Elizabeth A. Noser

Constraint-Induced Movement Therapy During Early Stroke Rehabilitation

Background. Limited data are available about the effectiveness of early rehabilitation after stroke. Objective. This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome. Methods. Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand. Results. Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS. Conclusions. Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere.

Is Intra-Arterial Thrombolysis Safe After Full-Dose Intravenous Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke?

Background and Purpose— The optimal approach for acute ischemic stroke patients who do not respond to intravenous recombinant tissue plasminogen activator (IV rt-PA) is uncertain. This study evaluated the safety and response to intra-arterial thrombolytics (IATs) in patients unresponsive to full-dose IV rt-PA. Methods— A case series from a prospectively collected database on consecutive acute ischemic stroke patients treated with IATs after 0.9 mg/kg IV rt-PA during a 7-year interval was collected. Primary outcome measures included symptomatic intracranial hemorrhage and mortality. As indicators of response, secondary outcome measures were recanalization and discharge disposition. Results— Sixty-nine patients (mean±SD age, 60±13 years; range, 26 to 85 years; 55% male) with a median pretreatment National Institutes of Health Stroke Scale score of 18 (range, 6 to 39) were included. IV rt-PA was started at 124±32 minutes (median, 120 minutes) and IAT, at 288±57 minutes (median, 285 minutes). IATs consisted of reteplase (n=56), alteplase (n=7), and urokinase (n=6), with an average total dosage of 2.8 U, 8.6 mg, and 700 000 U, respectively. Symptomatic intracranial hemorrhage occurred in 4 of 69 (5.8%) patients; 3 cases were fatal. Recanalization was achieved in 50 (72.5%) and a favorable outcome (home or inpatient rehabilitation) in 38 (55%). Conclusions— IAT therapy after full-dose IV rt-PA in patients with persisting occlusion and/or lack of clinical improvement appears safe compared with IV rt-PA alone or low-dose IV rt-PA followed by IAT. A high rate of recanalization and favorable outcome can be achieved.

Yield and Accuracy of Urgent Combined Carotid/Transcranial Ultrasound Testing in Acute Cerebral Ischemia

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

Intraventricular hemorrhage: Anatomic relationships and clinical implications

Background: Spontaneous intracerebral hemorrhage (ICH) is frequently associated with intraventricular hemorrhage (IVH), which is an independent predictor of poor outcome. The purpose of this study was to examine the relationship between ICH volume and anatomic location to IVH, and to determine if ICH decompression into the ventricle is truly beneficial. Methods: We retrospectively analyzed the CT scans and charts of all patients with ICH admitted to our stroke center over a 3-year period. Outcome data were collected using our prospective stroke registry. Results: We identified 406 patients with ICH. A total of 45% had IVH. Thalamic and caudate locations had the highest IVH frequency (69% and 100%). ICH volume and ICH location were predictors of IVH (p < 0.001). Within each location, decompression ranges (specific volume ranges where ventricular rupture tends to occur) were established. Patients with IVH were twice as likely to have a poor outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when compared to patients without IVH. Caudate location was associated with a good outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was not associated with better outcome, regardless of parenchymal volume reduction (p = 0.72). Conclusions: Intraventricular hemorrhage (IVH) occurs in nearly half of patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH volume and location. IVH is likely to occur within the “decompression ranges” that take into account both ICH location and volume. Further, spontaneous ventricular decompression does not translate to better clinical outcome. This information may prove useful for future ICH trials, and to the clinician communicating with patients and families. GLOSSARY: ANOVA = analysis of variance; EVD = external ventricular drainage; HSD = honestly significant differences; ICC = interclass correlation coefficient; ICH = intracerebral hemorrhage; IVH = intraventricular hemorrhage; LOS = length of stay; mRS = modified Rankin Scale.

