Genetic Susceptibility Variants of Vascular Dementia among Asians: A Systematic Review and Meta-Analysis.

INTRODUCTION: Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous studies have investigated candidate genetic polymorphisms associated with VaD in Asia, the genetics of VaD remains unclear. METHODS: This review provides an updated meta-analysis of genetic polymorphisms associated with VaD in Asians, using the PRISMA guidelines. Published literature up to May 2021 was extracted from the PubMed, Scopus, Ovid, and EBSCOhost databases. Meta-analysis was conducted using the Open Meta analyst, Review Manager, and MedCalc® Statistical Software. Trial sequential analysis (TSA) was performed using TSA viewer software. RESULTS: A total of 46 eligible studies, comprising 23 genes and 35 single nucleotide polymorphisms, were retrieved. The meta-analysis was conducted on the following genetic polymorphisms, APOE ε2/3/4, MTHFR rs1801131, ACE rs4340 (I/D) gene polymorphism, and a PSEN1 intron 8 variant. The pooled odds ratio (ORs) revealed a significant increase in the risk of VaD in the apolipoprotein E (APOE) ε4 allelic model (OR, 1.79, p < 0.001), and the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism T allele in the allelic model (OR, 1.23, p = 0.013). CONCLUSION: Our findings provide evidence that genetic polymorphisms of the APOE ε4 allele and MTHFR rs1801133 T allele increase the risk of developing VaD in Asians. However, future large-scale investigations examining particularly on South-Eastern and West-Asian populations are highly recommended.

Malaysia Stroke Council guide on acute stroke care service during COVID-19 Pandemic.

On the 18th of March 2020, the Malaysia government declared a movement control order (MCO) due to the unprecedented COVID-19 pandemic. Although the majority of patients presented with respiratory-related symptoms, COVID-19 patients may present atypically with neurological manifestations and may even have an increased risk of stroke. The Malaysia Stroke Council is concerned regarding the level of care given to stroke patients during this pandemic. During the recent National Stroke Workflow Steering Committee meeting, a guide was made based on the currently available evidences to assist Malaysian physicians providing acute stroke care in the hospital setting in order to provide the best stroke care while maintaining their own safety. The guide comprises of prehospital stroke awareness, hyperacute stroke care, stroke care unit and intensive care unit admission, post-stroke rehabilitation and secondary prevention practice. We urge continuous initiative to provide the best stroke care possible and ensure adequate safety for both patients and the stroke care team.

Acute Stroke Registry Malaysia, 2010-2014: Results from the National Neurology Registry.

BACKGROUND: Stroke remains a major health burden worldwide. The incidence and prevalence rates of stroke are decreasing in developed countries, an opposite trend is taking place in the Asia Pacific, where an increasing number of patients are being diagnosed with acute stroke. The results of the present study on acute stroke in multi-ethnic Malaysia will significantly contribute to the global stroke epidemiological data. We aimed to present epidemiological data of stroke including incidence and prevalence rates as well as associated risk factors from a prospective nationwide hospital-based registry from 2010 to 2014. METHODS: Patients diagnosed with stroke upon admission at the hospital were prospectively enrolled into the registry from January 1, 2010, to December 31, 2014. Descriptive analyses were performed. RESULTS: A total of 7668 patients were available for analysis. On average, patients were aged 62.7 years (standard deviation of 12.5). Ischemic stroke accounts for 79.4% of the cohort with a slightly higher proportion of male patients (55%). Ischemic stroke incidence is estimated to increase annually by 29.5% and hemorrhagic stroke by 18.7%. Hypertension is a major risk factor for both ischemic and hemorrhagic strokes regardless of stroke event with an excess of 8.4% hypertensive female compare to male patients (P ≤ .001). Majority of patients with ischemic and hemorrhagic strokes experienced mild and moderate stroke with 11.7% and 21.1%, respectively, documented as severe (P ≤ .001). CONCLUSIONS: The incidence and prevalence of stroke in Malaysia increased dramatically in the 5-year study period. Therefore, implementation of risk factor control strategies is important to prevent further increase of stroke burden in the country.

National Stroke Registry (NSR): Terengganu and Seberang Jaya experience.

