Displaying publications 81 - 100 of 101 in total

Abstract:
Sort:
  1. Lim KS, Wong KY, Chee YC, Fong SL, Yu X, Ng CG, et al.
    Epilepsy Behav, 2023 Nov;148:109455.
    PMID: 37774547 DOI: 10.1016/j.yebeh.2023.109455
    OBJECTIVE: People with epilepsy (PWE) have a high prevalence of developing depression and anxiety. The objective is to determine the feasibility of brief screening tools to screen for depression and anxiety in epilepsy, and the predictive factors.

    METHOD: This is a cross-sectional study in the neurology clinic in a tertiary teaching hospital in Kuala Lumpur. The screening tools used were the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the General Anxiety Disorder Form (GAD-7).

    RESULTS: Five hundred and eighty-five patients were recruited in this study, and 50.8% of them were male, predominantly Chinese (46.7%), with a mean age of seizure onset of 21.8 ± 16.1 years. The majority had focal seizures (75.0%), and 41.9% had seizure remission. There were 15.5% who scored ≥15 in the NDDI-E, and 17.0% had moderate or severe anxiety (scored ≥10 in the GAD-7). In a regression model to predict the NDDI-E score, the age of seizure onset recorded a higher beta value (β = -0.265, p =

  2. Koh MY, Lai ST, Lim KS, Lim SYH, Chin J, Chia ZJ, et al.
    Asia Pac J Public Health, 2023 Nov;35(8):524-528.
    PMID: 37864316 DOI: 10.1177/10105395231207238
    We investigated the COVID-19 pandemic's impact on values and religiosity in multi-ethnic Malaysia. Values were measured as changes in values, daily activities, and life priorities using a 5-point Likert scale (-2 to +2). Centrality of Religiosity Scale measured changes in religiosity. Around 176 predominantly female (66.5%), Chinese (68.2%) respondents, aged 35.5 ± 14.1 completed the survey. Most life values changed positively: a sense of security at home (2, interquartile range [IQR]: 1-2), connection with family (1, 1-2), and contribution to society (1, 1-2). Certain life priorities' importance increased: health (2, IQR 2-2), family (2, 2-2), and happiness (2, 1-2); except power and money. These significant positive changes in values and religiosity varied between genders and ethnicities.
  3. Fong SL, Thuy Le MA, Lim KS, Khosama H, Ohnmar O, Savath S, et al.
    Epilepsia, 2023 Aug;64(8):2116-2125.
    PMID: 37243851 DOI: 10.1111/epi.17668
    OBJECTIVE: One of the objectives of the Intersectoral Global Action Plan on epilepsy and other neurological disorders for 2022 to 2031 is to ensure at least 80% of people with epilepsy (PWE) will have access to appropriate, affordable, and safe antiseizure medications (ASMs) by 2031. However, ASM affordability is a significant issue in low- and middle-income countries, preventing PWE from accessing optimal treatment. This study aimed to determine the affordability of the newer (second and third generation) ASMs in resource-limited countries in Asia.

    METHODS: We conducted a cross-sectional survey by contacting country representatives in lower-middle-income countries (LMICs) in Asia, including Indonesia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Vietnam, India, Bangladesh, and Pakistan, and the upper-middle-income country Malaysia, from March 2022 to April 2022. The affordability of each ASM was calculated by dividing the 30-day ASM cost by the daily wage of the lowest paid unskilled laborers. Treatment costing 1 day's wage or less for a 30-day supply of chronic disease is considered affordable.

    RESULTS: Eight LMICs and one upper-middle-income country were included in this study. Lao PDR had no newer ASM, and Vietnam had only three newer ASMs. The most frequently available ASMs were levetiracetam, topiramate, and lamotrigine, and the least frequently available was lacosamide. The majority of the newer ASMs were unaffordable, with the median number of days' wages for a 30-day supply ranging from 5.6 to 14.8 days.

    SIGNIFICANCE: All new generation ASMs, whether original or generic brands, were unaffordable in most Asian LMICs.

