Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale <or=2) at 3 months, intracranial hemorrhage (ICH), and recurrent ischaemic stroke. RESULTS: Sixty-five (6.2%) of 1048 IVT-treated patients had SAO. Amongst SAO-patients, 1.5% (1/65) patients died, compared to 11.2% (110/983) in the non-SAO-group (P = 0.014). SAO-patients reached independence more often than non-SAO-patients (75.4% versus 58.9%; OR 2.14 (95% CI 1.20-3.81; P = 0.001). This association became insignificant after adjustment for age, gender, and stroke severity (OR 1.41 95% CI 0.713-2.788; P = 0.32). Glucose level and (to some degree) stroke severity but not age predicted 3-month-independence in IVT-treated SAO-patients. ICHs (all/symptomatic) were similar in SAO- (12.3%/4.6%) and non-SAO-patients (13.4%/5.3%; P > 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Diffusion tensor imaging shows structural remodeling of stroke mirror region: results from a pilot study.

Background: The role of the non-injured hemisphere in stroke recovery is poorly understood. In this pilot study, we sought to explore the presence of structural changes detectable by diffusion tensor imaging (DTI) in the contralesional hemispheres of patients who recovered well from ischemic stroke. Methods: We analyzed serial DTI data from 16 stroke patients who had moderate initial neurological deficits (NIHSS scores 3-12) and good functional outcome at 3-6 months (NIHSS score 0 or modified Rankin Score ≤1). We segmented the brain tissue in gray and white matter (GM and WM) and measured the apparent diffusion coefficient (ADC) and fractional anisotropy in the infarct, in the contralesional infarct mirror region as well as in concentrically expanding regions around them. Results: We found that GM and WM ADC significantly increased in the infarct region (p < 0.01) from acute to chronic time points, whereas in the infarct mirror region, GM and WM ADC increased (p < 0.01) and WM fractional anisotropy decreased (p < 0.05). No significant changes were detected in other regions. Conclusion: DTI-based metrics are sensitive to regional structural changes in the contralesional hemisphere during stroke recovery. Prospective studies in larger cohorts with varying levels of recovery are needed to confirm our findings.

Intravenous thrombolysis in nonagenarians with ischemic stroke.

Background and Purpose-Demographic changes will result in a rapid increase of patients age >= 90 years (nonagenarians), but little is known about outcomes in these patients after intravenous thrombolysis (IVT) for acute ischemic stroke. We aimed to assess safety and functional outcome in nonagenarians treated with IVT and to compare the outcomes with those of patients age 80 to 89 years (octogenarians).Methods-We analyzed prospectively collected data of 284 consecutive stroke patients age >= 80 years treated with IVT in 7 Swiss stroke units. Presenting characteristics, favorable outcome (modified Rankin scale [mRS] 0 or 1), mortality at 3 months, and symptomatic intracranial hemorrhage (SICH) using the National Institute of Neurological Disorders and Stroke (NINDS) and Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria were compared between nonagenarians and octogenarians.Results-As compared with octogenarians (n=238; mean age, 83 years), nonagenarians (n=46; mean age, 92 years) were more often women (70% versus 54%; P=0.046) and had lower systolic blood pressure (161 mm Hg versus 172 mm Hg; P=0.035). Patients age >= 90 years less often had a favorable outcome and had a higher incidence of mortality than did patients age 80 to 89 years (14.3% versus 30.2%; P=0.034; and 45.2% versus 22.1%; P=0.002; respectively), while more nonagenarians than octogenarians experienced a SICH (SICHNINDS, 13.3% versus 5.9%; P=0.106; SICHSITS-MOST, 13.3% versus 4.7%; P=0.037). Multivariate adjustment identified age >= 90 years as an independent predictor of mortality (P=0.017).Conclusions-Our study suggests less favorable outcomes in nonagenarians as compared with octogenarians after IVT for ischemic stroke, and it demands a careful selection for treatment, unless randomized controlled trials yield more evidence for IVT in very old stroke patients. (Stroke. 2011; 42: 1967-1970.)

Association of ischaemic stroke subtype with long-term cardiovascular events.