The National Stroke Registry (NSR) was established in 2009 under National Neurology Registry (NNeuR) . The main objectives of NSR were to describe the demographic and disease pattern of stroke patients in Malaysia, to examine the risk factors and evaluate the specified treatment and outcomes. This prospective observational study was carried out from August 2009 until December 2010 using a standardized case report form which involved two participating hospital, namely Hospital Sultanah Nur Zahirah, Kuala Terengganu and Hospital Seberang Jaya, Pulau Pinang. There were 1018 patients registered. Ischemic stroke accounted for the majority of cases (73.3%). The most common risk factor was hypertension (75.5 %), followed by diabetes mellitus, previous stroke or Transient Ischemic Attack (TIA), hyperlipidemia and active smoker: 45.6%, 25.1%, 22.4%, and 19.4%, respectively. Overall, our stroke management, based on nine stroke key performance indicators (KPI) still needs to be improved. There was a total of 121 mortality cases with the main contributing factor was massive cerebral bleed (21.6%). In conclusion, the findings highlight the important of primary and secondary stroke management. Further and continuous observation with more site date provider (SDP) involvement is needed to get a more comprehensive data on stroke in Malaysia.

Implications of immunosuppressive agents in cardiovascular risks and carotid intima media thickness among lupus nephritis patients.

INTRODUCTION: Patients with systemic lupus erythematosus, particularly with lupus nephritis (LN), are at risk of premature cardiovascular (CV) disease. OBJECTIVE: To determine the association between immunosuppressive medications, traditional CV risk factors and carotid intima media thickness (CIMT) among patients with LN. METHODOLOGY: This was a cross-sectional study in which consecutive LN patients attending the Nephrology/SLE Clinic were evaluated for traditional CV risk factors. Detailed information on their treatment was obtained from their medical records. CIMT, an excellent marker of subclinical atherosclerosis, was measured by B Mode carotid ultrasound. RESULTS: A total of 82 patients with LN with a mean age of 33.9 ± 9.8( )years were recruited. More than half had hypertension (n = 55, 67.1%) and dyslipidemia (n = 43, 52.4%) as traditional CV risks. Longer history and higher cumulative dose of corticosteroids were associated with hypertension, but use of intravenous methylprednisolone was associated with lower systolic and diastolic blood pressure and lower serum total cholesterol and triglyceride levels (p < 0.05 each). Hydroxychloroquine use was associated with lower total serum cholesterol and serum low-density lipoprotein levels (p < 0.05). Although the use of cyclosporine A (CyA) was associated with hypertension (p < 0.05), those who received a lower cumulative dose of CyA had thicker CIMT (r (s) = -0.33, p =0.01) and CyA use remained an independent predictor of CIMT during linear regression analysis. There were no associations between CIMT and cumulative dose and duration of steroids, hydroxychloroquine, azathioprine, mycophenolic acid and cyclophosphamide. CONCLUSION: Aggressive treatment of severe LN and the use of CyA as a steroid-sparing agent may have protective effects against premature atherosclerosis.

Spinal cord compression following traditional confinement massage.

We describe a case of tetraparesis in a 33-year-old woman following neck manipulation performed by a traditional confinement mid-wife. An MRI of the cervical spine revealed a fracture of the second cervical vertebra with atlanto-axial subluxation that resulted in cord compression.

Validation study of the Mini-Mental State Examination in a Malay-speaking elderly population in Malaysia.

BACKGROUND/AIMS: In view of the differing sensitivity and specificity of the Mini-Mental State Examination (MMSE) in the non-English-speaking populations, we conducted the first validation study of the Malay version (M-MMSE) in Malaysia among 300 subjects (from the community and outpatient clinics). METHODS: Three versions were used: M-MMSE-7 (serial 7), M-MMSE-3 (serial 3) and M-MMSE-S (spell 'dunia' backwards). Dementia was assessed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV. The optimal cutoff scores were obtained from the receiver operating characteristics curves. RESULTS: Seventy-three patients (24.3%) had dementia and 227 (75.7%) were controls. Three hundred patients completed the M-MMSE-7, 160 the M-MMSE-3 and 145 the M-MMSE-S. All 3 versions were valid and reliable in the diagnosis of dementia. The optimal cutoff scores varied with each version and gender. In the control group, significant gender differences were observed in the patients with the lowest educational status. Increasing educational levels significantly improved the M-MMSE performance in both genders. CONCLUSION: All 3 versions of the M-MMSE are valid and reliable as a screening tool for dementia in the Malaysian population, but at different cutoff scores. In those with the lowest educational background, gender-adjusted cutoff scores should be applied.

