Displaying publications 41 - 60 of 113 in total

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  1. Tan AH, Toh TH, Low SC, Fong SL, Chong KK, Lee KW, et al.
    J Mov Disord, 2018 Sep;11(3):149-151.
    PMID: 30086616 DOI: 10.14802/jmd.18017
  2. Lim SY, Ishiura H, Ramli N, Shibata S, Almansour MA, Tan AH, et al.
    Parkinsonism Relat Disord, 2020 05;74:25-27.
    PMID: 32289521 DOI: 10.1016/j.parkreldis.2020.03.025
    Two ethnic Chinese men with clinico-radiologic features of Fragile X-associated tremor-ataxia syndrome (FXTAS) were found on genetic testing to have neuronal intranuclear inclusion disease (NIID), highlighting that NIID should be considered in the differential diagnosis of FXTAS. NIID may also be much more common than FXTAS in certain Asian populations.
  3. Lim SY, Mason WP, Young NP, Chen R, Bower JH, McKeon A, et al.
    Arch. Neurol., 2009 Oct;66(10):1285-7.
    PMID: 19822786 DOI: 10.1001/archneurol.2009.203
    OBJECTIVE:
    To describe and provide audiovisual documentation of a syndrome of polymyoclonus, laryngospasm, and cerebellar ataxia associated with adenocarcinoma and multiple neural cation channel autoantibodies.

    DESIGN:
    Case report with video.

    SETTING:
    University hospitals. Patient A 69-year-old woman presented with subacute onset of whole-body tremulousness and laryngospasm attributed to gastroesophageal reflux.

    RESULTS:
    Further evaluation revealed polymyoclonus, cerebellar ataxia, and laryngospasm suspicious of an underlying malignant neoplasm. Surface electromyography of multiple limb muscles confirmed the presence of polymyoclonus. The patient was seropositive for P/Q-type voltage-gated calcium channel antibody; subsequently, whole-body fluorine 18 fluorodeoxyglucose positron emission tomography and cervical lymph node biopsy revealed widespread metastatic adenocarcinoma. Follow-up serologic evaluation revealed calcium channel antibodies (P/Q type and N type) and potassium channel antibody.

    CONCLUSIONS:
    We highlight the importance of recognizing polymyoclonus. To our knowledge, this is also the first description of a syndrome of polymyoclonus, laryngospasm, and ataxia associated with adenocarcinoma and these cation channel antibodies.
  4. Chang YP, Yang CJ, Hu KF, Chao AC, Chang YH, Hsieh KP, et al.
    Neuropsychiatr Dis Treat, 2016;12:1037-46.
    PMID: 27175081 DOI: 10.2147/NDT.S99365
    Pneumonia is the leading cause of death in patients with Parkinson's disease (PD). However, few studies have been performed to explore the risk factors for pneumonia development in patients with PD.
  5. Suwarnalata G, Tan AH, Isa H, Gudimella R, Anwar A, Loke MF, et al.
    PLoS One, 2016;11(4):e0153725.
    PMID: 27100827 DOI: 10.1371/journal.pone.0153725
    Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.
  6. Fong SL, Dy Closas AMF, Lim TT, Lean PL, Loh EC, Lim SY, et al.
    Parkinsonism Relat Disord, 2023 Apr;109:105332.
    PMID: 36948111 DOI: 10.1016/j.parkreldis.2023.105332
    The diagnostic approach to sleep-related movements disorders is seldom discussed. We report a case of fatal familial insomnia who initially presented with persistent limb movements in sleep, which later progressed to a state of agrypnia excitata. Here, the evaluation of abnormal movements in sleep is discussed using a step-by-step diagnostic approach. Although no cure is available for fatal familial insomnia, prompt recognition of this condition is important to facilitate proper management, including the involvement of interdisciplinary neuropalliative care.
  7. Lim KB, Lim SY, Hor JW, Krishnan H, Mortadza F, Lim JL, et al.
    Parkinsonism Relat Disord, 2024 Apr 22;123:106980.
    PMID: 38657381 DOI: 10.1016/j.parkreldis.2024.106980
    BACKGROUND: Screening for orthostatic hypotension (OH) is integral in Parkinson's disease (PD) management, yet evidence-based guidelines on best practice methods for diagnosing OH in PD are lacking.

