Phosphodiesterase 5 inhibition as a therapeutic target for ischemic stroke: A systematic review of preclinical studies

Background tPA (tissue‐type plasminogen activator) remains the only approved drug for acute ischemic stroke, with a potentially serious adverse effect: hemorrhagic transformation. The effects of antithrombotic agents on tPA‐induced hemorrhagic transformation after ischemic stroke are not clearly defined. We performed a systematic review and meta‐analysis in preclinical studies aiming to evaluate the efficacy of antithrombotic agents on tPA‐induced hemorrhagic transformation after ischemic stroke. Methods and Results We conducted a systematic review and meta‐analysis of studies testing antithrombotic agents in animal models of tPA‐induced hemorrhagic transformation. The pooled effects were calculated using random‐effects models, and heterogeneity was explored through meta‐regression and subgroup analyses. Publication bias was assessed using trim and fill method and the Egger test. The efficacy of 18 distinct interventions was described in 22 publications. The pooled data showed a significant improvement in cerebral hemorrhage, infarct size, and neurobehavioral outcome in treated compared with control animals (standardized mean difference, 0.45 [95% CI, 0.11–0.78]; standardized mean difference, 1.18 [95% CI, 0.73–1.64]; and standardized mean difference, 0.91 [95% CI, 0.49–1.32], respectively). Subgroup analysis indicated that quality score, random allocation, control of temperature, anesthetic used, stroke model used, route of drug delivery, time of drug administration, and time of assessment were significant factors that influenced the effects of interventions. Conclusions Administration with antiplatelet agents revealed statistically significant improvement in all the outcomes. Anticoagulant agents showed significant effects in infarct size and neurobehavioral score, but fibrinolytic agents did not show any significant improvement in all the outcomes. The conclusions should be interpreted cautiously given the heterogeneity and publication bias identified in this analysis.

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Microbubbles combined with ultrasound therapy in ischemic stroke: A systematic review of in-vivo preclinical studies

PLoS ONE ◽

10.1371/journal.pone.0191788 ◽

2018 ◽

Vol 13 (2) ◽

pp. e0191788 ◽

Cited By ~ 15

Author(s):

Laurent Auboire ◽

Charles A. Sennoga ◽

Jean-Marc Hyvelin ◽

Fréderic Ossant ◽

Jean-Michel Escoffre ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Ultrasound Therapy ◽

Preclinical Studies

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SERUM GLIAL FIBRILLARY ACIDIC PROTEIN IN THE DIFFERENTIAL DIAGNOSIS OF INTRACEREBRAL HEMORRHAGE AND ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW AND DIAGNOSTIC TEST ACCURACY META-ANALYSIS

10.26226/morressier.58e389add462b802923855f8 ◽

2017 ◽

Author(s):

Aristeidis Katsanos

Keyword(s):

Systematic Review ◽

Differential Diagnosis ◽

Ischemic Stroke ◽

Glial Fibrillary Acidic Protein ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Diagnostic Test ◽

Meta Analysis ◽

Diagnostic Test Accuracy ◽

Test Accuracy

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Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.5.peds19126 ◽

2019 ◽

Vol 24 (5) ◽

pp. 558-571 ◽

Cited By ~ 3

Author(s):

Kartik Bhatia ◽

Hans Kortman ◽

Christopher Blair ◽

Geoffrey Parker ◽

David Brunacci ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Neurological Outcomes

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.

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