Biomedical subjects

James C Grotta

Publications and source records attributed to James C Grotta.

At least 19 recordsLinked to original sources

PubMed2006

Is intra-arterial thrombolysis safe after full-dose intravenous recombinant tissue plasminogen activator for acute ischemic stroke?

BACKGROUND AND PURPOSE: The optimal approach for acute ischemic stroke patients who do not respond to intravenous recombinant tissue plasminogen activator (IV rt-PA) is uncertain. This study evaluated the safety and response to intra-arterial thrombolytics (IATs) in patients unresponsive to full-dose IV rt-PA. METHODS: A case series from a prospectively collected database on consecutive acute ischemic stroke patients treated with IATs after 0.9 mg/kg IV rt-PA during a 7-year interval was collected. Primary outcome measures included symptomatic intracranial hemorrhage and mortality. As indicators of response, secondary outcome measures were recanalization and discharge disposition. RESULTS: Sixty-nine patients (mean+/-SD age, 60+/-13 years; range, 26 to 85 years; 55% male) with a median pretreatment National Institutes of Health Stroke Scale score of 18 (range, 6 to 39) were included. IV rt-PA was started at 124+/-32 minutes (median, 120 minutes) and IAT, at 288+/-57 minutes (median, 285 minutes). IATs consisted of reteplase (n=56), alteplase (n=7), and urokinase (n=6), with an average total dosage of 2.8 U, 8.6 mg, and 700 000 U, respectively. Symptomatic intracranial hemorrhage occurred in 4 of 69 (5.8%) patients; 3 cases were fatal. Recanalization was achieved in 50 (72.5%) and a favorable outcome (home or inpatient rehabilitation) in 38 (55%). CONCLUSIONS: IAT therapy after full-dose IV rt-PA in patients with persisting occlusion and/or lack of clinical improvement appears safe compared with IV rt-PA alone or low-dose IV rt-PA followed by IAT. A high rate of recanalization and favorable outcome can be achieved.

Acute Disease↗

PubMed2006

Safety and tolerability of arundic acid in acute ischemic stroke.

Arundic acid (AA; ONO-2506), a novel modulator of astrocyte activation, may improve neuronal survival after stroke. We conducted a multicenter, dose-escalating, randomized, double-blind Phase I trial of AA in acute ischemic stroke. Subjects were randomized to treatment with AA or placebo in sequential dose tiers of 2-12 mg/kg/h (10-16 patients/group) within 24 h of stroke onset. Study drug was infused for 1 h daily over 7 days, and follow-up terminated at 40 days. Neurological and functional outcomes were evaluated through Day 40 as exploratory endpoints. A total of 92 subjects were enrolled with no dose-related pattern of serious adverse events (AEs). Premature terminations caused by AEs occurred in four (8.2%) patients treated with AA and five (11.6%) treated with placebo. Two subjects treated with AA (4.1%) and four given placebo (9.3%) died. Exploratory efficacy analysis showed a trend toward improvement in the change from baseline National Institutes of Health Stroke Scale (NIHSS) in the 8 mg/kg/h AA group on Days 3 (p=0.023 vs. placebo), 7 (p=0.002), 10 (p=0.003), and 40 (p=0.018). A dose of 8 mg/kg/h AA produced a favorable trend in reduction of NIHSS that should be confirmed in a future clinical trial.

Aged↗

PubMed2006

Does clinical-CT 'mismatch' predict early response to treatment with recombinant tissue plasminogen activator?

BACKGROUND: We hypothesized that patients with clinically severe strokes but less severe early ischemic changes on brain CT (i.e., clinical-CT mismatch) may respond better to intravenous recombinant tissue plasminogen activator (i.v. rt-PA) within 3 h of symptom onset. METHODS: In this secondary analysis of the CLOTBUST data, patients with middle cerebral artery occlusions on transcranial Doppler (TCD) were treated with i.v. rt-PA. Alberta Stroke Program Early CT Scores were obtained with raters blinded to the NIH Stroke Scale and TCD results. Two mismatch criteria and three criteria of response to therapy were explored. RESULTS: Of 126 patients, 67% had a mismatch type 1 and 74% had a mismatch type 2. The presence of clinical-CT mismatch by either definition did not correlate with any of the three criteria of response to rt-PA. Recanalization was a strong determinant of response, whether or not mismatch was present. CONCLUSIONS: Mismatch between severity of neurological deficit and CT findings is common but does not predict response to rt-PA therapy given within 3 h.

