Showing papers in "Stroke in 2007"
TL;DR: In this paper, the authors provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke and provide information for healthcare policy makers.
Abstract: Purpose— Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Methods— Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Council’s Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years. Results— Managem...
2,263 citations
TL;DR: The reported data support the view that the modified Rankin scale is a valuable instrument for assessing the impact of new stroke treatments, and patient comorbidities and socioeconomic factors should be considered in properly applying and interpreting the mRS.
Abstract: Background and Purpose— The modified Rankin scale (mRS), a clinician-reported measure of global disability, is widely applied for evaluating stroke patient outcomes and as an end point in randomized clinical trials. Extensive evidence on the validity of the mRS exists across a large but fragmented literature. As new treatments for acute ischemic stroke are submitted for agency approval, an appreciation of the mRS’s attributes, specifically its relationship to other stroke evaluation scales, would be valuable for decision-makers to properly assess the impact of a new drug on treatment paradigms. The purpose of this report is to assemble and systematically assess the properties of the mRS to provide decision-makers with pertinent evaluative information. Methods— A Medline search was conducted to identify reports in the peer-reviewed medical literature (1957–2006) that provide information on the structure, validation, scoring, and psychometric properties of the mRS and its use in clinical trials. The selecti...
1,458 citations
TL;DR: Recanalization is strongly associated with improved functional outcomes and reduced mortality and is an appropriate biomarker of therapeutic activity in early phase trials of thrombolytic treatment in acute ischemic stroke.
Abstract: Background and Purpose— For a biomarker to serve as an auxiliary or surrogate outcome measure, it must be tightly correlated with and causally related to functional clinical outcome. Vessel recanalization is a potential surrogate outcome marker for functional outcome in trials of thrombolytic and mechanical recanalization therapies in acute stroke, but the correlation of recanalization and clinical outcome has not been previously systematically reviewed. Methods— Through Medline search, we identified and abstracted recanalization and outcome data from all articles published between 1985 and 2002 that assessed vessel recanalization, either spontaneous or therapeutically induced, in acute ischemic stroke. Results— Fifty-three studies encompassing 2066 patients reported recanalization rates. Recanalization rates categorized according to intervention were: spontaneous (24.1%), intravenous fibrinolytic (46.2%), intra-arterial fibrinolytic (63.2%), combined intravenous–intra-arterial (67.5%), and mechanical (83...
1,385 citations
TL;DR: Recombinant activated factor VII was associated with a 38% relative reduction in mortality and significantly improved functional outcome among survivors, despite a 5% frequency of arterial thromboembolic events (primarily ischemic stroke and myocardial infarction).
Abstract: background Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality. Among patients who undergo computed tomography (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can reduce hematoma growth after intracerebral hemorrhage. methods We randomly assigned 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 µg of rFVIIa per kilogram of body weight (108 patients), 80 µg per kilogram (92 patients), or 160 µg per kilogram (103 patients) within one hour after the baseline scan. The primary outcome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. results Hematoma volume increased more in the placebo group than in the rFVIIa groups. The mean increase was 29 percent in the placebo group, as compared with 16 percent, 14 percent, and 11 percent in the groups given 40 µg, 80 µg, and 160 µg of rFVIIa per kilogram, respectively (P = 0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduced by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P = 0.01). Sixty-nine percent of placebo-treated patients died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the patients who were given 40, 80, and 160 µg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 percent in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral infarction, occurred in 7 percent of rFVIIa-treated patients, as compared with 2 percent of those given placebo (P=0.12). conclusions Treatment with rFVIIa within four hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves functional outcomes at 90 days, despite a small increase in the frequency of thromboembolic adverse events.
1,080 citations
TL;DR: Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intrusion, and the prevention of recurrent intrusion.
Abstract: Purpose— The aim of this statement is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage. Methods— A formal literature search of Medline was performed through the end date of August 2006. The results of this search were complemented by additional articles on related issues known to the writing committee. Data were synthesized with the use of evidence tables. The American Heart Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 5 expert peer reviewers and by the members of the Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years’ time. Results— Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intracerebral hemorrhag...
