Christianson, Teresa J.

Background and Purpose— Transient ischemic attacks are a frequent diagnosis in the emergency department setting, yet expert opinion as to the proper follow-up and need for hospitalization differs widely. Recently, an effort has been made to risk-stratify patients presenting with transient ischemic attacks through scoring systems such as the ABCD and ABCD2 scales. The aim of our study was to independently validate these scores using a population-based cohort. Methods— Using the data from the Rochester Stroke and Transient Ischemic Attack Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, Minn, with a diagnosis of incident transient ischemic attack from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The end points of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data. Results— Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9 of 36 cases [25%]) occurred in patients with low or intermediate risk scores (≤4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days. Conclusions— Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a transient ischemic attack. Adding hyperglycemia and a history of hypertension to the predictive model could be useful, but the value of these additions need to be evaluated further.

Background Treatment group imbalances in baseline stroke severity in the NINDS intravenous t-PA for acute stroke treatment trial led to controversy regarding the efficacy of tissue plasminogen activator (t-PA) in the treatment of acute ischemic stroke. Purpose Describe the steps used to independently re-evaluate this trial. Methods NIH appointed an independent multidisciplinary committee that gained access to the original data. We undertook analyses of t-PA efficacy accounting for this imbalance, as well as analyses to identify subgroups that experienced additional harm or benefit from t-PA. Analyses of time from stroke onset to treatment (OTT), blood pressure, and intracerebral hemorrhage are given as illustrations. Results Despite subgroup imbalances in baseline stroke severity, when t-PA was administered to acute ischemic stroke patients according to study protocol, there was a statistically significant and clinically important benefit of t-PA treatment resulting in a higher likelihood of having a favorable clinical outcome at 3 months. Moreover, we were unable to identify subgroups of patients between which t-PA treatment effect differed, albeit these analyses had low power. These data failed to support the NINDS investigators' conclusion that effect of t-PA therapy diminished with increasing values of OTT within the protocol-specified 3 h time limit. In addition, the blood pressure measurements were highly variable and inconsistently determined so as to be too unreliable for inclusion in analysis. Conclusion With new NIH requirements for data-sharing, the frequency of re-analysis of clinical trial data may increase substantially. This re-evaluation provides a blueprint for future re-evaluations of other trials. These best practices include re-analysis of the study data, after suitable replication, by an independent multidisciplinary committee, including a skilled statistical programmer analyst. Primary investigators should address significant errors determined in such re-analyses. Clinical Trials 2008; 5: 308—315. http://ctj.sagepub.com

Object The authors reviewed the long-term outcome of focal resection in a large group of patients who had intractable partial nonlesional epilepsy, including mesial temporal lobe sclerosis (MTS), and who were treated consecutively at a single institution. The goal of this study was to evaluate the long-term efficacy of epilepsy surgery and the preoperative factors associated with seizure outcome. Methods This retrospective analysis included 399 consecutive patients who underwent epilepsy surgery at Mayo Clinic in Rochester, Minnesota, between 1988 and 1996. The mean age of the patients at surgery was 32 ± 12 years (range 3–69 years), and the mean age at seizure onset was 12 ± 11 years (range 0–55 years). There were 214 female (54%) and 185 male (46%) patients. The mean duration of epilepsy was 20 ±12 years (range 1–56 years). The preceding values are given as the mean ± standard deviation. Of the 399 patients, 237 (59%) had a history of complex partial seizures, 119 (30%) had generalized seizures, 26 (6%) had simple partial seizures, and 17 (4%) had experienced a combination of these. Preoperative evaluation included a routine and video-electroencephalography recordings, magnetic resonance imaging of the head according to the seizure protocol, neuropsychological testing, and a sodium amobarbital study. Patients with an undefined epileptogenic focus and discordant preoperative studies underwent an intracranial study. The mean duration of follow up was 6.2 ± 4.5 years (range 0.6–15.7 years). Seizure outcome was categorized based on the modified Engel classification. Time-to-event analysis was performed using Kaplan–Meier curves and Cox regression models to evaluate the risk factors associated with outcomes. Among these patients, 372 (93%) underwent temporal and 27 (7%) had extratemporal resection of their epileptogenic focus. Histopathological examination of the resected specimens revealed MTS in 113 patients (28%), gliosis in 237 (59%), and normal findings in 49 (12%). Based on the Kaplan–Meier analysis, the probability of an Engel Class I outcome (seizure free, auras, or seizures related only to medication withdrawal) for the overall patient group was 81% (95% confidence interval [CI] 77–85%) at 6 months, 78% (CI 74–82%) at 1 year, 76% (CI 72–80%) at 2 years, 74% (CI 69–78%) at 5 years, and 72% (CI 67–77%) at 10 years postoperatively. The rate of Class I outcomes remained 72% for 73 patients with more than 10 years of follow up. If a patient was in Class I at 1 year postoperatively, the probability of seizure remission at 10 years postoperatively was 92% (95% CI 89–96%); almost all seizures occurred during the 1st year after surgery. Factors predictive of poor outcome from surgery were normal pathological findings in resected tissue (p = 0.038), male sex (p = 0.035), previous surgery (p < 0.001), and an extratemporal origin of seizures (p < 0.001). Conclusions The response to epilepsy surgery during the 1st follow-up year is a reliable indicator of the long-term Engel Class I postoperative outcome. This finding may have important implications for patient counseling and postoperative discontinuation of anticonvulsant medications.

Background and Purpose— Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee “to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial.” Methods— The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA. Results— A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences. Conclusions— These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.