Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. METHODS: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. RESULTS: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. CONCLUSIONS: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

Fluid-attenuated inversion recovery vascular hyperintensities: an important imaging marker for cerebrovascular disease.

Vascular hyperintensities have been noted on FLAIR sequences obtained in the setting of acute stroke and intracranial steno-occlusive disease. The presence of FVHs likely represents disordered blood flow, often from collaterals distal to arterial occlusion or stenosis. As opposed to other vessel signs seen in arterial insufficiency, FVH is unique in that it does not represent thrombus, but rather sluggish or disordered blood flow through vessels. This review will discuss the diagnostic and prognostic value of FVH and its impact on clinical decision-making.

Angiography reveals that fluid-attenuated inversion recovery vascular hyperintensities are due to slow flow, not thrombus.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are commonly encountered on MR imaging studies performed shortly after the onset of acute ischemic stroke. Prior reports have speculated regarding the pathogenesis of this finding, yet definitive correlative angiographic studies have not been performed. We studied the pathophysiologic and hemodynamic correlates of FVH on conventional angiography and concurrent MR imaging sequences. MATERIALS AND METHODS: Retrospective review of FLAIR and gradient-refocused echo MR imaging sequences acquired immediately before conventional angiography for acute stroke was conducted in a blinded fashion. The presence, location, and morphology of FVH were noted and correlated with markers of thrombotic occlusion and collateral flow on angiography. Angiographic collaterals were graded on a 5-point scale incorporating extent and hemodynamic aspects. RESULTS: A prospective ischemic stroke registry of 632 patients was searched to identify 74 patients (mean age, 63.4 +/- 20 years; 48% women) having undergone FLAIR sequences immediately before angiography. Median time from FLAIR to angiography was 2.9 hours (interquartile range, 1.1-4.7 hours). FVH were present in 53/74 (72%) of all acute stroke cases with subsequent angiography. FVH distal to an arterial occlusion were associated with a high grade of leptomeningeal collateral blood flow. CONCLUSIONS: FVH are observed in areas of blood flow proximal and distal to stenosis or occlusion and are noted with more extensive collateral circulation.

Are elevated admission calcium levels associated with better outcomes after ischemic stroke?

Calcium (Ca(2+)) and magnesium (Mg(2+)) influence the molecular pathways of ischemic neuronal death. The authors evaluated the impact of admission serum Ca(2+) and Mg(2+) levels, on incident stroke severity and discharge functional outcome. After adjusting for covariates, higher admission Ca(2+) was significantly associated with lesser stroke severity and better discharge functional outcome. Admission Mg(2+) was not an independent clinical outcome prognosticator.

Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke.

Recent data suggest that women obtain greater benefit than men from IV fibrinolysis for acute ischemic stroke. It is unknown whether this gender-thrombolysis advantage extends to those treated with intra-arterial (IA) thrombolysis. The authors evaluated the independent effect of gender among ischemic stroke patients treated with IA fibrinolysis and found no differences in short-term clinical and angiographic outcomes between men and women who received IA thrombolysis for acute ischemic stroke.

Premorbid antiplatelet use and ischemic stroke outcomes.

OBJECTIVE: To evaluate the independent effect of premorbid antiplatelet use on incident ischemic stroke severity and outcome at discharge. METHODS: The authors studied consecutive patients presenting within 24 hours of ischemic stroke over a 1-year period. National Institutes of Health Stroke Scale (NIHSS) score at presentation was used as index of stroke severity and a modified Rankin scale of 0 to 1 at discharge as index of good functional outcome. Patients were categorized according to their premorbid antiplatelet use as antiplatelet-inclusive (AI) and no antiplatelet (NA). Demographic data, risk factors, pertinent laboratory tests, other medications, and stroke mechanisms were controlled for across the two groups using multivariate logistic regression. RESULTS: A total of 260 individuals met study criteria: 92 patients were on antiplatelet agents prior to admission, 168 were on no antiplatelets. Pretreatment with antiplatelet was associated with lower presenting median NIHSS (4.5 vs 7, p = 0.005). Antiplatelet use was associated with less severe stroke at presentation in those having no history of stroke or TIA (4.8 vs 8.0, p = 0.03) but not in those with a prior history of stroke or TIA (4.9 vs 4.9, p = 0.987). The likelihood of a good outcome was increased in those on antiplatelets after adjusting for other variables (OR 2.105, p = 0.0073). CONCLUSIONS: Prestroke use of antiplatelet may be associated with reduced severity of incident ischemic strokes in those with no prior history of stroke or TIA, and with an increased likelihood of a good discharge outcome regardless of prior cerebrovascular event history.