1,021 citations
TL;DR: DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke, and the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicaniectomy trials.
Abstract: Background and Purpose— Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial. Methods— DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. Results— A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy surviv...
763 citations
TL;DR: In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced the mortality rate compared with that after medical therapy.
Abstract: Background and Purpose— There is no effective medical treatment of malignant middle cerebral artery (MCA) infarction. The purpose of this clinical trial was to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction. Methods— We conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score ≤3) at 6 months’ follow-up (primary outcome) between the 2 treatment groups. Results— After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patie...
726 citations
TL;DR: Prerecombinant tissue plasminogen activator, systolic blood pressure, glucose, and Thrombolysis in Brain Ischemia flow grade at the occlusion site were the negative independent predictors for complete recanalization in the final model.
Abstract: Background and Purpose— The objective of this study was to examine clinical outcomes and recanalization rates in a multicenter cohort of stroke patients receiving intravenous tissue plasminogen activator by site of occlusion localized with bedside transcranial Doppler. Angiographic studies with intraarterial thrombolysis suggest more proximal occlusions carry greater thrombus burden and benefit less from local therapy. Methods— Using validated transcranial Doppler criteria for specific arterial occlusion (Thrombolysis in Brain Ischemia flow grades), we compared the rate of dramatic recovery (National Institutes of Health Stroke Scale score ≤2 at 24 hours) and favorable outcomes at 3 months (modified Rankin Scale ≤1) for each occlusion site. We determined the likelihood of recanalization at various occlusion sites and its predictors. Then, stepwise logistic regression was used to determine predictors of complete recanalization. Results— Three hundred thirty-five patients had a mean age 69±13 years and 48.5...
654 citations
TL;DR: A randomized trial of standard intravenous rt-PA as compared with a combined intravenous and intra-arterial approach to recanalization for ischemic stroke is warranted and has begun.
Abstract: Background and purpose The purpose of this study was to further investigate the feasibility and safety of a combined intravenous and intra-arterial approach to recanalization for ischemic stroke. Methods Subjects, ages 18 to 80, with a baseline NIHSS > or =10 had intravenous recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes) within 3 hours of onset. For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro-infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis. Results The 81 subjects had a median baseline NIHSS score of 19. The median time to initiation of intravenous rt-PA was 142 minutes as compared with 108 minutes for placebo and 90 minutes for rt-PA-treated subjects in the NINDS rt-PA Stroke Trial (P or =2.7) and better outcomes than NINDS rt-PA-treated subjects as measured by the Barthel Index and Global Test Statistic. Conclusions A randomized trial of standard intravenous rt-PA as compared with a combined intravenous and intra-arterial approach is warranted and has begun.
617 citations
TL;DR: Function and quality-of-life SIS scores after treatment were significantly higher among survivors who achieved a favorable transition compared with those who did not, indicating a gait velocity gain that results in a transition to a higher class of ambulation results in better function and quality of life, especially for household ambulators.
Abstract: Background and Purpose—Gait velocity is a powerful indicator of function and prognosis after stroke. Gait velocity can be stratified into clinically meaningful functional ambulation classes, such as household ambulation (0.4 m/s), limited community ambulation (0.4 to 0.8 m/s), and full community ambulation (0.8 m/s). The purpose of the current study was to determine whether changes in velocity-based community ambulation classification were related to clinically meaningful changes in stroke-related function and quality of life. Methods—In subacute stroke survivors with mild to moderate deficits who participated in a randomized clinical trial of stroke rehabilitation and had a baseline gait velocity of 0.8 m/s or less, we assessed the effect of success versus failure to achieve a transition to the next class on function and quality of life according to domains of the Stroke Impact Scale (SIS). Results—Of 64 eligible participants, 19 were initially household ambulators, and 12 of them (68%) transitioned to limited community ambulation, whereas of 45 initially limited community ambulators, 17 (38%) became full community ambulators. Function and quality-of-life SIS scores after treatment were significantly higher among survivors who achieved a favorable transition compared with those who did not. Among household ambulators, those who transitioned to limited or full community ambulation had significantly better SIS scores in mobility (P0.0299) and participation (P0.0277). Among limited community ambulators, those who achieved the transition to full community ambulatory status had significantly better scores in SIS participation (P0.0085). Conclusions—A gait velocity gain that results in a transition to a higher class of ambulation results in better function and quality of life, especially for household ambulators. Household ambulators possibly had more severe stroke deficits, reducing the risk of “ceiling” effects in SIS-measured activities of daily living and instrumental activities of daily living. Outcome assessment based on transitions within a mobility classification scheme that is rooted in gait velocity yields potentially meaningful indicators of clinical benefit. Outcomes should be selected that are clinically meaningful for all levels of severity. (Stroke. 2007;38:2096-2100.)
