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  1. Lim KS, Fong SL, Yu X, Lim YH, Wong KY, Lai ST, et al.
    Epilepsy Behav, 2024 Jun;155:109778.
    PMID: 38636139 DOI: 10.1016/j.yebeh.2024.109778
    INTRODUCTION: Depression and anxiety are prevalent in epilepsy patients, but psychiatric or psychological services may not be accessible to all patients. This study aimed to determine the effectiveness of the 20-minute mindful breathing on the psychological well-being of PWE using an instructional video.

    METHOD: This was a pilot, assessor-blinded, randomized controlled trial. The intervention group received a guided video and was briefed to perform the exercise twice a week for two weeks while the waitlist control group only received the video upon completion of the study. The subjects were assessed at three-time points (T0: Baseline, T1: 2 weeks after the intervention, T2: 4 weeks after intervention), using the Neurological Disorders Depression Index (NDDI-E), General Anxiety Disorder (GAD-7), Quality of Life in Epilepsy Inventory (QOLIE-31) and Mindfulness Attention Awareness Scale (MAAS).

    RESULTS: Twenty patients were recruited, with 10 in the intervention and waitlist-control groups. Compared with the waitlist-control group, participants in the intervention group showed significant improvement in NDDI-E at T1 (p = 0.022) but not at T2 (p = 0.056) and greater improvement in GAD-7 at T1 and T2 but not statistically significant. The QOLIE-31 overall score in the intervention group has significantly improved at T1 (p = 0.036) and T2 (p = 0.031) compared to the waitlist-control group. For MAAS, the intervention group also had an increased score at T2 (p = 0.025).

    CONCLUSION: The 20-minute mindfulness breathing exercise has an immediate effect in improving depression and quality of life among people with epilepsy.

  2. Fong SL, Shauna A, Lim KS, Ng CG, Yu X, Lai ST, et al.
    Epilepsy Behav, 2025 Feb;163:110196.
    PMID: 39662320 DOI: 10.1016/j.yebeh.2024.110196
    INTRODUCTION: Psychiatric comorbidities such as depression and anxiety disorders are highly prevalent among people with epilepsy (PWE). These two co-occurring chronic illnesses could lead to double stigma and negatively impact every aspect of psychiatric and epilepsy care for PWE, especially in help-seeking behavior. We aimed to identify the socio-demographic and clinical factors contributing to reluctance to be referred to a psychiatrist among PWE.

    METHODS: A prospective cross-sectional study was conducted at a tertiary teaching hospital in Kuala Lumpur, Malaysia. Psychological screening was done using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and General Anxiety Disorder (GAD-7) questionnaire. Patients screened positive were offered psychiatric referrals and given an early psychiatric clinic appointment if they agreed to the referral. The reasons for those who refused the referral were noted.

    RESULTS: Out of 585 patients, 91 (15.5 %) were screened positive for depression and/or anxiety. Eighteen patients were excluded from the study due to pre-existing psychiatric disorders. Of the remaining 73 patients, 23 (31.5 %) agreed to be referred to a psychiatrist. Only 17 (23.3 %) attended the psychiatrist appointment. A total of 11 (15.1 %) and one (1.4 %) patients were subsequently diagnosed with major depressive disorder and generalized anxiety disorder, respectively. Another 50 (68.5 %) patients were not referred to a psychiatrist, predominantly (n = 43, 58.9 %) due to reluctance to be referred to a psychiatrist. The reasons included avoidance of referral likely related to stigma (n = 22, 51.2 %), self-reliance, family and caregivers' disapproval of referral, and logistic difficulty. The mean scores in NDDI-E and GAD-7 in the referred group were higher than the not-referred group but not statistically significant (NDDI-E: 17.8 ± 3.6 vs. 16.5 ± 2.5, p = 0.072; GAD-7: 12.4 ± 5.70 vs. 9.8 ± 5.4, p = 0.061).

    CONCLUSION: A significant number of PWE were reluctant to receive psychiatric referrals predominantly due to self-avoidance or family and caregiver disapproval of referral likely related to stigma. An integrated epilepsy care management model is recommended.

  3. 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.

  4. Tan CT, Goh KJ, Wong KT, Sarji SA, Chua KB, Chew NK, et al.
    Ann Neurol, 2002 Jun;51(6):703-8.
    PMID: 12112075
    An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.
  5. Haerian BS, Lim KS, Tan HJ, Mohamed EH, Tan CT, Raymond AA, et al.
    Epileptic Disord, 2011 Mar;13(1):65-75.
    PMID: 21388909 DOI: 10.1684/epd.2011.0419
    Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.
  6. 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 =

  7. 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.
  8. 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.