Brain Ischemia↗

PubMed2006

Neuronal expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and 15d-prostaglandin J2--mediated protection of brain after experimental cerebral ischemia in rat.

Existing experimental evidence suggests that PPARgamma may play a beneficial role in neuroprotection from various brain pathologies. Here we found that focal cerebral ischemia induced by middle cerebral/common carotid arteries occlusion (MCA/CCAo) induced up-regulation of PPARgamma messenger RNA in the ischemic hemisphere as early as 6 h after the ischemic event. The increased PPARgamma mRNA expression was primarily associated with neurons in the ischemic penumbra, suggesting an important role for PPARgamma in neurons after ischemia. Intraventricular injection of 15d-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a proposed endogenous PPARgamma agonist, into the ischemic rat brains significantly increased the PPARgamma-DNA-binding activity and reduced infarction volume at 24 h after reperfusion. We propose that PPARgamma up-regulation in response to ischemia may contribute to PPARgamma activation in the presence of PPARgamma agonists. Activation of PPARgamma in neurons at an early stage after ischemia may represent a pro-survival mechanism against ischemic injury.

Animals↗

PubMed2006

Peroxisome-proliferator-activated receptor-gamma (PPARgamma) activation protects neurons from NMDA excitotoxicity.

A growing body of evidence indicates that the transcription factor PPARgamma plays a beneficial role in various neurological diseases. The postulated principal mechanism underlying the beneficial effects of PPARgamma is due to its anti-inflammatory properties. However, PPARgamma exists in neurons where it may provide additional effects that regulate neuronal vulnerability. In the present study, we employed in vitro and in vivo models of excitotoxic neuronal injury to test hypothesis on the neuroprotective role of PPARgamma. The endogenous PPARgamma ligand, 15d-Delta(12,14)-Prostaglandin J2 (15d-PGJ2), and a selective thiazolidinedione PPARgamma agonist, ciglitazone, significantly reduced neuronal death in response to glutamate and NMDA-mediated, but not kainate-mediated toxicity. This neuroprotective effect of 15d-PGJ2 and ciglitazone was linked to increased PPARgamma DNA binding activity as it was fully reversed by the pretreatment of neurons with selective PPARgamma antagonists and anti-PPARgamma antibody. It was not due to the blockade of NMDA-receptor-mediated Ca++ entry. Our data demonstrate that PPARgamma activation may represent a potential target for treatment of numerous acute and chronic neurological diseases with pathologies that involve excitotoxic damage.

Analysis of Variance↗

PubMed2006

Argatroban tPA stroke study: study design and results in the first treated cohort.

BACKGROUND: The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute stroke is linked to clot lysis and artery recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. There are no human data on this combination. DESIGN: We report the first phase of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose-escalation, safety and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 hours. After standard-dose intravenous rtPA administration, a 100-mug/kg bolus of argatroban followed by infusion of 1 mug/kg per minute for 48 hours was adjusted to a target partial thromboplastin time of 1.75 times that of the control group. RESULTS: Fifteen patients (including 10 men) were enrolled, with a mean +/- SD age of 61 +/- 13 years. All patients had middle cerebral artery occlusions. Baseline median National Institute of Health Stroke Scale score was 14 (range, 4-25). The mean +/- SD time from symptom onset to argatroban bolus administration was 172 +/- 53 minutes. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 1 patient and there was 1 death. Recanalization was complete in 6 patients and partial in another 4, and reocclusion occurred in 3 within 2 hours of rtPA bolus administration. CONCLUSION: The safety of low-dose argatroban combined with intravenous rtPA may be within acceptable limits, and its efficacy for producing fast and complete recanalization is promising, but a larger cohort of patients is required to confirm these preliminary observations.

Adolescent↗

PubMed2006

Latest advances in intracerebral hemorrhage.

Despite the fact that intracerebral hemorrhage (ICH) is the deadliest and least treatable of all stroke subtypes, historically researchers have directed most of their efforts toward ischemic strokes. However in the past few years this tendency has been changing, and several studies are showing very interesting results that allow us to believe that in the following years ICH management will change dramatically, paralleling the recent revolution that ischemic stroke treatment experienced in the past decade. Studies offering a better understanding of risk factors, pathophysiology, and treatment will help in primary and secondary prevention and also in developing therapeutic strategies to reduce brain damage. This review comments on some of the most relevant publications during the past year in any field related to ICH.

