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.

Gender disparities and thrombolysis use among patient with first-ever ischemic stroke in Malaysia.

OBJECTIVE: Gender as an independent predictor in stroke has been well documented. However, data on gender differences among first-ever ischemic stroke in developing country are limited. We aim to describe gender effects on clinical characteristics, thrombolysis treatment received, and outcomes of patients with first-ever ischemic stroke. METHODS: Data were extracted from the prospective multiethnic stroke registry, National Neurology Registry (NNEUR). Descriptive analysis and logistic regression were performed. RESULTS: A total of 4762 first-ever ischemic stroke patients admitted to 13 government hospitals from July 2009 to June 2015 were available for this study. Slightly over half were male (55.1%), and they were 1.7 years younger than female (mean age, 63.6 versus 61.9 years, p < 0.001). Gender-age-adjusted incidence was observed to be higher in females (66.7 per 100,000) compared to males (57.4 per 100,000). First-ever ischemic stroke incidence increased by 24.3 and 11.2% among female and male annually. Female experienced significantly poorer functional outcome and greater 30-day in-hospital mortality compared to male. In subgroup analysis, only 31 (0.65%) patients were treated with thrombolysis. DISCUSSION: First-ever ischemic stroke incidence increased by 24.3 and 11.2% among female and male annually. There were distinct symptoms at hospital presentation between genders. All our patients discharged home regardless of genders. In summary, Malaysian female first-ever ischemic stroke was older, present with severe stroke, greater number of risk factors and poorer functional outcome and 30-day in-hospital mortality compared to male.

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.

Sleep-disordered breathing in patients with Parkinson's disease.

INTRODUCTION: There are limited studies reporting the frequency of sleep-disordered breathing (SDB) in Parkinson's disease (PD), and the figures quoted are variable, ranging from 2.5 to 66 percent. This study aimed to determine the prevalence and types of SBD in PD patients attending the Universiti Kebangsaan Malaysia Medical Centre neurology clinic, and the correlation between the subjective sleep symptoms using the Parkinson's disease sleep scale (PDSS) and the objective measurements using polysomnography (PSG). METHODS: This was a cross-sectional study involving 46 PD patients over a period of six months. The patients' demographic data, Hoehn and Yahr staging and PDSS scores were collected. The patients were then subjected to overnight PSG using the Somnomedic system. RESULTS: There were 27 male and 19 female patients with a mean age of 64.0+/-9.7 years. 29 were Chinese, 15 Malay and 2 Indian. The mean duration of illness was 5.8+/-4.3 years. The mean PDSS score was 120.3+/-13.5. SDB was found in 54.6 percent of the patients (apnoeahypopnoea index [AHI] 5 and above), with 27.3 percent having moderate and severe SDB (AHI 15 and above). The median AHI was 6.7 (range 0-40.4). The prevalence of SDB in PD patients based on the AHI cutoffs were 27.3 percent for mild, 18.2 percent for moderate and 9.1 percent for severe. There were statistically significant positive correlations between the AHI and the neck circumference and between the AHI and the waist-hip ratio. There was no significant correlation between the AHI and PDSS, or the AHI and disease severity. CONCLUSION: There was a high prevalence of SBD in our PD patients, which was comparable to other studies. Obstructive sleep apnoea was the dominant type of SBD. There was no correlation between the subjective sleep symptoms using the PDSS and the objective measurements using PSG.

Sleep disturbances in Malaysian patients with Parkinson's disease using polysomnography and PDSS.

BACKGROUND: Sleep disturbances such as sleep fragmentation, sleep disordered breathing (SDB), periodic limb movements (PLM), excessive daytime somnolence (EDS) and insomnia are prevalent in Parkinson's disease (PD). However, studies in the Asian population are limited. METHODS: This was a cross-sectional study involving 46 Malaysians with PD using polysomnography (PSG) and standardized translated Parkinson's disease sleep scale (PDSS). Overnight PSG recordings, UPDRS and PDSS scores, and baseline demographic data were obtained. RESULTS: Data from 44 patients were analysed. Thirty-six patients (81.8%) had PSG-quantified sleep disorders. Twenty-three (52.3%) had sleep fragmentation, 24 (54.6%) had SDB and 14 (32%) had PLM. EDS was present in 9.1%. Insomnia was reported by 31.8%. Patients with sleep fragmentation had significantly higher UPDRS scores and lower PDSS insomnia sub-scores. The UPDRS scores correlated negatively with the TST and sleep efficiency. All patients with EDS had SDB (p=0.056). The PDSS insomnia sub-items correlated with sleep fragmentation on PSG. CONCLUSION: : The prevalence of sleep disorders based on PSG and PDSS in our PD patients was high, the commonest being sleep fragmentation and SDB, while EDS was the least prevalent. Problem specific sub-items of the PDSS were more accurate in predicting the relevant PSG-related changes compared to the PDSS as a whole.