  9. Abubakar S, Teoh BT, Sam SS, Chang LY, Johari J, Hooi PS, et al.
    Emerg Infect Dis, 2013 Dec;19(12):1989-91.
    PMID: 24274071 DOI: 10.3201/eid1912.120530
    An outbreak of fever associated with myalgia and myositis occurred in 2012 among 89 of 92 college students and teachers who visited Pangkor Island, Malaysia. The Sarcocystis nesbitti 18S rRNA gene and sarcocysts were obtained from muscle tissues of 2 students. Our findings indicate emergence of S. nesbitti infections in humans in Malaysia.
  10. Haerian BS, Baum L, Kwan P, Cherny SS, Shin JG, Kim SE, et al.
    Mol Neurobiol, 2016 10;53(8):5457-67.
    PMID: 26452361 DOI: 10.1007/s12035-015-9457-y
    Gamma-aminobutyric acid receptor (GABA-A) is the most common receptor of fast synaptic inhibition in the human brain. Gamma protein encoded by the GABRG2 gene is one of the subunits of the GABA-A receptor, which plays an essential role in the function of this receptor. Several studies have identified various febrile seizure (FS) and epilepsy risk variants of GABRG2 gene in different populations, but some others did not support these results. The aim of this case-control study is to investigate whether GABRG2 polymorphisms contribute to susceptibility for FS and epilepsy in pooled data of three cohorts, from Malaysia (composed of Malay, Chinese, and Indian), Hong Kong, and Korea. Furthermore, the pooled dataset of these cohorts with previous reports were meta-analyzed for determining the risk effect size of the rs211037 polymorphism on FS and symptomatic epilepsy (SE). The rs211037, rs210987, rs440218, rs2422106, rs211014, and rs401750 polymorphisms were genotyped in the 6442 subjects (1729 epilepsy and 4713 controls). Results of the case-control study showed associations between rs211037 and the risk of SE in the pooled data from all cohorts (T vs. C, p = 3 × 10(-5), and TT vs. CC, p = 2 × 10(-5)) and the risk of partial seizure in the combined data of Malaysia and Hong Kong (both T vs. C and TT vs. CC, p = 2 × 10(-6)). The rs211037-rs210987 and rs2422106-rs211014-rs401750 haplotypes were also associated with susceptibility to SE in Chinese. Meta-analysis of all Asians identified association between rs211037 and FS and SE (T vs. C, p = 4 × 10(-4), and p = 4 × 10(-3), respectively). In conclusion, rs211037 alone may be a risk factor for FS, partial seizure, and SE, and in linkage disequilibrium with rs210987 can contribute to FS and SE in Asians, particularly in Chinese.
  11. Ong HM, Ibrahim PAS, Chong CN, Tan CT, Schee JP, Avumegah MS, et al.
    J Infect, 2025 Feb;90(2):106398.
    PMID: 39755279 DOI: 10.1016/j.jinf.2024.106398
    OBJECTIVE: To evaluate the long-term humoral immune response to Nipah virus (NiV) in a cohort of 25 survivors after 25 years of post-infection.

    METHODS: A total of 25 survivors of NiV infection from the 1998 outbreak were recruited for sample collection. The serum IgG antibody response to NiV antigens, specifically nucleocapsid (N), fusion glycoprotein (F) and attachment glycoprotein (G) was evaluated using ELISA. Additionally, the samples were tested for neutralizing antibodies and memory B cell responses.

    RESULTS: Detection rates of anti-NiV-F and anti-NiV-G were 56% and 60%, respectively, among the survivors at a 1:100 dilution, whereas only 20% were specifically reactive to rNiV-N. Notably, all samples that tested positive for NiV-F and NiV-G at this dilution also exhibited neutralizing antibodies, highlighting the specificity of these assays. Live virus neutralization assay showed that 72% of survivors had detectable neutralizing antibodies, with varying titers, indicating long-lasting immune memory. Furthermore, memory B cell responses specific to NiV-F and NiV-G were observed in six randomly selected survivors, suggesting the presence of enduring immunological memory.

    CONCLUSIONS: These findings highlight the potential of NiV-F and NiV-G as reliable markers for NiV exposure and underscore the need for continuous surveillance and research. Such efforts are crucial for advancing vaccine development and improving preparedness for future NiV outbreaks.

