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  1. Harston GW, Tee YK, Blockley N, Okell TW, Thandeswaran S, Shaya G, et al.
    Brain, 2015 Jan;138(Pt 1):36-42.
    PMID: 25564491 DOI: 10.1093/brain/awu374
    The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.
    Matched MeSH terms: Brain Ischemia/complications*
  2. Hamidon BB, Joseph JP, Raymond AA
    Med J Malaysia, 2007 Jun;62(2):114-6.
    PMID: 18705441
    Subclinical cerebral infarcts (SCI) have been increasingly shown to cause a significant clinical impact. However, there are limited data available on Asian patients. The objectives of this study were to determine the prevalence of SCI in ischaemic stroke patients seen in the Hospital Universiti Kebangsaan Malaysia (HUKM) and to identify its associated risk factors. We evaluated the brain computed tomography (CT) evidence of subclinical infarcts in ischaemic stroke patients. The patients were selected from those who were on regular follow up in the neurology clinic following an ischaemic stroke. The risk factors associated with subclinical infarct were documented. The brain CTs were done during acute admission and reviewed for SCI. Sixty-one patients were enrolled in this study. Twenty-two (36.1%) out of the 61 patients had SCI. The risk factors for SCI in our study were hypertension (OR 14.16 CI 2.04-97.89), diabetes mellitus (OR 12.48; CI 1.95-79.77) and leukoaraiosis (OR 28.39; CI 2.33-284.16). Subclinical cerebral infarcts were present in about one third of our ischaemic stroke patients. This finding is higher than in previous studies done on Caucasians. Hypertension, diabetes mellitus and leukoaraiosis independently predict SCI.

    Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
    Matched MeSH terms: Brain Ischemia/complications*
  3. Hamidon BB, Raymond AA
    Med J Malaysia, 2006 Aug;61(3):288-91.
    PMID: 17240577 MyJurnal
    Gastrointestinal (GI) bleeding is one of the most serious complications after an acute ischaemic stroke and may affect stroke outcome. We identified predictors and the eventual outcome of gastrointestinal bleeding during the in-patient period following the commencement of aspirin. This was a study of patients with acute ischaemic stroke admitted to Universiti Kebangsaan Malaysia Hospital from June 2000 to January 2001. A single observer, using predefined diagnostic criteria recorded information on demography, risk factors and GI bleeding that occurred during the inpatient period. One hundred and fifteen patients with acute ischaemic stroke were enrolled in the study. Gastrointestinal bleeding was observed in 6 (5.2%) patients. Using univariate analysis, the independent predictors of gastrointestinal bleeding were age (OR 1.25; 95% CI 1.07 to 1.50), and middle cerebral artery (MCA) territory infarcts (OR 9.47; 95% CI 1.62 to 55.5). Using multivariate analysis, the presence of gastrointestinal bleeding increased mortality (OR 24.97; 95% CI 1.97 to 316.91). Older age, and large MCA infarct predict the development gastrointestinal bleeding. Stroke mortality was independently predicted by gastrointestinal bleeding. Prophylactic treatment in elderly patients with large cerebral infarcts may be an area for further investigation.
    Matched MeSH terms: Brain Ischemia/complications*
  4. Seow SC, How AK, Chan SP, Teoh HL, Lim TW, Singh D, et al.
    J Stroke Cerebrovasc Dis, 2018 Aug;27(8):2182-2186.
    PMID: 29678635 DOI: 10.1016/j.jstrokecerebrovasdis.2018.03.019
    BACKGROUND: Occult atrial fibrillation (AF) is not uncommon in patients with stroke. In western cohorts, insertable loop recorders (ILRs) have been shown to be the gold-standard and are cost-effective for AF detection. Anticoagulation for secondary stroke prevention is indicated if AF is detected. The incidence of occult AF among Asian patients with cryptogenic stroke is unclear.

    METHODS: Patients with cryptogenic stroke referred between August 2014 and February 2017 had ILRs implanted. Episodes of AF >2 minutes duration were recorded using proprietary algorithms within the ILRs, whereupon clinicians and patients were alerted via remote monitoring. All AF episodes were adjudicated using recorded electrograms. Once AF was detected, patients were counseled for anticoagulation.

