Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with Thrombocytopenia.

OBJECTIVE: To determine the safety of intravenous (IV) recombinant tissue plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS) who had a platelet count <100,000 /mm3. METHODS: We reviewed the charts of all patients who received IV rtPA for AIS during a 9.6-year period at our stroke center. Those with platelets <100,000/mm3 were identified. Head computed tomography scans performed in 24-36 hours postthrombolysis were reviewed to evaluate the rate of symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 835 patients received IV rtPA for AIS during this period. A total of 5 patients were identified to have a platelet count <100,000/mm3. One of them (20%) developed sICH post-IV tPA administration .The mean platelet count of those 5 patients was 63,000 ± 19,000/mm3. To the best of our knowledge, only 21 thrombocytopenic patients have been reported to receive IV rtPA for AIS in the medical literature. Combining our 5 cases with 21 patients previously reported, we have 26 AIS patients who had a platelet count <100,000/mm3 and received IV rtPA, with 2 of them developing sICH (7.7 %). Comparing the rate of sICH among this group with the patients with normal platelet count in our cohort, there was no statistically significant difference (7.7% versus 6.04%, P value = .73). CONCLUSION: IV rtPA for AIS might be safe in patients with platelet count <100,000/mm3 and it is reasonable not to delay IV rtPA administration while waiting for the platelet count result, unless there is strong suspicion for abnormal platelet count.

Prior Asymptomatic Parenchymal Hemorrhage Does Not Increase the Risk for Intracranial Hemorrhage after Intravenous Thrombolysis.

BACKGROUND: The NINDS trial demonstrated the efficacy of intravenous (IV) recombinant tissue plasminogen activator (rtPA) in improving the neurologic outcome in patients presenting with acute ischemic strokes. Patients who had a prior history of intracranial hemorrhage (ICH) were excluded from this trial, possibly due to a hypothetical increase in the subsequent bleeding risk. Thus, there is little data available, whether against or in favor of, the use of IV rtPA in patients with prior ICH. We aim to aid in determining the safety of IV rtPA in such patients through a retrospective hospital-based single center study. METHODS: We reviewed the brain imaging of all patients who received IV rtPA at our comprehensive stroke center from January 2006 to April 2014 for evidence of prior ICH at the time of IV rtPA administration. Their outcomes were determined in terms of subsequent development of symptomatic ICH as defined by the NINDS trial. RESULTS: Brain imaging for 640 patients was reviewed. A total of 27 patients showed evidence of prior ICH at the time of IV thrombolysis, all intra-parenchymal. Only 1 patient (3.7%) developed subsequent symptomatic ICH after the administration of IV rtPA. Of the remaining 613 patients who received IV rtPA, 25 patients (4.1%) developed symptomatic ICH. CONCLUSION: This retrospective study provides Level C evidence that patients with imaging evidence of prior asymptomatic intra-parenchymal hemorrhage presenting with an acute ischemic stroke do not show an increased risk of developing symptomatic ICH after IV thrombolysis.

Transesophageal echocardiogram in the evaluation of acute ischemic stroke of young adults.