  12. Tai MS, Viswanathan S, Rahmat K, Nor HM, Kadir KA, Goh KJ, et al.
    Sci Rep, 2016 12 13;6:38802.
    PMID: 27958312 DOI: 10.1038/srep38802
    Tuberculous meningitis (TBM) causes significant morbidity and mortality. The primary objective was to re-examine the concept of "TB zone" and "ischaemic zone" in cerebral infarction in patients with tuberculous meningitis. The secondary objective was to evaluate cerebral infarction, vasculitis and vasospasm in tuberculous meningitis infections. Between 2009 and 2014, TBM patients were recruited. Neuroimaging was performed and findings of cerebral infarction, vasculitis and vasospasm were recorded. Infarcts were classified based on arterial supply and Hsieh's classification. Fifty-one TBM patients were recruited of whom 34 patients (67%) had cerebral infarction. Based on Hsieh's classification, 20 patients (59%) had infarcts in both "TB zone" and "ischaemic zones". 12 patients (35%) had infarcts in "ischaemic zone" and two (6%) patients had infarcts in "TB zone". In terms of vascular supply, almost all patients (35/36) had infarcts involving perforators and cortical branches. 25 patients (73%) and 14 patients (41%) had infarcts supplied by lateral lenticulostriate and medial lenticulostriate arteries respectively. 15 patients (37%) had vasculitis. Vasospasm was present in six patients (15%). 29 patients (85%) with cerebral infarction also had leptomeningeal enhancement (p = 0.002). In summary, infarcts involved mainly perforators and cortical branches, rather than "TB zone" versus "ischaemic zone".
  13. 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.

  14. Lim SY, Tan AH, Ahmad-Annuar A, Klein C, Tan LCS, Rosales RL, et al.
    Lancet Neurol, 2019 09;18(9):865-879.
    PMID: 31175000 DOI: 10.1016/S1474-4422(19)30195-4
    1·8 billion people of diverse ethnicities and cultures live in the Western Pacific Region. The increasing longevity of populations in this region is a major contributor to the exponential increase in Parkinson's disease prevalence worldwide. Differences exist between Parkinson's disease in the Western Pacific Region and in Europe and North America that might provide important insights into our understanding of the disease and approaches to management. For example, some genetic factors (such as LRRK2 mutations or variants) differ, environmental exposures might play differential roles in modulating the risk of Parkinson's disease, and fewer dyskinesias are reported, with some differences in the profile of non-motor symptoms and comorbidities. Gaps in awareness of the disease and inequitable access to treatments pose challenges. Further improvements in infrastructure, clinical governance, and services, and concerted collaborative efforts in training and research, including greater representation of the Western Pacific Region in clinical trials, will improve care of patients with Parkinson's disease in this region and beyond.
  15. Gopalai AA, Lim JL, Li HH, Zhao Y, Lim TT, Eow GB, et al.
    Mol Genet Genomic Med, 2019 Nov;7(11):e604.
    PMID: 31487119 DOI: 10.1002/mgg3.604
    BACKGROUND: The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K-R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population.

    METHODS: Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age- and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay.

    RESULTS: A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta-analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H.

    CONCLUSION: This study reports that the N551K-R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

  16. Choo XY, Lim SY, Chinna K, Tan YJ, Yong VW, Lim JL, et al.
    Neurol Sci, 2020 Oct;41(10):2831-2842.
    PMID: 32314118 DOI: 10.1007/s10072-020-04396-4
    INTRODUCTION: Little is known regarding the educational needs and perspectives of people living with Parkinson's disease (PD), particularly in Asia.

    OBJECTIVE: To assess knowledge and perceptions regarding PD in a large multiethnic urban Asian cohort of patients and caregivers.

    METHODS: We conducted a survey at a university hospital neurology clinic, using a novel Knowledge and Perception of Parkinson's Disease Questionnaire (KPPDQ).

    RESULTS: The KPPDQ had satisfactory psychometric properties among patients and caregivers. Five hundred subjects were recruited with a 97% response rate (211 patients, 273 caregivers). Non-motor symptoms such as urinary problems, visual hallucinations and pain were relatively poorly recognized. Many (≈ 50-80%) respondents incorrectly believed that all PD patients experience tremor, that PD is usually familial, and that there is a cure for PD. About one-half perceived PD to be caused by something the patient had done in the past, and that PD medications were likely to cause internal organ damage. Issues of stigma/shame were relevant to one-third of patients, and 70% of patients perceived themselves to be a burden to others. Two-thirds of participants felt that PD imposed a heavy financial toll. Participants were about equally divided as to whether they would consider treatment with deep brain stimulation, tube feeding or invasive ventilation. Over three-quarters of patients expressed a preference to die at home.