Animals↗

PubMed2006

Using telemedicine to facilitate thrombolytic therapy for patients with acute stroke.

BACKGROUND: Recent stroke-care requirements state that all stroke patients should be screened for intravenous recombinant tissue plasminogen activator (rt-PA) and treated, if the appropriate inclusion and exclusion criteria are met. Two community hospitals 90-130 miles east of Houston deployed telemedicine (videoteleconferencing) to provide acute stroke consultative services. DEVELOPING A TELEMEDICINE CAPACITY: According to the Brain Attack Coalition's recommendations, neurosurgical services need to be accessible within two hours. Given their incomplete neurology coverage, the remote-site hospitals identified telemedicine as the best option, with the University of Texas Health Science Center at Houston stroke team as the provider of expertise. RESULTS: In the 13 months preceding the telemedicine project (January 2003-March 2004), 2 (.8%) of 327 patients received rt-PA, compared with 14 (4.3%) of 328 patients during the telemedicine project (April 2004-May 2005), p < .001). Seven patients had > or = 4 points improvement in a stroke scale at 24 hours posttreatment. Three patients worsened during the 24-hour assessment. No intracerebral hemorrhages occurred. Door-to-needle median time was 85 minutes (range, 27-165 minutes). DISCUSSION: Telemedicine facilitated thrombolytic therapy for acute stroke patients and is intended not to replace care provided by remote-site providers but rather to address a time- and spatially related emergency need.

Acute Disease↗

PubMed2006

15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-gamma, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPARgamma is linked to anti-inflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) acts as a physiologic agonist for PPARgamma. In this study, we found that injection of 15d-PGJ2 into the locus of striatal hematoma increased PPARgamma-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ2 significantly reduced nuclear factor-kappaB (NF-kappaB) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d-PGJ2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ2 at the onset of ICH is associated with activation of PPARgamma and elevation of catalase expression, suppression of NF-kappaB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.

Animals↗

PubMed2006

Functional reorganization and recovery after constraint-induced movement therapy in subacute stroke: case reports.

Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke.

Aged↗

PubMed2006

Alteplase for acute ischemic stroke.

Alteplase, an intravenously administered form of recombinant tissue plasminogen activator (rt-PA), remains the only US FDA-approved thrombolytic treatment for acute ischemic stroke within 3 h of symptom onset. Patients treated with intravenous rt-PA are at least 30% more likely to have minimal or no disability at 3 months compared with placebo. Despite an increased risk of symptomatic intracranial hemorrhage, rt-PA does not increase mortality. The benefit achieved with rt-PA is cost effective and sustained 1 year after treatment. Despite its clear benefit, rt-PA remains underutilized. Although the future of acute ischemic stroke treatment will most likely involve a multi-faceted treatment approach, the primary objective remains to establish recanalization of the involved vessel. For patients with acute ischemic stroke within the first 3 h of symptom onset, rt-PA remains the first step in accomplishing this goal.

Brain Ischemia↗

PubMed2005

Telemedicine-guided carotid and transcranial ultrasound: a pilot feasibility study.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) and carotid duplex (CD) provide rapid and safe screening for stroke patients but are highly operator dependent. We explored the feasibility of telemedicine (TM)-guided TCD/CD administered by a health care provider inexperienced with ultrasound. METHODS: Dual video screens transmitted real-time TCD/CD images and sound to a neurosonographer. TM TCD/CD characteristics were compared with an in-person (IP) examination independently obtained on the same patient. We compared carotid stenosis, thrombolysis in brain ischemia (TIBI) flow grades, and the time spent on testing. RESULTS: We examined 8 subjects with a median age of 51 (31 to 63 range). IP and TM successfully examined 100% of internal carotid and middle cerebral arteries, 50% versus 44% of anterior cerebral artery, and 100% versus 88% of the basilar arteries, respectively. The median time in minutes IP versus TM was 15 (range 10 to 35) and 30 (15 to 50) for CD (P=0.07) and 18 (15 to 30) and 45 (30 to 55) for TCD (P=0.002), respectively. TM correctly identified all normal CD/TCD examinations in 7 subjects. In 1 patient, TM identified carotid occlusion but misread TIBI flow grades in both middle cerebral arteries. CONCLUSIONS: Our pilot study showed the feasibility of TCD/CD by an inexperienced health professional guided by a sonographer via TM. Tests were completed within times comparable to outpatient setting in a vascular laboratory.