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.

Recurrent Bell's palsy in a young woman.

Bell's palsy is a benign lower motor neuron facial nerve disorder. It is almost always unilateral. We report a 20-year-old nulliparous woman with five episodes of recurrent Bell's palsy. A review of recent medical literature revealed a paucity of case reports involving an individual with five episodes of recurrent Bell's palsy, with none found in Asian neurology medical literature. Despite the multiple episodes of Bell's palsy recurrences, the patient did not suffer much neurological sequelae from the disease.

Ultrasound-guided botulinum toxin A injection: an alternative treatment for dribbling.

Dribbling (sialorrhoea) affects about 10 per cent of patients with chronic neurological disease. The variety of treatments currently available is unsatisfactory. This study was a clinical trial of the efficacy of ultrasound-guided, intraglandular injection of botulinum toxin A for dribbling, performed within the otorhinolaryngology department of the National University of Malaysia. Both pairs of parotid and submandibular glands received 25 U each of botulinum toxin A. Twenty patients were enrolled in the study. The median age was 15 years. All 20 patients (or their carers) reported a distinct improvement in symptoms after injection. Using the Wilcoxon signed rank test, there were significant reductions in dribbling rating score, dribbling frequency score, dribbling severity score, dribbling visual analogue score and towel changes score, comparing pre- and post-injection states (p<0.001). There were no complications or adverse effects during or after the injection procedure. Intraglandular, major salivary gland injection of botulinum toxin A is an effective treatment to reduce dribbling. Ultrasound guidance enhances the accuracy of this procedure and minimises the risk of complication.

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.

Leukoaraiosis as a predictor for mortality and morbidity after an acute ischaemic stroke.

INTRODUCTION: Leukoaraiosis (LA) is a term that defines an abnormal appearance of the subcortical white matter of the brain on neuroimaging. This study was done to evaluate the predictive value of LA in terms of mortality, disability and cognitive decline at three months post-stroke and also to identify the risk factors that are independently associated with LA in a stroke population. METHODS: This was a prospective observational study of all patients with acute ischaemic stroke who were admitted to Hospital Universiti Kebangsaan Malaysia from June to November 2004. A single observer using the pre-defined diagnostic criteria recorded the information on demography, Barthel Index and mini-mental state examination. LA was diagnosed on brain computed tomography alone. RESULTS: 60 patients were recruited into the study. Three patients (five percent) died and LA was present in 29 patients (48 percent). There was no significant association between LA and mortality (p-value equals 0.89). The independent risk factors that were associated with LA were age (odds-ratio [OR] 4.43; 95 percent confidence interval [CI] 1.28-15.27) and hypertension (OR 14.3; 95 percent CI 1.40-147.42). There was a significant association between LA with early dementia (OR 3.53; 95 percent CI 1.19-10.49). However, LA did not significantly predict any functional disability (Barthel Index is less than 60) in the study population (p-value equals 0.45). CONCLUSION: Development of LA correlates significantly with ageing and hypertension. The presence of LA can also predict early cognitive dysfunction but is not associated with functional disability at three months post-stroke.

Angioinvasive cerebral aspergillosis presenting as acute ischaemic stroke in a patient with diabetes mellitus.

Cerebral angioinvasive aspergillosis is a rare manifestation of disseminated aspergillosis which may result in stroke in immunocompromised individuals. Reports of such disease in patients with diabetes mellitus are rare. We describe a 45-year-old man with diabetes mellitus who presented with a three-day history of right-sided limb weakness and aphasia. Cerebral computed tomography showed features of an acute infarct involving the left anterior and middle cerebral arteries. He was initially treated for an acute ischaemic stroke. Further history revealed that he was investigated for a growth in the sphenoid sinus two months earlier. Culture of the biopsied material from the sphenoid sinus grew Aspergillus fumigatus. Magnetic resonance imaging showed an extension of the growth to the brain, causing the acute ischaemic stroke. He was subsequently diagnosed with angioinvasive cerebral aspergillosis and was commenced on intravenous amphotericin B. Unfortunately, he succumbed to his illness despite treatment.

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.

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.