INTRODUCTION: Acute ischemic stroke (AIS) in the young age (≤50 years) is a major cause of disability. The underlying mechanism of AIS in this age group is usually different from elderly. Transthoracic echocardiography (TTE) is used to detect the potential cardiac sources of embolism in AIS patients. Transthoracic echocardiogram (TEE) is superior to detect specific underlying cardio-aortic source of embolism when compared to TTE. We aim to evaluate the diagnostic yield and therapeutic impact of TEE in AIS of young adults. METHODS: We retrospectively reviewed the consecutive patients with AIS in our comprehensive center in a 5-year period from our prospectively collected registry. We selected patients with age ≤50 years who had acute infarcts on brain magnetic resonance imaging or head computed tomography and underwent TEE as part of their diagnostic workup. Demographic details including, age, gender, body mass index, cardiovascular risk factors profile, and TEE findings were collected. RESULTS: Among a total 7,930 patients, 876 (11.04%) were found to be ≤50 years old. Among those, TEE was done in 113 patients (12.8%) in addition to TTE. Those who underwent TEE had a mean age of 40.4 ± 7.9 years, 60 were male (53%), 7 (6.2%) had a history of coronary artery disease, 38 (33%) had a history of diabetes, and 45 (40%) had a history of smoking. TEE showed new abnormal findings in a total of 15 patients (13.2%) that were not reported in their TTEs. Out of these, left atrial appendage thrombus was found in 5, infective endocarditis in 4, atrial septal aneurysms associated with patent foramen ovale (PFO) in 3, and spontaneous mobile echo density in three patients. Overall, new findings from TEE resulted in change in the secondary stroke prevention strategy in 14 patients of those who underwent TEE (12.3%). TEE also confirmed the presence of PFO, which was present on TTE with bubble study in 20 (17.6%) patients. CONCLUSION: TEE may provide additional information in the evaluation of the AIS in young adults, which could lead to change of the secondary stroke prevention strategy.

Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials.

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders. Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings. Conclusions and Relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

First Food and Drug Administration-approved prospective trial of primary intracranial stenting for acute stroke: SARIS (stent-assisted recanalization in acute ischemic stroke).

BACKGROUND AND PURPOSE: Acute revascularization is associated with improved outcomes in ischemic stroke patients. However, it is unclear which method of intraarterial intervention, if any, is ideal. Numerous case series and cardiac literature parallels suggest that acute stenting may yield high revascularization levels with low associated morbidity. We therefore conducted a Food and Drug Administration-approved prospective pilot trial to evaluate the safety of intracranial stenting for acute ischemic stroke. METHODS: Eligibility criteria included presentation or=8, angiographic demonstration of focal intracerebral artery occlusion

Delays in door-to-needle time for acute ischemic stroke in the emergency department: A comprehensive stroke center experience.

BACKGROUND: Current American Stroke Association guidelines recommend initiating intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) within 60min of patient arrival, given the benefits of IVT for AIS are time dependent. This study aimed to identify the delaying factors in door-to-needle time (DTN) in the emergency department of one of the largest comprehensive stroke centers in New York State. We also recommended measures to reduce the delays. METHODS: We retrospectively reviewed the medical charts of all AIS patients who received IVT in our emergency department patients between April 1, 2012 and December 31, 2015 to identify those with a DTN time of >60min. We categorized the factors causing the delay into different groups. For each group, we recommended measures to reduce the treatment delays. RESULTS: A total of 487 patients received IVT for AIS during the 3.7-year period. Of these, 96 patients (20.4%) met our DTN time delay criteria. Delays for obtaining stroke imaging and hypertension control were the most common factors. Thirty eight patients (39.5%) had delay in obtaining CT-based stroke imaging. Twenty-two patients (22.9%) required control of elevated blood pressure prior to IVT. Other causes for delay in DTN time included delay in stroke triage and paging (11.4%), fluctuating neurological symptoms (7.2%), uncertainty about diagnosis (12.5%), delays associated with obtaining consent (9.3%), and uncertainty about the time of symptom onset (5.2%). CONCLUSION: Important and common causes of delay in IVT for AIS were identified in a review of charts at our comprehensive stroke center. The authors recommend strategies to achieve faster DTN time for each of the delaying factor categories including faster acquisition and interpretation of stroke imaging, more effective triage protocols and faster blood pressure control for AIS patients who are eligible for IVT.

Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm?

BACKGROUND: Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms. AIMS AND/OR HYPOTHESIS: To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms. METHODS: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm. RESULTS: A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8·3-year period. Thirty-three (5·2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial thrombolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4·8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location. CONCLUSION: Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra-arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke patients who harbor unruptured intracranial aneurysms less than 10 mm in diameter. Their listing in exclusion criteria for intravenous thrombolysis should be reconsidered to assure appropriate use of acute reperfusion therapy in this group of patients.