem (SES) and perceived social support (MSPSS), than the low employability group. Logistic regression analysis showed that tertiary education level (AOR 3.42, CI: 1.46-8.00), higher self-determination (WSDI, AOR 1.09, CI: 1.012-1.17), lower family overprotection (AOR 0.76, CI: 0.61-0.95), and generalised epilepsy (AOR 4.17, CI: 1.37-12.70) were significant predictors for higher employability in PWE.

    CONCLUSION: Ability to work (education level), clinical factor (type of epilepsy) and psychological factor (self-determined motivation and family overprotection) were important factors affecting employability in PWE.

    Study site: neurology clinic Universiti Malaya Medical Centre (UMMC)
  7. 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.

  8. Khor SB, Lim KS, Fong SL, Ho JH, Koh MY, Tan CT
    Epilepsy Res, 2022 Feb 11;181:106887.
    PMID: 35180637 DOI: 10.1016/j.eplepsyres.2022.106887
    BACKGROUND: This is a follow-up study on mortality in adult patients in Malaysia. This study aimed to determine the cause of death and the factors associated with epilepsy-related death in PWE in Malaysia.

    METHOD: Deceased PWE from 2005 to 2020 were identified from the National Registry Department of Malaysia. The details of the cause of death and predictors for epilepsy-related deaths was ascertained from medical records and phone interviews.

    RESULT: There were a total of 227 deaths, 144 (63.4%) were male, two (0.9%) underwent autopsy and 46.3% passed away in the community. The majority of deaths (55.5%) were due to causes unrelated to epilepsy. Forty-five (19.8%) death were related to epilepsy, of which, 22 (9.7%) were due to death directly related to epilepsy including probable SUDEP (5.3%) and status epilepticus (4.4%). The cause of death was unknown in 56 (24.7%) cases. Binary logistic regression analysis identified 3 predictors for epilepsy-related deaths, i.e., structural causes (OR 3.09, 95% CI 1.100-8.691, p = 0.032), younger age of death (OR 2.35, 95% CI 1.039-5.333, p = 0.040) and history of brain surgery (OR 8.09, 95% CI 2.014-32.510, p = 0.003). Twelve (5.3%) had probable SUDEP. The incidence rate of probable SUDEP was 0.42 per 1000 person-years. The majority of them had intellectual disability (9/12), generalized tonic-clonic seizures (9/12), and 2 or more ASMs (9/12).

    CONCLUSION: Epilepsy-related deaths accounted for 20% of the deaths in PWE, associated with structural cause, younger age of death, and previous brain surgery. Probable SUDEP is not uncommon in Malaysia and could be under-diagnosed.

  9. Tan JK, Khoo CS, Beh HC, Hod R, Baharudin A, Yahya WNNW, et al.
    Epilepsy Res, 2021 Dec;178:106772.
    PMID: 34763265 DOI: 10.1016/j.eplepsyres.2021.106772
    BACKGROUND: Depression is the most frequent psychiatric comorbidity of epilepsy. However, clinicians often neglect to screen for depressive symptoms among patients with epilepsy and, therefore, fail to detect depression. Many studies have described the risks associated with depression in patients with epilepsy, but few studies have elaborated whether these risks are similar in those with undiagnosed depression, especially in a multiethnic community.

    METHODS: In the present cross-sectional study conducted at a tertiary teaching hospital, we aimed to investigate the prevalence and associated risk factors of undiagnosed depression in patients with epilepsy. We recruited patients with epilepsy aged 18-65 years after excluding those with background illnesses that may have contributed to the depressive symptoms. In total, 129 participants were recruited. We collected their demographic and clinical details before interviewing them using two questionnaires-the Neurological Disorders Depression Inventory for Epilepsy and Beck's Depression Inventory-II. Subsequently, if a participant screened positive for depression, the diagnosis was confirmed using the Diagnostic and Statistical Manual of Mental Disorders questionnaire, and a psychiatric clinic referral was offered.

    RESULTS: Among the 129 participants, 9.3 % had undiagnosed major depressive disorder, and there was a female preponderance (66.7 %). The risk factors for undiagnosed depression among patients with epilepsy included low socioeconomic background (p = 0.026), generalized epilepsy (p = 0.036), and temporal lobe epilepsy (p = 0.010). Other variables such as being underweight and unmarried were more common among patients diagnosed with depression than without but no statistically significant relationship was found.