  4. Sha'ari HM, Haerian BS, Baum L, Tan HJ, Rafia MH, Kwan P, et al.
    Mol Neurobiol, 2016 07;53(5):2869-2877.
    PMID: 25876511 DOI: 10.1007/s12035-015-9150-1
    Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese.
  5. Lim KS, Tan AH, Lim CS, Chua KH, Lee PC, Ramli N, et al.
    PLoS One, 2015;10(8):e0135470.
    PMID: 26270344 DOI: 10.1371/journal.pone.0135470
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke caused by mutations in NOTCH3 gene. We report the first case of CADASIL in an indigenous Rungus (Kadazan-Dusun) family in Kudat, Sabah, Malaysia confirmed by a R54C (c.160C>T, p.Arg54Cys) mutation in the NOTCH3. This mutation was previously reported in a Caucasian and two Korean cases of CADASIL. We recruited two generations of the affected Rungus family (n = 9) and found a missense mutation (c.160C>T) in exon 2 of NOTCH3 in three siblings. Two of the three siblings had severe white matter abnormalities in their brain MRI (Scheltens score 33 and 50 respectively), one of whom had a young stroke at the age of 38. The remaining sibling, however, did not show any clinical features of CADASIL and had only minimal changes in her brain MRI (Scheltens score 17). This further emphasized the phenotype variability among family members with the same mutation in CADASIL. This is the first reported family with CADASIL in Rungus subtribe of Kadazan-Dusun ethnicity with a known mutation at exon 2 of NOTCH3. The penetrance of this mutation was not complete during the course of this study.
  6. Le VT, Thuy Le MA, Nguyen DH, Tang LNP, Pham TA, Nguyen AM, et al.
    Epilepsia Open, 2022 Dec;7(4):710-717.
    PMID: 36136063 DOI: 10.1002/epi4.12650
    OBJECTIVE: Although epilepsy surgery is more effective than medical therapy for drug-resistant patients, it is underutilized in both high-income and low- and middle-income countries. In light of our efforts to establish an epilepsy surgery program in a resource-limited setting, this study aimed to determine the outcome of the epilepsy surgery program in Ho Chi Minh City (HCMC), Vietnam.

    METHODS: In 2018, we developed the HCMC epilepsy core multidisciplinary team with members from various hospitals and centers. The team typically included neurologists, neurosurgeons, neuropsychologists, psychiatrists, and nursing specialists. Presurgical evaluations were performed for patients with drug-resistant epilepsy, fulfilling the ILAE criteria, with an epileptogenic lesion (mesial temporal sclerosis, low-grade gliomas, or focal cortical dysplasia). All epilepsy surgeries were performed in two epilepsy surgery centers in HCMC between 2018 and 2021. The patients were followed up for at least 12 months.

    RESULTS: Fifty-two patients with drug-resistant epilepsy underwent presurgical evaluation, of which 35 underwent surgery. Among the 52 patients, 20 (38.5%) underwent surgery after showing concordance among the results of standard presurgical assessments such as semiology, scalp interictal or ictal electroencephalography, and brain imaging. Among the 26 people with epilepsy who required more advanced evaluations, 15 underwent surgery with intraoperative electrocorticography to delineate the optimal resection borders. The outcomes of Engel Class I and Class II were achieved in 29/35 (82.8%) and 6/35 (17.2%) patients, respectively.

    SIGNIFICANCE: The epilepsy surgery program with a multicentered collaborative model in a resource-limited setting showed favorable outcomes in HCMC, Vietnam.

  7. Hakeem H, Feng W, Chen Z, Choong J, Brodie MJ, Fong SL, et al.
    JAMA Neurol, 2022 Oct 01;79(10):986-996.
    PMID: 36036923 DOI: 10.1001/jamaneurol.2022.2514
    IMPORTANCE: Selection of antiseizure medications (ASMs) for epilepsy remains largely a trial-and-error approach. Under this approach, many patients have to endure sequential trials of ineffective treatments until the "right drugs" are prescribed.

    OBJECTIVE: To develop and validate a deep learning model using readily available clinical information to predict treatment success with the first ASM for individual patients.

    DESIGN, SETTING, AND PARTICIPANTS: This cohort study developed and validated a prognostic model. Patients were treated between 1982 and 2020. All patients were followed up for a minimum of 1 year or until failure of the first ASM. A total of 2404 adults with epilepsy newly treated at specialist clinics in Scotland, Malaysia, Australia, and China between 1982 and 2020 were considered for inclusion, of whom 606 (25.2%) were excluded from the final cohort because of missing information in 1 or more variables.