    CONCLUSIONS: Important knowledge gaps, misperceptions and perspectives on PD were identified, highlighting the need for further efforts to raise awareness and provide accurate information regarding PD, and to address patient's and caregivers' needs and preferences.

  17. Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, et al.
    Am J Pathol, 2002 Dec;161(6):2153-67.
    PMID: 12466131
    In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.
  18. Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK, Yeat CM, et al.
    Parkinsonism Relat Disord, 2014 May;20(5):535-40.
    PMID: 24637123 DOI: 10.1016/j.parkreldis.2014.02.019
    BACKGROUND: Recent studies reported a high prevalence of small intestinal bacterial overgrowth (SIBO) in Parkinson's disease (PD), and a possible association with gastrointestinal symptoms and worse motor function. We aimed to study the prevalence and the potential impact of SIBO on gastrointestinal symptoms, motor function, and quality of life in a large cohort of PD patients.
    METHODS: 103 Consecutive PD patients were assessed using the lactulose-hydrogen breath test; questionnaires of gastrointestinal symptoms and quality of life (PDQ-39); the Unified PD Rating Scale (UPDRS) including "on"-medication Part III (motor severity) score; and objective and quantitative measures of bradykinesia (Purdue Pegboard and timed test of gait). Patients and evaluating investigators were blind to SIBO status.
    RESULTS: 25.3% of PD patients were SIBO-positive. SIBO-positive patients had a shorter mean duration of PD (5.2 ± 4.1 vs. 8.1 ± 5.5 years, P = 0.007). After adjusting for disease duration, SIBO was significantly associated with lower constipation and tenesmus severity scores, but worse scores across a range of "on"-medication motor assessments (accounting for 4.2-9.0% of the variance in motor scores). There was no association between SIBO and motor fluctuations or PDQ-39 Summary Index scores.
    CONCLUSIONS: This is the largest study to date on SIBO in PD. SIBO was detected in one quarter of patients, including patients recently diagnosed with the disease. SIBO was not associated with worse gastrointestinal symptoms, but independently predicted worse motor function. Properly designed treatment trials are needed to confirm a causal link between SIBO and worse motor function in PD.
    KEYWORDS: Gastrointestinal dysfunction; Parkinson's disease/Parkinsonism; Small intestinal bacterial overgrowth
  19. 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.
  20. Tan AH, Mahadeva S, Marras C, Thalha AM, Kiew CK, Yeat CM, et al.
    Parkinsonism Relat Disord, 2015 Mar;21(3):221-5.
    PMID: 25560322 DOI: 10.1016/j.parkreldis.2014.12.009
    BACKGROUND: Some studies have suggested that chronic Helicobacter pylori (HP) infection can aggravate the neurodegenerative process in Parkinson's disease (PD), and targeted intervention could potentially modify the course of this disabling disease. We aimed to study the impact of HP infection on motor function, gastrointestinal symptoms, and quality of life in a large cohort of PD patients.
    METHODS: 102 consecutive PD patients underwent (13)C urea breath testing and blinded evaluations consisting of the Unified Parkinson's Disease Rating Scale (UPDRS) including "On"-medication motor examination (Part III), objective and quantitative measures of bradykinesia (Purdue Pegboard and timed gait), Leeds Dyspepsia Questionnaire, and PDQ-39 (a health-related quality of life questionnaire).
    RESULTS: 32.4% of PD patients were HP-positive. HP-positive patients were older (68.4 ± 7.3 vs. 63.8 ± 8.6 years, P = 0.009) and had worse motor function (UPDRS Part III 34.0 ± 13.0 vs. 27.3 ± 10.0, P = 0.04; Pegboard 6.4 ± 3.3 vs. 8.0 ± 2.7 pins, P = 0.04; and timed gait 25.1 ± 25.4 vs. 15.5 ± 7.6 s, P = 0.08). In the multivariate analysis, HP status demonstrated significant main effects on UPDRS Part III and timed gait. The association between HP status and these motor outcomes varied according to age. Gastrointestinal symptoms and PDQ-39 Summary Index scores did not differ between the two groups.
    CONCLUSIONS: This is the largest cross-sectional study to demonstrate an association between HP positivity and worse PD motor severity.
    KEYWORDS: Gastrointestinal dysfunction; Helicobacter pylori; Parkinson's disease
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