    CONCLUSION: The prevalence of undiagnosed depression among patients with epilepsy was higher than that in population-based studies conducted in Western countries. Although questionnaires to screen for depression are widely available, some clinicians rarely use them and, therefore, fail to identify patients who may benefit from psychosocial support and treatment that would improve their disease outcomes and quality of life. The present study indicated that clinicians should use screening questionnaires to identify undiagnosed depression in people with epilepsy.

  10. Fong SL, Lim KS, Tan L, Zainuddin NH, Ho JH, Chia ZJ, et al.
    Epilepsy Res, 2021 02;170:106551.
    PMID: 33440303 DOI: 10.1016/j.eplepsyres.2021.106551
    INTRODUCTION: The lifetime prevalence of epilepsy varies greatly from 1.5-14.0 per 1000 persons among the Asian countries. We aim to study the prevalence of epilepsy in Malaysia to have a better insight into the burden of disease in the country.

    METHODS: A population-based door-to-door survey was carried out throughout the country, using questionnaire for brief screening in ascertainment of epilepsy, using a questionnaire and its validated multilingual versions. Respondents who were screened positive underwent second-stage diagnostic phone interview by neurologists/ research assistants.

    RESULTS: A total 16, 686 respondents participated in the survey and 646 (3.8 %) respondents were screened positive during the first stage interview. A total of 185 consented for second stage diagnostic interview and 118 (63.8 %) respondents were contacted successfully for the second stage diagnostic phone interview, of which 17 (14.4 %) respondents were diagnosed to have epilepsy. An additional 68 (57.6 %) respondents had febrile seizures only. After applying a weighting factor to each respondent to adjust for non-response and for the varying probabilities of selection, the adjusted lifetime epilepsy prevalence was 7.8 in 1000 population, and the adjusted prevalence for active epilepsy was 4.2 in 1000 population in Malaysia.

    CONCLUSION: The prevalence of lifetime epilepsy in Malaysia is 7.8 per 1000 persons.

  11. Audrey C, Lim KS, Ahmad Zaki R, Fong SL, Chan CY, Sathis Kumar T, et al.
    Epilepsy Res, 2022 Nov;187:107033.
    PMID: 36274423 DOI: 10.1016/j.eplepsyres.2022.107033
    OBJECTIVES: Prevalence of seizures in brain tumors vary substantially between studies even with similar histopathological types. We aimed to identify the seizure prevalence of the commonest types of brain tumors.

    METHODS: Systematic computerized search of PubMed, Embase, and Web of Science were performed. The meta-analysis of pooled prevalence and 95 % confidence interval (CI) for tumor-related seizures were calculated by using a random effect model. Based on the 2014 epilepsy definition, a mean seizure prevalence of 60 % is used to indicate high seizure prevalence in this study.

    RESULTS: 74 studies that reported seizure prevalence with 23,116 patients were included in this meta-analysis. These tumors has higher seizure incidence rate (at least 60 %) with pooled prevalence of 63 % for adult with low-grade astrocytoma (95 % CI: 57-68 %), 65 % for oligodendroglioma (95% CI: 57-72 %), 72 % for oligoastrocytoma (95 % CI: 67-77 %), 81 % for ganglioglioma (95 % CI: 66-97 %) and 94 % for DNET (94 % CI: 83-100 %).

    CONCLUSION: This study highlights the type of brain tumors that carry a high seizure prevalence. Screening for subtle seizures and early management of seizures may be beneficial in patients with low-grade astrocytoma (adult), oligodendroglioma, oligoastrocytoma, ganglioglioma or DNET brain tumor.

