Intra-arterial thrombolysis in 100 patients with acute stroke due to middle cerebral artery occlusion

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the safety and efficacy of local intra-arterial thrombolysis (LIT) using urokinase in patients with acute stroke due to middle cerebral artery (MCA) occlusion. METHODS: We analyzed clinical and radiological findings and functional outcome 3 months after LIT with urokinase of 100 consecutive patients. To measure outcome, the modified Rankin scale (mRs) score was used. RESULTS: Angiography showed occlusion of the M1 segment of the MCA in 57 patients, of the M2 segment in 21, and of the M3 or M4 segment in 22. The median National Institutes of Health Stroke Scale (NIHSS) score at admission was 14, and, on average, 236 minutes elapsed from symptom onset to LIT. Forty-seven patients (47%) had an excellent outcome (mRs score 0 to 1), 21 (21%) a good outcome (mRs score 2), and 22 (22%) a poor outcome (mRs score 3 to 5). Ten patients (10%) died. Excellent or good outcome (mRs score < or =2) was seen in 59% of patients with M1 or M2 and 95% of those with M(3) or M(4) MCA occlusions. Recanalization as seen on angiography was complete (thrombolysis in myocardial infarction [TIMI] grade 3) in 20% of patients and partial (TIMI grade 2) in 56% of patients. Age <60 years (P<0.05), low NIHSS score at admission (P<0.00001), and vessel recanalization (P=0.0004) were independently associated with excellent or good outcome and diabetes with poor outcome (P=0.002). Symptomatic cerebral hemorrhage occurred in 7 patients (7%). CONCLUSIONS: LIT with urokinase that is administered by a single organized stroke team is safe and can be as efficacious as thrombolysis has been in large multicenter clinical trials.

Thrombolysis in patients with acute stroke caused by cervical artery dissection: analysis of 9 patients and review of the literature

BACKGROUND: Results of recently published studies suggest that intravenous thrombolysis (IVT) and local intra-arterial thrombolysis (LIT) are feasible procedures in acute stroke after cervical artery dissection (CAD). OBJECTIVES: To describe 9 patients with acute stroke caused by CAD who were treated by LIT (n = 7) or IVT (n = 2) and to review the literature. METHODS: Retrospective analysis of clinical and neuroradiological findings; literature review from 1980 to present. MAIN OUTCOME MEASURE: Modified Rankin Scale (mRS) score. RESULTS: Of 7 patients treated with LIT, 3 had good outcomes (mRS score of 0-2) and 4 had bad outcomes (mRS score of 3-6) at 3 months. The 2 patients who had received IVT recovered to mRS scores of 0 and 3. Twenty-one patients were identified in the literature. Overall (N = 30), in the IVT group (n = 19), the outcome was good in 8 patients (42%) and bad in 11 (58%); in the LIT group (n = 11), 6 patients (55%) had a good outcome and 5 (45%) had a bad outcome. Overall, 47% (14/30) of the patients (IVT and LIT groups) had a good outcome. Total mortality was 13% (4/30). There were no secondary complications due to extension of wall hematoma or angiography. One symptomatic hemorrhage occurred. CONCLUSIONS: Thrombolysis is feasible in acute stroke caused by CAD. Local complications from extension of wall hematoma did not occur. Further prospective studies are needed to determine the safety and efficacy of thrombolysis in the special circumstance of acute stroke caused by CAD.

Transcatheter closure of patent foramen ovale with radiofrequency: acute and intermediate term results in 144 patients

AIMS: Currently available devices for transcatheter closure of patent foramen ovale (PFO) which rely on a permanent implant have limitations, including late complications. The study objective was to evaluate the safety, feasibility, and effectiveness of the PFx Closure System, the first transcatheter technique for PFO closure without an implantable device. METHODS AND RESULTS: A prospective study of 144 patients was conducted at nine clinical sites from October 2005 through August 2007. All patients had a history of cryptogenic stroke, transient ischemic attack, migraines, or decompression illness. The mean balloon stretched diameter of the PFO was 7.9 +/- 2.5 mm. Technical success (successful application of radiofrequency energy) was achieved in 130 patients. One patient required a transfusion as a result of blood loss during the procedure. There were no other major procedural complications. There were no recurrent strokes, deaths, conduction abnormalities, or perforations following the procedure. At a mean follow-up of 6 months, successful closure was achieved in 79 patients (55%). In PFOs with balloon sized or stretched diameters less than 8 mm, the closure rate was 72% (53/74). CONCLUSION: This study demonstrates that transcatheter closure of a PFO without a permanent implant is technically feasible and safe. Further technique and device modifications are required to achieve higher closure rates.