Impact of acute stroke team emergency calls on in-hospital delays in acute stroke care.

INTRODUCTION: Acute stroke is a medical emergency. Therefore, early recognition and rapid activation of the medical system are important prerequisites for successful management. We sought to investigate the impact of our new Acute Stroke Team emergency call system (AST) on admission delays from the emergency department (ED) to the stroke care unit (SCU) and on the subsequent length of stay (LOS) and in-hospital mortality. METHODS: We retrospectively analysed data obtained from the Austin Hospital stroke unit database and the electronic medical record/patient tracking system for the 5 months before (August to December 2004) and after (January to May 2005) the introduction of the AST. RESULTS: Data for 352 patients were extracted. Of these, there were 260 (73.9%) patients with ischaemic stroke, 38 (10.8%) with intracerebral haemorrhage and 54 (15.3%) with transient ischaemic attack (TIA). One hundred and seventy-two patients were admitted before and 180 after AST introduction. There were 70 AST calls from January to May 2005. Baseline characteristics of both groups were similar. Between the two groups, the median (Q1,Q3) time from door to CT scan was significantly reduced from 104 (60,149) to 82 (40,132) minutes. The LOS was significantly reduced from 6 (3,9) to 3 (2,7) days. There was no significant impact on mortality. CONCLUSION: The introduction of AST has reduced the time from door to brain CT scan. This is an important finding as the window period for thrombolysis is short and early diagnosis is crucial.

The predictors of subclinical cerebral infarcts in ischaemic stroke patients.

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.

Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after stroke.

Botulinum toxin is effective in reducing spasticity post stroke. As there are limited data on post stroke spasticity in Asia, we undertake this study to determine the effectiveness and safety of intramuscular injection of botulinum toxin type-A (BTX-A), in the treatment of chronic focal post-stroke hand spasticity, and the impact of BTX-A on the activities of daily living and quality of life, in comparison to placebo, in Malaysian stroke patients. This was a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of BTX-A in 27 subjects with wrist and finger spasticity after a stroke. The outcome measures were assessed with the Modified Ashworth Scale (MAS) to assess spasticity of the flexor muscles, Barthel Index (BI) for activities of daily living and EQ-5D and EQ VAS for quality of life. Assessments were performed at baseline and 1 and 3 months after injection. Compared to placebo, the BTX-A group had greater improvement in the flexor tone of the wrist and fingers (p = 0.001 and p < 0.001, respectively), at first month follow-up visit and sustained the improvement through to three months. Although there was an improvement in the measures of global function and quality of life in the BTX-A group, there was no significant improvement in between the two groups. No serious BTX-A related adverse effects were reported. The results of this study demonstrate that intramuscular injection of botulinum toxin A is safe and effective in the treatment of chronic focal post-stroke spasticity of the hand.

Exogenously-induced apparent hypermineralocorticoidism associated with ingestion of "asam boi".

A 31-year-old woman presented with a one-week history of headache, generalised lethargy, weakness and poor appetite. Clinical examination showed that her blood pressure was 200/120 mmHg. On an earlier occasion, her blood pressure was found to be normal by a general practitioner whom she last visited three months earlier when she had an upper respiratory tract infection. Investigations showed hypokalaemia, suppressed serum renin and aldosterone. Further history was taken and revealed that she had been craving for guava fruits which she ate with flavoured "asam boi" (containing glycyrrhizic acid) at least three spoonfuls twice a day for the past six weeks. The hypertension and hypokalaemia resolved after two weeks of stopping the "asam boi". Her clinical picture was compatible with exogenously-induced hypermineralocortoidism.

Risk factors for developing sleep-disordered breathing in patients with recent ischaemic stroke.

