Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. 5-12 Experimental and clinical data also provide some evidence that statins may have neuroprotective effects after acute cerebral ischemia. [7][8][9][10][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In animal models, treatment with statins either before, or early after, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function. [5][6][7][8][9][10]13,14 Data are conflicting regarding the relationship between acute statin therapy and outcome after human ischemic stroke. Some authors have reported improved survival and functional outcome associated with statin treatment, but these findings have not been consistently replicated. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][31][32][33][34][35][36] Interpretations can be difficult because of limited sample sizes in some reports and possible bias in statin allocation in other studies, particularly those in which statins were allocated in a nonrandomized fashion. Some authors have also reported worse outcomes in patients treated with the combination of acute statins and intravenous thro...

BackgroundThe development of intracranial hemorrhage (ICH) in acute ischemic stroke is associated with a higher neutrophil to lymphocyte ratio (NLR) in peripheral blood. Here, we studied whether the predictive value of NLR at admission also translates into the occurrence of hemorrhagic complications and poor functional outcome after endovascular treatment (EVT).MethodsWe performed a retrospective analysis of consecutive patients with anterior circulation ischemic stroke who underwent EVT at a tertiary care center from 2012 to 2016. Follow-up scans were examined for non-procedural ICH and scored according to the Heidelberg Bleeding Classification. Demographic, clinical, and laboratory data were correlated with the occurrence of non-procedural ICH.ResultsWe identified 187 patients with a median age of 74 years (interquartile range [IQR] 60–81) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 18 (IQR 13–22). A bridging therapy with recombinant tissue-plasminogen activator (rt-PA) was performed in 133 (71%). Of the 31 patients with non-procedural ICH (16.6%), 13 (41.9%) were symptomatic. Patients with ICH more commonly had a worse outcome at 3 months (p = 0.049), and were characterized by a lower body mass index, more frequent presence of tandem occlusions, higher NLR, larger intracranial thrombus, and prolonged rt-PA and groin puncture times. In a multivariate analysis, higher admission NLR was independently associated with ICH (OR 1.09 per unit increase, 95% CI (1.00–1.20, p = 0.040). The optimal cutoff value of NLR that best distinguished the development of ICH was 3.89.ConclusionsNLR is an independent predictor for the development of ICH after EVT. Further studies are needed to investigate the role of the immune system in hemorrhagic complications following EVT, and confirm the value of NLR as a potential biomarker.

Background: In Central/Eastern European countries, cerebrovascular diseases are among the leading causes of mortality. We aimed to determine the incidence of first-ever stroke (FES) in the north-western part of Croatia. Methods: A population-based prospective incidence study was conducted between July 1, 2007, and June 30, 2009. Cases were sought from multiple overlapping sources. Incidence rates by stroke type and gender were calculated. Results: A total of 1,487 events were recorded, 1,017 of which were FESs. European age-adjusted incidence rates (per 100,000 population) were: total FESs 223.6 [women/men rate ratio (w/m RR) = 0.65 (95% CI 0.57–0.73)]; ischemic stroke 162.4 (w/m RR = 0.65, 0.56–0.76); intracerebral hemorrhage 28.4 (w/m RR = 0.44, 0.30–0.63); subarachnoid hemorrhage 7.2 (w/m RR = 1.18, 0.55–2.54); unknown etiology 25.5 (w/m RR = 0.78, 0.54–1.14). Adjusted incidence rates of ischemic strokes by subtype were: cardioembolic 52.9 (w/m RR = 0.77, 0.59–0.99); large-artery atherosclerosis 14.4 (w/m RR = 0.22, 0.13–0.38); small-artery occlusion 24.5 (w/m RR = 0.53, 0.37–0.77) and ‘other or uncertain causes’ 70.6 (w/m RR = 0.77, 0.62–0.97). Thirty-day case-fatality rate was 23.5% overall and 17.1% for ischemic stroke. Conclusions: The incidence of FES and 30-day mortality of patients with ischemic strokes in the studied population is higher than in Western European countries.

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Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab. Nivolumab targets the immune-check point inhibitor programmed cell death-1 and was used for squamous non-small cell lung cancer. Partly reversible neurologic and psychiatric symptoms and unremarkable brain magnetic resonance imaging (MRI) were observed after the first course. Neurological symptoms progressed and recurrent seizures developed after the second course. Brain MRI disclosed multiple edematous and confluent supra- and infratentorial lesions, partly with contrast-enhancement. We excluded autoimmune and paraneoplastic causes and performed ancillary investigations to rule out common and opportunistic infections. Eventually, postmortem histopathological analysis of the brain revealed a necrotizing process, which contrasts previous cases reporting parenchymal immune cell infiltration or demyelination. Appropriate diagnostic pathways and treatment algorithms need to be implemented for the work-up of CNS toxicity and irAEs related to immune checkpoint inhibitor treatment.