581 citations
TL;DR: Age, gender, population, size, site, and type of aneurysm should be considered in the decision whether to treat an unruptured aneurYSm and pooled multivariable analyses of individual data are needed to identify independent risk factors and to provide more reliable risk estimates for individual patients.
Abstract: Background and Purpose— We updated our previous review from 1996 on the risk of rupture of unruptured intracranial aneurysms, aiming to include the newly published articles. Methods— We reviewed all studies from our former meta-analysis and performed a Medline search for new studies published after 1996. We calculated overall risks of rupture for studies with a mean follow-up time of 10 years. Relative risks (RR) were calculated by comparing the risk of rupture in patients with and without potential risk factors. We aimed to perform multivariable analyses of the different risk factors with meta-regression analysis. Results— We included 19 studies (10 new) with 4705 patients and 6556 unruptured aneurysms (follow-up 26 122 patient-years). The overall rupture risks were 1.2% (follow-up 10 years). In the univariable analysis, statistically significant risk factors for rupture were age >60 years (RR 2.0; 95% confidence interval [...
TL;DR: The computed tomography angiography spot sign is associated with the presence and extent of hematoma progression and further studies are warranted to validate the ability of this sign to predict clinical outcomes.
Abstract: Background and Purpose— Morbidity and mortality in spontaneous intracerebral hemorrhage (ICH) are correlated with hematoma progression. We hypothesized that the presence of tiny, enhancing foci (“spot sign”) within acute hematomas is associated with hematoma expansion. Methods— We prospectively studied 39 consecutive patients with spontaneous ICH by computed tomography angiography within 3 hours of symptom onset. Scans were reviewed by 3 readers. Patients were dichotomized according to the presence or absence of the spot sign. Clinical and radiological outcomes were compared between groups. The predictive value of this sign was assessed in a multivariate analysis. Results— Thirteen patients (33%) demonstrated 31 enhancing foci. Baseline clinical variables were similar in both groups. Hematoma expansion occurred in 11 patients (28%) on follow-up. Seventy-seven percent of patients with and 4% without hematoma expansion demonstrated the spot sign (P<0.0001). Sensitivity, specificity, positive predictive valu...
TL;DR: Strong localization of aneurysm-type remodeling to the region of accelerating flow suggests that a combination of high wallShear stress and a high gradient in wall shear stress represents a “dangerous” hemodynamic condition that predisposes the apical vessel wall to aneurYSm formation.
Abstract: Background and Purpose— Arterial bifurcation apices are common sites for cerebral aneurysms, raising the possibility that the unique hemodynamic conditions associated with flow dividers predispose the apical vessel wall to aneurysm formation. This study sought to identify the specific hemodynamic insults that lead to maladaptive vascular remodeling associated with aneurysm development and to identify early remodeling events at the tissue and cellular levels. Methods— We surgically created new branch points in the carotid vasculature of 6 female adult dogs. In vivo angiographic imaging and computational fluid dynamics simulations revealed the detailed hemodynamic microenvironment for each bifurcation, which were then spatially correlated with histologic features showing specific tissue responses. Results— We observed 2 distinct patterns of vessel wall remodeling: (1) hyperplasia that formed an intimal pad at the bifurcation apex and (2) destructive remodeling in the adjacent region of flow acceleration that resembled the initiation of an intracranial aneurysm, characterized by disruption of the internal elastic lamina, loss of medial smooth muscle cells, reduced proliferation of smooth muscle cells, and loss of fibronectin. Conclusions— Strong localization of aneurysm-type remodeling to the region of accelerating flow suggests that a combination of high wall shear stress and a high gradient in wall shear stress represents a “dangerous” hemodynamic condition that predisposes the apical vessel wall to aneurysm formation.
