The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals.
Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] # 4 points from baseline or NIHSS 5 0) and major neurologic improvement (NIHSS # 8 points from baseline or NIHSS 5 0) at 7 days and favorable (modified Rankin Scale [mRS] # 2) and excellent functional outcome (mRS # 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS $ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS $ 4 points from baseline or death within 36 hours, and 3-month death. Statins are recommended for primary and secondary stroke prevention in patients at risk of cerebrovascular events.
Results1 In addition to reducing the risk of first and recurrent ischemic stroke, statin treatment may also improve outcome through pleiotropic non-cholesterol-dependent effects.
2An association between statin use before stroke and favorable outcome has been previously reported.3-5 Moreover, a prospective clinical trial showed that statin withdrawal during the first 3 days after a stroke event was associated with increased risk of death or dependency at 3 months. 6 To date, very few studies have investigated the effect of statin use in the acute phase on ischemic stroke outcome.7-9 The Stroke Prevention with Aggressive Reductions in Cholesterol Levels (SPARCL) trial showed a trend toward less severity for outcome 90 days after stroke with atorvastatin administration (80 mg), compared with placebo, in patients having a stroke during the trial.
10So far, few studies have assessed the efficacy and safety of statin treatment in ischemic stroke patients treated with IV thrombolysis. Two recent meta-analyses showed that prior statin use may increase the risk of symptomatic intracerebral hemorrhage (sICH) within 36 hours after IV recombinant tissue plasminogen activator (rtPA), though without influencing 3-month functional outcome. 11,12 Two large observational studies reported that previous treatment with statin was not an independent predictor of functional outcome or of ICH. 13,14 The aim of the THRombolysis and STatins (THRaST) study was to assess the impact of statin use in the acute phase of ischemic stroke on clinical outcome in patients treated with IV thrombolysis.Authors' affiliations are listed at the end of the article. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
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