    EXPOSURES: One of 7 antiseizure medications.

    MAIN OUTCOMES AND MEASURES: With the use of the transformer model architecture on 16 clinical factors and ASM information, this cohort study first pooled all cohorts for model training and testing. The model was trained again using the largest cohort and externally validated on the other 4 cohorts. The area under the receiver operating characteristic curve (AUROC), weighted balanced accuracy, sensitivity, and specificity of the model were all assessed for predicting treatment success based on the optimal probability cutoff. Treatment success was defined as complete seizure freedom for the first year of treatment while taking the first ASM. Performance of the transformer model was compared with other machine learning models.

    RESULTS: The final pooled cohort included 1798 adults (54.5% female; median age, 34 years [IQR, 24-50 years]). The transformer model that was trained using the pooled cohort had an AUROC of 0.65 (95% CI, 0.63-0.67) and a weighted balanced accuracy of 0.62 (95% CI, 0.60-0.64) on the test set. The model that was trained using the largest cohort only had AUROCs ranging from 0.52 to 0.60 and a weighted balanced accuracy ranging from 0.51 to 0.62 in the external validation cohorts. Number of pretreatment seizures, presence of psychiatric disorders, electroencephalography, and brain imaging findings were the most important clinical variables for predicted outcomes in both models. The transformer model that was developed using the pooled cohort outperformed 2 of the 5 other models tested in terms of AUROC.

    CONCLUSIONS AND RELEVANCE: In this cohort study, a deep learning model showed the feasibility of personalized prediction of response to ASMs based on clinical information. With improvement of performance, such as by incorporating genetic and imaging data, this model may potentially assist clinicians in selecting the right drug at the first trial.

  8. Inoue Y, Tiamkao S, Zhou D, Cabral-Lim L, Lim KS, Lim SH, et al.
    Epilepsia Open, 2024 Apr 04.
    PMID: 38576178 DOI: 10.1002/epi4.12929
    OBJECTIVE: Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS).

    METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs.

    RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p 

  9. Iwayama T, Mizuno K, Yildiz E, Lim KS, Yi SM, Lynn YJ, et al.
    Epilepsia Open, 2024 Dec;9(6):2283-2293.
    PMID: 39325044 DOI: 10.1002/epi4.13051
    OBJECTIVE: Epilepsy is a neurological disorder characterized by recurrent seizures, exhibiting variance in prevalence and treatment availability across diverse geopolitical contexts and cultural milieus. The stigma associated with epilepsy is a significant global issue affecting the quality of life (QOL) of people with epilepsy (PWE). This study aims to examine the relationship between self-stigma and depressive symptoms in PWE, with a particular emphasis on understanding the manifestations of these across different cultural contexts. We aim to enhance the provision of customized care to diverse cultural settings, fostering the adoption of healthier lifestyles for PWE.

    METHODS: We recruited PWE who received treatment at specialized medical facilities for epilepsy in Japan, Malaysia (Chinese, Malay), and Turkey from February to October 2023. The Epilepsy Self-Stigma Scales (ESSS), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and Generalized Anxiety Disorder 7 (GAD-7) in local languages were used to assess self-stigma, depressive symptoms, and anxiety.

    RESULTS: The ESSS total scores were significantly higher among the Turkish and Japanese cohorts (F [3, 406] = 6.57, p 

  10. Fong MWK, Lim KS, Fong SL, Chen C, Kwan SY, Lee CC, et al.
    Neurophysiol Clin, 2025 Jan;55(1):103033.
    PMID: 39644808 DOI: 10.1016/j.neucli.2024.103033
    BACKGROUND: Invasive/ intracranial EEG forms an important component of assessment for epilepsy surgery in many patients with Drug-Resistant Epilepsy (DRE). Intracranial EEG has been poorly utilized though Southeast Asia (SEA) and Oceania. This study aimed to document the development of stereo-EEG (SEEG) across the region and highlight regional barriers to utilization and access.

    METHODS: A survey was developed by multicenter consensus. The survey captured institutional characteristics, geographic distributions, intracranial EEG utilization, and barriers to SEEG. Respondents were representative epilepsy centers across the region.

