Digvijaya Navalkele

Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population

Background: Earlier tissue plasminogen activator treatment improves ischemic stroke outcome, but aspects of the time-benefit relationship still not well delineated are: (1) the degree of additional benefit accrued with treatment in the first 60 minutes after onset, and (2) the shape of the time-benefit curve through 4.5 hours. Methods: We analyzed patients who had acute ischemic stroke treated with intravenous tissue plasminogen activator within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset-to-treatment time was analyzed as a continuous, potentially nonlinear variable and as a categorical variable comparing patients treated within 60 minutes of onset with later epochs. Results: Among 65 384 tissue plasminogen activator–treated patients, the median onset-to-treatment time was 141 minutes (interquartile range, 110–173) and 878 patients (1.3%) were treated within the first 60 minutes. Treatment within 60 minutes, compared with treatment within 61 to 270 minutes, was associated with increased odds of discharge to home (adjusted odds ratio, 1.25; 95% confidence interval, 1.07–1.45), independent ambulation at discharge (adjusted odds ratio, 1.22; 95% confidence interval, 1.03–1.45), and freedom from disability (modified Rankin Scale 0–1) at discharge (adjusted odds ratio, 1.72; 95% confidence interval, 1.21–2.46), without increased hemorrhagic complications or in-hospital mortality. The pace of decline in benefit of tissue plasminogen activator from onset-to-treatment times of 20 through 270 minutes was mildly nonlinear for discharge to home, with more rapid benefit loss in the first 170 minutes than later, and linear for independent ambulation and in-hospital mortality. Conclusions: Thrombolysis started within the first 60 minutes after onset is associated with best outcomes for patients with acute ischemic stroke, and benefit declined more rapidly early after onset for the ability to be discharged home. These findings support intensive efforts to organize stroke systems of care to improve the timeliness of thrombolytic therapy in acute ischemic stroke.

Clotting Factors to Treat Thrombolysis-related Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke

BACKGROUND Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor administration may be a treatment option. OBJECTIVE To determine if treatment with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was associated with improved outcomes in sICH. METHODS We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related sICH, including cases with subsequent intra-arterial therapy. Outcomes were Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion. RESULTS Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%; 18 received FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome, mRS score of 2 or less. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%), respectively. There was no difference in hematoma expansion between the 2 groups. CONCLUSIONS We found no evidence that treatment for sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small because of the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.

Central Nervous System Vasculitis

Abstract Inflammation of arteries supplying the central nervous system is one of the rare causes of ischemic and hemorrhagic stroke. Diagnosis of CNS vasculitis is challenging and often delayed due to slow onset of nonspecific symptoms prior to sudden presentation with stroke, seizures, or altered mental status. Diagnostic testing is imperfect and often requires a sequence of supportive studies, typically including at least one invasive test: lumbar puncture, catheter angiography, and/or brain biopsy. Treatment for CNS vasculitis carries its own challenges in terms of monitoring for disease control and drug toxicities or infections related to immunosuppression. This chapter reviews common presentations, diagnostic strategies, common mimics, and treatment for CNS vasculitis.

Factor VIII in Acute Cerebral Ischemia Pilot Study: Biomarker in Patients With Large Vessel Occlusion?:

We conducted a prospective serial laboratory cohort study to assess the correlation of factor VIII (FVIII) levels in response to thrombolysis in patients with large vessel occlusion (LVO) and acute ischemic stroke (AIS). Patients with AIS with anterior circulation LVO were eligible for enrollment if treated within 4.5 hours from last seen normal with intravenous tissue plasminogen activator (tPA). Patients (n = 29) had a mean age of 71 years and median National Institute of Health Stroke Scale of 14. Baseline pre-tPA FVIII was not significantly correlated with clot burden score (−0.147, P = .447) or vessel recanalization (−0.133, P = .499). Median FVIII decreased significantly from baseline to 6 hours post-tPA (282% to 161%, P = .002), but delta in FVIII level did not correlate with vessel recanalization (0.013, P = .948). There was no difference between median FVIII level at baseline and 90 days post-AIS. FVIII level decreased significantly after tPA, but baseline FVIII level and early change in FVIII level were not significant predictors of clot burden, vessel recanalization after thrombolysis, or symptomatic hemorrhage.

Higher prehospital blood pressure prolongs door to needle thrombolysis times: A target for quality improvement?

BACKGROUND Per the American Heart Association guidelines, blood pressure (BP) should be less than 185/110 to be eligible for stroke thrombolysis. No studies have focused on prehospital BP and its impact on door to needle (DTN) times. We hypothesized that DTN times would be longer for patients with higher prehospital BP. METHODS We conducted a retrospective review of acute ischemic stroke patients who presented between January 2010 and December 2010 to our emergency department (ED) through emergency medical services within 3 hours of symptom onset. Patients were categorized into 2 groups: prehospital BP greater than or equal to 185/110 (group 1) and less than 185/110 (group 2). Blood pressure records were abstracted from emergency medical services run sheets. Primary outcome measure was DTN time, and secondary outcome measures were modified Rankin Score at discharge, symptomatic intracranial hemorrhage, length of stay in stroke unit, and discharge disposition. RESULTS A total of 107 consecutive patients were identified. Of these, 75 patients (70%) were thrombolysed. Mean DTN times were significantly higher in group 1 (adjusted mean [95% confidence interval], 86minutes [76-97] vs 56minutes [45-68]; P<.0001). A greater number of patients required antihypertensive medications before thrombolysis in the ED in group 1 compared to group 2 (54% vs 27%; P=.02). CONCLUSION Higher prehospital BP is associated with prolonged DTN times and DTN time remains prolonged if prehospital BP greater than or equal to 185/110 is untreated before ED arrival. Prehospital BP control could be a potential area for improvement to reduce DTN times in patients with acute ischemic stroke.