scholarly journals Fifty Years of Acute Ischemic Stroke Treatment: A Personal History

2021 ◽  
pp. 1-15
Author(s):  
James C. Grotta
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Systems Of Care ◽  
Medical Science ◽  
Tissue Type ◽  
Stroke Units ◽  
Stroke Treatment

<b><i>Background:</i></b> It has been 50 years since the first explorations of the physiology of cerebral ischemia by measuring cerebral blood flow (CBF), and 25 years since the approval of tissue plasminogen activator for treating acute ischemic stroke. My personal career began and matured during those eras. Here, I provide my perspective on the evolution of acute stroke research and treatment from 1971 to the present, with some in-depth discussion of the National Institutes of Neurologic Disease and Stroke (NINDS) tissue-type plasminogen activator (tPA) stroke trial and development of mobile stroke units. <b><i>Summary:</i></b> Studies of CBF and metabolism in acute stroke patients revealed graded tissue injury that was dependent on the duration of ischemia. Subsequent animal research unraveled the biochemical cascade of events occurring at the cellular level after cerebral ischemia. After a decade of failed translation, the development of a relatively safe thrombolytic allowed us to achieve reperfusion and apply the lessons from earlier research to achieve positive clinical results. The successful conduct of the NINDS tPA stroke study coupled with positive outcomes from companion tPA studies around the world created the specialty of vascular neurology. This was followed by an avalanche of research in imaging, a focus on enhancing reperfusion through thrombectomy, and improving delivery of faster treatment culminating in mobile stroke units. <b><i>Key Messages:</i></b> The last half century has seen the birth and evolution of successful acute stroke treatment. More research is needed in developing new drugs and catheters to build on the advances we have already made with reperfusion and also in evolving our systems of care to get more patients treated more quickly in the prehospital setting. The history of stroke treatment over the last 50 years exemplifies that medical “science” is an evolving discipline worth an entire career’s dedication. What was impossible 50 years ago is today’s standard of care, what we claim as dogma today will be laughed at a decade from now, and what appears currently impossible will be tomorrow’s realities.

scholarly journals Update on therapies for acute ischemic stroke

2000 ◽  
Vol 8 (5) ◽  
pp. 1-5 ◽  
Author(s):  
Dean D. Kindler ◽  
George A. Lopez ◽  
Bradford B. Worrall ◽  
Karen C. Johnston
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Emerging Therapies ◽  
Type Plasminogen Activator ◽  
Acute Cerebral Ischemia ◽  
Promising Treatment

Acute ischemic stroke is now considered a neurological emergency for which there are new therapies. Neurosurgeons and neurologists need to remain apprised of advances in this field. The authors discuss approved and emerging therapies for patients suffering from acute ischemic stroke, based on a review of recent publications. Currently, intravenous tissue-type plasminogen activator is the only Food and Drug Administration–approved therapy for acute ischemic stroke. Intraarterial delivery of thrombolytics is a promising treatment and may be effective in selected patients. Other therapies for acute cerebral ischemia are intriguing but still in the investigational stages.

DWI Lesion Characteristics As A Predictor For Outcome In Acute Stroke Patients Treated By IV-tPA

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
H Aref ◽  
S Farag ◽  
S Helmy ◽  
H Mahmoud
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
P Value ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Iv Tpa

Abstract Background Thrombolysis with tissue-type plasminogen activator (IV-tPA) is a well-proved, widely used treatment in acute ischemic stroke patients, many predictors of functional outcome have been proposed as Age, vascular risk factors, initial clinical evaluation on admission using National institute of health stroke scale(NIHSS), functional state of patient(b.L) baseline before stroke and 3 months (3m) after stroke using modified Rankin stroke scale (MRS)and the most controversial Diffusion weighted image characteristics (volume, heterogeneity) Objective To evaluate DWI MRI characteristics (volume, heterogeneity) as a predictor for outcome in Acute stroke patients treated by IV-tPA Patients and Methods This study will be done on a sample of 100 acute ischemic stroke Egyptian patients receiving intra-venous tissue -type plasminogen activator presenting to Ain-Shams university hospitals Results Highly statistically significant (p-value &lt; 0.001) Positive correlation (r = 0.394) between volume (DWI) and MRS (3m) post discharge in studied patients, No statistically significant (pvalue &gt; 0.05) relation between heterogeneity and other studied parameters (MRS, NIHSS D & ADC values) in studied patients Conclusion DWI infarct volume is a predictor for outcome in acute ischemic stroke patients treated by tPA