    RESULTS: Four epilepsy centers with established intracranial/ SEEG and two centers from a country without any access to SEEG participated. The responses identified that 1. Access to SEEG remained highly restricted across the region with an estimated one capable epilepsy center per 100 million people; 2. The region includes over half a billion people living in countries with no access to SEEG; 3. Staffing/ financial constraints were universal factors that limited growth of services or development of new services; 4. SEEG numbers have plateaued as a result of these challenges.

    CONCLUSION: The study puts into real numbers the challenges faced by the region in accessing SEEG. SEEG remains highly underutilized and future approaches should focus on regional training and referral pathways.

  11. Roxas A, Mehndiratta MM, Bornstein N, Macdonell R, Lim KS, Ng PW, et al.
    J Neurol Sci, 2017 Nov 15;382:108-115.
    PMID: 29111001 DOI: 10.1016/j.jns.2017.09.022
    OBJECTIVE: To survey AOAN member countries regarding their organizational structure, postgraduate neurology training program, and resources for neurological care provision.

    METHODOLOGY: A cross-sectional survey using a 36-item questionnaire was conducted among country representatives to AOAN from August 2015 to August 2016.

    RESULTS: A total of 18/20 AOAN member countries participated in the survey. All the countries have organized association with regular meetings, election of officers and neurology training program. In 9/18 countries, professionals other than neurologists were eligible for affiliation. In 11/18 countries, prior Internal medicine training (or equivalent postgraduate housemanship) is prerequisite to neurology program. Recertification examination is not a practice, but submission of CME is required in 7/18 countries to maintain membership. 12/18 countries publish peer-reviewed journals with at least 1 issue per year. Subspecialty training is offered in 14/18 countries. The ratio of neurologist to population ranges from 1:14,000 to as low as 1:32 million with 9/18 having <1 neurologist per 100,000 population. 6/18 countries have at least 1 specialized center solely for neurological diseases. In government-funded hospitals, the lag time to be seen by a neurologist and/or obtain neuroimaging scan ranges from 1day to 3months. All except one country have several medical- and lay- advocacy or support groups for different neurological conditions.

    IMPLICATIONS: The data generated can be used for benchmarking to improve neurological care, training, collaborative work and research in the field of neurosciences among the AOAN member countries. The paper presented several strategies used by the different organizations to increase their number of neurologists and improve the quality of training. Sharing of best practices, academic networking, exchange programs and use of telemedicine have been suggested.

  12. 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.

  13. Lim KS, Khoo CS, Fong SL, Tan HJ, Fong CY, Mohamed AR, et al.
    J Clin Neurosci, 2023 Aug;114:25-31.
    PMID: 37279626 DOI: 10.1016/j.jocn.2023.05.006
    INTRODUCTION: Early and effective treatment is fundamental in status epilepticus (SE) management. At the initiative of the Epilepsy Council of Malaysia, this study aimed to determine the treatment gap in SE across different healthcare settings in Malaysia.

    METHODS: A web-based survey was sent to clinicians involved in the management of SE, across all states and at all levels of healthcare services.

    RESULTS: A total of 158 responses were received from 104 health facilities, including 23 tertiary government hospitals (95.8% of all government tertiary hospitals in Malaysia), 4 (80.0%) universities, 14 (6.7%) private, 15 (11.5%) district hospitals and 21 clinics. Intravenous (IV) diazepam was available in 14 (93.3%) district and 33 (80.5%) tertiary hospitals for prehospital management. Non-IV benzodiazepine (rectal diazepam and intramuscular midazolam) was not widely available in prehospital services (75.8% and 51.5%). Intramuscular midazolam was underutilised (60.0% in district and 65.9% in tertiary hospitals). IV sodium valproate and levetiracetam were only available in 66.7% and 53.3% of the district hospitals, respectively. Electroencephalogram (EEG) services were available in only 26.7% of the district hospitals. Non-pharmacological therapies such as ketogenic diet, electroconvulsive therapy, and therapeutic hypothermia were not available in most district and tertiary hospitals for refractory and super-refractory SE.

    CONCLUSIONS: We identified several gaps in the current practice of SE management, including limited availability and underutilization of non-IV midazolam in prehospital services, underutilization of non-IV midazolam and other second-line ASMs, and lack of EEG monitoring in district hospitals and limited treatment options for refractory and super-refractory SE in tertiary hospitals.