TL;DR: Although most prognostic factors for outcome after SAH are present on admission and are not modifiable, a substantial contribution to outcome is made by factors developing after admission and which may be more easily influenced by treatment.
Abstract: Background and Purpose— The purpose of this study was to describe prognostic factors for outcome in a large series of patients undergoing neurosurgical clipping of aneurysms after subarachnoid hemorrhage (SAH). Methods— Data were analyzed from 3567 patients with aneurysmal SAH enrolled in 4 randomized clinical trials between 1991 and 1997. The primary outcome measure was the Glasgow outcome scale 3 months after SAH. Multivariable logistic regression with backwards selection and Cox proportional hazards regression models were derived to define independent predictors of unfavorable outcome. Results— In multivariable analysis, unfavorable outcome was associated with increasing age, worsening neurological grade, ruptured posterior circulation aneurysm, larger aneurysm size, more SAH on admission computed tomography, intracerebral hematoma or intraventricular hemorrhage, elevated systolic blood pressure on admission, and previous diagnosis of hypertension, myocardial infarction, liver disease, or SAH. Variables present during hospitalization associated with poor outcome were temperature >38°C 8 days after SAH, use of anticonvulsants, symptomatic vasospasm, and cerebral infarction. Use of prophylactic or therapeutic hypervolemia or prophylactic-induced hypertension were associated with a lower risk of unfavorable outcome. Time from admission to surgery was significant in some models. Factors that contributed most to variation in outcome, in descending order of importance, were cerebral infarction, neurological grade, age, temperature on day 8, intraventricular hemorrhage, vasospasm, SAH, intracerebral hematoma, and history of hypertension. Conclusions— Although most prognostic factors for outcome after SAH are present on admission and are not modifiable, a substantial contribution to outcome is made by factors developing after admission and which may be more easily influenced by treatment.
Journal Article•
TL;DR: A robot-based therapy showed improvements in hand motor function after chronic stroke, and reorganization of motor maps during the current therapy was task-specific, a finding useful when considering generalization of rehabilitation therapy.
Abstract: Robots can improve motor status after stroke with certain advantages, but there has been less emphasis to date on robotic developments for the hand. The goal of this study was to determine whether a hand-wrist robot would improve motor function, and to evaluate the specificity of therapy effects on brain reorganization. Subjects with chronic stroke producing moderate right arm/hand weakness received 3 weeks therapy that emphasized intense active movement repetition as well as attention, speed, force, precision and timing, and included virtual reality games. Subjects initiated hand movements. If necessary, the robot completed movements, a feature available at all visits for seven of the subjects and at the latter half of visits for six of the subjects. Significant behavioural gains were found at end of treatment, for example, in Action Research Arm Test (34 +/- 20 to 38 +/- 19, P< 0.0005) and arm motor Fugl-Meyer score (45 +/- 10 to 52 +/- 10, P < 0.0001). Results suggest greater gains for subjects receiving robotic assistance in all sessions as compared to those receiving robotic assistance in half of sessions. The grasp task practiced during robotic therapy, when performed during functional MRI, showed increased sensorimotor cortex activation across the period of therapy, while a non-practiced task, supination/pronation, did not. A robot-based therapy showed improvements in hand motor function after chronic stroke. Reorganization of motor maps during the current therapy was task-specific, a finding useful when considering generalization of rehabilitation therapy.
TL;DR: The trial was aborted prematurely and the primary end point did not reach statistical significance, but secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome.
Abstract: Background and Purpose— The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset.
Methods— Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index.
Results— The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat more frequent in the UK group than in the control group (49.1% and 38.6%, OR: 1.54, 95% CI: 0.73 to 3.23) but did not reach a significant level ( P =0.345). However, excellent functional outcome (modified Rankin Scale 0 to 1) at 90 days, a preplanned secondary end point, was more frequent in the UK group than in the control group (42.1% and 22.8%, P =0.045, OR: 2.46, 95% CI: 1.09 to 5.54). There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group ( P =0.017). The 90-day cumulative mortality was 5.3% in the UK group and 3.5% in the control group ( P =1.000), and intracerebral hemorrhage within 24 hours of treatment occurred in 9% and 2%, respectively ( P =0.206).