Interdisciplinary Cardiovascular and Neurologic Outpatient Rehabilitation in Patients Surviving Transient Ischemic Attack or Stroke With Minor or No Residual Deficits

Objective To evaluate the feasibility and effectiveness of a comprehensive outpatient rehabilitation program combining secondary prevention and neurorehabilitation to improve vascular risk factors, neurologic functions, and health-related quality of life (HRQOL) in patients surviving a transient ischemic attack (TIA) or stroke with minor or no residual deficits. Design Prospective interventional single-center cohort study. Setting University hospital. Participants Consecutive consenting patients having sustained a TIA or stroke with 1 or more vascular risk factors (N=105) were included. Interventions Three-month hospital-based secondary prevention and neurorehabilitation outpatient program with therapeutic and educational sessions twice a week. Patients were evaluated at entry and program end. Main Outcome Measures Impact on vascular risk factors, neurological outcome, and HRQOL. Results A total of 105 patients entered the program and 95 patients completed it. Exercise capacity (P<.000), smoking status (P=.001), systolic (P=.001) and diastolic (P=.008) blood pressure, body mass index (P=.005), low-density lipoprotein cholesterol (P=.03), and triglycerides (P=.001) improved significantly. Furthermore, the 9-Hole-Peg-Test (P<.000), Six-minute Walking Test (P<.000), and One Leg Stand Test (P<.011) values as well as HRQOL improved significantly. The program could be easily integrated into an existing cardiovascular prevention and rehabilitation center and was feasible and highly accepted by patients. Conclusions Comprehensive combined cardiovascular and neurologic outpatient rehabilitation is feasible and effective to improve vascular risk factors, neurologic functions, and HRQOL in patients surviving TIA or stroke with minor or no residual deficits.

New Technologies and Concepts for Rehabilitation in the Acute Phase of Stroke: A Collaborative Matrix

The process of developing a successful stroke rehabilitation methodology requires four key components: a good understanding of the pathophysiological mechanisms underlying this brain disease, clear neuroscientific hypotheses to guide therapy, adequate clinical assessments of its efficacy on multiple timescales, and a systematic approach to the application of modern technologies to assist in the everyday work of therapists. Achieving this goal requires collaboration between neuroscientists, technologists and clinicians to develop well-founded systems and clinical protocols that are able to provide quantitatively validated improvements in patient rehabilitation outcomes. In this article we present three new applications of complementary technologies developed in an interdisciplinary matrix for acute-phase upper limb stroke rehabilitation – functional electrical stimulation, arm robot-assisted therapy and virtual reality-based cognitive therapy. We also outline the neuroscientific basis of our approach, present our detailed clinical assessment protocol and provide preliminary results from patient testing of each of the three systems showing their viability for patient use.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

Age dependency of safety and outcome of endovascular therapy for acute stroke

Elderly patients generally experience less favorable outcomes and higher mortality after acute stroke than younger patients. The aim of this study was to analyze the influence of age on outcome and safety after endovascular therapy in a large cohort of patients aged between 20 and 90 years. We prospectively acquired data of 1,000 stroke patients treated with endovascular therapy at a single center. Logistic regression analysis was performed to determine predictors of outcome and linear regression analysis to evaluate the association of age and outcome after 3 months. Younger age was an independent predictor of favorable outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate regression analysis. There was a linear relationship between age and outcome. Ever increase in 26 years of age was associated with an increase in the modified Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral hemorrhage and did not influence recanalization success (p = 0.674). Advancing age was associated with a decline of favorable outcomes and survival after endovascular therapy. This decline was linear from age 20 to 90 years, but was not related to lower recanalization rates or higher bleeding risk in the elderly. The efficacy of endovascular stroke therapy seems to be preserved also in the elderly and other factors than efficacy of endovascular therapy such as decreased plasticity are likely to explain the worse outcome with advancing age.

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15min on and 15min off) starting 45min after middle cerebral artery occlusion and lasting 4h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans.

