Oliver C. Singer

Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke

BACKGROUND Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. METHODS We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). RESULTS The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). CONCLUSIONS In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

Human Motor Corpus Callosum: Topography, Somatotopy, and Link between Microstructure and Function

The corpus callosum (CC) is the principal white matter fiber bundle connecting neocortical areas of the two hemispheres. Although an object of extensive research, important details about the anatomical and functional organization of the human CC are still largely unknown. Here we focused on the callosal motor fibers (CMFs) that connect the primary motor cortices (M1) of the two hemispheres. Topography and somatotopy of CMFs were explored by using a combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure. CMF microstructure was assessed by fractional anisotropy (FA), and CMF functional connectivity between the hand areas of M1 was measured by interhemispheric inhibition using paired-pulse transcranial magnetic stimulation. CMFs mapped onto the posterior body and isthmus of the CC, with hand CMFs running significantly more anteriorly and ventrally than foot CMFs. FA of the hand CMFs but not FA of the foot CMFs correlated linearly with interhemispheric inhibition between the M1 hand areas. Findings demonstrate that CMFs connecting defined body representations of M1 map onto a circumscribed region in the CC in a somatotopically organized manner. The significant and topographically specific positive correlation between FA and interhemispheric inhibition strongly suggests that microstructure can be directly linked to functional connectivity. This provides a novel way of exploring human brain function that may allow prediction of functional connectivity from variability of microstructure in healthy individuals, and potentially, abnormality of functional connectivity in neurological or psychiatric patients.

MRI-Based and CT-Based Thrombolytic Therapy in Acute Stroke Within and Beyond Established Time Windows An Analysis of 1210 Patients

Background and Purpose— The use of intravenous thrombolysis is restricted to a minority of patients by the rigid 3-hour time window. This window may be extended by using modern imaging-based selection algorithms. We assessed safety and efficacy of MRI-based thrombolysis within and beyond 3 hours compared with standard CT-based thrombolysis. Methods— Five European stroke centers pooled the core data of their CT- and MRI-based prospective thrombolysis databases. Safety outcomes were predefined as symptomatic intracranial hemorrhage and mortality. Primary efficacy outcome was a favorable outcome (modified Rankin Scale 0 to 1). We performed univariate and multivariate analyses for all end points, including age, National Institutes of Health Stroke Scale, treatment group (CT <3 hours, MRI <3 hours and >3 hours), and onset to treatment time as variables. Results— A total of 1210 patients were included (CT <3 hours: N=714; MRI <3 hours: N=316; MRI >3 hours: N=180). Median age, National Institutes of Health Stroke Scale, and onset to treatment time were 69, 67, and 68.5 years (P=0.66); 12, 13, and 14 points (P=0.019); and 130, 135, and 240 minutes (P<0.001). Symptomatic intracranial hemorrhage rates were 5.3%, 2.8%, and 4.4% (P=0.213); mortality was 13.7%, 11.7%, and 13.3% (P=0.68). Favorable outcome occurred in 35.4%, 37.0%, and 40% (P=0.51). Age and National Institutes of Health Stroke Scale were independent predictors for all safety and efficacy outcomes. The overall use of MRI significantly reduced symptomatic intracranial hemorrhage (OR: 0.520, 95% CI: 0.270 to 0.999, P=0.05). Beyond 3 hours, the use of MRI significantly predicted a favorable outcome (OR: 1.467; 95% CI: 1.017 to 2.117, P=0.040). Within 3 hours and for all secondary end points, there was a trend in favor of MRI-based selection over standard <3-hour CT-based treatment. Conclusion— Despite significantly longer time windows and significantly higher baseline National Institutes of Health Stroke Scale scores, MRI-based thrombolysis is safer and potentially more efficacious than standard CT-based thrombolysis.

Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging†

The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion‐weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis.

Serum S100B Predicts a Malignant Course of Infarction in Patients With Acute Middle Cerebral Artery Occlusion

Background and Purpose— Early predictors of infarct volume may improve therapeutic decisions in patients with acute cerebral ischemia. We investigated whether measurements of serum astroglial protein S100B can predict a malignant course of infarction in acute middle cerebral artery (MCA) occlusion. Methods— We included 51 patients (24 women, mean age 69.1±12.4 years) admitted within 6 hours after stroke symptom onset caused by proximal MCA occlusion, as shown by magnetic resonance angiography (n=39), intra-arterial angiography (n=4), or transcranial duplex sonography (n=8). Blood samples were drawn at hospital admission and 8, 12, 16, 20, and 24 hours after symptom onset. Serum S100B concentrations were determined using a fully automated immunoluminometric assay. A malignant course of infarction was defined as the occurrence of clinical signs of cerebral herniation within the first 7 days of treatment or the clinical decision to perform decompressive hemicraniectomy caused by critical space-occupying swelling as detected by repeated neuroimaging. Results— Sixteen patients developed malignant infarction (31%). Beginning with the 12-hour value, mean S100B serum concentrations were significantly higher in patients with a malignant course compared with those without (12 hours 1.23±1.24 versus 0.29±0.45 μg/L; 16 hours 1.80±1.65 versus 0.38±0.53 μg/L; 20 hours 1.90±1.53 versus 0.44±0.48 μg/L; and 24 hours 2.41±1.59 versus 0.57±0.66 μg/L; all P <0.001). A 12-hour S100B value >0.35 μg/L predicted malignant infarction with 0.75 sensitivity and 0.80 specificity. A 24-hour value >1.03 μg/L provided 0.94 sensitivity and 0.83 specificity. Conclusions— The serum marker S100B can predict a malignant course of infarction in proximal MCA occlusion. This finding may improve the identification and monitoring of patients at particularly high risk for herniation.

