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Stem cells in stroke repair: current success and future prospects

Gopurappilly R, Pal R, Mamidi MK, Dey S, Bhonde R, Das AK

CNS Neurol Disord Drug Targets, 2011 Sep 1;10(6):741-56.
PMID: 21838668

Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a narrow therapeutic time window. However, regeneration of the brain after ischemic damage is still active days and even weeks after stroke occurs, which might provide a second window for treatment. Neurorestorative processes like neurogenesis, angiogenesis and synaptic plasticity lead to functional improvement after stroke. Stem cells derived from various tissues have the potential to perform all of the aforementioned processes, thus facilitating functional recovery. Indeed, transplantation of stem cells or their derivatives in animal models of cerebral ischemia can improve function by replacing the lost neurons and glial cells and by mediating remyelination, and modulation of inflammation as confirmed by various studies worldwide. While initially stem cells seemed to work by a 'cell replacement' mechanism, recent research suggests that cell therapy works mostly by providing trophic support to the injured tissue and brain, fostering both neurogenesis and angiogenesis. Moreover, ongoing human trials have encouraged hopes for this new method of restorative therapy after stroke. This review describes up-to-date progress in cell-based therapy for the treatment of stroke. Further, as we discuss here, significant hurdles remain to be addressed before these findings can be responsibly translated to novel therapies. In particular, we need a better understanding of the mechanisms of action of stem cells after transplantation, the therapeutic time window for cell transplantation, the optimal route of cell delivery to the ischemic brain, the most suitable cell types and sources and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment. An integrated approach of cell-based therapy with early-phase clinical trials and continued preclinical work with focus on mechanisms of action is needed.

Matched MeSH terms: Brain Ischemia/therapy
Fulltext Althesin therapy - an adjunct for intracranial pressure control regimes? A preliminary report

Delilkan AE, Namazie M

Med J Malaysia, 1983 Mar;38(1):39-42.
PMID: 6633333

A retrospective report (1970-1980) on patients (non-head injuries and head-injuries) admitted with cerebral ischaemia into the intensive therapy unit is presented. The principles of management to reduce and control intracranial pressure are outlined. Since 1978 continuous intravenous infusion with Althesin has been used instead of barbiturates in the regime. Mortality rate fell from 83.7 percent (1970-1977) to 43.7 percent (1978-1980) for non head injury patients and from 72.1 percent (1970-1977) to 45.6 percent (1978-1980) in the head injured group, the differences between the periods being statistically significant. The possible influencing factors are mentioned. The quality of salvage and survival requires investigation.

Matched MeSH terms: Brain Ischemia/therapy
Assessment of arterial collateralization and its relevance to intra-arterial therapy for acute ischemic stroke

Ramaiah SS, Mitchell P, Dowling R, Yan B

J Stroke Cerebrovasc Dis, 2014 Mar;23(3):399-407.
PMID: 23601372 DOI: 10.1016/j.jstrokecerebrovasdis.2013.03.012

Evidence from recent randomized controlled studies comparing intra-arterial (IA) therapy with intravenous tissue plasminogen activator highlighted the mismatch between recanalization success and clinical outcomes in patients presenting with acute ischemic stroke. There is emerging interest in the impact of arterial collateralization, as determined by leptomeningeal anastomoses (LMAs), on the treatment outcomes of IA therapy. The system of LMA constitutes the secondary network of cerebral collateral circulation apart from the Circle of Willis. Both anatomic and angiographic studies confirmed significant interindividual variability in LMA. This review aims to outline the current understanding of arterial collateralization and its impact on outcomes after IA therapy for acute ischemic stroke, underpinning the possible role of arterial collateralization assessment as a selection tool for patients most likely to benefit from IA therapy.

Matched MeSH terms: Brain Ischemia/therapy*
Fulltext A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke

Hamidon BB, Abdullah SA, Zawawi MF, Sukumar N, Aminuddin A, Raymond AA

Med J Malaysia, 2006 Mar;61(1):59-66.
PMID: 16708735 MyJurnal

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.

Matched MeSH terms: Brain Ischemia/therapy
Fulltext Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results

Ghoreishi A, Arsang-Jang S, Sabaa-Ayoun Z, Yassi N, Sylaja PN, Akbari Y, et al.

J Stroke Cerebrovasc Dis, 2020 Dec;29(12):105321.
PMID: 33069086 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105321

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.
METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.
RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p

Matched MeSH terms: Brain Ischemia/therapy*
A hospital-based study on ischaemic stroke characteristics, management, and outcomes in Sarawak: Where do we stand?

King TL, Tiong LL, Kaman Z, Zaw WM, Abdul Aziz Z, Chung LW

J Stroke Cerebrovasc Dis, 2020 Sep;29(9):105012.
PMID: 32807427 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105012

BACKGROUND: Located on the Borneo Island, Sarawak is the largest state of Malaysia and has a population distinctive from Peninsular Malaysia. The ischaemic stroke data in Sarawak had not been reported despite the growing number of patients annually. We aimed to investigate patient characteristics, management, and outcomes of ischaemic stroke in Sarawak and benchmark the results with national and international published data.
METHODS: We included ischaemic stroke cases admitted to Sarawak General Hospital between June 2013 and August 2018 from Malaysia National Stroke Registry. We performed descriptive analyses on patient demographics, cardiovascular risk factors, prior medications, smoking status, arrival time, thrombolysis rate, Get With The Guidelines (GWTG)-Stroke measures, and outcomes at discharge. We also numerically compared the results from Sarawak with the published data from selected national and international cohorts.
RESULTS: We analysed 1435 ischaemic stroke cases. The mean age was 60.1±13.2 years old; 64.9% were male; median baseline National Institute of Health Stroke Scale was seven points. Hypertension was the most prevalent risk factor of ischaemic stroke; 12.7% had recurrent stroke; 13.7% were active smokers. The intravenous thrombolysis rate was 18.8%. We achieved 80-90% in three GWTG-Stroke performance measures and 90-98% in four additional quality measures in our ischaemic stroke management. At discharge, 57% had modified Rankin Scale of 0-2; 6.7% died during hospitalisation. When compared with selected national and international data, patients in Sarawak were the youngest; Sarawak had more male and more first-ever stroke. Thrombolysis rate in Sarawak was higher compared with most studies in the comparison. Functional outcome at discharge in Sarawak was better than national cohort but still lagging behind when compared with the developed countries. In-hospital mortality rate in Sarawak was slightly lower than the national data but higher when compared with other countries.
CONCLUSION: Our study described characteristics, management, and outcomes of ischaemic stroke in Sarawak. We achieved high compliance with most of GTWG-Stroke performance and quality indicators. Sarawak had better outcomes than the national results on ischaemic stroke. However, there is still room for improvement when compared with other countries. Actions are needed to reduce the cardiovascular burdens for stroke prevention, enhance healthcare resources for stroke care, and improve intravenous thrombolysis treatment in Sarawak.

Matched MeSH terms: Brain Ischemia/therapy*