METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times.
RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence.
DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.
METHODS: A literature review was conducted for systematic reviews, meta-analyses, and scoping reviews published between January 1, 2020 and January 1, 2023. Literature assessing individuals with pre-existing neurological diseases and COVID-19 infection was included. Information regarding infection severity was extracted, and potential limitations were identified.
RESULTS: Thirty-nine articles met inclusion criteria, with data assessing >3 million patients from 51 countries. 26/51 (50.9%) of countries analyzed were classified as high income, while the remaining represented middle-low income countries (25/51; 49.0%). A majority of evidence focused on the impact of cerebrovascular disease (17/39; 43.5%) and dementia (5/39; 12.8%) on COVID-19 severity and mortality. 92.3% of the articles (36/39) suggested a significant association between neurological conditions and increased risk of severe COVID-19 and mortality. Cerebrovascular disease, dementia, Parkinson's disease, and epilepsy were associated with increased COVID severity and mortality.
CONCLUSION: Pre-existing neurological diseases including cerebrovascular disease, Alzheimer's disease and other dementias, epilepsy, and Parkinson's disease are significant risk factors for severity of COVID-19 infection and mortality in the acute infectious period. Given that 61.5% (24/39) of the current evidence only includes data from 2020, further updated literature is crucial to identify the relationship between chronic neurological conditions and clinical characteristics of COVID-19 variants.
METHODS: Literature reviews were undertaken to inform summaries of the following: vitamin D status globally and in Asian and Malaysian populations, vitamin D status among individuals with common medical conditions, and current recommendations to achieve vitamin D sufficiency through sun exposure, food intake and supplementation. Recommendations were based on the findings of the literature reviews, recent European guidance on vitamin D supplementation, the 2018 road map for action on vitamin D in low- and middle-income countries, and research recommendations proposed by the Malaysian Ministry of Health in 2017.
RESULTS: Recommendations on assessment of vitamin D in the adult Malaysian population include using serum or plasma 25-hydroxyvitamin D concentration as a biomarker, widespread participation by Malaysian laboratories in the Vitamin D Standardization Program, adoption of the US Endocrine Society definitions of vitamin D deficiency and insufficiency, and development of a comprehensive nationwide vitamin D status study. Specific high-risk groups are identified for vitamin D assessment and recommendations relating to loading doses and ongoing management are also made.
CONCLUSION: This Position Paper provides individual clinicians and national stakeholder organisations with clear recommendations to achieve vitamin D sufficiency in the adult population of Malaysia.
MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities.
RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.
METHODS: We retrospectively analyzed one-year data from our stroke registry that began with the establishment of our hyperacute stroke service at Universiti Putra Malaysia Teaching Hospital from April 2020 until May 2021.
RESULTS: Setting up acute stroke services during the pandemic with constrained manpower and implementation of COVID-19 SOPs, was challenging. There was a significant dip of stroke admission from April to June 2020 due to the Movement Control Order (MCO) implemented by the government to curb the spread of COVID-19. However, the numbers of stroke admission steadily rose approaching 2021, after the implementation of recovery MCO. We managed to treat 75 patients with hyperacute stroke interventions i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT) or both. Despite implementing COVID-19 SOPs and using magnetic resonance imaging (MRI) as our first line acute stroke imaging modality, clinical outcomes in our cohort were encouraging; almost 40% of patients who underwent hyperacute stroke treatment had early neurological recovery (ENR), and only 33% of patients had early neurological stability (ENS). In addition, we were able to maintain our door-to-imaging (DTI) and door-to-needle (DTN) time in line with international recommendations.
CONCLUSIONS: Our data reflects that COVID-19 SOPs did not deter successful delivery of hyperacute stroke services in our center. However, bigger and multi center studies are required to support our findings.