    RESULTS: Seventy-one patients with cryptogenic stroke, (age 61.9 ± 13.5 years, 77.5% male, mean CHA2DS2VASc score of 4.2 ± 1.3) had ILRs implanted. Time from stroke to the ILR implant was a median of 66 days. Duration of ILR monitoring was 345 ± 229 days. The primary endpoint of AF detection at 6 months was 12.9%; and at 12 months it was 15.2%. Median time to detection of AF was 50 days. The AF episodes were all asymptomatic and lasted a mean of 77 minutes (± 118.9). Anticoagulation was initiated in all but 1 patient found to have AF.

    CONCLUSIONS: The incidence of occult AF is high in Asian patients with cryptogenic stroke and comparable to western cohorts. The combination of ILR and remote monitoring is a highly automated, technologically driven, and clinically effective technique to screen for AF.

    Matched MeSH terms: Brain Ischemia/complications*
  5. Noradina AT, Hamidon BB, Roslan H, Raymond AA
    Singapore Med J, 2006 May;47(5):392-9.
    PMID: 16645689
    There are several studies that reported a higher frequency of sleep-disordered breathing (SDB) among ischaemic stroke patients with increasing evidence linking SDB and cardiovascular complications. Many showed prevalence between 43 percent and 72 percent, taking the apnoea-hypopnoea index (AHI) equal to or greater than ten. The main objective of this study was to determine the frequency of SDB in recent ischaemic stroke patients admitted to Hospital Universiti Kebangsaan Malaysia (HUKM) and the relationship between SDB and known risk factors of ischaemic stroke.
    Matched MeSH terms: Brain Ischemia/complications*
  6. Hamidon BB, Nabil I, Raymond AA
    Med J Malaysia, 2006 Dec;61(5):553-7.
    PMID: 17623955 MyJurnal
    Dysphagia occurs frequently after a stroke. It is a major problem as patients are at risk of malnutrition and aspiration pneumonia. We aimed to identify the risk factors for and outcome of dysphagia over the first one month after an acute ischaemic stroke. Patients with acute first-ever ischaemic stroke admitted to the medical ward of Hospital Universiti Kebangsaan Malaysia (HUKM) between July 2004 and December 2004 were prospectively examined. Observation was done using pre-defined criteria. Demographic data, risk factors, and type of stroke were recorded on admission. The assessment of dysphagia was made using standardized clinical methods. All patients were followed up for three months. One hundred and thirty four patients were recruited in the study. Fifty-five patients (41%) had dysphagia at presentation. This number was reduced to 29 (21.6%) patients at one month. Logistic regression analysis revealed that age of more than 75 years [OR 5.20 (95% CI 1.89 - 14.30)], diabetes mellitus [OR 2.91 (95% CI 1.07 - 7.91)] and MCA infarct [OR 2.48 (95% CI 1.01-6.14)] independently predicts the occurrence of dysphagia after an acute stroke. Dysphagia at presentation was found to be an independent predictor of mortality at one-month [OR 5.28 (95% CI 1.51-18.45)] post ischaemic infarct. Dysphagia occurred commonly in ischaemic stroke. Advance age, diabetes mellitus and large infarcts were independently associated with the presence of dysphagia. Early stroke mortality can be independently predicted by the presence of dysphagia.
    Matched MeSH terms: Brain Ischemia/complications*
  7. Hamidon BB, Abdullah SA, Zawawi MF, Sukumar N, Aminuddin A, Raymond AA
    Med J Malaysia, 2006 Mar;61(1):59-66.
    PMID: 16708735 MyJurnal
    Dysphagia following stroke is common problem and is of particular concern because of its potental for malnutrition. Nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tube feeding are recognized methods for nutritional support for patients with persistent neurologic dysphagia. However, the former is associated with tube dislodgement and blockage that might compromise the patients' nutritional status. There have been few randomized prospective studies to date comparing the efficacy and safety of these 2 modes of dysphagia management in stroke patients. The objective of this study was to compare PEG with NG tube feeding after acute dysphagic stroke in terms of nutritional status and treatment failure. This was a randomized prospective clinical trial. A total of 23 consecutive patients who fulfilled the criteria were recruited from the medical wards in Hospital Universiti Kebangsaan Malaysia. The diagnosis of stroke (acute cerebral infarct) was based on clinical and brain computed tomographic (CT scan) findings; and the diagnosis of dysphagia was done clinically by using the 'swallowing test'. At recruitment, upper-arm skin fold thickness (triceps and biceps) and mid-arm circumference were measured; and blood was drawn for serum albumin level. They were then followed up at 4 weeks where the above tests were repeated. A total of 22 patients completed the study (12 patients in the NG group and 10 patients in the PEG group). Serum albumin levels (p = 0.045) were significantly higher in the PEG as compared to the NG group at 4 weeks post-intervention. There