    METHODS: We investigated the frequency and correlates of OH, symptomatic OH, and neurogenic OH, in a large consecutively recruited PD cohort (n = 318), and compared the diagnostic performance of the sit-to-stand vs. the supine-to-stand blood pressure (BP) test. We evaluated the utility of continuous BP monitoring and tilt table testing in patients with postural symptoms or falls who were undetected to have OH with clinic-based BP measurements. Disease severity, fluid intake, orthostatic and overactive bladder symptoms, falls, comorbidities and medication history were evaluated.

    RESULTS: Patients' mean age was 66.1 ± 9.5years, with mean disease duration 7.8 ± 5.5years. OH frequency was 35.8 % based on the supine-to-stand test. OH in PD was significantly associated with older age, lower body mass index, longer disease duration, worse motor, cognitive and overactive bladder symptoms and functional disabilities, falls, and lower fluid intake. A similar profile was seen with asymptomatic OH. Three quarters of OH were neurogenic, with the majority also having supine hypertension. The sit-to-stand test had a sensitivity of only 0.39. One quarter of patients were additionally diagnosed with OH during continuous BP monitoring.

    CONCLUSIONS: The sit-to-stand test substantially underdiagnoses OH in PD, with the important practice implication that supine-to-stand measurements may be preferred. Screening for OH is warranted even in asymptomatic patients. Adequate fluid intake, treatment of urinary dysfunction and falls prevention are important strategies in managing PD patients with OH.

  8. Lim SY, Pajo AT, Dy Closas AMF, Hor JW, Toh TS, Ngim SJ, et al.
    Parkinsonism Relat Disord, 2025 Jan;130:107162.
    PMID: 39406616 DOI: 10.1016/j.parkreldis.2024.107162
    Recent studies highlight an over-representation of progressive supranuclear palsy, with atypical features, in South Asians. We offer additional insights, including an over-representation of PSP among Malaysian patients of Indian compared to other Asian ancestries. However, RBD symptoms, hallucinations, and early onset were not more frequent in Indians vs. Chinese.
  9. Tan AH, Chong CW, Song SL, Teh CSJ, Yap IKS, Loke MF, et al.
    Mov Disord, 2018 01;33(1):174-176.
    PMID: 29083071 DOI: 10.1002/mds.27203
  10. Tan AH, Lim SY, Chong KK, A Manap MAA, Hor JW, Lim JL, et al.
    Neurology, 2021 02 02;96(5):e772-e782.
    PMID: 33046607 DOI: 10.1212/WNL.0000000000010998
    OBJECTIVE: To determine whether probiotics are effective for constipation, a common and often difficult-to-treat problem, in Parkinson disease (PD).

    METHODS: In this double-blind, randomized, placebo-controlled, single-center trial, 280 patients with PD were screened, and 72 eligible patients were block-randomized (1:1) to receive either multistrain probiotics capsules (n = 34) or identical-appearing placebo (n = 38), for 4 weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last 2 weeks of intervention compared with the 2-week preintervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome.

    RESULTS: SBM increased by 1.0 ± 1.2 per week after treatment with probiotics and decreased by 0.3 ± 1.0 per week in the placebo group (mean difference 1.3, 95% confidence interval 0.8-1.8, p < 0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency (p = 0.009) and quality of life related to constipation (p = 0.001). In the treatment group, 65.6% reported satisfaction with the intervention vs only 21.6% in the placebo group (p < 0.001). One patient (2.9%) in the treatment group withdrew due to a nonserious adverse event. Fecal calprotectin did not change significantly during the study.