Adult↗

PubMed2005

Intravenous TPA for very old stroke patients.

BACKGROUND: Although thrombolysis in patients with advanced age is considered more risky, some may benefit from TPA treatment. We studied safety and recanalization/recovery in patients older than 80 years treated with TPA and compared them with younger stroke patients. METHODS: We studied patients treated with intravenous TPA and divided them into younger (<80 years) and older (> or =80 years) groups for comparison. Diagnostic transcranial Doppler was completed before bolus, and patients were consequently monitored for up to 2 h when feasible. Clinical data included NIH Stroke Scale score, symptomatic intracranial hemorrhage (ICH) and discharge disposition. RESULTS: We studied 127 younger (mean 63 years, range 31-79) and 56 older patients (mean 84 years, range 80-93). Median baseline NIH Stroke Scale score was higher in the older group (18 vs. 14 points, NS). Occlusion locations, onset to needle time (median 130 vs. 120 min) as well as improvement at 24 h (median 5 vs. 4 points) were similar in both groups. Transcranial Doppler monitoring showed similar partial or complete recanalization rates (66 vs. 66%), onset to recanalization time (median 160 vs. 158 min) and reocclusion rates (26 vs. 25%). Symptomatic and fatal ICH was not higher in the older group (7.1 and 3.5% vs. 6.3 and 3.9%, NS). There was higher mortality among older patients (20 vs. 11%, NS). At discharge, 23% of older patients went home, 41% underwent rehabilitation and 16% were transferred to skilled nursing facilities, compared with 31, 43 and 15% respectively, in the younger group. CONCLUSION: After intravenous TPA treatment, patients over 80 years of age have similar recanalization, short-term improvement and symptomatic ICH rates compared with younger patients. However, older patients tend to have higher in-hospital mortality.

Adult↗

PubMed2005

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.

BACKGROUND: Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. SUMMARY OF REVIEW: The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. CONCLUSIONS: The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

Brain Ischemia↗

PubMed2005

Houston paramedic and emergency stroke treatment and outcomes study (HoPSTO).

BACKGROUND AND PURPOSE: Establishment of stroke centers, combined with accurate paramedic diagnosis and rapid transport, is essential to deliver acute stroke therapy. We wanted to measure and improve paramedic and hospital performance through implementation of the Brain Attack Coalition and American Stroke Association guidelines. METHODS: Pre-intervention and active-intervention phases with parallel data measurement points were used. The study involved six hospitals comprising the majority of acute-stroke admissions in Houston, Tex. Hospital, paramedic, and patient data were collected prospectively pre-intervention and during the active-intervention phase on all suspected acute-stroke patients admitted by Houston Fire Department-Emergency Medical Services. A multilevel educational intervention included paramedic, hospital, and community education. Paramedic diagnostic accuracy, hospital-performance efficiency, and thrombolytic treatment rates were the main outcome measures of the study. RESULTS: Four hundred forty-six patients (74 per month) were transported in the pre-intervention phase to participating hospitals (59.8% of all suspected stroke patients transported city wide by Houston Fire Department-Emergency Medical Services), compared with 1072 patients (89 per month, or 68.7%) transported in the active-intervention phase (P<0.001). Accuracy of paramedic diagnosis of stroke increased from 61% to 79%. Admission within 2 hours of symptom onset increased from 58% to 62% (P=0.002). Thrombolysis rates increased in 4 of 6 centers, with 1 post- tissue plasminogen activator hemorrhage (3.7%) reported. CONCLUSIONS: A multilevel educational program improves rapid hospitalization and paramedic diagnostic accuracy and increases the number of patients presenting for evaluation within the 3-hour tissue plasminogen activator window. Stroke center development supports safe thrombolytic practice in community settings.

Aged↗

PubMed2005

Safety and feasibility of a lower dose intravenous TPA therapy for ischemic stroke beyond the first three hours.

