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.