    CONCLUSIONS: Multistrain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action.

    CLINICALTRIALSGOV IDENTIFIER: NCT03377322.

    CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for people with PD, multistrain probiotics significantly increased the average number of SBM per week.

  11. Lim SY, Lim JL, Ahmad-Annuar A, Lohmann K, Tan AH, Lim KB, et al.
    Neurodegener Dis, 2020;20(1):39-45.
    PMID: 32580205 DOI: 10.1159/000508131
    Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall "real world" PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.
  12. Tan YJ, Lim SY, Yong VW, Choo XY, Ng YD, Sugumaran K, et al.
    J Clin Densitom, 2020 07 30;24(3):351-361.
    PMID: 32888777 DOI: 10.1016/j.jocd.2020.07.001
    Osteoporotic fractures are common in Parkinson's disease (PD). Standard dual-energy X-ray absorptiometry (DXA) measuring bone mineral density (BMD) at the femoral neck and lumbar spine (central sites) has suboptimal sensitivity in predicting fracture risk in the general population. An association between sarcopenia and osteoporosis in PD has not been studied. We compared BMD and osteoporosis prevalence in PD patients vs controls; determined the osteoporosis detection rates using central alone vs central plus distal radius DXA; and analyzed factors (in particular, sarcopenia) associated with osteoporosis. One hundred and fifty-six subjects (102 patients with PD, 54 spousal/sibling controls) underwent femoral neck-lumbar spine-distal radius DXA. Seventy-three patients and 46 controls were assessed for sarcopenia using whole-body DXA and handgrip strength. Patients underwent clinical and serum biochemical evaluations. PD patients had significantly lower body mass index compared to controls. After adjustment for possible confounders, distal radius BMD and T-scores were significantly lower in PD patients compared to controls, but not at the femoral neck/lumbar spine. With distal radius DXA, an additional 11.0% of patients were diagnosed with osteoporosis (32.0% to 43.0%), vs 3.7% in controls (33.3% to 37.0%) additionally diagnosed; this increase was largely driven by the markedly higher detection rate in female PD patients. Female gender (adjusted odds ratio [ORadjusted] = 11.3, 95% confidence interval [CI]: 2.6-48.6) and sarcopenia (ORadjusted = 8.4, 95% CI: 1.1-64.9) were independent predictors for osteoporosis in PD. Distal radius DXA increased osteoporosis detection, especially in female PD patients, suggesting that diagnostic protocols for osteoporosis in PD could be optimized. A close association between osteoporosis and sarcopenia was documented for the first time in PD, which has important implications for clinical management and future research.
  13. Miyasaki JM, Lim SY, Chaudhuri KR, Antonini A, Piemonte M, Richfield E, et al.
    Mov Disord, 2022 Jan;37(1):182-189.
    PMID: 34431560 DOI: 10.1002/mds.28773
    BACKGROUND: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited.

    OBJECTIVE: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care.

    METHODS: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e-mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated.

    RESULTS: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle- and high-income countries. Government-funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty-nine percent worked in multidisciplinary teams. The majority endorsed trigger-based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills.

    CONCLUSIONS: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society.

  14. Chaudhuri KR, Rukavina K, McConvey V, Antonini A, Lorenzl S, Bhidayasiri R, et al.
    Expert Rev Neurother, 2021 06;21(6):615-623.
    PMID: 33905283 DOI: 10.1080/14737175.2021.1923480
    Introduction: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities.Areas covered: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly - as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.Expert opinion: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms - both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term.
  15. Toh TS, Chong CW, Lim SY, Bowman J, Cirstea M, Lin CH, et al.
    Parkinsonism Relat Disord, 2022 Jan;94:1-9.
    PMID: 34844021 DOI: 10.1016/j.parkreldis.2021.11.017
    BACKGROUND: Gut microbiome alterations have been reported in Parkinson's disease (PD), but with heterogenous findings, likely due to differences in study methodology and population. We investigated the main microbiome alterations in PD, their correlations with disease severity, and the impact of study and geographical differences.