Thrombus Burden Is Associated With Clinical Outcome After Intra-Arterial Therapy for Acute Ischemic Stroke

Background and Purpose— Studies have established a relation between recanalization and improved clinical outcome in acute ischemic stroke patients; however, intra-arterial clot size has not been routinely assessed. The aim of the study was to determine the impact of intra-arterial thrombus burden on intra-arterial treatment (IAT) and clinical outcome. Methods— A retrospective review of our IAT stroke database included procedure time, recanalization, symptomatic intracranial hemorrhage, poor outcome (modified Rankin Scale score ≥4 at discharge), and mortality. The modified Thrombolysis in Myocardial Infarction thrombus grade was dichotomized into grades 0 to 3 (no clot or moderate thrombus, <2 vessel diameters) versus grade 4 (large thrombus, >2 vessel diameters). Results— Data were collected on 135 patients with thrombus grading. The baseline median National Institutes of Health Stroke Scale score was higher in patients of grade 4 compared with grades 0 to 3 (19 vs 17, P=0.012). Grade 4 thrombi required longer (median, range) times for IAT (113, 37 to 415 minutes vs 74, 22 to 215 minutes, respectively; P<0.001) and higher rates of mechanical clot disruption (wire, angioplasty, snare, stent, or Merci retriever) compared with grades 0 to 3 (76% vs 53%, P=0.005). There were no differences in rates of symptomatic intracranial hemorrhage (6.6% vs 4.1%, P=0.701) or recanalization (50% vs 61%, P=0.216) in grade 4 versus grades 0 to 3. Multivariate analysis adjusted for age, baseline National Institutes of Health Stroke Scale score, and artery of involvement showed that grade 4 thrombi were independently associated with poor outcome (odds ratio=2.4; 95% CI, 1.06 to 5.57; P=0.036) and mortality (odds ratio=4.0; 95% CI, 1.2 to 13.2; P=0.023). Conclusions— High thrombus grade as measured by the modified Thrombolysis in Myocardial Infarction criteria may be a risk factor that contributes to poor clinical outcome.

Functional Reorganization and Recovery After Constraint-Induced Movement Therapy in Subacute Stroke: Case Reports

Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke. This research was supported by a US PHS grant to Harvey Levin. We thank Magda Jungman, Eva Salmeron, Jenny Lai, and Thao Tran for assisting with patient enrollment, therapy, and assessment testing, Courtney Russell, Gurpreet Sarao, and Vibha Tare for coordinating the project, Christine Joy and Elizabeth Pienkos for assistance with collecting the TMS data, David Lane for statistical advice, and the patients for their patience and willingness to participate in this study. Scott Burgin is now at the University of Rochester.

Benefits of Stroke Treatment Using a Mobile Stroke Unit Compared With Standard Management The BEST-MSU Study Run-In Phase

Background and Purpose— Faster treatment with intravenous tissue-type plasminogen activator (tPA) is likely to improve outcomes. Optimizing prehospital triage by mobile stroke units (MSUs) may speed treatment times. The Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit (BEST-MSU) study was launched in May 2014 using the first MSU in the United States to compare stroke management using an MSU versus standard management (SM). Herein, we describe the results of the prespecified, nonrandomized run-in phase designed to obtain preliminary data on study logistics. Methods— The run-in phase consisted of 8 MSU weeks when all-patient care occurred on the MSU and 2 SM weeks when the MSU nurse met personnel on scene or at the emergency department to ensure comparability with MSU patients. Telemedicine was independently performed in 9 MSU cases. Results— Of 130 alerts, 24 MSU and 2 SM patients were enrolled. Twelve of 24 MSU patients received tPA on board; 4 were treated within 60 minutes of last seen normal, and 4 went on to endovascular treatment. There were no hemorrhagic complications. Four had primary intracerebral hemorrhage. Agreement on tPA eligibility between the onsite and telemedicine physician was 90%. Conclusions— The run-in phase provided a tPA treatment rate of 1.5 patients per week, assured us that treatment within 60 minutes of onset is possible, and enabled enrollment of patients on SM weeks. We also recognized the opportunity to assess the effect of the MSU on endovascular treatment and intracerebral hemorrhage. Challenges include the need to control biased patient selection on MSU versus SM weeks and establish inter-rater agreement for tPA treatment using telemedicine.

