Brett C. Meyer

A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear. METHODS In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead). RESULTS Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14). CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.).

A Review of the Evidence for the Use of Telemedicine Within Stroke Systems of Care A Scientific Statement From the American Heart Association/American Stroke Association

The aim of this new statement is to provide a comprehensive and evidence-based review of the scientific data evaluating the use of telemedicine for stroke care delivery and to provide consensus recommendations based on the available evidence. The evidence is organized and presented within the context of the American Heart Association’s Stroke Systems of Care framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class of evidence. Evidence-based recommendations are included for the use of telemedicine in general neurological assessment and primary prevention of stroke; notification and response of emergency medical services; acute stroke treatment, including the hyperacute and emergency department phases; hospital-based subacute stroke treatment and secondary prevention; and rehabilitation.

A Modified National Institutes of Health Stroke Scale for Use in Stroke Clinical Trials Preliminary Reliability and Validity

Background and Purpose— The National Institutes of Health Stroke Scale (NIHSS) is accepted widely for measuring acute stroke deficits in clinical trials, but it contains items that exhibit poor reliability or do not contribute meaningful information. To improve the scale for use in clinical research, we used formal clinimetric analyses to derive a modified version, the mNIHSS. We then sought to demonstrate the validity and reliability of the new mNIHSS. Methods— The mNIHSS was derived from our prior clinimetric studies of the NIHSS by deleting poorly reproducible or redundant items (level of consciousness, face weakness, ataxia, dysarthria) and collapsing the sensory item into 2 responses. Reliability of the mNIHSS was assessed with the certification data originally collected to assess the reliability of investigators in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA (recombinant tissue plasminogen activator) Stroke Trial. Validity of the mNIHSS was assessed with the outcome results of the NINDS rtPA Stroke Trial. Results— Reliability was improved with the mNIHSS: the number of scale items with poor &kgr; coefficients on either of the certification tapes decreased from 8 (20%) to 3 (14%) with the mNIHSS. With the use of factor analysis, the structure underlying the mNIHSS was found identical to the original scale. On serial use of the scale, goodness of fit coefficients were higher with the mNIHSS. With data from part I of the trial data, the proportion of patients who improved ≥4 points within 24 hours after treatment was statistically significantly increased by tPA (odds ratio, 1.3; 95% confidence limits, 1.0, 1.8;P =0.05). Likewise, the odds ratio for complete/nearly complete resolution of stroke symptoms 3 months after treatment was 1.7 (95% confidence limits, 1.2, 2.6) with the mNIHSS. Other outcomes showed the same agreement when the mNIHSS was compared with the original scale. The mNIHSS showed good responsiveness, ie, was useful in differentiating patients likely to hemorrhage or have a good outcome after stroke. Conclusions— The mNIHSS appears to be identical clinimetrically to the original NIHSS when the same data are used for validation and reliability. Power appears to be greater with the mNIHSS with the use of 24-hour end points, suggesting the need for fewer patients in trials designed to detect treatment effects comparable to rtPA. The mNIHSS contains fewer items and might be simpler to use in clinical research trials. Prospective analysis of reliability and validity, with the use of an independently collected cohort, must be obtained before the mNIHSS is used in a research setting.

Efficacy of site-independent telemedicine in the STRokE DOC trial: a randomised, blinded, prospective study

BACKGROUND To increase the effective use of thrombolytics for acute stroke, the expertise of vascular neurologists must be disseminated more widely. We prospectively assessed whether telemedicine (real-time, two-way audio and video, and digital imaging and communications in medicine [DICOM] interpretation) or telephone was superior for decision making in acute telemedicine consultations. METHODS From January, 2004, to August, 2007, patients older than 18 years who presented with acute stroke symptoms at one of four remote spoke sites were randomly assigned, through a web-based, permuted blocks system, to telemedicine or telephone consultation to assess their suitability for treatment with thrombolytics, on the basis of standard criteria. The primary outcome measure was whether the decision to give thrombolytic treatment was correct, as determined by central adjudication. Secondary outcomes were the rate of thrombolytic use, 90-day functional outcomes (Barthel index [BI] and modified Rankin scale [mRS]), the incidence of intracerebral haemorrhages, and technical observations. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00283868. FINDINGS 234 patients were assessed prospectively. 111 patients were randomised to telemedicine, and 111 patients were randomised to telephone consultation; 207 completed the study. Mean National Institutes of Health stroke scale score at presentation was 9.5 (SD 8.1) points (11.4 [8.7] points in the telemedicine group versus 7.7 [7.0] points in the telephone group; p=0.002). One telemedicine consultation was aborted for technical reasons, although it was included in the analyses. Correct treatment decisions were made more often in the telemedicine group than in the telephone group (108 [98%] vs 91 [82%], odds ratio [OR] 10.9, 95% CI 2.7-44.6; p=0.0009). Intravenous thrombolytics were used at an overall rate of 25% (31 [28%] telemedicine vs 25 [23%] telephone, 1.3, 0.7-2.5; p=0.43). 90-day functional outcomes were not different for BI (95-100) (0.6, 0.4-1.1; p=0.13) or for mRS score (0.6, 0.3-1.1; p=0.09). There was no difference in mortality (1.6, 0.8-3.4; p=0.27) or rates of intracerebral haemorrhage after treatment with thrombolytics (2 [7%] telemedicine vs 2 [8%] telephone, 0.8, 0.1-6.3; p=1.0). However, there were more incomplete data in the telephone group than in the telemedicine group (12%vs 3%, 0.2, 0.1-0.3; p=0.0001). INTERPRETATION The authors of this trial report that stroke telemedicine consultations result in more accurate decision making compared with telephone consultations and can serve as a model for the effectiveness of telemedicine in other medical specialties. The more appropriate decisions, high rates of thrombolysis use, improved data collection, low rate of intracerebral haemorrhage, low technical complications, and favourable time requirements all support the efficacy of telemedicine for making treatment decisions, and might enable more practitioners to use this medium in daily stroke care.

Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) Final Results

Background and Purpose— Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. Methods— Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results– In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). Conclusion— This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

Recommendations for the Implementation of Telemedicine Within Stroke Systems of Care A Policy Statement From the American Heart Association

In 2005, the American Stroke Association formed a task force on the development of stroke systems to propose a new framework for stroke care delivery that would emphasize linkages rather than silos in the chain of stroke survival and provide a blueprint for large organizations or state and federal agencies on how to implement a more coordinated approach to stroke care.1 The stroke systems of care model (SSCM) recommends implementation of telemedicine and aeromedical transport to increase access to acute stroke care in neurologically underserved areas, as do the latest American Stroke Association guidelines for the early management of adults with ischemic stroke.2 The present report was commissioned by the American Heart Association to address how telemedicine might help address current barriers to improved stroke care delivery in the United States within the framework of the SSCM. Telemedicine has been defined broadly as “the use of telecommunications technologies to provide medical information and services” (p 483).3 Technically, this encompasses all aspects of medicine practiced at a distance, including use of telephone, fax, and electronic mail technology, as well as the use of interactive full-motion integrated video and audio, that brings together patients and providers separated by distance.4 In the early part of the twentieth century, electrocardiograms and electroencephalograms were transmitted over ordinary analogue telephone lines, and in 1920, medical advice service for sea craft via Morse code and voice radio was established. Expensive and cumbersome 2-way closed-circuit television systems used in the 1960s to transmit radiographs and evaluate patients have been replaced by low-cost, personal computer–based solutions for videoconferencing and transmission of physiological data from clinics or patient homes or from inaccessible sites such as ships, aircraft, and geographically remote regions.5 Telemedicine has been proposed as an alternative means of managing many different diseases and …

Prospective reliability of the STRokE DOC wireless/site independent telemedicine system.

The San Diego wireless telemedicine stroke evaluation arrangement described by Meyer et al.1 is unusual. Our similar REACH (Remote Evaluation of Acute isCHemic stroke) system at the Medical College of Georgia (MCG) uses secure Internet connections to evaluate acute stroke patients in rural hospitals of north central Georgia in the Nations “stroke belt.” Like the San Diego system, REACH uses any broadband (DSL or cable modem) Internet accessible computer, nationwide. However, without a broadband wireless bubble over Augusta, Georgia, consulting …The authors evaluated a site-independent telemedicine system. Telemedicine may be limited by the need for fixed connectivity. Wireless and site-independent technologies eliminate this limitation. Twenty-five stroke patients underwent evaluations by remote and bedside examiners. Ten of 15 (67%) NIH Stroke Scale and 9 of 11 (82%) Modified NIH Stroke Scale items showed excellent interrater reliability. Spearman correlations were > or =0.93. This Internet system is reliable and valid. Further studies should assess its use in acute stroke.

