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Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West

Chong HT, Ramli N, Lee KH, Kim BJ, Ursekar M, Dayananda K, et al.

Can J Neurol Sci, 2006 Feb;33(1):95-100.
PMID: 16583730

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.
Progressive and accelerated weight and body fat loss in Parkinson's disease: A three-year prospective longitudinal study

Yong VW, Tan YJ, Ng YD, Choo XY, Sugumaran K, Chinna K, et al.

Parkinsonism Relat Disord, 2020 08;77:28-35.
PMID: 32615497 DOI: 10.1016/j.parkreldis.2020.06.015

INTRODUCTION: Although weight loss is common in Parkinson's disease (PD), longitudinal studies assessing weight and body composition changes are limited.
METHODS: In this three-year longitudinal study, 125 subjects (77 PD patients and 48 spousal/sibling controls) underwent clinical, biochemical and body composition assessments using dual-energy X-ray absorptiometry.
RESULTS: Patients were older than controls (65.6 ± 8.9 vs. 62.6 ± 7.1, P = 0.049), with no significant differences in gender, comorbidities, dietary intake and physical activity. Clinically significant weight loss (≥5% from baseline weight) was recorded in 41.6% of patients, with a doubling of cases (6.5 to 13.0%) classified as underweight at study end. Over three years, patients demonstrated greater reductions in BMI (mean -1.2 kg/m2, 95%CI-2.0 to -0.4), whole-body fat percentage (-2.5% points, 95%CI-3.9 to -1.0), fat mass index (FMI) (-0.9 kg/m2, 95%CI-1.4 to -0.4), visceral fat mass (-0.1 kg, 95%CI-0.2 to 0.0), and subcutaneous fat mass (-1.9 kg, 95%CI-3.4 to -0.5) than in controls, with significant group-by-time interactions after adjusting for age and gender. Notably, 31.2% and 53.3% of patients had FMI<3rd (severe fat deficit) and <10th centiles, respectively. Muscle mass indices decreased over time in both groups, without significant group-by-time interactions. Multiple linear regression models showed that loss of body weight and fat mass in patients were associated with age, dyskinesia, psychosis and constipation.
CONCLUSIONS: We found progressive loss of weight in PD patients, with greater loss of both visceral and subcutaneous fat, but not muscle, compared to controls. Several associated factors (motor and non-motor disease features) were identified for these changes, providing insights on possible mechanisms and therapeutic targets.
Fulltext Cerebral infarction pattern in tuberculous meningitis

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".
PINK1 p.Leu347Pro mutations in Malays: Prevalence and illustrative cases

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.
Fulltext Individually-tailored multifactorial intervention to reduce falls in the Malaysian Falls Assessment and Intervention Trial (MyFAIT): A randomized controlled trial

Tan PJ, Khoo EM, Chinna K, Saedon NI, Zakaria MI, Ahmad Zahedi AZ, et al.

PLoS One, 2018;13(8):e0199219.
PMID: 30074996 DOI: 10.1371/journal.pone.0199219

OBJECTIVE: To determine the effectiveness of an individually-tailored multifactorial intervention in reducing falls among at risk older adult fallers in a multi-ethnic, middle-income nation in South-East Asia.

DESIGN: Pragmatic, randomized-controlled trial.

SETTING: Emergency room, medical outpatient and primary care clinic in a teaching hospital in Kuala Lumpur, Malaysia.

PARTICIPANTS: Individuals aged 65 years and above with two or more falls or one injurious fall in the past 12 months.

INTERVENTION: Individually-tailored interventions, included a modified Otago exercise programme, HOMEFAST home hazards modification, visual intervention, cardiovascular intervention, medication review and falls education, was compared against a control group involving conventional treatment.

PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was any fall recurrence at 12-month follow-up. Secondary outcomes were rate of fall and time to first fall.

RESULTS: Two hundred and sixty-eight participants (mean age 75.3 ±7.2 SD years, 67% women) were randomized to multifactorial intervention (n = 134) or convention treatment (n = 134). All participants in the intervention group received medication review and falls education, 92 (68%) were prescribed Otago exercises, 86 (64%) visual intervention, 64 (47%) home hazards modification and 51 (38%) cardiovascular intervention. Fall recurrence did not differ between intervention and control groups at 12-months [Risk Ratio, RR = 1.037 (95% CI 0.613-1.753)]. Rate of fall [RR = 1.155 (95% CI 0.846-1.576], time to first fall [Hazard Ratio, HR = 0.948 (95% CI 0.782-1.522)] and mortality rate [RR = 0.896 (95% CI 0.335-2.400)] did not differ between groups.

CONCLUSION: Individually-tailored multifactorial intervention was ineffective as a strategy to reduce falls. Future research efforts are now required to develop culturally-appropriate and affordable methods of addressing this increasingly prominent public health issue in middle-income nations.

TRIAL REGISTRATION: ISRCTN Registry no. ISRCTN11674947.

Study site: emergency department, medical outpatients and primary care clinic at a teaching hospital in Kuala Lumpur, Malaysia
Fulltext Rationale and design for the detection and neurological impact of cerebrovascular events in non-cardiac surgery patients cohort evaluation (NeuroVISION) study: a prospective international cohort study

Mrkobrada M, Chan MTV, Cowan D, Spence J, Campbell D, Wang CY, et al.

BMJ Open, 2018 07 06;8(7):e021521.
PMID: 29982215 DOI: 10.1136/bmjopen-2018-021521

OBJECTIVES: Covert stroke after non-cardiac surgery may have substantial impact on duration and quality of life. In non-surgical patients, covert stroke is more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac surgery.NeuroVISION is a multicentre, international, prospective cohort study that will characterise the association between perioperative acute covert stroke and postoperative cognitive function.
SETTING AND PARTICIPANTS: We are recruiting study participants from 12 tertiary care hospitals in 10 countries on 5 continents.
PARTICIPANTS: We are enrolling patients ≥65 years of age, requiring hospital admission after non-cardiac surgery, who have an anticipated length of hospital stay of at least 2 days after elective non-cardiac surgery that occurs under general or neuraxial anaesthesia.
PRIMARY AND SECONDARY OUTCOME MEASURES: Patients are recruited before elective non-cardiac surgery, and their cognitive function is measured using the Montreal Cognitive Assessment (MoCA) instrument. After surgery, a brain MRI study is performed between postoperative days 2 and 9 to determine the presence of acute brain infarction. One year after surgery, the MoCA is used to assess postoperative cognitive function. Physicians and patients are blinded to the MRI study results until after the last patient follow-up visit to reduce outcome ascertainment bias.We will undertake a multivariable logistic regression analysis in which the dependent variable is the change in cognitive function 1 year after surgery, and the independent variables are acute perioperative covert stroke as well as other clinical variables that are associated with cognitive dysfunction.
CONCLUSIONS: The NeuroVISION study will characterise the epidemiology of covert stroke and its clinical consequences. This will be the largest and the most comprehensive study of perioperative stroke after non-cardiac surgery.
TRIAL REGISTRATION NUMBER: NCT01980511; Pre-results.
Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma

Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.

Nat Genet, 2016 May;48(5):556-62.
PMID: 27064256 DOI: 10.1038/ng.3540

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.