Cerebral venous thrombosis in multi-ethnic patients from Malaysia

@#Background & Objectives: The literature on cerebral venous thrombosis (CVT) in South East Asia is limited. The objectives were to evaluate the clinical profile, predisposing factors and clinical outcome of the CVT patients in Malaysia. Methods: We conducted a retrospective descriptive study of the CVT patients admitted to the neurology ward. The clinical presentation, predisposing factors, radiological findings, treatment and prognostic characteristics were evaluated from the charts. Clinical outcome on discharge and six months was measured by Modified Rankin Scale (mRS) scores. Poor outcome and good outcome was defined as Modified Rankin Scale (mRS) scores of 3-6 and 0-2 respectively. Results: Forty nine CVT patients who presented between 2007 and 2017 were recruited. The mean age was 43.51±16.52. The patients consisted of 39 Malaysians (13 Indians, 12 Malays, 12 Chinese, one Iban, one Eurasian descent), and ten non-Malaysians. Thirty (61.2%) patients were women. The most common presenting complaint was headache (75.5%). Six percent had multiple risk factors, whereas 51% had idiopathic CVT. The most common predisposing factors were oral contraceptive pill use (18.4%), followed by infection (12.2%), especially central nervous system (CNS) infection (6.1%); 11.8% had prothrombotic disorder. The most common location for CVT was superior sagittal sinus (83.7%). On neuroimaging, 77.6% had parenchymal lesions, 53.1% had venous infarcts and 38.8% had intracerebral haemorrhage, one patient had CVT complicated by rare venous collateral channels. Poor outcome on discharge and at six months was 38.8% and 33.3% respectively. On univariate analysis, female gender (p=0.002), seizures (p=0.037) and cerebral oedema (p=0.018) were associated with poor functional outcome. On binary logistic regression, female gender (OR=14.50, 95% CI 2.10-99.94,p=0.003) and seizures (OR=6.54, 95% CI 1.33-32.07, p=0.017) were associated with poor outcome. Conclusion: The CVT patients in this study had a higher proportion of CNS infections. Poor outcome was independently associated with female gender and seizures.

Predictors of functional outcome in patients with stroke thrombolysis in a tertiary hospital in Malaysia

INTRODUCTION@#Intravenous (IV) thrombolysis with alteplase (rt-PA) is effective in ischaemic stroke. The primary objective was to evaluate predictors of functional outcome in acute ischaemic stroke (AIS) patients treated with IV rt-PA. The secondary objective was to assess the outcome with the modified Rankin scale (mRS). We also examined the predictive value of the Totaled Health Risks in Vascular Events (THRIVE) score.@*METHODS@#AIS patients treated with IV rt-PA from February 2012 to August 2016 were recruited. Demographic data, National Institutes of Health Stroke Scale (NIHSS) scores, timing and neuroradiological findings were recorded. Patients received a dose of 0.9 mg/kg IV rt-PA within 4.5 hours of symptom onset. mRS score was evaluated at discharge and three months, and good and poor clinical outcomes were defined as scores of 0-2 and 3-6, respectively. Baseline THRIVE scores were assessed.@*RESULTS@#36 patients received IV rt-PA. 20 (55.6%) patients had an mRS score of 0-2 at three months. Based on THRIVE score, 86.1% had a good or moderately good prognosis. On univariate analysis, poor outcome was associated with NIHSS score before rt-PA (p = 0.03), THRIVE score (p = 0.02), stroke subtype (p = 0.049) and diabetes mellitus (DM; p = 0.06). Multiple logistic regression showed that outcome was significantly associated with NIHSS score before rt-PA (p = 0.032) and DM (p = 0.010).@*CONCLUSION@#Our newly developed Malaysian IV rt-PA service is safe, with similar outcomes to the published literature. Functional outcome after thrombolysis was associated with baseline NIHSS score and DM.

Moyamoya disease in a young woman with intraand extracranial vessels involvement on vessel wall imaging

@#Moyamoya disease (MMD) was first described in 1957 as “bilateral hypoplasia of internal carotid arteries (ICAs)”.1 Aside from involving the intracranial arteries, MMD can also affect extracranial ICAs and external carotid arteries (ECAs).2-4 High resolution magnetic resonance (MR) vessel wall imaging (VWI) is increasingly being used to help with the diagnosis and characterization of the condition focusing mainly on intracranial vessels and extracranial ICAs.5-9 We present a case of a young woman with MMD, demonstrating vessel wall enhancement of nonstenotic maxillary branches of bilateral ECAs.

