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James C Grotta

Publications and source records attributed to James C Grotta.

At least 37 records · Page 2Linked to original sources
PubMed2005

Wheel-running modestly promotes functional recovery after a unilateral cortical lesion in rats.

BACKGROUND: We aimed to determine whether early or delayed wheel-running (W) after a cortical lesion in rats influences functional recovery and protein expression involving synaptic plasticity. METHODS: 57 rats were arranged in 4 groups: (1) Sham, (2) NMDA, (3) W-24 h or (4) W-72 h (W-24 h and W-72 h means wheel-running for 14 days starting day 1 or day 3 after NMDA lesion). NMDA produced a standardized lesion in the unilateral sensorimotor cortex and detectable behavioral deficits. Synaptogenesis was measured by immunohistochemistry. RESULTS: Wheel-running starting after 24 h had no detectable effect, but it significantly speeded functional recovery when delayed to after 72 h. These results were in accordance with a marker linked to synaptogenesis. CONCLUSION: Wheel-running starting 3 days, but not 1 day, after an NMDA lesion is associated with improved functional recovery.

Animals↗
PubMed2004

Aggressive mechanical clot disruption: a safe adjunct to thrombolytic therapy in acute stroke?

BACKGROUND AND PURPOSE: This study evaluated the safety and efficacy of aggressive mechanical clot disruption (AMCD) in acute stroke patients with persisting middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion after thrombolytic therapy. METHODS: Retrospective case series were used from a prospectively collected stroke database on consecutive acute ischemic stroke patients treated with intra-arterial (IA) thrombolytics and mechanical clot disruption during a 5-year interval. Thrombolytic dosage, endovascular techniques, immediate and final recanalization rates, symptomatic hemorrhage, mortality, and outcome were determined. RESULTS: Thirty-two patients received AMCD. Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 18, and median time to initiation of IA treatment was 261 minutes from symptom onset. ICA occlusion was noted in 16 patients and MCA occlusion in 16 patients: 22 received combined IV/IA thrombolytics, 3 received IV thrombolytics, 6 received IA thrombolytics, and 1 patient received no thrombolytics before AMCD. No immediate periprocedural complications were noted. Immediate recanalization was achieved in 38% (50% MCA, 25% ICA) and final recanalization in 75% (88% MCA, 63% ICA) of patients. Favorable outcome occurred in 19 (59%) patients, symptomatic cerebral hemorrhage in 3 (9.4%) patients, and mortality in 4 (12.5%) patients. CONCLUSIONS: AMCD can be performed safely with comparable intracerebral hemorrhage and mortality rates to other IA therapies even after use of intravenous thrombolytics in selected patients. Early deployment of this technique leads to immediate recanalization in one third of patients. AMCD may potentially shorten the time to flow restoration and improve overall recanalization rates achieved with IA therapy.

Adult↗
PubMed2004

Beyond subgroup analysis: improving the clinical interpretation of treatment effects in stroke research.

In large clinical trials designed to determine efficacy of an experimental treatment, patients are enrolled with presence or absence of various risk factors, such as diabetes or history of atrial fibrillation. A treatment-by-risk factor interaction indicates that the treatment effect may depend on the risk factor presence or absence. It is important to identify such interaction, since a treatment may fail or cause adverse events in the presence of the risk. Although statistical methods exist to identify such interaction, they are underutilized in clinical stroke research. This paper reviews the notion of treatment-by-risk factor interaction and identifies two types of interaction, quantitative and qualitative, using a graphical technique and statistical testing. We illustrate how to avoid drawing the erroneous conclusions regarding the treatment effect on subgroups when failing to detect an interaction, and provide rigorous tools to estimate the treatment effect on subgroups when an interaction is observed. Applications are presented using the data collected from the NINDS t-PA stroke studies. In stroke clinical trials, a treatment-by-risk factor interaction must be considered if the data permit. The graphical approach provides a heuristic illustration of interactions. Qualitative interactions are more important than quantitative interactions on therapeutic conclusion. Results of NINDS t-PA stroke studies confirmed our previous conclusions on the treatment t-PA benefit within 3-h therapeutic window. No subgroup of patients would lead a physician to withhold the t-PA treatment.

Algorithms↗
PubMed2004

Combining insulin-like growth factor derivatives plus caffeinol produces robust neuroprotection after stroke in rats.