METHODS: This cross-sectional online questionnaire study was conducted nationwide among 627 HCPs in Malaysia using the Acute Stroke Management Questionnaire (ASMaQ). Multiple logistic regression was used to predict the relationship between the independent variables (age, gender, years of service, profession, work setting, work sector, seeing stroke patients in daily practice, and working with specialists) and the outcome variable (good vs poor knowledge).
RESULTS: Approximately 76% (95% CI [73-79%]) of HCPs had good overall knowledge of stroke. The highest proportion of HCPs with good knowledge was noted for General Stroke Knowledge (GSK) [88.5% (95% CI [86-91%])], followed by Advanced Stroke Management (ASM) [61.2% (95% CI [57-65%])] and Hyperacute Stroke Management (HSM) [58.1% (95% CI [54-62%])]. The odds of having poor knowledge of stroke were significantly higher among non-doctor HCPs [adjusted OR = 3.46 (95% CI [1.49-8.03]), P = 0.004]; among those not seeing stroke patients in daily practice [adjusted OR = 2.67 (95% CI [1.73-4.10]), P < 0.001]; and among those working without specialists [adjusted OR = 2.41 (95% CI [1.38-4.18]), P = 0.002].
CONCLUSIONS: Stroke education should be prioritised for HCPs with limited experience and guidance. All HCPs need to be up-to-date on the latest AIS management and be able to make a prompt referral to an appropriate facility. Therefore, more stroke patients will benefit from advanced stroke care.
METHODS: We searched PubMed, Medline, Cochrane library, ClinicalTrials.gov, and EMBASE for studies from December 31, 2019, to December 15, 2020, enrolling consecutive patients with COVID-19 presenting with neurologic manifestations. Risk of bias was examined with the Joanna Briggs Institute scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% confidence intervals (CIs) were calculated for neurologic manifestations. Odds ratio (ORs) and 95% CIs were calculated to determine the association of neurologic manifestations with disease severity and mortality. Presence of heterogeneity was assessed with I 2, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.
RESULTS: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 patients with COVID-19, 89% of whom were hospitalized. Forty-one neurologic manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurologic symptoms included fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%), and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurologic diagnosis (pooled prevalence 2%). In patients with COVID-19 ≥60 years of age, the pooled prevalence of acute confusion/delirium was 34%, and the presence of any neurologic manifestations in this age group was associated with mortality (OR 1.80, 95% CI 1.11-2.91).
DISCUSSION: Up to one-third of patients with COVID-19 analyzed in this review experienced at least 1 neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with nearly a doubling of mortality. Results must be interpreted with the limitations of observational studies and associated bias in mind.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020181867.
CASE PRESENTATION: We report the first case of Longitudinal Extensive Transverse Myelitis (LETM) in Malaysia following administration of the chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine. A 25-year-old female presented with bilateral lower limb weakness and inability to walk with a sensory level up to T8 with absent visual symptoms. Urgent gadolinium-enhanced magnetic resonance imaging (MRI) of the spine showed long segment TM over the thoracic region. Cerebrospinal fluid autoantibodies for anti-aquaporin-4 and anti-myelin-oligodendrocyte were negative. A diagnosis of LETM following vaccination was made, and the patient was started on a high dose of intravenous methylprednisolone. The patient eventually made a recovery following treatment.
CONCLUSION: LETM is a rare but serious adverse reaction following vaccination. Previously reported cases showed an onset of symptoms between 10 to 14 days post-vaccination, suggesting a delayed immunogenic reaction. However, the incidence of myelitis in COVID-19 is much more common, far greater than the risk associated with vaccination.
Methods: A systematic literature search was performed using the Medline, Cochrane, and Embase databases from inception to 20 October 2018. Primary outcome for meta-analyses was the changes in hepatic enzyme levels (alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase). We also performed a meta-analysis on changes in insulin resistance, glycemic, and lipid parameters using SGLT2Is as a secondary objective.
