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  1. Viswanathan S, Rose N, Masita A, Dhaliwal JS, Puvanarajah SD, Rafia MH, et al.
    Mult Scler Int, 2013;2013:614716.
    PMID: 24455266 DOI: 10.1155/2013/614716
    Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.
  2. Viswanathan S, Arip M, Mustafa N, Dhaliwal JS, Rose N, Muda S, et al.
    Mult Scler Int, 2014;2014:568254.
    PMID: 25548676 DOI: 10.1155/2014/568254
    Background. In the past the occurrence of neuromyelitis optica in Malaysia was thought to be uncommon and the frequency of anti-aquaporin-4 Ig G antibody was unknown. Objective. To evaluate the frequency of anti-aquaporin-4 Ig G antibody (Anti-AQP4 antibody) amongst patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) and the differences between the seropositive and seronegative groups. Methods. Retrospectively, 96 patients with NMO/high risk syndromes for NMOSD (HRS-NMOSD) were identified out of 266 patients with idiopathic inflammatory demyelinating disease from a single center hospital based registry. Anti-AQP4 seropositivity was found in 38/48 (79.2%) with NMO, 12/21 (57.1%) with brain involvement at high risk for NMOSD, 12/15 (80%) with transverse myelitis (i.e., 11/15 with relapsing transverse myelitis and one with monophasic transverse myelitis), and 3/7 (42.8%) with relapsing optic neuritis. Sixty-five out of 96 patients, that is, 67.7%, with NMO/HRS for NMOSD were seropositive. Seropositivity was significantly associated with female gender, a higher number of mean relapses, that is, 5.15 ± 4.42 versus 2.10 ± 1.68, longer length of spinal cord lesions, that is, 6.6 ± 4.9 versus 2.9 ± 2.5, vertebral bodies, higher EDSS, 4.5 ± 2.4 versus 2.4 ± 2.6, presence of paroxysmal tonic spasms, and blindness (unilateral/bilateral); P < 0.001. Longitudinally extensive cord lesions (contiguous or linear), presence of lesions in the cervical and thoracic regions, and involvement of the central gray matter or holocord regions on axial scans, were also significantly associated with seropositivity; P < 0.001. Conclusion. NMO and HRS for NMOSD are present in larger numbers than previously thought in Malaysia. More than 2/3rds are seropositive. Seropositive and seronegative NMO/NMOSD have differences that are useful in clinical practice.
  3. Fong SL, Lim KS, Tan L, Aris T, Khalid RA, Ali RA, et al.
    Epilepsy Behav, 2019 08;97:206-211.
    PMID: 31252280 DOI: 10.1016/j.yebeh.2019.05.033
    INTRODUCTION: Prevalence studies of epilepsy in Asia revealed a prevalence ranging from 1.5 to 14.0 per 1000 among Asian populations. However, the prevalence of epilepsy in Malaysia is not available for comparison with other countries. This study aimed to translate and validate a Malay brief screening instruments for ascertainment of epilepsy.

    METHOD: We translated into Malay a brief screening instrument for ascertainment of epilepsy designed and validated by Ottman et al., using the three-stage cross-cultural adaptation process developed by the International Quality of Life Assessment (IQOLA) project. We then administered the translated questionnaire via online survey to 162 cases (patients with epilepsy under follow-up care at the neurology clinic in University of Malaya Medical Centre, Kuala Lumpur) and 146 controls with no known history of epilepsy for validation.

    RESULTS: Applying the most liberal definition for a positive screen, we obtained a sensitivity of 96.3% (95% confidence interval [CI]: 91.8-98.5%), with a specificity of 66.4% (95% CI: 58.1-73.0%) and positive predictive value (PPV) of 2.0%. The most stringent definition for a positive screen (only epilepsy) resulted in a sensitivity of 97.4% (95% CI: 62.0-72.6%), specificity of 98.6% (95% CI: 94.6-99.7%), and PPV of 26.6%. Narrowing the definition of a positive screen decreased sensitivity but improved PPVs. When compared to the original English questionnaire, the sensitivities were similar for all four definitions of a positive screen.

    CONCLUSION: This is the first validated epilepsy screening questionnaire in the Malay language and represents a useful tool for the ascertainment of epilepsy in population-based studies.

  4. Hwong WY, Ng SW, Tong SF, Ab Rahman N, Law WC, Kaman Z, et al.
    Front Neurol, 2022;13:1048807.
    PMID: 36504666 DOI: 10.3389/fneur.2022.1048807
    INTRODUCTION: Translation of evidence into clinical practice for use of intravenous thrombolysis in acute stroke care has been slow, especially across low- and middle-income countries. In Malaysia where the average national uptake was poor among the public hospitals in 2018, one hospital intriguingly showed comparable thrombolysis rates to high-income countries. This study aimed to explore and provide in-depth understanding of factors and explanations for the high rates of intravenous stroke thrombolysis in this hospital.

    METHODS: This single case study sourced data using a multimethod approach: (1) semi-structured in-depth interviews and focus group discussions, (2) surveys, and (3) review of medical records. The Tailored Implementation of Chronic Diseases (TICD) framework was used as a guide to understand the determinants of implementation. Twenty-nine participants comprising the Hospital Director, neurologists, emergency physicians, radiologists, pharmacists, nurses and medical assistants (MAs) were included. Thematic analyses were conducted inductively before triangulated with quantitative analyses and document reviews.