BACKGROUND AND PURPOSE: Insulin-like growth factor-1 (IGF-1) and caffeinol are both neuroprotective and probably have different mechanisms of action; therefore, they may be more effective in combination. METHODS: We tested the N-terminal tripeptide of IGF-1, Gly-Pro-Glu (GPE), and its analogue, G2MePE, alone and with caffeinol in a rat middle cerebral artery (MCA) suture occlusion model. We randomly assigned rats to 6 groups of 8 to 12 animals: (1) control; (2) GPE, 3 mg/kg per hour; (3) G2MePE, 0.3 mg/kg per hour; (4) caffeinol, a mixture of caffeine (10 mg/kg) with ethanol (0.32 g/kg); (5) GPE with caffeinol (combination of group 2 with 4); and (6) G2MePE with caffeinol (combination of group 3 with 4). Drugs were started 75 minutes after suture occlusion, at the start of reperfusion. Three days after MCA occlusion, neurological deficit (Neurological Deficit Score [NDS]) and lesion volume were measured. RESULTS: GPE and caffeinol improved NDS by 34% and 36%, respectively (P<0.01), and also decreased cortical but not striatal lesion volume compared with control (GPE cortex, 121 mm3; caffeinol cortex, 134 mm3; and control, 221 mm3; P<0.01). GPE plus caffeinol did not have more efficacy than either GPE or caffeinol alone. G2MePE slightly improved NDS (19.7%, P=0.05) but not lesion volume. However, G2MePE plus caffeinol very significantly improved NDS (64%) and lesion volume in both cortex (combination 95 mm3 versus control 221 mm3) and striatum (combination 74 mm3 versus control 110 mm3) (P<0.001), and was significantly more effective than either caffeinol or G2MePE alone. CONCLUSIONS: Both GPE and caffeinol significantly protect cortex after MCA occlusion. At the doses used in this study, the GPE analogue G2MePE by itself had minimal protective effects, but when combined with caffeinol, it demonstrated robust beneficial effects on cortical and subcortical lesion size and behavioral deficit. Further study of this combination appears justified.

Animals↗
PubMed2004

Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia.

BACKGROUND AND PURPOSE: We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). METHODS: NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, > or =50% stenoses or thrombus in the symptomatic artery. RESULTS: One hundred and fifty patients (70 women, mean age 66+/-15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS > or =10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. CONCLUSIONS: Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.

Acute Disease↗
PubMed2004

Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke.

BACKGROUND: Transcranial Doppler ultrasonography that is aimed at residual obstructive intracranial blood flow may help expose thrombi to tissue plasminogen activator (t-PA). Our objective was to determine whether ultrasonography can safely enhance the thrombolytic activity of t-PA. METHODS: We treated all patients who had acute ischemic stroke due to occlusion of the middle cerebral artery with intravenous t-PA within three hours after the onset of symptoms. The patients were randomly assigned to receive continuous 2-MHz transcranial Doppler ultrasonography (the target group) or placebo (the control group). The primary combined end point was complete recanalization as assessed by transcranial Doppler ultrasonography or dramatic clinical recovery. Secondary end points included recovery at 24 hours, a favorable outcome at three months, and death at three months. RESULTS: A total of 126 patients were randomly assigned to receive continuous ultrasonography (63 patients) or placebo (63 patients). Symptomatic intracerebral hemorrhage occurred in three patients in the target group and in three in the control group. Complete recanalization or dramatic clinical recovery within two hours after the administration of a t-PA bolus occurred in 31 patients in the target group (49 percent), as compared with 19 patients in the control group (30 percent; P=0.03). Twenty-four hours after treatment of the patients eligible for follow-up, 24 in the target group (44 percent) and 21 in the control group (40 percent) had dramatic clinical recovery (P=0.7). At three months, 22 of 53 patients in the target group who were eligible for follow-up analysis (42 percent) and 14 of 49 in the control group (29 percent) had favorable outcomes (as indicated by a score of 0 to 1 on the modified Rankin scale) (P=0.20). CONCLUSIONS: In patients with acute ischemic stroke, continuous transcranial Doppler augments t-PA-induced arterial recanalization, with a nonsignificant trend toward an increased rate of recovery from stroke, as compared with placebo.

Acute Disease↗
PubMed2004

Constraint-induced movement therapy.

Constraint-induced movement therapy improves outcome after chronic stroke, conforms experimental observations of neuronal plasticity, and proves the efficacy of intensive occupational therapy. More acutely instituted constraint-induced movement therapy has both practical and theoretic risks and benefits that deserve further careful evaluation.

Animals↗
PubMed2004

Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.

BACKGROUND: Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment. METHODS: We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage. FINDINGS: Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002). INTERPRETATION: The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.

Aged↗
PubMed2004

Ischemic stunning of the brain: early recanalization without immediate clinical improvement in acute ischemic stroke.

