Transcranial ultrasonography can identify the children with sickle cell disease who are at highest risk for cerebral infarction. Periodic ultrasound examinations and the selective use of transfusion therapy could make the primary prevention of stroke an achievable goal.

Stroke is an important complication of sickle cell disease. Stroke prediction is clinically important because it offers the possibility of primary prevention. In 1992, transcranial Doppler (TCD) evidence of elevated intracranial internal carotid or middle cerebral artery velocity was demonstrated to be associated strongly with an increased risk of ischemic stroke. This study extends the original study and includes 125 more children, longer follow-up, and intracranial hemorrhage in the stroke-risk model. Elevated time averaged mean maximum blood flow velocity, especially when velocity is 200 cm/sec or greater by TCD, was associated strongly with stroke risk. The cases not predicted by TCD point to the need for more information on the optimal timing of TCD surveillance for stroke risk.

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Background Minocycline is a promising anti-inflammatory and protease inhibitor that is effective in multiple pre-clinical stroke models. We conducted an early phase trial of intravenous (IV) minocycline in acute ischemic stroke. Methods Following an open label, dose escalation design, minocycline was administered IV within 6 hours of stroke symptom onset in preset dose tiers of 3, 4.5, 6, or 10 mg/kg daily over 72 hours. Minocycline concentrations for pharmacokinetic analysis were measured in a subset of patients. Subjects were followed for 90 days. Results Sixty patients were enrolled, 41 at the highest dose tier of 10 mg/kg. Overall age (65±13.7), race (83% white) and sex (47% female) were consistent across the doses. The mean baseline NIHSS was 8.5±5.8 and 60% received tPA. Minocycline infusion was well tolerated with only 1 dose limiting toxicity at the 10 mg/kg dose. No severe hemorrhages occurred in tPA treated patients. Pharmacokinetic analysis (n=22) revealed a half life of about 24 hours and linearity of parameters over doses. Conclusions 1.) Minocycline is safe and well tolerated up to doses of 10 mg/kg IV alone and in combination with tPA. 2.) The half life of minocycline is about 24 hours, allowing every 24 hour dosing. 3.) Minocycline may be an ideal agent to use with tPA.

Background and Purpose-The modified Rankin Scale (mRS) is a popular primary stroke outcome measure, but its usefulness is limited by suboptimal reliability (inter-rater agreement). Methods-We developed and tested the reliability of a simplified mRS questionnaire (smRSq) in 50 patients after stroke seen in outpatient clinics. Randomly chosen paired raters administered the smRSq within 20 minutes of each other and the ratings were blinded until the end of this study. Results-Agreement among the raters was 78%, the statistic was 0.72 (95% CI, 0.58 -0.86), and the weighted w statistic taking into account the extent of disagreement was 0.82 (95% CI, 0.72-0.92). The average time to administer the smRSq was 1.67 minutes. Conclusions-The smRSq appears to have very good reliability that is similar to that of a structured interview mRS and is considerably less time-consuming. (Stroke. 2010;41:1048-1050.)Key Words: clinometrics Ⅲ modified Rankin Scale Ⅲ outcome assessment R eliability (consistency) of measurements is of paramount importance in scientific research. 1 The modified Rankin Scale (mRS) 2 is a popular primary outcome measure in acute stroke trials, but its usefulness is limited by suboptimal reliability (inter-rater agreement). There is considerable variability in the reported reliability of the mRS. 3 A structured interview mRS that takes Ϸ15 minutes to administer was developed to help improve the mRS reliability. 4 In a recent systematic review the overall agreement between mRS raters without a standardized rating approach was 71%, the kappa () statistic was 0.46 (95% CI, 0.41-0.51), and the weighted kappa ( w ) statistic, taking into account the extent of all disagreements, was 0.90 (95% CI, 0.86 -0.94). 3 Using the structured interview mRS, the overall agreement was Ϸ73%, was 0.62 (95% CI, 0.56 -0.69), and w was 0.87 (95% CI, 0.75-1.00). 3,5,6 Inter-rater agreement was significantly improved with the structured interview mRS among raters with varied professional backgrounds, 7 which simulates a multicenter clinical trial. In an effort to simplify, standardize, and increase further the reliability of the mRS, we developed a simplified mRS questionnaire (smRSq) and tested it among raters with varied professional experiences. Materials and MethodsFour stroke faculty members with a total of 63 years experience applying the traditional unstructured mRS jointly created the smRSq (Figure). Using the key issues distinguishing between consecutive mRS categories, we created relatively simple questions that could be answered "yes" or "no" by patients or caregivers with little or no explanation. The key mRS issues were having no residual symptoms (0), being able to resume all prestroke activities (Յ1), being able to live independently (Յ2), being able to walk without assistance (Յ3), and not requiring constant supervision (Յ4).We screened patients for this study consecutively in 4 weekly clinics staffed by the stroke specialists and in 2 weekly resident continuity clinics at the Medical College of Georgia. Eligibility f...

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We studied heart rate following unilateral hemispheric inactivation by intracarotid amobarbital in 25 patients undergoing preoperative evaluation for epilepsy surgery. Heart rate increased after left hemisphere inactivation, but decreased following right hemisphere inactivation. The results are consistent with differential left/right cerebral hemispheric effects on autonomic function, and appear related to functional and anatomic asymmetries in both the central and peripheral nervous systems.

The Stroke Prevention Trial in Sickle Cell Anemia (STOP) was a randomized multicenter controlled trial comparing prophylactic blood transfusion with standard care in sickle cell anemia (SCA) children aged 2 to 16 years selected for high stroke risk by transcranial Doppler (TCD). More than 2000 children were screened with TCD to identify the 130 high-risk children who entered the randomized trial. A total of 5613 TCD studies from 2324 children were evaluated. We also collected information on stroke. We describe the changes in TCD with repeated testing and report the outcome without transfusion in the STOP screened cohort. Risk of stroke was higher with abnormal TCD than with normal or conditional TCD (P < .001) or inadequate TCD (P ‫؍‬ .002), and risk with conditional TCD was higher than with normal TCD (P < .001). Repeated TCD in 1215 children showed that the condition of 9.4% of children became abnormal during observation. Younger patients and those with higher initial flow velocities were most likely to convert to abnormal TCDs. Screening in STOP confirmed the predictive value of TCD for stroke. Substantial differences in the probability of conversion to abnormal TCD were observed, with younger children and those with higher velocity more likely to have an abnormal TCD with rescreening.