Conclusions— The trial was aborted prematurely and the primary end point did not reach statistical significance. Nevertheless, the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome.
TL;DR: Younger age, larger lumen size, and incomplete occlusion were risk factors for late retreatment after EVT, and early retreatments were earlier; whereas EVT retreatments continued to be performed throughout the follow-up period.
Abstract: Background and Purpose— Because the long-term security of endovascular treatments remains uncertain, a follow-up study of the patients treated in the International Subarachnoid Aneurysm Trial was performed to compare the frequency, timing, and consequences of aneurysm recurrence. Methods— Patient data were reclassified by actual treatment performed. Aneurysm and patient characteristics, including occlusion grades, time and type of retreatment, and clinical outcomes, were compared. The relationship between these variables and late retreatment as a surrogate for recurrence was analyzed by means of the Cox proportional hazards model. Results— Retreatment was performed in 191 of 1096 (17.4%) patients after primary endovascular coiling (EVT) and in 39 of 1012 patients (3.8%) after neurosurgical clipping. After EVT, 97 (8.8%) patients were retreated early and 94 (9.0%) late, 7 (0.6%) after rebleeding and 87 (8.3%) without. The mean time to late retreatment was 20.7 months. After neurosurgical clipping, 30 (2.9%...
TL;DR: The Gugging Swallowing Screen offers a quick and reliable method to identify stroke patients with dysphagia and aspiration risk and provides less discomfort for those patients who can continue with their oral feeding routine for semisolid food while refraining from drinking fluids.
Abstract: Background and Purpose— Acute-onset dysphagia after stroke is frequently associated with an increased risk of aspiration pneumonia. Because most screening tools are complex and biased toward fluid swallowing, we developed a simple, stepwise bedside screen that allows a graded rating with separate evaluations for nonfluid and fluid nutrition starting with nonfluid textures. The Gugging Swallowing Screen (GUSS) aims at reducing the risk of aspiration during the test to a minimum; it assesses the severity of aspiration risk and recommends a special diet accordingly. Methods— Fifty acute-stroke patients were assessed prospectively. The validity of the GUSS was established by fiberoptic endoscopic evaluation of swallowing. For interrater reliability, 2 independent therapists evaluated 20 patients within a 2-hour period. For external validity, another group of 30 patients was tested by stroke nurses. For content validity, the liquid score of the fiberoptic endoscopic evaluation of swallowing was compared with t...
TL;DR: In a subgroup analysis from PROactive, pioglitazone reduced the risk of recurrent stroke significantly in high-risk patients with type 2 diabetes.
Abstract: Background and Purpose— Diabetes is an important risk factor for stroke. We conducted analyses in patients who had entered the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) with a history of stroke or without stroke. Methods— The prospective, double-blind PROactive (mean duration, 34.5 months) randomized 5238 patients with type 2 diabetes and a history of macrovascular disease to pioglitazone (titrated to 45 mg) or placebo, in addition to current diabetes and cardiovascular medications. Cardiovascular end-point events were independently adjudicated. This analysis evaluated the risk of stroke and other cardiovascular outcomes in patients with (n=984) and without (n=4254) prior stroke. Results— In patients with previous stroke (n=486 in the pioglitazone group and n=498 in the placebo group), there was a trend of benefit with pioglitazone for the primary end point of all-cause death, nonfatal myocardial infarction, acute coronary syndrome, and cardiac intervention (including cor...
TL;DR: The Pipeline NED is a trackable, bio- and hemocompatible device able to occlude saccular aneurysms with preservation of the parent artery and small, adjacent branch vessels.