Thrombolytic Therapy in an Adolescent Ischemic Stroke

We report the case of a 16-year-old Caucasian girl who developed acute onset of left hemiplegia, left hemisensory deficit, and dysarthria. After a negative computed tomographic scan of the brain, the patient was given intravenous recombinant tissue plasminogen activator according to established adult guidelines. The patient experienced a marked improvement within 24 hours. Stroke etiology was determined to be a paradoxical embolus via a patent foramen ovale associated with pelvic vein thrombosis. This case illustrates the importance of early recognition of stroke and the utility of thrombolytics in treating ischemic infarcts in the adolescent population. (J Child Neurol 2001;16:286-288).

Establishing the First Mobile Stroke Unit in the United States

Background and Purpose— Recently, the Mobile Stroke Unit (MSU) concept was introduced in Germany demonstrating prehospital treatment of more patients within the first hour of symptom onset. However, the details and complexities of establishing such a program in the United States are unknown. We describe the steps involved in setting up the first MSU in the United States. Methods— Implementation included establishing leadership, fund-raising, purchase and build-out, knitting a collaborative consortium of community stakeholders, writing protocols to ensure accountability, radiation safety, purchasing supplies, licensing, insurance, establishing a base station, developing a communication plan with city Emergency Medical Services, Emergency Medical Service training, staffing, and designing a research protocol. Results— The MSU was introduced after ≈1 year of preparation. Major obstacles to establishing the MSU were primarily obtaining funding, licensure, documenting radiation safety protocols, and establishing a smooth communication system with Emergency Medical Services. During an 8 week run-in phase, ≈2 patients were treated with recombinant tissue-type plasminogen activator per week, one-third within 60 minutes of symptom onset, with no complications. A randomized study to determine clinical outcomes, telemedicine reliability and accuracy, and cost effectiveness was formulated and has begun. Conclusion— The first MSU in the United States has been introduced in Houston, TX. The steps needed to accomplish this are described.

Anticoagulation After Cardioembolic Stroke: To Bridge or Not to Bridge?

BACKGROUND Most patients with cardioembolic stroke require long-term anticoagulation. Still, uncertainty exists regarding the best mode of starting long-term anticoagulation. Design, Setting, and Patients We conducted a retrospective review of all patients with cardioembolic stroke admitted to our center from April 1, 2004, to June 30, 2006, and not treated with tissue plasminogen activator. Patients were grouped by treatment: no treatment, aspirin only, aspirin followed by warfarin sodium, intravenous heparin sodium in the acute phase followed by warfarin (heparin bridging), and full-dose enoxaparin sodium combined with warfarin (enoxaparin bridging). Outcome measures and adverse events were collected prospectively. Laboratory values were captured from the records. MAIN OUTCOME MEASURES Symptomatic hemorrhagic transformation, stroke progression, and discharge modified Rankin Scale score. RESULTS Two hundred four patients were analyzed. Recurrent stroke occurred in 2 patients (1%). Progressive stroke was the most frequent serious adverse event, seen in 11 patients (5%). Hemorrhagic transformation occurred in a bimodal distribution-an early benign hemorrhagic transformation and a late symptomatic hemorrhagic transformation. All of the symptomatic hemorrhagic transformation cases were in the enoxaparin bridging group (10%) (P = .003). Systemic bleeding occurred in 2 patients (1%) and was associated with heparin bridging (P = .04). CONCLUSIONS Anticoagulation of patients with cardioembolic stroke can be safely started with warfarin shortly after stroke. Heparin bridging and enoxaparin bridging increase the risk for serious bleeding.