Results: Eight eligible randomized controlled studies were eligible for analysis. Meta-analysis showed the efficacy of two SLT2Is, dapagliflozin, and canagliflozin in reducing these enzymes level. TSA showed that canagliflozin significantly reduced the gamma-glutamyl transpeptidase level by weighted mean difference (-5.474, 95% confidence interval (CI): -6.289??-4.659) compared to others comparators, and the evidence is conclusive. Dapagliflozin also had a statistically significant reduction in glycated hemoglobin, which is a parameter of glycemic control and homeostatic model assessment for insulin sensitivity (HOMA-IR), which is a parameter of insulin sensitivity by a weight mean difference, -0.732 (95% CI: -1.087??-0.378) and -0.804 (95% CI: -1.336??0.272), respectively.
Conclusions: This study indicated that canagliflozin effectively improves liver function parameters among patients with diabetes, while dapagliflozin is more effective in improving glycemic indices and insulin sensitivity.
METHODS: Included trials were assessed using Cochrane risk of bias instrument. We performed meta-analysis with random-effects model and random errors were evaluated with TSA. We performed the search for the eligible randomized controlled trial (RCT) through Medline, Cinahl, Cochrane Central Register of Controlled Trials and also PubMed.
RESULTS: A total of 370 subjects sourced from seven eligible RCTs were entered into the analysis. The pooled results demonstrated the significant reduction with the use of qigong of the systolic blood pressure [weighted mean difference (WMD), - 10.66 mmHg (95% confidence interval (CI) = - 17.69,-3.62, p
METHODS: This is a systematic review protocol describing essential reporting items based on the PRISMA for systematic review protocols (PRISMA-P) (Registration number: CRD42020220636). We aim to review the effectiveness, tolerability, and safety of hf-rTMS at DLPFC in randomised controlled trials (RCTs) as migraine prophylactic treatment. We will search Scopus, Cumulative Index to Nursing and Allied Health Literature Plus, PubMed, Cochrane Central Register of Controlled Trials and Biomed Central for relevant articles from randomised controlled clinical trials that used hf-rTMS applied at DLPFC for the treatment of migraine. The risk of bias will be assessed using the version 2 "Risk of bias" tool from Cochrane Handbook for Systematic Reviews of Interventions Version 6.1. We will investigate the evidence on efficacy, tolerability and safety and we will compare the outcomes between the hf-rTMS intervention and sham groups.
DISCUSSION: This systematic review will further determine the efficacy, safety, and tolerability of hf-rTMS applied at DLPFC for migraine prophylaxis. It will provide additional data for health practitioners and policymakers about the usefulness of hf-rTMS for migraine preventive treatment.
METHODS: Using the national hospital admission records database, we included all stroke patients who were discharged alive between 2008 and 2015 for this secondary data analysis. The risk of readmissions was described in proportion and trends. Reasons were coded according to the International Classification of Diseases, 10th Edition. Multivariable logistic regression was performed to identify factors associated with readmissions.
RESULTS: Among 151729 patients, 11 to 13% were readmitted within 28 days post-discharge from their stroke events each year. The trend was constant for ischemic stroke but decreasing for hemorrhagic stroke. The leading causes for readmissions were recurrent stroke (32.1%), pneumonia (13.0%) and sepsis (4.8%). The risk of 28-day readmission was higher among those with stroke of hemorrhagic (adjusted odds ratio (AOR): 1.52) and subarachnoid hemorrhage (AOR: 2.56) subtypes, and length of index admission >3 days (AOR: 1.48), but lower among younger age groups of 35-64 (AORs: 0.61-0.75), p values <0.001.
CONCLUSION: The risk of 28-day readmission remained constant from 2008 to 2015, where one in eight stroke patients required readmission, mainly attributable to preventable causes. Age, ethnicity, stroke subtypes and duration of the index admission influenced the risk of readmission. Efforts should focus on minimizing potentially preventable admissions, especially among those at higher risk.