Abstract: Background and Purpose— We report a preclinical study of a new endoluminal device for aneurysm occlusion to test the hypothesis that the device, even without use of intrasaccular coil placement, could occlude saccular aneurysms without causing substantial parent artery compromise or compromise of adjacent, small branch arteries. Methods— The Pipeline Neuroendovascular Device (Pipeline NED; Chestnut Medical Technologies, Inc) is a braided, tubular, bimetallic endoluminal implant aimed at occlusion of saccular aneurysms through flow disruption along the aneurysm neck. The device was implanted across the necks of 17 elastase-induced aneurysms in the New Zealand white rabbit model and followed for 1 month (n=6), 3 months (n=5), and 6 months (n=6). In each subject, a second device was implanted in the abdominal aorta to cover the origins of lumbar arteries. Aneurysm occlusion rates by angiography (grade 1, complete occlusion; grade 2, near-complete occlusion; and grade 3, incomplete occlusion) were documented....
TL;DR: The results support the efficacy of programs incorporating mental practice for rehabilitating affected arm motor function in patients with chronic stroke and significant reductions in affected arm impairment and significant increases in daily arm function are clinically significant.
Abstract: Background and Purpose— Mental practice (MP) of a particular motor skill has repeatedly been shown to activate the same musculature and neural areas as physical practice of the skill. Pilot study results suggest that a rehabilitation program incorporating MP of valued motor skills in chronic stroke patients provides sufficient repetitive practice to increase affected arm use and function. This Phase 2 study compared efficacy of a rehabilitation program incorporating MP of specific arm movements to a placebo condition using randomized controlled methods and an appropriate sample size.
Method— Thirty-two chronic stroke patients (mean=3.6 years) with moderate motor deficits received 30-minute therapy sessions occurring 2 days/week for 6 weeks, and emphasizing activities of daily living. Subjects randomly assigned to the experimental condition also received 30-minute MP sessions provided directly after therapy requiring daily MP of the activities of daily living; subjects assigned to the control group received the same amount of therapist interaction as the experimental group, and a sham intervention directly after therapy, consisting of relaxation. Outcomes were evaluated by a blinded rater using the Action Research Arm test and the upper extremity section of the Fugl-Meyer Assessment.
Results— No pre-existing group differences were found on any demographic variable or movement scale. Subjects receiving MP showed significant reductions in affected arm impairment and significant increases in daily arm function (both at the P <0.0001 level). Only patients in the group receiving MP exhibited new ability to perform valued activities.
Conclusions— The results support the efficacy of programs incorporating mental practice for rehabilitating affected arm motor function in patients with chronic stroke. These changes are clinically significant.
TL;DR: In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.
Abstract: Background and Purpose— The purpose of this study was to assess the safety and performance of the Wingspan stent system and Gateway percutaneous transluminal angioplasty balloon catheter in the treatment of high-grade, intracranial atherosclerotic lesions in patients who had failed medical therapy. Methods— In this prospective, multicenter, single-arm study, medically refractory patients with a modified Rankin score ≤3 and recurrent symptoms attributable to angiographically demonstrated intracranial stenosis ≥50% in a vessel 2.5 to 4.5 mm in diameter were enrolled. Intracranial lesions were predilated with an undersized Gateway balloon catheter to 80% of the native vessel diameter, followed by deployment of the self-expanding Wingspan stent to facilitate further remodeling of the atherosclerotic plaque and to maintain vessel patency. Neurologic examinations and angiograms were performed at 6 months after the procedure. Results— Among the 45 patients enrolled, the degree of stenosis was reduced from a baseline of 74.9±9.8% to 31.9±13.6% after stenting and 28±23.2% at the 6-month follow-up. The 30-day composite ipsilateral stroke/death rate was 4.5% (2/44); at the 6-month follow-up, the ipsilateral stroke/death rate was 7.0%, the rate for all strokes was 9.7%, and all-cause mortality was 2.3%. Physician-reported follow-up in 43 patients (average of 13 months) conducted outside the study protocol (not adjudicated by the clinical event committee) reported 1 additional ipsilateral stroke. Conclusions— In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.
TL;DR: Clinical evidence is emerging demonstrating that stroke-induced immunodepression in humans not only exists, but has very similar features to those characterized in rodent experiments.