Effect of Incomplete (Spontaneous and Postthrombolytic) Recanalization After Middle Cerebral Artery Occlusion A Magnetic Resonance Imaging Study

Background and Purpose— Early reperfusion is one of the best predictors of good outcome after acute middle cerebral artery (MCA) occlusion. The purpose of this study was to analyze the frequency and relevance of incomplete recanalization for tissue and clinical outcome. Methods— From a larger acute stroke database (Kompetenznetzwerk Schlaganfall B5), all patients (n=82) with MCA main stem occlusion (excluding carotid T-occlusions) were selected. These patients had received a multiparametric stroke MRI protocol including diffusion- and perfusion-weighted imaging (DWI, PWI) and MR angiography (MRA) within 6 hours after symptom onset, at day 1 and after 1 week. Recanalization status was determined with MRA on day 1 (according to Thrombolysis In Myocardial Infarction flow grades) and used to group patients into those with persistent occlusion (0) or minimal (1), partial (2), or complete (3) recanalization. Results— Incomplete recanalization according to MRI criteria was found in 39 patients (grade 1: n=20; grade 2: n=19), complete recanalization in 10, and persistent occlusion in 33. There was no statistically significant difference in any of the clinical (National Institutes of Health Stroke Scale score) or MRI baseline parameters (DWI lesion, PWI deficit, mismatch volume, mismatch ratio). However, lesion growth was smaller in patients with recanalization (even in patients with only minimal recanalization) and outcome was related to the degree of recanalization (mean modified Rankin score at 90 days: 3.36, 2.70, 1.79, and 1.44 for the groups with no, minimal, partial, and complete recanalization, respectively). Both incomplete and complete recanalization was more frequent in patients receiving thrombolysis. Conclusions— Incomplete recanalization on day 1 is a frequent MR finding after MCA main stem occlusion, indicating a more favorable clinical course than persistent occlusion. MR indicators of early recanalization could be useful surrogates of efficacy in thrombolytic trials.

Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study

Early identification of patients at risk of space‐occupying “malignant” middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life‐saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset.

Mechanical recanalization in basilar artery occlusion: The ENDOSTROKE study

A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion.

Practical limitations of acute stroke MRI due to patient-related problems

Patient-related factors may make MRI impractical in an emergency setting. The authors prospectively assessed the limitations on obtaining MRI in 141 consecutive acute stroke patients. MRI was not feasible in 28 (19.9%) patients owing to patient-related issues. Apart from MR contraindications (n = 14; 9.9%), the main factors precluding MRI were a diminished level of consciousness, vomiting, agitation, and hemodynamic compromise. In the subgroup of patients ineligible for MRI because of medical reasons (n = 11), intracerebral hemorrhage was frequent (n = 9; 73%).

A Simple 3-Item Stroke Scale: Comparison With the National Institutes of Health Stroke Scale and Prediction of Middle Cerebral Artery Occlusion

Background and Purpose— The purpose of the study was to design a simple stroke scale that requires minimal training but reflects initial stroke severity and is predictive of middle cerebral artery (MCA) occlusion. Methods— The new stroke scale assessed 3 parameters: (1) level of consciousness, (2) gaze, and (3) motor function. Each item was graded 0 to 2, where 0 indicated normal findings and 2 severe abnormalities (ie, profound drowsiness or worse, forced gaze deviation, and severe hemiparesis, respectively). During a study period of 11 months, patients presenting with acute stroke symptoms (onset ≤6 hours) were examined by a stroke neurologist assessing the new scale as well as the National Institutes of Health Stroke Scale (NIHSS). In addition, 83 patients received acute magnetic resonance angiography (MRA; as part of an acute stroke protocol). Results— The new stroke scale was strongly associated with the NIHSS. Interobserver reliability of the new scale was high (intraclass correlation coefficient 0.947). Using post hoc analysis, a score of ≥4 predicted proximal vessel occlusion (T-segment or M1-segment occlusion of the MCA on MRA) almost as accurately (overall accuracy 0.86) as an NIHSS score of ≥14 (overall accuracy 0.93). Conclusions— The new stroke scale reflects acute stroke severity well and predicts proximal MCA occlusion with reasonable accuracy. However, the clinical scale needs further evaluation before it can be recommended as a tool for the triage of acute stroke patients.