BACKGROUND: The most common reason that patients do not receive intravenous tissue plasminogen activator (TPA) is the inability to meet the strict 3-hour treatment window. The risk/benefit ratio is more unfavorable beyond this time, but some patients might still benefit. We designed a pilot study with the hypothesis that lower dose TPA might be safe in selected patients treated beyond 3 h. SUBJECTS AND METHODS: To determine the range of symptomatic hemorrhage and good outcome, we prospectively gave i.v. TPA 0.6 mg/kg up to 60 mg (15% bolus, 85% infusion over 30 min) to patients with ischemic stroke beyond the first 3 h after last known to be normal. Other eligibility criteria were: NIH Stroke Scale > or =4, normal head CT scan, and clinical suspicion or transcranial Doppler (TCD) evidence of a proximal arterial occlusion. RESULTS: 28 patients were treated, median age 65 (range 24-88) years, median baseline NIHSS score 18 (range 7-34) points. TPA bolus was given 372 +/- 158 min after stroke onset (range 189-720). Symptomatic hemorrhage occurred in 3/28 (11%) patients, including 1 fatal bleed. Overall mortality was 6/28 (21%). Partial or complete recanalization was found in 8/20 (40%) TCD monitored patients within 2 h after TPA bolus. Early major improvement occurred in 4/28 (14%) patients. CONCLUSIONS: Lower dose i.v. TPA in patients presenting beyond 3 h carries a risk of intracerebral hemorrhage. However, recanalization with dramatic recovery can still occur.

Adult↗

PubMed2005

New era for management of primary hypertensive intracerebral hemorrhage.

This discussion focuses on recent reports relevant to improved understanding and future directions in the management of intracerebral hemorrhage (ICH). Prevention is possible with adequate treatment of hypertension; microbleeds, apolipoprotein genotype, and cholesterol treatment have been examined in relation to ICH risk. Hematoma products, matrix metalloproteinases, inflammatory markers, and means to attenuate injury have also received attention. The multifaceted character of perihematomal edema has been further defined but evidence for perihematomal ischemia remains elusive. New data on acute blood pressure reinforces the need for a clinical trial. With the lack of efficacy found in the International Surgical Trial in Intracerebral Hemorrhage (ISTICH), a landmark surgical trial, emphasis is shifting to minimally invasive and catheter/thrombolytic-based technologies for clot evacuation. On the medical side, activated factor VII has been shown to control hemorrhage growth. Looking forward, stem cell therapies for ICH are under investigation and some outcome studies are shedding new rays of hope.

Antihypertensive Agents↗

PubMed2005

The impact of imbalances in baseline stroke severity on outcome in the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study.

STUDY OBJECTIVE: The National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator (rtPA) Stroke Study demonstrated a clinically meaningful and statistically significant benefit of tissue plasminogen activator (tPA). Adjusting for the baseline National Institutes of Health (NIH) Stroke Scale, the benefit of tPA remained. However, other authors suggest that an imbalance in baseline stroke severity between the tPA and placebo groups confounded the results. Another issue that has been raised concerns a possible increase in early mortality for individuals given tPA. In post hoc subgroup analysis, we describe the effect of tPA across a spectrum of time from stroke onset to treatment and stroke severity subgroups. Stroke severity was based on the NIH Stroke Scale. We also compare early mortality (2-week and 30-day) in the tPA and placebo groups. METHODS: Using combined data from the 2 NINDS rtPA Stroke Study trials, we performed post hoc subgroup analyses of 3-month favorable outcome (defined by the NIH Stroke Scale, Barthel, Rankin, and Glasgow Outcome Scales). We categorized patients from the trials into onset to treatment (0 to 90 minutes, 91 to 180 minutes) by NIH Stroke Scale (< or =5, 6 to 20, >20) subgroups. Analyses were adjusted for all variables previously shown to be associated with favorable outcome at 3 months. We also compared early mortality within onset-to-treatment subgroups. RESULTS: For all the 12 specified onset-to-treatment-NIH Stroke Scale subgroups, the adjusted odds ratio for a favorable 3-month outcome was greater than 1.0 and favored tPA. We detected no difference in mortality between patients treated with rtPA and those treated with placebo by 2 weeks posttreatment (rtPA=9%, placebo=13%; P =.49) or by 30 days (rtPA=11%, placebo=16%; P =.30). CONCLUSION: These are descriptive post hoc subgroup analyses. Using cut points defined in previous critiques of the NINDS trials, these analyses give results consistent with previous NINDS Study Group reports. Baseline NIH Stroke Scale imbalance does not account for the better outcome of rtPA-treated patients.

Brain Ischemia↗