  14. Fong SL, Lim KS, Lim SH, Octaviana F, Tran TC, Thuy Le MA, et al.
    Neurol Educ, 2025 Mar;4(1):e200201.
    PMID: 40104779 DOI: 10.1212/NE9.0000000000200201
    BACKGROUND AND OBJECTIVES: This study aims to describe the variations in neurology training pathways in all Association of Southeast Asian Nations (ASEAN) countries.

    METHODS: A cross-sectional survey using questionnaires was conducted among the representatives of ASEAN countries from October 2023 to March 2024.

    RESULTS: Neurology training programs are available in 9 of the 11 ASEAN countries except Timor Leste and Cambodia. Despite the growing number of neurologists, with a doubling of the neurologist-to-patient ratio in most countries in the past 2 decades, the neurologist density per 100,000 population remained low. Thailand, Singapore, and Brunei Darussalam have more than 1 neurologist per 100,000 population compared with 2007 when only Singapore and Brunei Darussalam had more than this ratio. In Cambodia, Lao People's Democratic Republic (PDR), Myanmar, and Timur Leste, although the number of neurologists has increased substantially, the ratio of neurologists remains low, with less than 1 in a million population in Myanmar, 1:625,000 population in Lao PDR, 1:526,000 population in Cambodia, and 1:430,000 in Timur Leste. The total duration of training from undergraduate to certified neurologist varies greatly because of compulsory internal medicine (IM) training and postinternship services. To enroll in neurology training, candidates in 4 countries (Brunei, Singapore, Malaysia, and Myanmar) must have completed IM as a prerequisite. Candidates from Thailand and Indonesia must fulfill their 2-year compulsory government or general practice service requirement before they are eligible for neurology training. After fulfilling the eligibility criteria to enter neurology training, the overall training duration ranges from 3 to 13 years. Malaysia and Myanmar are countries where candidates spend more than 10 years becoming certified neurologists.

    DISCUSSION: The number of neurologists and the neurologist-to-patient ratio have improved since 2007 in ASEAN countries. Diverse neurology curricula and the variable duration to complete neurology training and subspecialty practice are the main challenges in improving neurology training in ASEAN countries.

  15. Shakeshaft A, Panjwani N, McDowall R, Crudgington H, Peña Ceballos J, Andrade DM, et al.
    Ann Clin Transl Neurol, 2021 01;8(1):138-152.
    PMID: 33264519 DOI: 10.1002/acn3.51255
    OBJECTIVE: Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta-analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs).

    METHODS: 322 participants with JME and 126 age and gender-matched controls completed the Barratt's Impulsiveness Scale (BIS-brief) alongside information on seizure history and AED use. We compared group BIS-brief scores and assessed associations of JME BIS-brief scores with seizure characteristics and AED adverse effects.

    RESULTS: The mean BIS-brief score in JME was 18.1 ± 4.4 compared with 16.2 ± 4.1 in controls (P = 0.0007). Elevated impulsivity was associated with male gender (P = 0.027), frequent absence seizures (P = 0.0004) and lack of morning predominance of myoclonus (P = 0.008). High impulsivity significantly increased the odds of a psychiatric adverse event on levetiracetam (P = 0.036), but not any other psychiatric or somatic adverse effects.

    INTERPRETATION: Trait impulsivity is elevated in JME and comparable to scores in personality and neurotic disorders. Increased seizure frequency and absence of circadian seizure pattern moderate BIS score, suggesting disruption of both cortico-striatal and thalamocortical networks as a shared mechanism between seizures and impulsivity in JME. These findings warrant consideration of impulsivity as a distinct target of intervention, and as a stratifying factor for AED treatment in JME, and perhaps other types of epilepsy. The role of impulsivity in treatment adherence and psychosocial outcome requires further investigation.

  16. Shi YW, Min FL, Zhou D, Qin B, Wang J, Hu FY, et al.
    Neurology, 2017 Jun 06;88(23):2183-2191.
    PMID: 28476759 DOI: 10.1212/WNL.0000000000004008
    OBJECTIVE: To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug-induced cutaneous adverse reactions.

    METHODS: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.

    RESULTS: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10(-15)). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10(-5)) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.

    CONCLUSIONS: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.