    RESULTS: Favorable factors contributing to the uptake included: (1) cohesiveness of team members which comprised of positive interprofessional team dynamics, shared personal beliefs and values, and passionate leadership, and (2) facilitative work process through simplification of workflow and understanding the rationale of the sense of urgency. Patient factors was a limiting factor. Almost two third of ischemic stroke patients arrived at the hospital outside the therapeutic window time, attributing patients' delayed presentation as a main barrier to the uptake of intravenous stroke thrombolysis. One other barrier was the availability of resources, although this was innovatively optimized to minimize its impact on the uptake of the therapy. As such, potential in-hospital delays accounted for only 3.8% of patients who missed the opportunity to receive thrombolysis.

    CONCLUSIONS: Despite the ongoing challenges, the success in implementing intravenous stroke thrombolysis as standard of care was attributed to the cohesiveness of team members and having facilitative work processes. For countries of similar settings, plans to improve the uptake of intravenous stroke thrombolysis should consider the inclusion of interventions targeting on these modifiable factors.

  5. 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.

  6. Hwong WY, Ng SW, Tong SF, Ab Rahman N, Law WC, Wong SK, et al.
    BMC Health Serv Res, 2024 Jan 05;24(1):34.
    PMID: 38183003 DOI: 10.1186/s12913-023-10397-8
    BACKGROUND: Translation into clinical practice for use of intravenous thrombolysis (IVT) for the management of ischemic stroke remains a challenge especially across low- and middle-income countries, with regional inconsistencies in its rate. This study aimed at identifying factors that influenced the provision of IVT and the variation in its rates in Malaysia.

    METHODS: A multiple case study underpinning the Tailored Implementation for Chronic Diseases framework was carried out in three public hospitals with differing rates of IVT using a multiple method design. Twenty-five in-depth interviews and 12 focus groups discussions were conducted among 89 healthcare providers, along with a survey on hospital resources and a medical records review to identify reasons for not receiving IVT. Qualitative data were analysed using reflective thematic method, before triangulated with quantitative findings.

    RESULTS: Of five factors identified, three factors that distinctively influenced the variation of IVT across the hospitals were: 1) leadership through quality stroke champions, 2) team cohesiveness which entailed team dynamics and its degree of alignment and, 3) facilitative work process which included workflow simplification and familiarity with IVT. Two other factors that were consistently identified as barriers in these hospitals included patient factors which largely encompassed delayed presentation, and resource constraints. About 50.0 - 67.6% of ischemic stroke patients missed the opportunity to receive IVT due to delayed presentation.

    CONCLUSIONS: In addition to the global effort to explore sustainable measures to improve patients' emergency response for stroke, attempts to improve the provision of IVT for stroke care should also consider the inclusion of interventions targeting on health systems perspectives such as promoting quality leadership, team cohesiveness and workflow optimisation.

  7. Gopalai AA, Lim SY, Chua JY, Tey S, Lim TT, Mohamed Ibrahim N, et al.
    Biomed Res Int, 2014;2014:867321.
    PMID: 25243190 DOI: 10.1155/2014/867321
    The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson's disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P = 0.019) and 1.2-fold (P = 0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies.
  8. Lim JL, Lohmann K, Tan AH, Tay YW, Ibrahim KA, Abdul Aziz Z, et al.
    J Neural Transm (Vienna), 2022 Jan;129(1):37-48.
    PMID: 34779914 DOI: 10.1007/s00702-021-02421-0
    GBA variants are associated with increased risk and earlier onset of Parkinson's disease (PD), and more rapid disease progression especially with "severe" variants typified by p.L483P. GBA mutation screening studies from South-East Asia, with > 650 million inhabitants of diverse ancestries, are very limited. We investigated the spectrum of GBA variants, and associated clinico-demographic features, in a multi-ethnic PD cohort in Malaysia. Patients (n = 496) were recruited from seven centres, primarily of Chinese (45%), Malay (37%), and Indian (13%) ethnicities. All GBA coding exons were screened using a next-generation sequencing-based PD gene panel and verified with Sanger sequencing. We identified 14 heterozygous GBA alleles consisting of altogether 17 missense variants (8 classified as pathogenic or likely pathogenic for PD) in 25 (5.0%) patients, with a substantially higher yield among early (
  9. Tan AH, Lohmann K, Tay YW, Lim JL, Ahmad-Annuar A, Ramli N, et al.
    Parkinsonism Relat Disord, 2020 10;79:34-39.
    PMID: 32861104 DOI: 10.1016/j.parkreldis.2020.08.015
    BACKGROUND: An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK-PINK1 are also limited.

    METHODS: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.

    RESULTS: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented.

    CONCLUSIONS: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.

  10. Lim JL, Ng EY, Lim SY, Tan AH, Abdul-Aziz Z, Ibrahim KA, et al.
    Neurol Sci, 2021 Oct;42(10):4203-4207.
    PMID: 33559030 DOI: 10.1007/s10072-021-05056-x
    BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry.

    METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.

    RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.

    CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.

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