NIHSS Training and Certification Using a New Digital Video Disk Is Reliable

Background and Purpose— NIH Stroke Scale certification is required for participation in modern stroke clinical trials and as part of good clinical care in stroke centers. The existing training and certification videotapes, however, are more than 10 years old and do not contain an adequate balance of patient findings. Methods— After producing a new NIHSS training and demonstration DVD, we selected 18 patients representing all possible scores on 15 scale items for a new certification DVD. Patients were divided into 3 certification groups of 6 patients each, balanced for lesion side, distribution of scale item findings, and total score. We sought to measure interrater reliability of the certification DVD using methodology previously published for the original videotapes. Raters were recruited from 3 experienced stroke centers. Each rater watched the new training DVD and then evaluated one of the 3 certification groups. Results— Responses were received from 112 raters: 26.2% of all responses came from stroke nurses, 34.1% from emergency departments/other physicians, and 39.6% from neurologists. One half (50%) of raters were previously NIHSS-certified. Item responses were tabulated, scoring performed as previously published, and agreement measured with unweighted &kgr; coefficients for individual items and an intraclass correlation coefficient for the overall score. &kgr; ranged from 0.21±0.05 (ataxia) to 0.92±0.09 (LOC-C questions). Of 15 items, 2 showed poor, 11 moderate, and 2 excellent agreement based on &kgr; scores. The intraclass correlation coefficient for total score was 0.94 (95% confidence interval, 0.84 to 1.00). Reliability scores were similar among specialists and centers, and there were no differences between nurses and physicians. &kgr; scores trended higher among raters previously certified. Conclusions— These certification DVDs are reliable for NIHSS certification, and scoring sheets have been posted on a web site for real-time, online certification.

Identification of Nonischemic Stroke Mimics Among 411 Code Strokes at the University of California, San Diego, Stroke Center

BACKGROUND Code Stroke systems are widely used to expedite emergency treatment of patients with stroke. Code Stroke for mimic patients-those without a stroke cause-wastes resources. We investigated how many times a Code Stroke was initiated for patients who did not have a stroke appropriate for thrombolysis. METHODS We conducted a retrospective review of the discharge diagnoses of all patients who presented to our emergency department as a Code Stroke. A patient was considered a stroke mimic if a stroke code was activated, but none of the first 3 International Classification of Diseases, Ninth Revision codes on discharge were transient ischemic attack-related or ischemic stroke-related. RESULTS A total of 411 patients presented to the emergency department as Code Stroke. In all, 104 (25.3%) were discharged without a diagnosis of stroke or transient ischemic attack. The diagnoses in this group were intracranial hemorrhage in 19 patients, subarachnoid hemorrhage 6, subdural hematoma 3, old deficit 11, hypotension 11, seizure 10, intoxication 8, hypoglycemia 7, mass lesion 6, migraine 5, and other 18. In all, 33 of 307 eligible patients (10.7%) were treated with tissue-type plasminogen activator. None of the patients with a stroke mimic received tissue-type plasminogen activator. In 44 of 104 stroke mimics (42.3%), the acute disease was caused by a severe neurologic condition other than ischemic cerebrovascular disease. Only 60 of 411 stroke codes (14.6%) were initiated for patients without a severe and acute neurologic condition. CONCLUSIONS In our community, 25.5% of all Code Strokes were initiated for stroke mimics. Most mimic patients had an illness likely to benefit from urgent neurologic evaluation.

Can comprehensive stroke centers erase the 'weekend effect'?

Background: Prior epidemiological work has shown higher mortality in ischemic stroke patients admitted on weekends, which has been termed the ‘weekend effect’. Our aim was to assess stroke patient outcomes in order to determine the significance of the ‘weekend effect’ at 2 comprehensive stroke centers. Methods: Consecutive stroke patients were identified using prospective databases. Patients were categorized into 4 groups: intracerebral hemorrhage (ICH group), ischemic strokes not treated with IV t-PA (intravenous tissue plasminogen activator; IS group), acute ischemic strokes treated with IV t-PA (AIS-TPA group), and transient ischemic attack (TIA group). Weekend admission was defined as the period from Friday, 17:01, to Monday, 08:59. Patients treated beyond the 3-hour window, receiving intra-arterial therapy, or enrolled in nonobservational clinical trials were excluded. Patient demographics, NIHSS scores, and admission glucose levels were examined. Adverse events, poor functional outcome (modified Rankin scale, mRS, 3–6), and mortality were compared. Results: A total of 2,211 patients were included (1,407 site 1, 804 site 2). Thirty-six percent (800/2,211) arrived on a weekend. No significant differences were found in the ICH, IS, AIS-TPA, or TIA groups with respect to the rate of symptomatic ICH, mRS on discharge, discharge disposition, 90-day mRS, or 90-day mortality when comparing weekend and weekday groups. Using multivariate logistic regression to adjust for site, age, admission NIHSS, and blood glucose, weekend admission was not a significant independent predictive factor for in-hospital mortality in all strokes (OR = 1.10, 95% CI 0.74–1.63, p = 0.631). Conclusions: Our results suggest that comprehensive stroke centers (CSC) may ameliorate the ‘weekend effect’ in stroke patients. These results may be due to 24/7 availability of stroke specialists, advanced neuroimaging, or ongoing training and surveillance of specialized nursing care available at CSC. While encouraging, these results require confirmation in prospective studies.