  12. Chan CK, Lim KS, Low SK, Tan CT, Ng CC
    Epilepsy Res, 2023 Jan;189:107070.
    PMID: 36584483 DOI: 10.1016/j.eplepsyres.2022.107070
    Epilepsy is a complex neurological disease that can be caused by both genetic and environmental factors. Many studies have been conducted to investigate the genetic risk variants and molecular mechanisms of epilepsy. Disruption of excitation-inhibition balance (E/I balance) is one of the widely accepted disease mechanisms of epilepsy. The maintenance of E/I balance is an intricate process that is governed by multiple proteins. Using whole exome sequencing (WES), we identified a novel GABRA1 c.448G>A (p.E150K) variant and ERBB4 c.1972A>T (p.I658F, rs190654033) variant in a Malaysian Chinese family with genetic generalized epilepsy (GGE). The GGE may be triggered by dysregulation of E/I balance mechanism. Segregation of the variants in the family was verified by Sanger sequencing. All family members with GGE inherited both variants. However, family members who carried only one of the variants did not show any symptoms of GGE. Both the GABRA1 and ERBB4 variants were predicted damaging by MutationTaster and CADD, and protein structure analysis showed that the variants had resulted in the formation of additional hydrogen bonds in the mutant proteins. GABRA1 variant could reduce the efficiency of GABAA receptors, and constitutively active ERBB4 receptors caused by the ERBB4 variant promote internalization of GABAA receptors. The interaction between the two variants may cause a greater disruption in E/I balance, which is more likely to induce a seizure. Nevertheless, this disease model was derived from a single small family, further studies are still needed to confirm the verifiability of the purported disease model.
  13. Akyuz E, Arulsamy A, Hasanli S, Yilmaz EB, Shaikh MF
    Epilepsy Res, 2023 Feb;190:107093.
    PMID: 36652852 DOI: 10.1016/j.eplepsyres.2023.107093
    Epilepsy is one of the most recognizable neurological diseases, globally. Epilepsy may be accompanied by various complications, including vision impairments, which may severely impact one's quality of life. These visual phenomena may occur in the preictal, ictal and/or postictal periods of seizures. Examples of epilepsy associated visual phenomena include visual aura, visual hallucinations, transient visual loss and amaurosis (blindness). These ophthalmologic signs/symptoms of epilepsy may be temporary or permanent and may vary depending of the type of epilepsy and location of the seizure foci (occipital or temporal lobe). Some visual phenomena may even be utilized to diagnose the epilepsy type, although solely depending on visual symptoms for diagnosis may lead to mistreatment. Some antiseizure medications (ASMs) may also contribute to certain visual disturbances, thereby impacting its therapeutic efficiency for patients with epilepsy (PWE). Although the development of visual comorbidities has been observed diversely among PWE, there may still be a lack of understanding on their relevance and manifestation in epilepsy, which may contribute to the rate of misdiagnosis and the current scarcity in therapeutic relieve. Therefore, this mini narrative review aimed to discuss the common epilepsy associated visual phenomena, based on the available literature. This review also showcased the relationship between the type of visual complications and the site of seizure onset, as well as compared the visual phenomena between occipital lobe epilepsy and temporal lobe epilepsy. Evaluation of these findings may be crucial in reducing the risk of permanent seizure/epilepsy related vision deficits among PWE.
  14. Beheshti S, Ershadi S, Zamani F, Azimzadeh M, Wesal MW
    Epilepsy Res, 2023 Nov;197:107234.
    PMID: 37793283 DOI: 10.1016/j.eplepsyres.2023.107234
    Ghrelin is a peptide, which has been shown to affect seizures. However, there is not a consensus about its real impact on the control of seizure severity. We assessed the influence of intra-amygdala injections of a ghrelin receptor (GHSR) antagonist, as well as a GHSR inverse agonist on the electrical kindling-induced seizures. Two unipolar electrodes and a tripolar electrode twisted with a guide cannula were implanted in the skull surface or the basolateral amygdala of adult male rats, respectively. A rapid electrical kindling protocol was applied for kindling epileptogenesis. The stimulations were applied until rats showed three consecutive stage five seizures. Each rat was considered as its control. D-Lys-3-GHRP-6 (1, 12.5, and 25 μg/rat) or [D-Arg, D-phe, D-Trp, heu] substance P (D-SP) (50, 500 and 5000 ng/rat) as the GHSR antagonist or inverse agonist were injected into the basolateral amygdala. Seizure parameters including after-discharge duration (ADD), stage five duration (S5D), and seizure stage (SS) were documented thirty minutes following administration of the drugs or saline. Antagonism of the GHSR in the amygdala, significantly increased seizure induction in the kindled rats, in a dose-dependent manner, and induced spontaneous seizures leading to status epilepticus. Conversely, D-SP had a dose-dependent anticonvulsant activity, indicated by decreased ADD and S5D. The results show that GHSR inverse agonism suppressed seizure severity in the rat amygdala kindling model, whereas GHSR antagonism made seizures more severe. Therefore, when considering the ghrelin system to modulate seizures, it is crucial to note the differential impact of various GHSR ligands.
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