INTRODUCTION: 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. METHODS: This was a cross-sectional, prospective study involving 28 consecutive acute ischaemic stroke patients admitted to HUKM over three months. Sleep studies were done within one to four weeks after stroke onset. Demographical data and associated risk factors were recorded and data were analysed. RESULTS: There were 20 men and eight women, with mean age of 60.3 +/- 8.9 years. There were eight Malay, 16 Chinese and four Indian patients. The prevalence of SDB in ischaemic stroke depending on the AHI cut-off was: 92.8 percent for AHI greater than or equal to five, 78.5 percent for AHI greater than or equal to ten, 44.5 percent for AHI greater than or equal to 15, and 37.7 percent for AHI greater than or equal to 20. We discovered that diabetes mellitus and smoking history were important factors predicting significant SDB (AHI greater than or equal to 15) in recent ischaemic stroke cases. CONCLUSION: There was a high prevalence of SDB in recent ischaemic stroke patients in HUKM, comparable to other studies. Diabetes mellitus and smoking history were strong predictors of the occurrence of SDB after an ischaemic stroke.

The prognostic value of tissue factor levels in acute ischaemic stroke.

INTRODUCTION: There is no biological marker that can accurately predict the prognosis after an acute ischaemic stroke. The main objective of this study was to evaluate the prognostic value of tissue factor (thromboplastin) levels in first ischaemic stroke. METHODS: This was a prospective study of all patients with first ischaemic stroke conducted from October 2003 to February 2004. Plasma for tissue factor levels was kept at -80 degrees Celsius and was analysed at the end of the study period by an independent person. The activities of daily living (ADL) were assessed by using the Barthel index (BI) on admission and at one month after the stroke onset. Any death or recurrent events were recorded. RESULTS: 50 patients were recruited into the study. The median tissue factor level was 184.5 +/- 97.3 pg/ml. Only age (p-value is 0.027) and middle cerebral artery (MCA) infarcts (p-value is 0.038) were found to be significant independent predictors for severe disability at one month with BI equal to or less than 9. There was no correlation of tissue factor level with BI at one month post-stroke (r equals -0.028, p-value is 0.846) and there was also no significant relationship between levels of tissue factor and recurrent events (p-value is 0.41). CONCLUSION: There is no correlation between tissue factor levels with acute ischaemic stroke outcome.

An acute pharyngeal-cervical-brachial (PCB) variant of Guillain-Barre syndrome presenting with isolated bulbar palsy.

Acute Guillain-Barre syndrome (GBS) is characterized by an acute onset of limb weakness and areflexia. There are a few rare variants that have been described and one of them is the pharyngeal-cervical-brachial (PCB) variant (oropharynx, neck, and proximal upper limb muscles). However, in this patient, the only presentation was bulbar involvement with fast recovery within days. This is likely to be the milder form of PCB that has rarely been described before. A 19-year-old Malay lady presented with progressive dysphagia associated with nasal voice for one week duration. There was no limb weakness. Examination showed generalized areflexia. Pharyngeal and palatal muscles were markedly weak. Cerebrospinal fluid (CSF) examination showed raised protein level. Nerve conduction studies revealed generalized demyelinating motor polyneuropathy consistent with GBS. The patient fully recovered within three days and was discharged well.

The risk factors of gastrointestinal bleeding in acute ischaemic stroke.

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.

Risk factors and outcome of dysphagia after an acute ischaemic stroke.

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.

An open label comparative study of glimepiride versus repaglinide in type 2 diabetes mellitus Muslim subjects during the month of Ramadan.

This study was conducted to compare the treatment efficacy between a prandial glucose regulator, repaglinide and a new sulphonylurea, glimepiride in Muslim Type 2 diabetic patients who practice Ramadan fasting. Forty-one patients, previously treated with a sulphonylurea or metformin, were divided to receive either repaglinide (n=20, preprandially three-times daily) or glimepiride (n=21, preprandially once daily) 3 months before the month of Ramadan. During Ramadan, patients modified their eating pattern to two meals daily, and the triple doses of repaglinide were redistributed to two preprandial doses. Four point blood glucose monitoring were performed weekly during the month of Ramadan and the subsequent month. Measurements of the 4-point blood glucose were significantly lower in the glimepiride group compared to the repaglinide group both during and after Ramadan. The glycaemic excursion was better in the morning for the repaglinide group and better in the afternoon and evening for the glimepiride group during the Ramadan period. There was no statistically significant difference in the incidence of hypoglycaemia between the two groups during and after Ramadan. There was no difference in the glycaemic excursion post-Ramadan. The longer duration of action of glimepiride may offer an advantage over repaglinide during the 13.5 hours of fast in Ramadan for diabetic patients.

A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke.

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.

Case of severe refractory myasthenia gravis in HUKM.

A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.