BACKGROUND AND PURPOSE: Early arterial recanalization (ER) with intravenous tissue plasminogen activator (tPA) can lead to dramatic clinical recovery, whereas some patients do not experience immediate clinical improvement. METHODS: Consecutive patients received tPA 0.9 mg/kg IV within 3 hours after symptom onset. All had M1 or M2 middle cerebral artery occlusions on pretreatment transcranial Doppler. Patients were continuously monitored for 2 hours after bolus. ER was defined as the Thrombolysis in Brain Ischemia intracranial flow increase by >or=1 grade. Stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and recovery (modified Rankin Scale) were assessed independently of transcranial Doppler. RESULTS: One hundred twenty patients (mean age, 68+/-15 years; 63 women; median NIHSS, 17; range, 5 to 29; 90% with >or=10 points) received tPA at a median of 120 minutes, 50% within the first 2 hours. ER was observed in 73 patients (32 complete, 41 partial). No immediate clinical changes (n=23) or worsening (by 1 to 6 points on NIHSS, n=4) was observed in 37% of ERs (nonresponders). Complete ER was found in 8 of these 27 patients. At 24 hours, 22 of 27 patients (82%) had persisting deficits of NIHSS >or=10 points, yet 37% of these nonresponders (10 of 27) still achieved good outcome (modified Rankin score, 0 to 2) at 3 months. Among nonresponders with good outcome, 100% had detectable residual flow signals, and 70% had compensatory flow diversion on prebolus transcranial Doppler compared with 65% and 29% of nonresponders with poor outcome (P<0.05). Compared with responders (n=46), nonresponders had similar prebolus median NIHSS of 16 to 17 points, bolus times of 120 to 132 minutes, median speed of thrombolysis (30 minutes), and ER times of 190 to 193 minutes after onset. Reocclusion occurred in 3 of 4 patients with clinical worsening, 30% of other nonresponders, and 22% of responders. Symptomatic hemorrhage rate was 4% in both groups. At 3 months, mortality was 33% in nonresponders compared with 9% in responders (P=0.001). CONCLUSIONS: After successful arterial ER with tPA therapy, lack of early clinical changes or worsening is relatively common (37%) and appears to be independent of time to tPA bolus or reperfusion. However, with tPA alone, at least one third of these nonresponders still achieved good outcomes at 3 months, suggesting the possibility of a "stunned brain" syndrome with delayed recovery. Several different mechanisms may potentially account for this phenomenon.

Acute Disease↗
PubMed2004

Management of Primary Hypertensive Hemorrhage of the Brain.

Intracerebral hemorrhage (ICH) can be prevented by adequate treatment of hypertension. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers seem particularly effective. ICH also is associated with apolipoprotein E 4 genotype and with low cholesterol, but not statin therapy for high cholesterol. Microbleeds identified on magnetic resonance imaging scans also confer increased risk of ICH. Experimental drug regimens that target metalloproteinases and inflammation reduce damage in animal models of ICH, but none are proven effective in humans. Cerebral edema after ICH has varied mechanisms and significance, and may be another target for therapy. Cerebral blood flow is not substantially reduced in most patients with ICH. Lowering systolic blood pressure below 160 mm Hg in the first hours after ICH may prevent additional bleeding. Activated factor 7 is a promising new therapy to limit hematoma enlargement and consequently reduce morbidity and mortality after ICH. Dosages of 80 to 160 μg/kg given within the first 3 to 4 hours after symptom onset, or in patients at risk of additional bleeding such as those with coagulopathy, is logical but is unapproved. The role of activated factor 7 hopefully will be clarified by additional study. Open surgical evacuation of most spontaneous supratentorial hematomas has been shown to be ineffective in reducing mortality or disability except in certain circumstances, such as large or enlarging superficially located clots in patients who are awake. Stereotactic and endoscopic clot aspiration, often using instillation of lytic agents to liquefy the hematoma, is the most active area of surgical intervention research. Such minimally invasive approaches have been shown to safely produce more rapid removal of blood compared with standard treatment. This is particularly true for intraventricular hemorrhages. Future research will focus on the use of stem cells to restore the damaged architecture around the hematoma. The impressive scope and progress of ongoing clinical and basic research show that there is no longer a place for nihilism in the approach to ICH.

Journal Article↗
PubMed2004

A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest.