Multimodal 3 tesla MRI confirms intact arterial wall in acute stroke patients after stent-retriever thrombectomy

BACKGROUND AND PURPOSE The aim of this prospective study was to assess vascular integrity after stent-retriever thrombectomy. METHODS Dissection, contrast medium extravasation, and vasospasm were evaluated in 23 patients after thrombectomy with biplane or 3D-digital subtraction angiography and 3-Tesla vessel wall MRI. RESULTS Vasospasm was detected angiographically in 10 patients, necessitating intra-arterial nimodipine in 2 of them. Contrast extravasation, intramural hemorrhage, or iatrogenic dissection were not detected on multimodal MRI in any patient even after Y-double stent-retriever technique. CONCLUSIONS Our findings suggest that clinically relevant vessel wall injuries occur rarely after stent-retriever thrombectomy.

Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome: Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. METHODS Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], Pinteraction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], Pinteraction = .24) extensive CAD. CONCLUSIONS Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.

Response of day-to-day home blood pressure variability by antihypertensive drug class after transient ischemic attack or nondisabling stroke.

BACKGROUND AND PURPOSE Visit-to-visit variability in systolic blood pressure (SBP) is associated with an increased risk of stroke and was reduced in randomized trials by calcium channel blockers and diuretics but not by renin-angiotensin system inhibitors. However, time of day effects could not be determined. Day-to-day variability on home BP readings predicts stroke risk and potentially offers a practical method of monitoring response to variability-directed treatment. METHODS SBP mean, maximum, and variability (coefficient of variation=SD/mean) were determined in 500 consecutive transient ischemic attack or minor stroke patients on 1-month home BP monitoring (3 BPs, 3× daily). Hypertension was treated to a standard protocol. Differences in SBP variability from 3 to 10 days before to 8 to 15 days after starting or increasing calcium channel blockers/diuretics versus renin-angiotensin system inhibitors versus both were compared by general linear models, adjusted for risk factors and baseline BP. RESULTS Among 288 eligible interventions, variability in SBP was reduced after increased treatment with calcium channel blockers/diuretics versus both versus renin-angiotensin system inhibitors (-4.0 versus 6.9 versus 7.8%; P=0.015), primarily because of effects on maximum SBP (-4.6 versus -1.0 versus -1.0%; P=0.001), with no differences in effect on mean SBP. Class differences were greatest for early-morning SBP variability (3.6 versus 17.0 versus 38.3; P=0.002) and maximum (-4.8 versus -2.0 versus -0.7; P=0.001), with no effect on midmorning (P=0.29), evening (P=0.65), or diurnal variability (P=0.92). CONCLUSIONS After transient ischemic attack or minor stroke, calcium channel blockers and diuretics reduced variability and maximum home SBP, primarily because of effects on morning readings. Home BP readings enable monitoring of response to SBP variability-directed treatment in patients with recent cerebrovascular events.

Baclofen facilitates sleep, neuroplasticity, and recovery after stroke in rats.

OBJECTIVE Sleep disruption in the acute phase after stroke has detrimental effects on recovery in both humans and animals. Conversely, the effect of sleep promotion remains unclear. Baclofen (Bac) is a known non-rapid eye movement (NREM) sleep-promoting drug in both humans and animals. The aim of this study was to investigate the effect of Bac on stroke recovery in a rat model of focal cerebral ischemia (isch). METHODS Rats, assigned to three experimental groups (Bac/isch, saline/isch, or Bac/sham), were injected twice daily for 10 consecutive days with Bac or saline, starting 24 h after induction of stroke. The sleep-wake cycle was assessed by EEG recordings and functional motor recovery by single pellet reaching test (SPR). In order to identify potential neuroplasticity mechanisms, axonal sprouting and neurogenesis were evaluated. Brain damage was assessed by Nissl staining. RESULTS Repeated Bac treatment after ischemia affected sleep, motor function, and neuroplasticity, but not the size of brain damage. NREM sleep amount was increased significantly during the dark phase in Bac/isch compared to the saline/isch group. SPR performance dropped to 0 immediately after stroke and was recovered slowly thereafter in both ischemic groups. However, Bac-treated ischemic rats performed significantly better than saline-treated animals. Axonal sprouting in the ipsilesional motor cortex and striatum, and neurogenesis in the peri-infarct region were significantly increased in Bac/isch group. CONCLUSION Delayed repeated Bac treatment after stroke increased NREM sleep and promoted both neuroplasticity and functional outcome. These data support the hypothesis of the role of sleep as a modulator of poststroke recovery.