BACKGROUND AND PURPOSE: There is no strong evidence that all ischaemic stroke types are associated with high cardiovascular risk. Our aim was to investigate whether all ischaemic stroke types are associated with high cardiovascular risk. METHODS: All consecutive patients with ischaemic stroke registered in the Athens Stroke Registry between 1 January 1993 and 31 December 2010 were categorized according to the TOAST classification and were followed up for up to 10 years. Outcomes assessed were cardiovascular and all-cause mortality, myocardial infarction, stroke recurrence, and a composite cardiovascular outcome consisting of myocardial infarction, angina pectoris, acute heart failure, sudden cardiac death, stroke recurrence and aortic aneurysm rupture. The Kaplan-Meier product limit method was used to estimate the probability of each end-point in each patient group. Cox proportional hazards models were used to determine the independent covariates of each end-point. RESULTS: Two thousand seven hundred and thirty patients were followed up for 48.1 ± 41.9 months. The cumulative probabilities of 10-year cardiovascular mortality in patients with cardioembolic stroke [46.6%, 95% confidence interval (CI) 40.6-52.8], lacunar stroke (22.1%, 95% CI 16.2-28.0) or undetermined stroke (35.2%, 95% CI 27.8-42.6) were either similar to or higher than those of patients with large-artery atherosclerotic stroke (LAA) (28.7%, 95% CI 22.4-35.0). Compared with LAA, all other TOAST types had a higher probability of 10-year stroke recurrence. In Cox proportional hazards analysis, compared with patients with LAA, patients with any other stroke type were associated with similar or higher risk for the outcomes of overall mortality, cardiovascular mortality, stroke recurrence and composite cardiovascular outcome. CONCLUSIONS: Large-artery atherosclerotic stroke and cardioembolic stroke are associated with the highest risk for future cardiovascular events, with the latter carrying at least as high a risk as LAA stroke.

Acute multivessel revascularization improves 1-year outcome in ST-elevation myocardial infarction: a nationwide study cohort from the AMIS Plus registry.

BACKGROUND: The optimal strategy for percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) in multi-vessel disease (MVD), i.e., multi-vessel PCI (MV-PCI) vs. PCI of the infarct-related artery only (IRA-PCI), still remains unknown. METHODS: Patients of the AMIS Plus registry admitted with an acute coronary syndrome were contacted after a median of 378 days (interquartile range 371-409). The primary end-point was all-cause death. The secondary end-point included all major adverse cardiovascular and cerebrovascular events (MACCE) including death, re-infarction, re-hospitalization for cardiac causes, any cardiac re-intervention, and stroke. RESULTS: Between 2005 and 2012, 8330 STEMI patients were identified, of whom 1909 (24%) had MVD. Of these, 442 (23%) received MV-PCI and 1467 (77%) IRA-PCI. While all-cause mortality was similar in both groups (2.7% both, p>0.99), MACCE was significantly lower after MV-PCI vs. IRA-PCI (15.6% vs. 20.0%, p=0.038), mainly driven by lower rates of cardiac re-hospitalization and cardiac re-intervention. Patients undergoing MV-PCI with drug-eluting stents had lower rates of all-cause mortality (2.1% vs. 7.4%, p=0.026) and MACCE (14.1% vs. 25.9%, p=0.042) compared with those receiving bare metal stents (BMS). In multivariate analysis, MV-PCI (odds ratio, OR 0.69, 95% CI 0.51-0.93, p=0.017) and comorbidities (Charlson index ≥ 2; OR 1.42, 95% CI 1.05-1.92, p=0.025) were independent predictors for 1-year MACCE. CONCLUSION: In an unselected nationwide real-world cohort, an approach using immediate complete revascularization may be beneficial in STEMI patients with MVD regarding MACCE, specifically when drug-eluting stents are used, but not regarding mortality. This has to be tested in a randomized controlled trial.

The value of adding mirror therapy for upper limb motor recovery of subacute stroke patients: a randomized controlled trial.