Abstract P201: Octogenarian and Nonagenarian Outcomes Among Acute Ischemic Stroke Patients

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
RAJAN R GADHIA ◽  
Farhaan S Vahidy ◽  
Tariq Nisar ◽  
Destiny Hooper ◽  
David Chiu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Combined Treatment ◽  
Stroke Patients ◽  
Stroke Treatment ◽  
Intravenous Tissue Plasminogen Activator ◽  
Significant Difference ◽  
Acute Stroke Treatment ◽  
Iv Tpa

Objective: Most acute stroke treatment trials exclude patients above the age of 80. Given the clear benefit of revascularization with intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy (MT), we sought to assess functional outcomes in patients treated above the age of 80. Methods: We conducted a review of all patients admitted to Houston Methodist Hospital between January 2019 and August 2020 with an acute ischemic stroke (AIS) presentation[MOU1] for whom premorbid, discharge, and 90 day modified Rankin Scale scores were available. Patients were categorized by acute stroke treatment (IV tPA, MT, both or none[MOU2] ). mRS values were assessed during admission prior to discharge and at 90 days post stroke event. A delta mRS (Discharge vs. 90-day [MOU3] ) was defined and grouped as no change, improved, or worsened to assess overall functional disability in regards to the index stroke presentation. Results: A total of 865 patients with AIS presentation were included, of whom 651 (75.3%) were <80 years and 214 (24.7%) were > 80 years of age at presentation. A total of 208 patients received IV tPA, 176 underwent revascularization with MT only, 71 had both treatments, and 552 had no acute intervention. In patients >80 yrs who had no acute stroke intervention. mRS improvement was noted in 71.4% compared to 54.1% observed in those patients <80 years. Among patients who received IV tPA, 81.5% of > 80 years improved vs. 61.6% in the younger cohort. A similar trend was noted in the MT and combined treatment groups (76.2% vs. 71.2% and 78.6% vs. 79.3%, respectively). Conclusion: Based on our cohort of acute stroke patients, there was no significant difference in outcomes (as measured by delta mRS) for octogenarians and nonagenarians when compared to younger patients. There was a trend towards improvement in the elderly patients. Chronological age by itself may be an insufficient predictor of functional outcome among stroke patients and age cutoffs for enrollment of patients in acute stroke trials may need additional considerations.

Abstract TMP19: Intravenous Recombinant Tissue-type Plasminogen Activator Use in Young Adults With Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jodi A Dodds ◽  
Ying Xian ◽  
Shubin Sheng ◽  
Gregg Fonarow ◽  
Ronald A Matsouaka ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Older Patients ◽  
Young Patients ◽  
Tissue Type ◽  
Stroke Patients ◽  
Younger Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

Background: Intravenous recombinant tissue-type plasminogen activator (rt-PA) administration improves outcomes in acute ischemic stroke. However, young patients (<40 years old) presenting with stroke symptoms may experience delays in treatment due to misdiagnosis or a reluctance to treat since they do not fit the profile of a typical stroke patient. Methods: We analyzed data from the large national Get With The Guidelines–Stroke registry for acute ischemic stroke patients hospitalized between January 2009 and September 2015. Multivariable models with generalized estimating equations (GEE) were used to test for differences between younger (age 18-40) and older (age > 40) acute ischemic stroke patients, controlling for patient and hospital characteristics including stroke severity. Results: Of 1,320,965 AIS patients admitted to participating hospitals, 2.3% (30,448) were aged 18-40. Among these patients, 12.5% received rt-PA versus 8.8% of those aged >40 (p<0.001). Of patients arriving within 3.5 hours of symptom onset without contraindications, 68.7% of younger patients received IV rt-PA versus 63.3% of older patients (adjusted OR [aOR] 1.30, 95% CI 1.21 to 1.40), without evidence that age-related differences varied by sex (interaction p-value 0.25). Odds ratios of achieving target door-to-CT times and door-to-needle (DTN) times, and outcomes of rtPA-treated patients, are shown in the Table. Conclusions: Young acute ischemic stroke patients did not receive rt-PA treatment at lower rates than older patients. Outcomes were better and the rate of symptomatic intracranial hemorrhage was lower in the young patients. However, younger patients had significantly longer door-to-CT and DTN times, providing an opportunity to improve the care of these patients.