Topographic sleep EEG changes in the acute and chronic stage of hemispheric stroke.

After stroke, the injured brain undergoes extensive reorganization and reconnection. Sleep may play a role in synaptic plasticity underlying stroke recovery. To test this hypothesis, we investigated topographic sleep electroencephalographic characteristics, as a measure of brain reorganization, in the acute and chronic stages after hemispheric stroke. We studied eight patients with unilateral stroke in the supply territory of the middle cerebral artery and eight matched controls. All subjects underwent a detailed clinical examination including assessment of stroke severity, sleep habits and disturbances, anxiety and depression, and high-density electroencephalogram examination with 128 electrodes during sleep. The recordings were performed within 10 days after stroke in all patients, and in six patients also 3 months later. During sleep, we found higher slow-wave and theta activity over the affected hemisphere in the infarct area in the acute and chronic stage of stroke. Slow-wave, theta activity and spindle frequency range power over the affected hemisphere were lower in comparison to the non-affected side in a peri-infarct area in the patients' group, which persisted over time. Conversely, in wakefulness, only an increase of delta, theta activity and a slowing of alpha activity over the infarct area were found. Sleep slow-wave activity correlated with stroke severity and outcome. Stroke might have differential effects on the generation of delta activity in wakefulness and sleep slow waves (1-8 Hz). Sleep electroencephalogram changes over both the affected and non-affected hemispheres reflect the acute dysfunction caused by stroke and the plastic changes underlying its recovery. Moreover, these changes correlate with stroke severity and outcome.

The value of serial serum lactate measurements in predicting the extent of ischemic bowel and outcome of patients suffering acute mesenteric ischemia

BACKGROUND Acute mesenteric ischemia (AMI) is an emergency with a mortality rate up to 50 %. Detecting AMI continues to be a major challenge. This study assed the correlation of repeated preoperative serum lactate with bowel necrosis and to identify risk factors for a lethal outcome in patients with AMI. METHODS A retrospective study of 91 patients with clinically and pathologically confirmed AMI from January 2006 to December 2012 was performed. RESULTS In-hospital mortality rate was 42.9 %. Two hundred nine preoperative lactate measurements were analyzed (2.3 ± 1.1 values per patient). Less than or equal to six hours prior to surgery, the mean serum lactate level was significantly higher (4.97 ± 4.21 vs. 3.24 ± 3.05 mmol/L, p = 0.006) and the mean pH significantly lower (7.28 ± 0.12 vs. 7.37 ± 0.08, p = 0.001) compared to >6 h before surgery. Thirty-four patients had at least two lactate measurements within 24 h prior to surgery. In this subgroup, 17 patients (50 %) exhibited an increase, 17 patients (50 %) a decrease in lactate levels. Forward logistic regression analysis showed that length of necrotic bowel and the highest lactate value 24 h prior to surgery were independent risk factors for mortality (r (2)  = 0.329). CONCLUSION The value of serial lactate and pH measurements to predict the length of necrotic bowel is very limited. Length of necrotic bowel and lactate values are independent risk factors for mortality.

Endovascular Treatment of Acute Stroke: Evolution and Selection of Techniques and Instruments Based on Thrombus Imaging.

Mechanical thrombectomy provides higher recanalization rates than intravenous or intra-arterial thrombolysis. Finally this has been shown to translate into improved clinical outcome in six multicentric randomized controlled trials. However, within cohorts the clinical outcomes may vary, depending on the endovascular techniques applied. Systems aiming mainly for thrombus fragmentation and lacking a protection against distal embolization have shown disappointing results when compared to recent stent-retriever studies or even to historical data on local arterial fibrinolysis. Procedure-related embolic events are usually graded as adverse events in interventional neuroradiology. In stroke, however, the clinical consequences of secondary emboli have so far mostly been neglected and attributed to progression of the stroke itself. We summarize the evolution of instruments and techniques for endovascular, image-guided, microneurosurgical recanalization in acute stroke, and discuss how to avoid procedure-related embolic complications.