Abstract: Stroke affects the normally well-balanced interplay of the 2 supersystems: the nervous and the immune system Recent research elucidated some of the involved signals and mechanisms and, importantly, was able to demonstrate that brain-immune interactions are highly relevant for functional outcome after stroke Immunodepression after stroke increases the susceptibility to infection, the most relevant complication in stroke patients However, immunodepression after stroke may also have beneficial effects, for example, by suppressing autoaggressive responses during lesion-induced exposure of central nervous system-specific antigens to the immune system Thus, before immunomodulatory therapy can be applied to stroke patients, we need to understand better the interaction of brain and immune system after focal cerebral ischemia Until then, anticipating an important consequence of stroke-induced immunodepression, bacterial infection, preventive antibiotic strategies have been proposed In mouse experiments, preventive antibiotic treatment dramatically improves mortality and outcome Results of clinical studies on this issue are contradictory at present, and larger trials are needed to settle the question whether (and which) stroke patients should be preventively treated Nevertheless, clinical evidence is emerging demonstrating that stroke-induced immunodepression in humans not only exists, but has very similar features to those characterized in rodent experiments
TL;DR: The vasculature plays an important role for long-term striatal neurogenesis after stroke, and during several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density.
Abstract: Background and Purpose - Stroke induced by middle cerebral artery occlusion (MCAO) causes long-term formation of new striatal neurons from stem/progenitor cells in the subventricular zone (SVZ). We explored whether MCAO leads to hypoxia, changes in vessel density, and angiogenesis in the ipsilateral SVZ and adjacent striatum, and determined the relation between the migrating neuroblasts and the vasculature. Methods - Adult rats were subjected to 2 hours of MCAO. Hypoxia was studied by injecting Hypoxyprobe-1 during MCAO or 6 weeks later. Vessel density and length was estimated using stereology. New cells were labeled with 5'-bromo-2' deoxyuridine (BrdU) during weeks 1 and 2 or 7 and 8 after MCAO, and angiogenesis was assessed immunohistochemically with antibodies against BrdU and endothelial cell markers. Distance from neuroblasts to nearest vessel was measured using confocal microscopy. Results - The ischemic insult caused transient hypoxia and early, low-grade angiogenesis, but no damage or increase of vascular density in the SVZ. Angiogenesis was detected during the first 2 weeks in the dorsomedial striatum adjacent to the SVZ, which also showed long-lasting increase of vascularization. At 2, 6, and 16 weeks after MCAO, the majority of neuroblasts migrated through this area toward the damage, closely associated with blood vessels. Conclusions - The vasculature plays an important role for long-term striatal neurogenesis after stroke. During several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density. Optimizing vascularization should be an important strategy to promote neurogenesis and repair after stroke.
TL;DR: The role of BDNF is consolidated as a modulator of neurogenesis in the brain and as an enhancer of long-term functional neurological outcome after cerebral ischemia.
Abstract: Background and Purpose— The discovery of spontaneous neuronal replacement in the adult brain has shifted experimental stroke therapies toward a combined approach of preventing neuronal cell death a...
TL;DR: In a general population, carotid plaque area was a stronger predictor of first-ever myocardial infarction than was IMT, andCarotid atherosclerosis was a strong risk factor for MI in women than in men.
Abstract: Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). Methods— IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. Results— During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more ech...
TL;DR: An automated version of the SSS-TOAST, the Causative Classification System (CCS), is presented to facilitate its utility in multicenter settings and allows rapid analysis of patient data with excellent intra- and inter-examiner reliability, suggesting a potential utility in improving the fidelity of stroke classification in multicEnter trials or research databases in which accurate subtyping is critical.
Abstract: Background and Purpose— The SSS-TOAST is an evidence-based classification algorithm for acute ischemic stroke designed to determine the most likely etiology in the presence of multiple competing mechanisms. In this article, we present an automated version of the SSS-TOAST, the Causative Classification System (CCS), to facilitate its utility in multicenter settings. Methods— The CCS is a web-based system that consists of questionnaire-style classification scheme for ischemic stroke (http://ccs.martinos.org). Data entry is provided via checkboxes indicating results of clinical and diagnostic evaluations. The automated algorithm reports the stroke subtype and a description of the classification rationale. We evaluated the reliability of the system via assessment of 50 consecutive patients with ischemic stroke by 5 neurologists from 4 academic stroke centers. Results— The kappa value for inter-examiner agreement was 0.86 (95% CI, 0.81 to 0.91) for the 5-item CCS (large artery atherosclerosis, cardio-aortic em...