BACKGROUND: Upper limb paresis remains a relevant challenge in stroke rehabilitation. AIM: To evaluate if adding mirror therapy (MT) to conventional therapy (CT) can improve motor recovery of the upper limb in subacute stroke patients. DESIGN: Prospective, single-center, single-blind, randomised, controlled trial. SETTING: Subacute stroke patients referred to a Physical and Rehabilitation Medicine Unit between October 2009 and August 2011. POPULATION: Twenty-six subacute stroke patients (time from stroke <4 weeks) with upper limb paresis (Motricity Index â0/00¤ 77). METHODS: Patients were randomly allocated to the MT (N.=13) or to the CT group (N.=13). Both followed a comprehensive rehabilitative treatment. In addition, MT Group had 30 minutes of MT while the CT group had 30 minutes of sham therapy. Action Research Arm Test (ARAT) was the primary outcome measures. Motricity Index (MI) and the Functional Independence Measure (FIM) were the secondary outcome measures. RESULTS: After one month of treatment patients of both groups showed statistically significant improvements in all the variables measured (P<0.05). Moreover patients of the MT group had greater improvements in the ARAT, MI and FIM values compared to CT group (P<0.01, Glass's Î" Effect Size: 1.18). No relevant adverse event was recorded during the study. CONCLUSION: MT is a promising and easy method to improve motor recovery of the upper limb in subacute stroke patients. CLINICAL REHABILITATION IMPACT: While MT use has been advocated for acute patients with no or negligible motor function, it can be usefully extended to patients who show partial motor recovery. The easiness of implementation, the low cost and the acceptability makes this therapy an useful tool in stroke rehabilitation.

Molecular Mechanisms of Acute Brain Injury and Ensuing Neurodegeneration

Injury to the central nervous system (CNS), including stroke, traumatic brain injury andspinal cord injury, cause devastating and irreversible damage and loss of function. Forexample, stroke affects very large patient populations, results in major suffering for the patients and their relatives, and involves a significant cost to society. CNS damage implies disruption of the intricate internal circuits involved in cognition, the sensory-motor functions, and other important functions. There are currently no treatments available to properly restore such lost functions. New therapeutic proposals will emerge from an understanding of the interdependence of molecular and cellular responses to CNS injury, in particular the inhibitory mechanisms that block regeneration and those that enhanceneuronal plasticity...

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Background: Vorapaxar is a new oral protease-activatedreceptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (KaplanMeier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Understanding the multifaceted role of inflammatory mediators in ischemic stroke.

The evolution of ischemic brain damage is strongly affected by an inflammatory reaction that involves soluble mediators, such as cytokines and chemokines, and specialized cells activated locally or recruited from the periphery. The immune system affects all phases of the ischemic cascade, from the acute intravascular reaction due to blood flow disruption, to the development of brain tissue damage, repair and regeneration. Increased endothelial expression of adhesion molecules and blood-brain barrier breakdown promotes extravasation and brain recruitment of blood-borne cells, including macrophages, neutrophils, dendritic cells and T lymphocytes, as demonstrated both in animal models and in human stroke. Nevertheless, most anti-inflammatory approaches showing promising results in experimental stroke models failed in the clinical setting. The lack of translation may reside in the redundancy of most inflammatory mediators, exerting both detrimental and beneficial functions. Thus, this review is aimed at providing a better understanding of the dualistic role played by each component of the inflammatory/immune response in relation to the spatio-temporal evolution of ischemic stroke injury.

A new early and automated MRI-based predictor of motor improvement after stroke.

OBJECTIVES: In this study, we investigated the structural plasticity of the contralesional motor network in ischemic stroke patients using diffusion magnetic resonance imaging (MRI) and explored a model that combines a MRI-based metric of contralesional network integrity and clinical data to predict functional outcome at 6 months after stroke. METHODS: MRI and clinical examinations were performed in 12 patients in the acute phase, at 1 and 6 months after stroke. Twelve age- and gender-matched controls underwent 2 MRIs 1 month apart. Structural remodeling after stroke was assessed using diffusion MRI with an automated measurement of generalized fractional anisotropy (GFA), which was calculated along connections between contralesional cortical motor areas. The predictive model of poststroke functional outcome was computed using a linear regression of acute GFA measures and the clinical assessment. RESULTS: GFA changes in the contralesional motor tracts were found in all patients and differed significantly from controls (0.001 ≤ p < 0.05). GFA changes in intrahemispheric and interhemispheric motor tracts correlated with age (p ≤ 0.01); those in intrahemispheric motor tracts correlated strongly with clinical scores and stroke sizes (p ≤ 0.001). GFA measured in the acute phase together with a routine motor score and age were a strong predictor of motor outcome at 6 months (r(2) = 0.96, p = 0.0002). CONCLUSION: These findings represent a proof of principle that contralesional diffusion MRI measures may provide reliable information for personalized rehabilitation planning after ischemic motor stroke. Neurology® 2012;79:39-46.