scholarly journals Strategies Used by Hospitals to Improve Speed of Tissue-Type Plasminogen Activator Treatment in Acute Ischemic Stroke

Stroke ◽  
2014 ◽  
Vol 45 (5) ◽  
pp. 1387-1395 ◽  
Author(s):  
Ying Xian ◽  
Eric E. Smith ◽  
Xin Zhao ◽  
Eric D. Peterson ◽  
DaiWai M. Olson ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

scholarly journals Intravenous Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients With History of Stroke Plus Diabetes Mellitus

Stroke ◽  
2019 ◽  
Vol 50 (6) ◽  
pp. 1497-1503 ◽  
Author(s):  
Matthew E. Ehrlich ◽  
Li Liang ◽  
Haolin Xu ◽  
Andrzej S. Kosinski ◽  
Adrian F. Hernandez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Stroke Patients ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
History Of

scholarly journals Vepoloxamer Enhances Fibrinolysis of tPA (Tissue-Type Plasminogen Activator) on Acute Ischemic Stroke

Stroke ◽  
2019 ◽  
Vol 50 (12) ◽  
pp. 3600-3608 ◽  
Author(s):  
Chunyang Wang ◽  
Rui Huang ◽  
Chao Li ◽  
Mei Lu ◽  
Martin Emanuele ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Combination Treatment ◽  
Infarct Volume ◽  
Brain Perfusion ◽  
Artery Occlusion ◽  
Tissue Type ◽  
Pai 1

Background and Purpose— Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods— Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results— Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions— The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.

scholarly journals Catheter based selective hypothermia reduces stroke volume during focal cerebral ischemia in swine

2015 ◽  
Vol 8 (4) ◽  
pp. 418-422 ◽  
Author(s):  
Thomas K Mattingly ◽  
Lynn M Denning ◽  
Karen L Siroen ◽  
Barb Lehrbass ◽  
Pablo Lopez-Ojeda ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Stroke Volume ◽  
Acute Ischemic Stroke ◽  
Brain Mri ◽  
Global Cerebral Ischemia ◽  
Moderate Hypothermia ◽  
Stroke Model ◽  
Stroke Treatment ◽  
Endovascular Cooling

BackgroundTotal body hypothermia is an established neuroprotectant in global cerebral ischemia. The role of hypothermia in acute ischemic stroke remains uncertain. Selective application of hypothermia to a region of focal ischemia may provide similar protection with more rapid cooling and elimination of systemic side effects. We studied the effect of selective endovascular cooling in a focal stroke model in adult domestic swine.MethodsAfter craniotomy under general anesthesia, a proximal middle cerebral artery branch was occluded for 3 h, followed by 3 h of reperfusion. In half of the animals, selective hypothermia was induced during reperfusion using a dual lumen balloon occlusion catheter placed in the ipsilateral common carotid artery. Following reperfusion, the animals were sacrificed. Brain MRI and histology were evaluated by experts who were blinded to the intervention.Results25 animals were available for analysis. Using selective hypothermia, hemicranial temperature was successfully cooled to a mean of 26.5°C. Average time from start of perfusion to attainment of moderate hypothermia (<30°C) was 25 min. Mean MRI stroke volumes were significantly reduced by selective cooling (0.050±0.059 control, 0.005±0.011 hypothermia (ratio stroke:hemisphere volume) (p=0.046). Stroke pathology volumes were reduced by 42% compared with controls (p=0.256).ConclusionsSelective moderate hypothermia was rapidly induced using endovascular techniques in a clinically realistic swine stroke model. A significant reduction in stroke volume on MRI was observed. Endovascular selective hypothermia can provide neuroprotection within time frames relevant to acute ischemic stroke treatment.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy

2017 ◽  
Vol 12 (6) ◽  
pp. 659-666 ◽  
Author(s):  
Susanne Siemonsen ◽  
Nils D Forkert ◽  
Martina Bernhardt ◽  
Götz Thomalla ◽  
Martin Bendszus ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Trial Design ◽  
Mechanical Thrombectomy ◽  
Predictive Analytics ◽  
Stroke Patients ◽  
Tissue Plasminogen

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

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