BACKGROUND: Cardiac arrest causes devastating neurological morbidity and mortality. Mild/moderate hypothermia is neuroprotective after global cerebral ischemia. More rapid controlled attainment of the target temperature may increase efficacy. METHODS: We assessed the safety and feasibility of endovascular cooling in a single arm study of comatose patients who had been successfully resuscitated after cardiac arrest. Core temperature was reduced to a target of 33 degrees C for 24 h using a closed loop endovascular system placed in the inferior vena cava, followed by controlled rewarming. Primary outcomes were speed and accuracy of cooling, survival and GOS after 30 days. RESULTS: Thirteen patients were enrolled, six male, age 60 +/- 19 years. Time from cardiac arrest to return of spontaneous circulation was 14.3 min (range 5-32.5). It took 3h and 39 min (median 210 min, IQ 80-315) to reach 33 degrees C; cooling averaged 0.8 +/- 0.3 degrees C/h (range 0.22-1.12 degrees C/h). Temperature was tightly maintained for all patients averaging 32.7 +/- 0.5 degrees C. Rewarming lasted 18.3 +/- 5.9 h. Five patients (38%) had 30-day Glasgow Outcome Scores of 1-2. Four patients died, none related to the hypothermia procedure. No unanticipated or procedure-related adverse events occurred. CONCLUSION: In comatose survivors of cardiac arrest, hypothermia via endovascular methods is safe and feasible, and target temperatures can be achieved and controlled rapidly and precisely. More studies are needed to assess the efficacy of rapid endovascular hypothermia after cardiac arrest.

Catheters, Indwelling↗
PubMed2004

Treatment of acute intracerebral hemorrhage with epsilon-aminocaproic acid: a pilot study.

INTRODUCTION: Up to 40% of primary intracerebral hemorrhages (ICHs) expand within the first 24 hours (natural history). The authors aimed to study the safety and preliminary efficacy of epsilon-aminocaproic acid (EACA) in halting ICH enlargement. METHODS: Consecutive patients with hematoma volumes ranging from 5 to 80 mL were recruited within 12 hours of ICH onset. A total of 5 g EACA was infused during 1 hour and then 1 g/hour for 23 hours. Hematoma volume was compared on baseline, and 24-48-hour brain imaging. Consecutive untreated patients underwent the same imaging protocol. RESULTS: Three of the first five patients treated had HE>33% of their baseline volume. HE occurred in two of the nine untreated patients. The 80% confidence interval for HE in the treated patients was 32-88%. No thrombotic or other serious adverse events were attributed to EACA. CONCLUSION: It is unlikely that the rate of HE in patients given EACA within 12 hours of ICH is less than the natural history rate, although this treatment appears to be safe.

Acute Disease↗
PubMed2004

Clinical trials for cytoprotection in stroke.

To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase "failure to demonstrate efficacy" prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents.

Animals↗
PubMed2004

CLOTBUST: design of a randomized trial of ultrasound-enhanced thrombolysis for acute ischemic stroke.

BACKGROUND: Intravenous tissue plasminogen activator (TPA) therapy can be monitored with 2 MHz transcranial Doppler (TCD). This article describes the design of CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA), the first prospective international multicenter randomized clinical trial of noninvasive externally applied ultrasound to enhance systemic thrombolysis in human stroke. SUBJECTS: Patients with acute ischemic stroke eligible for intravenous TPA therapy within 3 hours of symptom onset who have detectable middle cerebral artery occlusion on a prebolus TCD are included in this trial. All patients receive standard 0.9 mg/kg TPA therapy. Patients are randomized (1:1) to either 2 hours of continuous monitoring with TCD or placebo monitoring. FDA-approved portable diagnostic TCD equipment and standard headframes (Marc series, Spencer Technologies, Seattle, WA) are used. Output of TCD units is set at 100% power achievable at depths of insonation that display the worst TIBI flow grade signals. METHODS AND END-POINTS: Acute MCA occlusion on prebolus TCD is defined as thrombolysis in brain ischemia (TIBI) flow grades 0-3. Treating physicians are blinded to randomization assignment, and certified scorers measure stroke severity using the National Institute of Health Stroke Scale (NIHSS). Safety of continuous TCD monitoring is determined by rates of symptomatic (NIHSS score increase by 4+ points) intracerebral hemorrhage within 72 hours after initial symptom onset. Potential enhancement of TPA therapy will be determined using combined primary end-point of early complete recanalization on TCD (TIBI flow grades 4-5), dramatic recovery (NIHSS < or = 3 points), or decline in the NIHSS > or = 10 points repeatedly measured every 30 minutes within 2 hours after TPA bolus. Other end-points include recovery at 24 hours and 3 months, modified Rankin scores (mRS) are obtained at 90 days, and favorable outcome is determined as NIHSS or mRS scores 0-1. CONCLUSIONS: The aim of phase II CLOTBUST trial is to determine the rates of early complete recanalization and dramatic/early clinical recovery in TPA + TCD and TPA groups. The sample size is set at 126 patients since a medium effect size (.50) is anticipated for TPA + TCD group vs TPA alone to achieve combined primary end-point.