METHODS: Subjects age 18 to 60 years will undergo a baseline evaluation to establish the diagnosis of migraine based on the International Classification of Headache Disorder 3rd Edition (ICHD-3). Those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or sham stimulation for 5 sessions within 2 weeks duration. Follow-up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial Doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin gene-related peptide and serum beta-endorphin. These procedures will be repeated at month 3 after receiving the last treatment. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at months 1, 2 and 3 after treatment sessions.
DISCUSSION: Following evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to almost normal level, the rTMS intervention will target left DLPFC in this study. An intermediate duration of treatment sessions is selected for this study. It is set to five treatment sessions given within 2 weeks duration.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03556722 . Registered on 14 June 2018.
METHODS: A cross-sectional study was conducted among 526 pregnant women with GDM in two tertiary hospitals in Malaysia. Diabetes-related QOL was assessed using the Asian Diabetes Quality of Life Scale (AsianDQoL). Socio-demographic characteristics, glucose monitoring treatments for GDM, past obstetric history, concurrent medical problems and a family history of diseases were captured from patient records. A multiple logistic regression was used for analysis.
RESULTS: A total of 526 respondents with GDM entered the analysis. The median age of the respondents was 32 (interquartile range = 7) while 82.3% were Malay women. More than half of the respondents (69.5%) received an oral hypoglycaemic agent (OHA), and/or diet modification in controlling their GDM. The study reported that 23.2% of the respondents had poor-to-moderate QOL. Those with a family history of depression and/or anxiety (adjusted Odds ratio [AOR] 6.934, 95% confidence interval [CI] 2.280-21.081), and a family history of GDM (AOR 1.814, 95% CI 1.185-2.778) were at higher odds of suffering from poor-to-moderate QOL compared to those without a family history. Similarly, those who received insulin, with or without OHA, and/or are on diet modification (AOR 1.955, 95% CI 1.243-3.074) were at higher odds of suffering from poor-to-moderate QOL compared to those receiving OHA and/or diet modification.
CONCLUSION: Nearly one-quarter of Malaysian women with GDM have poor-to-moderate QOL. GDM women with a family history of depression and/or anxiety, family history of GDM, and those who received insulin, with or without OHA, and/or are on diet modification were associated with poor-to-moderate QOL.
TRIAL REGISTRATION: NMRR-17-2264-37814.
Methods: This was a post-hoc case-control exploratory sub-analysis of a cross-sectional study among GDM women to determine which candidate single nucleotide polymorphisms (SNPs) related to neuroendocrine disorders may be associated with obesity. Factors were adjusted for socio-demographic characteristics and concurrent medical problems in this particular population. Pre-pregnancy BMI and concurrent medical profiles were obtained from maternal health records. Obesity is defined as BMI of ≥27.5 kg/m2 for Asian criteria-based BMI and >30 kg/m2 for International criteria-based BMI. Thirteen candidate genes were genotyped using Agena® MassARRAY and examined for association with pre-pregnancy obesity using multiple logistic regression analysis. The significant difference threshold was set at P value <0.05.
Results: Three hundred and twelve GDM women were included in this study; 60.9% and 44.2% of GDM patients were obese using Asian and International criteria-based BMI, respectively. GDM patients with AA or AG genotypes in specific SNP of brain-derived neurotrophic factor (BDNF) (G > A in rs6265) are more likely to be obese (adjusted odd ratio =2.209, 95% CI, 1.305, 3.739, P=0.003) compared to those who carry the GG genotype in the SNP adjusted for parity, underlying with asthma, heart disease, anaemia, education background in the International criteria-based BMI stratification group. On the other hand, there were no associations between other candidate genes (NRG1, FKBP5, RORA, OXTR, PLEKHG1, HTR2C, LHPP, SDK2, TEX51, EPHX2, NPY5R and ANO2) and maternal obesity.
Conclusions: In summary, BDNF rs6265 is significantly associated with pre-pregnancy obesity among GDM patients. The exact role of BDNF adjusted for diet intake and lifestyle factors merits further investigation.