    METHODS: After systematic screening, raw 16S rRNA gene sequences were obtained from ten case-control studies totaling 1703 subjects (969 PD, 734 non-PD controls; seven predominantly Caucasian and three predominantly non-Caucasian cohorts). Quality-filtered gene sequences were analyzed using a phylogenetic placement approach, which precludes the need for the sequences to be sourced from similar regions in the 16S rRNA gene, thus allowing a direct comparison between studies. Differences in microbiome composition and correlations with clinical variables were analyzed using multivariate statistics.

    RESULTS: Study and geography accounted for the largest variations in gut microbiome composition. Microbiome composition was more similar for subjects from the same study than those from different studies with the same disease status. Microbiome composition significantly differed between Caucasian and non-Caucasian populations. After accounting for study differences, microbiome composition was significantly different in PD vs. controls (albeit with a marginal effect size), with several distinctive features including increased abundances of Megasphaera and Akkermansia, and reduced Roseburia. Several bacterial genera correlated with PD motor severity, motor response complications and cognitive function.

    CONCLUSION: Consistent microbial features in PD merit further investigation. The large variations in microbiome findings of PD patients underscore the need for greater harmonization of future research, and personalized approaches in designing microbial-directed therapeutics.

  16. Hor JW, Lim SY, Khor ES, Chong KK, Song SL, Ibrahim NM, et al.
    J Mov Disord, 2021 Dec 24.
    PMID: 34937162 DOI: 10.14802/jmd.21085
    Objective: Converging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson's disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA.

    Methods: We recruited 169 subjects (71 PD, 38 MSA, and 60 age-similar nonneurological controls). Clinico-demographic data were collected. PD and MSA were subtyped and the severity assessed using the MDS-UPDRS and UMSARS, respectively. Fecal calprotectin and blood immune markers were analyzed.

    Results: Compared to controls (median: 35.7 [IQR: 114.2] μg/g), fecal calprotectin was significantly elevated in PD (median: 95.6 [IQR: 162.1] μg/g, p = 0.003) and even higher in MSA (median: 129.5 [IQR: 373.8] μg/g, p = 0.002). A significant interaction effect with age was observed; between-group differences were significant only in older subjects (i.e., ≥ 61 years) and became more apparent with increasing age. A total of 28.9% of MSA and 18.3% of PD patients had highly abnormal fecal calprotectin levels (≥ 250 μg/g); however, this difference was only significant for MSA compared to controls. Fecal calprotectin correlated moderately with selected blood immune markers in PD, but not with clinical features of PD or MSA.

    Conclusions: Elevated fecal calprotectin suggests a role for intestinal inflammation in PD and MSA. A more complete understanding of gut immune alterations could open up new avenues of research and treatment for these debilitating diseases.

  17. Lim SY, Tan ZK, Ngam PI, Lor TL, Mohamed H, Schee JP, et al.
    Parkinsonism Relat Disord, 2011 Dec;17(10):761-4.
    PMID: 21839665 DOI: 10.1016/j.parkreldis.2011.07.009
    There are limited data on the prevalence of impulsive-compulsive behaviors and subsyndromal impulsive-compulsive behaviors in Asian patients with Parkinson's disease, who are treated with lower dosages of dopaminergic medications.
  18. Tan AH, Cornejo-Olivas M, Okubadejo N, Pal PK, Saranza G, Saffie-Awad P, et al.
    Mov Disord Clin Pract, 2024 Jan;11(1):14-20.
    PMID: 38291851 DOI: 10.1002/mdc3.13903
  19. Closas AMFD, Lohmann K, Tan AH, Ibrahim NM, Lim JL, Tay YW, et al.
    J Mov Disord, 2023 Jan;16(1):91-94.
    PMID: 36537064 DOI: 10.14802/jmd.22109
    KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.
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