Endovascular treatment of symptomatic intracranial arterial stenosis: six-year experience in a single-center series of 42 consecutive patients with acute and mid-term results.

BACKGROUND: The limitations of the medical management of symptomatic intracranial arterial stenosis encourage the development of new therapeutic strategies such as intracranial stenting. OBJECTIVE: To report and analyze the results of a series of 42 patients treated with 3 different endovascular techniques: isolated angioplasty, balloon-expandable coronary stents, and the Wingspan self-expandable intracranial stent system. METHODS: Forty-two patients presenting with symptomatic intracranial arterial stenosis were treated with one of these techniques. Computed tomography angiography was performed 6 months after the procedure, and the clinical neurological statuses were categorized using the modified Rankin Scale and the National Institutes of Health Stroke Scale. RESULTS: A total of 42 lesions were treated: 9 with isolated angioplasty, 14 with balloon-expandable coronary stents, and 19 with Wingspan self-expandable intracranial stents. The mean patient age was 62.9 years, and the mean arterial diameter stenosis was 73.9%. Technical success was achieved in 97.6% of the patients. The overall incidence of procedural complications was 21.4%, and the postoperative permanent morbidity/mortality rate was 7.1%. There were 3 cases of in-stent thrombosis (1 fatal) and 5 cases of asymptomatic restenosis (11.9%), 3 in the isolated angioplasty group and 2 in the Wingspan self-expandable intracranial stent group (mean follow-up 20.4 months). The rate of restenosis was higher in the angioplasty group (33%) than in the coronary (0%) and Wingspan stent (10.5%) groups. CONCLUSION: Endovascular treatment of symptomatic intracranial stenosis has significant overall morbidity and mortality rates. Nevertheless, the very critical natural history of severe refractory lesions and the relatively favorable postoperative evolution suggest that it should be considered the first alternative strategy in cases in which medical therapy has failed.

Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study

Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

Neuromonitorage après coma aigu aux soins intensifs [Multimodal neuromonitoring for the critical care management of acute coma].

Management of neurocritical care patients is focused on the prevention and treatment of secondary brain injury, i.e. the number of pathophysiological intracerebral (edema, ischemia, energy dysfunction, seizures) and systemic (hyperthermia, disorders of glucose homeostasis) events that occur following the initial insult (stroke, hemorrhage, head trauma, brain anoxia) that may aggravate patient outcome. The current therapeutic paradigm is based on multimodal neuromonitoring, including invasive (intracranial pressure, brain oxygen, cerebral microdialysis) and non-invasive (transcranial doppler, near-infrared spectroscopy, EEG) tools that allows targeted individualized management of acute coma in the early phase. The aim of this review is to describe the utility of multimodal neuromonitoring for the critical care management of acute coma.

Acute ischemic cerebrovascular events on antiplatelet therapy: what is the optimal prevention strategy?

Even though patients who develop ischemic stroke despite taking antiplatelet drugs represent a considerable proportion of stroke hospital admissions, there is a paucity of data from investigational studies regarding the most suitable therapeutic intervention. There have been no clinical trials to test whether increasing the dose or switching antiplatelet agents reduces the risk for subsequent events. Certain issues have to be considered in patients managed for a first or recurrent stroke while receiving antiplatelet agents. Therapeutic failure may be due to either poor adherence to treatment, associated co-morbid conditions and diminished antiplatelet effects (resistance to treatment). A diagnostic work up is warranted to identify the etiology and underlying mechanism of stroke, thereby guiding further management. Risk factors (including hypertension, dyslipidemia and diabetes) should be treated according to current guidelines. Aspirin or aspirin plus clopidogrel may be used in the acute and early phase of ischemic stroke, whereas in the long-term, antiplatelet treatment should be continued with aspirin, aspirin/extended release dipyridamole or clopidogrel monotherapy taking into account tolerance, safety, adherence and cost issues. Secondary measures to educate patients about stroke, the importance of adherence to medication, behavioral modification relating to tobacco use, physical activity, alcohol consumption and diet to control excess weight should also be implemented.