Aged↗
PubMed2004

Ultrasound-enhanced thrombolysis for acute ischemic stroke: phase I. Findings of the CLOTBUST trial.

BACKGROUND: Tissue plasminogen activator (TPA) activity may be enhanced with ultrasound, potentially 2 MHz transcranial Doppler (TCD). The authors present Phase I data of the CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA). SUBJECTS AND METHODS: Nonrandomized stroke patients with proximal arterial occlusion on a prebolus TCD receiving intravenous 0.9 mg/kg TPA within 3 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. RESULTS: 55 patients (mean age 69 +/- 15 years, median baseline NIH Stroke Scale [NIHSS] 18, range 4-29, 90% with 3 9 points) were treated at 125 +/- 36 minutes from symptom onset. TCD monitoring began at 117 +/- 39 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 20 patients (36%). Dramatic recovery (NIHSS score < or = 3) occurred in 20% at 2 hours and in 24% at 24 hours. Overall improvement by > or = 4 NIHSS points was found in 49% at 24 hours. Improvement was associated with recanalization during or shortly after TPA infusion (phi r2 = .5, P = .03); however, in 6/20 patients with complete recanalization (30%), no immediate clinical change was noticed within 2 hours. Overall symptomatic hemorrhage rate was 5.5%. CONCLUSIONS: Continuous TCD insonation for up to 2 hours at maximum intensities allowed by current bio-safety guidelines is safe. Dramatic recovery and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis given with TCD monitoring.

Aged↗
PubMed2003

Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study.

BACKGROUND AND PURPOSE: Cryptogenic stroke is associated with an increased prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in Ischemic Stroke (PELVIS) study hypothesized that patients with cryptogenic stroke have an increased prevalence of pelvic deep venous thrombosis (DVT). METHODS: At 5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the pelvis within 72 hours of new symptom onset. Clinical data were then determined. Radiologists blinded to clinical data later read the scans. RESULTS: The 95 patients who met entry criteria were scanned. Their mean+/-SD age was 46+/-10 years, and time from stroke onset to pelvic MRV scan was 49+/-16 hours. Compared with those with stroke of determined origin (n=49), patients with cryptogenic stroke (n=46) were significantly younger, had a higher prevalence of patent foramen ovale (61% versus 19%), and had less atherosclerosis risk factors. Cryptogenic patients had more MRV scans with a high probability for pelvic DVT (20%) than patients with stroke of determined origin (4%, P<0.03), with most having an appearance of a chronic DVT. CONCLUSIONS: In this study of young stroke patients evaluated early after stroke, patients with cryptogenic stroke showed differences in several clinical features compared with patients with stroke of determined origin, including increased prevalence of pelvic DVT. The results require confirmation but suggest that paradoxical embolus from the pelvic veins may be the cause of stroke in a subset of patients classified as having cryptogenic stroke.

Adolescent↗
PubMed2003

Sustained benefit of a community and professional intervention to increase acute stroke therapy.

BACKGROUND: The ultimate test of an educational intervention is the sustainability of the effect after the intervention ceases. METHODS: The TLL Temple Foundation Stroke Project was a quasi-experimental study aimed at increasing Food and Drug Administration-approved acute stroke therapy in a nonurban community in east Texas. During the intensive community and professional intervention (phase 2), significantly more patients with acute stroke received intravenous tissue plasminogen activator (tPA) compared with the preintervention period (phase 1). In the comparison community, no change was noted. We present the results of tPA treatment in the 6 months after the intervention ended (phase 3). RESULTS: Two hundred thirty-eight patients had a validated stroke during phase 3. Among patients who experienced an ischemic stroke, 11.2% in the intervention group received intravenous tPA compared with 2.2% in phase 1 (P =.007). In the comparison group, 1.4% received intravenous tPA in phase 3 compared with 0.7% in phase 1 (P>.99). Among eligible candidates for treatment, 69.2% were treated in phase 3 in the intervention community compared with 13.6% in phase 1 (P =.002). In the comparison group, 20.0% were treated in phase 3 compared with 6.7% in phase 1 (P =.45). There was 1 protocol violation among the 9 patients treated in the intervention community in phase 3. CONCLUSIONS: There was a sustained benefit of the intervention in increasing tPA treatments in the intervention community even after cessation of the educational effort. Treatments in the control community remained few through all 3 phases of the study. A carefully planned multilevel intervention can improve community stroke treatments even in a nonurban community.

Drug Utilization↗