Clinical profile, risk factors and aetiology of young ischaemic stroke patients in Asia: A prospective, multicentre, observational, hospital-based study in eight cities

Background and Objective: There is a lack of international collaborative studies on young adults with ischaemic stroke in Asia. The aim of this study was to investigate risk factors, aetiology and outcome at hospital discharge of these patients across 8 participating countries in Asia. Methods: This was a prospective, observational, multicentre, hospital based cohort study. Consecutive young stroke patients with confirmed cerebral infarction between the ages of 18-49 were recruited from December 2011 to May 2012. Data was collected for patient demography, risk factors, investigations, clinical profile and TOAST classification. Outcome measures were death and independence (modified Rankin score≤ 2) at hospital discharge. Results: Two hundred and eighteen patients with the mean age was 40.8±6.7 years were recruited. There was a larger proportion of male patients with a ratio of 1.9:1. Traditional risk factors observed were hypertension (n=103; 47.3%), dyslipidaemia (n=93; 42.4%), smoking (n=85; 38.8%), diabetes (n=53; 24.3%), alcohol use (n=33; 15.0%), a previous history of stroke and transient ischaemic attacks (6.4%), family history (n=12; 5.5%), migraine (n=6;2.8%), pregnancy related (n=5; 2.3%) and numerous cardiac risk factors (0.9-5.5%). The majority suffered arterial infarction; n=216 (99.4%) while n=2 (0.6%) had venous strokes. The predominant stroke subtypes were large artery atherosclerosis (LAA); 29.8% and small vessel occlusion (SVO); 20.2%. LAA and SVO accounted for 37.5% of all stroke subtypes in the ≤36 year age-group. Cardioembolism (15.1%) and stroke of determined aetiology (14.7%) contributed to the other categories of identified stroke subtypes. Mortality on hospital discharge was 3.1% while 65.1% of patients were independent on discharge. Conclusion: This study demonstrated the substantial presence of premature atherosclerosis and conventional risk factors in young ischaemic stroke patients from 8 Asian cities. Venous infarction from cerebral venous thrombosis was rare in this study. Outcome on hospital discharge was poorer compared to Western studies. Detection of vascular risk factors and primary prevention measures should be initiated during late adolescence or early adulthood in urban Asia.

Mitochondrial neurogastrointestinal encephalomyo pathy (MNGIE) in a Malaysian patient with a novel mutation in thymidine phosphorylase gene: A case report

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare neurodegenerative multisystem disorder inherited in an autosomal recessive manner and characterized clinically by gastrointestinal dysmotility, cachexia, ophthalmoparesis and/or ptosis, peripheral neuropathy and leukoencephalopathy. Heterogenous causative mutations in the thymidine phosphorylase (TP) gene located on chromosome 22q13 have been identifi ed. This is the fi rst reported case of a 25-year-old Malaysian patient, of indigenous Bajau ethnicity who presented with recurrent abdominal pain before developing other clinical features of classical MNGIE. Biochemical correlates include elevated plasma levels of thymidine, deoxyuridine and lactate. The brain MRI showed diffuse leucoencephalopathy while nerve conduction studies were consistent with demyelinating polyneuropathy. Direct DNA sequencing of the nine coding exons of the TP gene showed both a novel and a previously described mutation. The former is a point mutation in exon 5 (NG_011860.1:g.7387C>T) at amino acid position 179, resulting in a stop codon and premature truncation of thymidine phosphorylase(TP) protein while the latter mutation occurred at exon 10 (NG_011860.1:g.9279C>T) resulting in a missense homozygous mutation at amino acid position 471. Defi nite diagnosis was based on clinical features, plasma and urinary nucleosides and the identifi cation of mutations in the TP gene. This case report adds to the knowledge of genotype-phenotype relationship of TP mutations and its occurrence among ethnic groups worldwide.