were statistically significant improvements in serum albumin level (p = 0.024) in the PEG group; and statistically significant reductions in serum albumin level (p = 0.047) in the NG group 4 weeks after the intervention. However, there were no significant differences in anthropometric parameters between the two groups and no significant changes in these parameters for each group 4 weeks after the intervention. Treatment failure occurred in 5 out of 10 patients (50.0%) in the NG group, but none in PEG group (p = 0.036). PEG tube feeding is more effective than NG tube feeding in improving the nutritional status (in terms of the serum albumin level) of patients with dysphagic stroke. NG tube feeding, in fact, reduced the nutritional status (in terms of the serum albumin level) of the patients.
    Matched MeSH terms: Brain Ischemia/complications*
  8. Hamidon BB, Sapiah S, Nawawi H, Raymond AA
    Med J Malaysia, 2004 Dec;59(5):631-7.
    PMID: 15889566 MyJurnal
    Increasing evidence suggests that inflammation plays an important role in the development of both cardiovascular and cerebrovascular events. Recently C-reactive protein (CRP) levels have been reported to be a prognostic factor for cerebrovascular and cardiovascular events. The main objective of the study was to evaluate the prognostic value of CRP levels in a first ever ischaemic stroke at one month. All ischaemic stroke patients who were admitted to Hospital Universiti Kebangsaan Malaysia (HUKM) between May 2002 and July 2002 were eligible for the study. CRP levels were taken within 72 hours after an acute ischaemic stroke. The functional ability was assessed using the Barthel Index (BI) after one month of stroke. During the study period 84 patients were admitted to HUKM with the diagnosis of ischaemic stroke; 49 patients were enrolled and 35 were excluded. Twenty-nine patients (59.2%) had elevated CRP levels (median 1.64+/-3.07 mg/dL, range 0.06 to 16.21 mg/dL). Elevated CRP levels were found to be a predictor of severe functional disability (BI<5) and were also associated with larger infarcts. In conclusion, elevated CRP levels are associated with poorer functional outcome and predict a larger infarct size.
    Matched MeSH terms: Brain Ischemia/complications
  9. Damodaran T, Hassan Z, Navaratnam V, Muzaimi M, Ng G, Müller CP, et al.
    Behav Brain Res, 2014 Dec 15;275:252-8.
    PMID: 25239606 DOI: 10.1016/j.bbr.2014.09.014
    Cerebral ischemia is one of the leading causes of death and long-term disability in aging populations, due to the frequent occurrence of irreversible brain damage and subsequent loss of neuronal function which lead to cognitive impairment and some motor dysfunction. In the present study, the real time course of motor and cognitive functions were evaluated following the chronic cerebral ischemia induced by permanent, bilateral occlusion of the common carotid arteries (PBOCCA). Male Sprague Dawley rats (200-300g) were subjected to PBOCCA or sham-operated surgery and tested 1, 2, 3 and 4 weeks following the ischemic insult. The results showed that PBOCCA significantly reduced step-through latency in a passive avoidance task at all time points when compared to the sham-operated group. PBOCCA rats also showed significant increase in escape latencies during training in the Morris water maze, as well as a reduction of the percentage of times spend in target quadrant of the maze at all time points following the occlusion. Importantly, there were no significant changes in locomotor activity between PBOCCA and sham-operated groups. The BDNF expression in the hippocampus was 29.3±3.1% and 40.1±2.6% on day 14 and 28 post PBOCCA, respectively compared to sham-operated group. Present data suggest that the PBOCCA procedure effectively induces behavioral, cognitive symptoms associated with cerebral ischemia and, consequently, provides a valuable model to study ischemia and related neurodegenerative disorder such as Alzheimer's disease and vascular dementia.
    Matched MeSH terms: Brain Ischemia/complications*
  10. Wei LK, Au A, Menon S, Gan SH, Griffiths LR
    J Stroke Cerebrovasc Dis, 2015 Sep;24(9):2017-25.
    PMID: 26187788 DOI: 10.1016/j.jstrokecerebrovasdis.2015.04.011
    The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks.
    Matched MeSH terms: Brain Ischemia/complications
  11. Damodaran T, Müller CP, Hassan Z
    Pharmacol Rep, 2019 Jun;71(3):443-448.
    PMID: 31003155 DOI: 10.1016/j.pharep.2019.01.012
    BACKGROUND: Chronic cerebral hypoperfusion (CCH) can induce the accumulation of reactive oxygen species, which leads to oxidative damage, neuronal injury, and central cholinergic dysfunction in vulnerable regions of the brain, such as the hippocampus and cerebral cortex. These effects can lead to significant cognitive impairments in clinical populations of vascular dementia (VaD). The present studies aimed to investigate the role of the cholinergic system in memory functions and hippocampal long-term potentiation (LTP) impairments induced by CCH in rats.

