A Systematic Search and Review of Registered Pharmacological Therapies Investigated to Improve Outcomes after a Stroke.

INTRODUCTION: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities. METHODS: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments. Data will be extracted from included papers, including patient demographics, study methods, keystroke inclusion criteria, details of intervention and control, and the reported outcomes. RESULT: "The best available studies" based on study design, study size, and/or date of publication for different therapies and stroke subtypes will be selected and graded for level of evidence by consensus. CONCLUSION: There are conflicting study results of pharmacological interventions after an acute stroke to enhance recovery. This systematic search and review will identify the best evidence and knowledge gaps in the pharmacological treatment of post-stroke patients as well as guide clinical decision-making and planning of future studies.

Whole-exome sequencing reveals the genetic causes and modifiers of moyamoya syndrome.

Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.

Stroke in Asia.

BACKGROUND: There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition. SUMMARY: In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia, which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy, and cerebral venous thrombosis. KEY MESSAGES: The review of selected literature and recent updates calls for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.

A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke.

Background: Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities. Methods: We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. "The best available studies" based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus. Results: Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as "the best studies" across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects. Conclusion: Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.

Stroke Burden in Malaysia.

Malaysia is located in the heart of South East Asia with two land masses, Peninsular Malaysia and East Malaysia which are separated by the South China Sea. Stroke or cerebrovascular disease is Malaysia's third leading cause of death. There were 47, 911 incident cases, 19,928 deaths, 443,995 prevalent cases, and 512,726 DALYs lost due to stroke in 2019. Successive national health and morbidity surveys from 2006 demonstrated a continuous rise in the prevalence of risk factors such as diabetes, hyperlipidaemia, and obesity. These risk factors are implicated in an increase in stroke incidence in those under 65 years of age, the largest increase of 53.3% and 50.4% in men and women, respectively, from the age strata of 35-39 years. The neurologist-to-patient ratio is 1:323,000 with the majority of neurologists working in urban centres. The healthcare system is provided predominantly by the public and private sectors. Concurrent use of traditional and complementary medicine is common and widely accepted. Challenges include delivering adequate care to rural communities, the low overall ischaemic stroke thrombolysis rates, and the high cost of thrombectomy devices for use in large vessel occlusions which have to be borne out-of-pocket by patients and their families. Effort is required to continue improving stroke care services in parallel with primary and secondary prevention strategies in the future, given the ageing population and the rising number of strokes in young adults nationally. Strategies include careful planning, inter-hospital cooperation, and increased allocation of resources from the government.

10th Anniversary of the Asia Pacific Stroke Organization: State of Stroke Care and Stroke Research in the Asia-Pacific.

The Asia Pacific Stroke Organization is the largest international and professional stroke group in the region. It has worked consistently over the last 10 years to gain visibility and consistency across the Asia-Pacific and beyond. The 10-year journey will be reviewed in the background of many internal and external developments including changes in Asia-Pacific stroke epidemiology, stroke care systems, and stroke service developments as well as major research studies in the Asia-Pacific.

Acute Ischaemic Stroke Successfully Treated with Thrombolytic Therapy and Endovascular Thrombectomy with Non-Contrast Computed Tomography and Computed Tomography Angiogram Protocol.

Early endovascular thrombectomy leads to improved outcomes for patients with proximal occlusions when started within 6 h from onset of symptoms. We present a case illustrating the flow of events for a patient who underwent endovascular thrombectomy in our centre after conventional imaging - a brain non-contrast computed tomography (NCCT) and CT angiogram (CTA) - achieving a door-to-groin time of 195 min. The patient is a 65-year-old who presented with signs and symptoms of a left middle cerebral artery (MCA) territory infarct. His National Institute of Health Stroke Scale (NIHSS) score was 15 on presentation and his brain NCCT showed an Alberta Stroke Programme Early CT Score (ASPECTS) of 8. His CTA showed a left MCA distal M1 occlusion with focal calcification and stenosis of the proximal left internal carotid artery. He was subsequently thrombosed and underwent thrombectomy successfully, with a door-to-groin-puncture time of 195 min. A TICI 2b reperfusion was achieved. His NIHSS score improved to 9 over the next 2 days. For cases with straightforward NCCT and CTA with no contraindications, endovascular thrombectomy should be pursued without delay. A review of the current available literature for the usage of NCCT and CTA as well as the importance of ASPECTS scoring in patient selection for endovascular thrombectomy was included.

Mechanical Thrombectomy for Life-Threatening Cerebral Venous Thrombosis: A Case Report.

Cerebral venous thrombosis (CVT) is a rare cause of stroke worldwide with a wide range of clinical presentations. Anticoagulation therapy has been regarded as the first line of management of CVT to prevent the progression of thrombosis and to re-establish the venous flow. We present a case of severe CVT who did not respond to conventional anticoagulation therapy but responded well to mechanical thrombectomy (MT). This report highlights the features of CVT to consider for early MT.

Streptococcus pneumoniae Meningitis and Intracranial Vasculopathy: Clinical Correlation with Improving Transcranial Doppler Hemodynamics.

Streptococcus pneumoniae are Gram-positive bacteria that are responsible for many types of illnesses including pneumonia, sinus infections, and community-acquired meningitis. One important complication of bacterial meningitis is intracranial vasculopathy. Possible etiologies include vasculitis, vasospasm, endocarditis, or intra-arterial thrombosis. We present a case report of S. pneumoniae meningitis treated with antibiotics in which clinical improvement correlated with serial transcranial Doppler ultrasonography (TCD) improvement, suggesting vasospasm or vasculitis as a possible mechanism for intracranial vasculopathy.

Cough-Induced Extracranial Internal Carotid Artery Dissection.

BACKGROUND: Coughing due to respiratory tract infections may lead to internal carotid artery (ICA) dissection. AIM: We are presenting a patient with an unusual cough-induced ICA dissection. CASE REPORT: A 42-year-old health care worker presented with bilateral hand numbness which resolved spontaneously. This initial episode was followed 9 days later with intermittent episodes of right hand and leg weakness with speech difficulty. Two days later, he had another episode of speech difficulty. One week prior to the first presentation, he had upper respiratory tract infection with ongoing strong bouts of coughing. Magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) of the brain showed early ischaemic changes at the left frontal and left parietal regions. MR angiography (MRA) showed high signal intensity at the left proximal ICA and poor flow beyond the left carotid bulb. Cerebral angiography revealed left ICA dissection. CONCLUSION: Proper identification of cough-induced extracranial ICA dissection is important because this is treatable.

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.