TL;DR: Although there was no difference between groups in gain of functional scores, the Lokomat group showed an advantage of robotic training over conventional physiotherapy in improvement of gait abnormality and body tissue composition.
Abstract: Background and Purpose— The success of gait rehabilitation after stroke depends on active walking exercises. However, the disabling after-effects of stroke often make such exercises impossible at the onset of therapy. To facilitate treadmill training of paraparetic patients, a robot-driven gait orthosis (Lokomat) was developed. We investigated the effects of the Lokomat when used with hemiparetic patients. Methods— The authors conducted a randomized, controlled pilot study of 30 acute stroke survivors. The treatment group received 30 minutes of robotic training daily and the control group 30 minutes of conventional physiotherapy daily in addition to 30 minutes of conventional physiotherapy for each group. Outcome measures were independence of gait, gait speed, gait parameters, and body tissue composition. Results— After 4 weeks of therapy, the walking ability of the Lokomat group and the control group expressed as the functional ambulation classification was significantly improved. The functional ambulati...
TL;DR: Activation of Rac and subsequently of the gp91phox containing NADPH oxidase promotes cerebral ROS formation, which then leads to Rho kinase–mediated endothelial cell contraction and disruption of the BBB, and inhibition of NAPDH oxidase is a promising approach to reduce brain injury after stroke.
Abstract: Background and Purpose—Cerebral ischemia/reperfusion is associated with reactive oxygen species (ROS) generation, and NADPH oxidases are important sources of ROS. We hypothesized that NADPH oxidases mediate blood-brain barrier (BBB) disruption and contribute to tissue damage in ischemia/reperfusion. Methods—Ischemia was induced by filament occlusion of the middle cerebral artery in mice for 2 hours followed by reperfusion. BBB permeability was measured by Evans blue extravasation. Monolayer permeability was determined from transendothelial electrical resistance of cultured porcine brain capillary endothelial cells. Results—BBB permeability was increased in the ischemic hemisphere 1 hour after reperfusion. In NADPH oxidase– knockout (gp91phox / ) mice, middle cerebral artery occlusion–induced BBB disruption and lesion volume were largely attenuated compared with those in wild-type mice. Inhibition of NADPH oxidase by apocynin prevented BBB damage. In porcine brain capillary endothelial cells, hypoxia/reoxygenation induced translocation of the NADPH oxidase activator Rac-1 to the membrane. In vivo inhibition of Rac-1 by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin or Clostridium difficile lethal toxin B also prevented the ischemia/reperfusion–induced BBB disruption. Stimulation of porcine brain capillary endothelial cells with H2O2 increased permeability, an effect attenuated by inhibition of phosphatidyl inositol 3-kinase or c-Jun N-terminal kinase but not blockade of extracellular signal–regulated kinase-1/2 or p38 mitogen-activated protein kinase. Inhibition of Rho kinase completely prevented the ROS-induced increase in permeability and the ROS-induced polymerization of the actin cytoskeleton. Conclusions—Activation of Rac and subsequently of the gp91phox containing NADPH oxidase promotes cerebral ROS formation, which then leads to Rho kinase–mediated endothelial cell contraction and disruption of the BBB. Inhibition of NAPDH oxidase is a promising approach to reduce brain injury after stroke. (Stroke. 2007;38:3000-3006.)
TL;DR: A growing number of studies highlight the potential of stem cell transplantation as a novel therapeutic approach for stroke, and the need to determine parameters that are critical for transplantation success is emphasized.
Abstract: No treatment currently exists to restore lost neurological function after stroke. A growing number of studies highlight the potential of stem cell transplantation as a novel therapeutic approach for stroke. In this review we summarize these studies, discuss potential mechanisms of action of the transplanted cells, and emphasize the need to determine parameters that are critical for transplantation success.