TT genotype of the methylenetetrahydrofolate reductase C677T polymorphism is an important determinant for homocysteine levels in multi-ethnic Malaysian ischaemic stroke patients

<p><b>INTRODUCTION</b>The functional point mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, has been reported to contribute to hyperhomocysteinaemia which is a risk factor for atherothrombotic ischaemic strokes. This study evaluated the prevalence of the C677T polymorphism of the gene in Malaysian ischaemic stroke subjects of Malay, Chinese and Indian ethnicities, and its association with homocysteine levels (tHcy).</p><p><b>MATERIALS AND METHODS</b>A total of 292 subjects were recruited, comprising 150 ischaemic stroke patients and 142 control subjects who were age and sex matched. Plasma homocysteine, serum folate and vitamin B12 were measured in all subjects. Genotyping was carried out using PCR-RFLP.</p><p><b>RESULTS</b>The homocysteine levels were significantly higher (P = 0.001) in the stroke group (11.35 ± 2.75 μmol/L) compared to the control group (10.38 ± 2.79 μmol/L). The MTHFR C677T genotype distribution for the stroke group was 46%, 40% and 14%, respectively for CC, CT and TT genotypes and 59.9%, 33.8% and 6.3%, respectively for the control group. The genotype and allelic frequencies were significantly different between the 2 groups, with P = 0.02 and P = 0.004 respectively. No significant difference was seen in the genotype distribution inter-ethnically. An increasing tHcy was seen with every additional T allele, and the differences in the tHcy for the different genotypes were significant in both the control (P <0.001) and stroke groups (P <0.001).</p><p><b>CONCLUSION</b>This study shows that TT genotype of the methylenetetrahydrofolate reductase C677T polymorphic gene is an important determinant for homocysteine levels in Malaysian ischaemic stroke patients.</p>

Ischaemic stroke in young adults: A comparative study between Malaysia and Australia

Background and Objectives: There is a paucity of comparative studies on young strokes between populations of different ethnicities and geographical regions. The purpose of this study was to compare the patterns, risk factors and etiologies of ischaemic stroke in younger patients between stroke registries in Malaysia and Australia. Methods: From January 2007 to March 2008, all consecutive ischaemic stroke patients from the age of 18 to 49 were studied. Results: There were 67 patients for Malaysia and 61 for Australia, with 4 deaths in the Malaysian series (case-fatality of 6%), and no deaths for Australia. The mean age was 41.5±8.8 yrs for Malaysia and 40.1±8.8 years for Australia. The ethnic origin was Malays, Chinese and Indian for Malaysia, and Caucasians (85%) for Australia. The sex ratio was M : F = 1.4 : 1 for Malaysia and 1.54 :1 for Australia. The differences in risk factors for Malaysia versus Australia were: Diabetes (OR 7.25; 95% CI 2.78-19.45), hypertension (OR 6.42; 95% CI 2.75-15.22) and chronic renal disease (OR 5.2; 95% CI 1.02-35.87). Conversely, smoking was a signifi cant risk factor for Australia (OR 2.75; 95% CI 1.2-6.37). The Malaysian patients have signifi cantly higher proportions of large vessel atherosclerosis and small vessel occlusion by TOAST classifi cation, accounting for 60% of patients, while the Australian series had greater proportions of cardioembolism and patients in the determined aetiologies category, specifi cally vascular dissection. Conclusion: There were signifi cantly more large vessel atherosclerosis and small vessel occlusion among young Malaysians with ischaemic stroke as compared to Australia.

Complication of acute stroke: A study in ten Asian countries

Background and Objective: There is a paucity of studies looking into the frequency of complications after stroke among Asians. We sought to determine the frequency and rate of complications among Asians after acute stroke. Methods: Consecutive patients with acute stroke among 10 participating Asian countries were included in the study. The frequency and timing of pre-determined complications, and their relation to area of admission were noted. Results: Of the 1,153 patients included in the study, 423 (41.9%) developed complications within the first 2 weeks of stroke. Recurrent stroke, chest infections and urinary tract infections were most commonly encountered, and were most frequent within the first week of stroke onset. A lower rate of complications was noted among patients admitted at an organized stroke unit. Conclusion: There is a similar rate of frequency and timing of complications after acute stroke among Asians as compared with other populations.