  17. Rubboli G, Beier CP, Selmer KK, Syvertsen M, Shakeshaft A, Collingwood A, et al.
    Brain Commun, 2023;5(3):fcad182.
    PMID: 37361715 DOI: 10.1093/braincomms/fcad182
    Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.
  18. Shakeshaft A, Panjwani N, Collingwood A, Crudgington H, Hall A, Andrade DM, et al.
    Sci Rep, 2022 Feb 21;12(1):2785.
    PMID: 35190554 DOI: 10.1038/s41598-022-06324-2
    Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p 
  19. Safeer V S M, Singh A, Nahan N, Madaan P, Winter SF, Prasad M, et al.
    JAMA Neurol, 2026 Nov 02.
    PMID: 42970304 DOI: 10.1001/jamaneurol.2026.3906
    IMPORTANCE: Despite the profound impact of neonatal and infantile-onset epilepsies on neurodevelopmental outcomes and mortality, consolidated global epidemiological evidence remains lacking.

    OBJECTIVES: To estimate the global incidence and prevalence of neonatal and infantile-onset epilepsies and epilepsy syndromes and to characterize their associated etiological profiles.

    DATA SOURCES: PubMed, Embase, Web of Science, and Scopus were searched from inception through December 18, 2025.

    STUDY SELECTION: Population-based observational studies reporting the incidence or prevalence of neonatal and infantile-onset epilepsies or epilepsy syndromes were eligible for inclusion.

    DATA EXTRACTION AND SYNTHESIS: Two authors independently and in duplicate performed study selection, data extraction, and quality assessment of included studies using the Joanna Briggs Institute Critical Appraisal checklist for prevalence studies. Generalized linear mixed-model random-effects meta-analysis was used to pool the estimates of incidence, prevalence, and etiology. Subgroup meta-analyses were conducted by country, World Health Organization (WHO) region, World Bank income, and diagnostic criteria. Metaregression was used to investigate the association between study-level covariates and pooled incidence estimates of infantile-onset epilepsy syndromes.

    MAIN OUTCOMES AND MEASURES: Cumulative incidence and prevalence of neonatal and infantile-onset epilepsies and epilepsy syndromes.

    RESULTS: A total of 86 population-based studies from 30 countries across 4 WHO regions were included. The pooled cumulative incidence of infantile-onset epilepsies within the first 2 years of life was 236.0 cases (95% CI, 164.7-338.2; 95% prediction interval [PI], 53.0-1044.3) per 100 000 live births. Among epilepsy syndrome subgroups, developmental and epileptic encephalopathies (DEEs) had the highest incidence at 67.7 cases (95% CI, 42.1-108.9; 95% PI, 7.1-636.1) per 100 000 live births. Infantile epileptic spasms syndrome (IESS) was the most incident DEE, with 31.6 cases (95% CI, 27.5-36.2; 95% PI, 13.7-72.6) per 100 000 live births. Among self-limited epilepsies, self-limited infantile epilepsy had the highest incidence at 13.0 cases (95% CI, 9.2-18.2; 95% PI, 6.4-26.4) per 100 000 live births. Subgroup analyses revealed limited geographical representativeness, with the majority of studies from high-income countries in the European Region.

    CONCLUSIONS AND RELEVANCE: The findings underscore a significant global burden of neonatal and infantile-onset epilepsies, primarily driven by DEEs, specifically IESS. Given substantial between-study heterogeneity, the pooled estimates should be interpreted as broad indicators rather than precise, generalizable rates. Geographic disparities, with a lack of data from the African and Eastern Mediterranean Regions, underscore the need for population-based studies in underrepresented regions and longitudinal research on survival, remission, and functional outcomes.

  20. Tsai MH, Muir AM, Wang WJ, Kang YN, Yang KC, Chao NH, et al.
    Neuron, 2020 Apr 22;106(2):237-245.e8.
    PMID: 32097630 DOI: 10.1016/j.neuron.2020.01.027
    Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We now implicate CEP85L as an important cause of posterior predominant LIS, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. We show that CEP85L is a centrosome protein localizing to the pericentriolar material, and knockdown of Cep85l causes a neuronal migration defect in mice. LIS1 also localizes to the centrosome, suggesting that this organelle is key to the mechanism of posterior predominant LIS.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links