    METHODS: Male Sprague Dawley rats were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham surgery. Then, PBOCCA rats received ip injections with, either vehicle (control group), the muscarinic receptor agonist oxotremorine (0.1 mg/kg), or the acetylcholinesterase inhibitor physostigmine (0.1 mg/kg). Cognitive functions were evaluated using a passive avoidance task and the Morris water maze test. In addition, hippocampal LTP was recorded in vivo under anaesthesia.

    RESULTS: The PBOCCA rats exhibited significant deficits in passive avoidance retention and spatial learning and memory tests. They also showed a suppression of LTP formation in the hippocampus. Oxotremorine and physostigmine significantly improved the learning and memory deficits as well as the suppression of LTP in PBOCCA rats.

    CONCLUSIONS: The present data suggest that the cholinergic system plays an important role in CCH-induced cognitive deficits and could be an effective therapeutic target for the treatment of VaD.

    Matched MeSH terms: Brain Ischemia/complications*
  12. Cheng YC, Stanne TM, Giese AK, Ho WK, Traylor M, Amouyel P, et al.
    Stroke, 2016 Feb;47(2):307-16.
    PMID: 26732560 DOI: 10.1161/STROKEAHA.115.011328
    BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years.

    METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.

    RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.

    CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.

    Matched MeSH terms: Brain Ischemia/complications
  13. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Fundam Clin Pharmacol, 2011 Jun;25(3):388-94.
    PMID: 20608996 DOI: 10.1111/j.1472-8206.2010.00846.x
    Statins can reduce the risk of stroke in at-risk populations and improve survival after acute ischemic stroke (AIS) among patients with previous statin use. This study aimed to investigate the impact of statin use before AIS onset on in-hospital mortality and identify the factors related to in-hospital mortality among patients with and without previous statin use. A retrospective cohort study of all patients with AIS attending hospital from June 1, 2008 to December 31, 2008. Data were collected from medical records including demographic information, diagnostic information, risk factors, previous statin use, and vital discharge status. Chi-square, Fisher's exact tests, student's t-test, and Mann-Whitney U test, whatever appropriate, were used to test the significance between the variables, and multiple logistic regression was used to identify factors associated with in-hospital mortality. Altogether, 386 patients with AIS were studied, of which 113 (29.3%) had a documented previous statin use. A total of 62 (16.1%) patients with AIS died in hospital. In-hospital mortality was significantly lower among previous statin users (P = 0.013). The presence of atrial fibrillation (AF) increased in-hospital mortality among patients with or without previous statin use. The independent predictors for in-hospital mortality among AIS patients without previous statin use were the presence of diabetes mellitus (P = 0.047), AF (P = 0.045), and renal impairment (P < 0.001). The prophylactic administration of statins significantly reduces post-AIS in-hospital mortality. Furthermore, the identification of predictors of in-hospital mortality might reduce death rates and enhance the application of specific therapeutic and management strategies to patients at a high risk of dying.
    Matched MeSH terms: Brain Ischemia/complications
  14. O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al.
    Lancet, 2016 Aug 20;388(10046):761-75.
    PMID: 27431356 DOI: 10.1016/S0140-6736(16)30506-2
    BACKGROUND:Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke.
    METHODS:We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals.
    FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001).
    INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke.
    FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.
    Matched MeSH terms: Brain Ischemia/complications
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