Background and Purpose— Convincing evidence of a causal relationship between sleep apnea and stroke has been shown recently in several prospective, well-designed studies. However, these studies have focused on middle-aged people, excluding the elderly population from analysis. To investigate whether sleep apnea represents an independent risk factor in this population, we performed a prospective longitudinal study in a population-based cohort of subjects from 70 to 100 years old. Methods— Within the context of the Vitoria Sleep Project, a population-based study designed to investigate the prevalence of sleep apnea in the population of Vitoria, Spain, we performed a 6-year longitudinal study in a subsample cohort of 394 noninstitutionalized, initially event-free subjects (70 to 100 years old, median 77.28 years, 57.1% males). Demographic and polysomnographic data and known confounding factors (age, sex, smoking and alcohol consumption status, body mass index, systolic and diastolic blood pressure, total serum cholesterol levels, and the presence or absence of diabetes mellitus, atrial fibrillation, and hypertension) were assessed at baseline. Hazard ratio for developing an ischemic stroke in relation to the apnea-hypopnea index at baseline was calculated. Results— Over the 6-year follow-up period, 20 ischemic strokes were registered. After adjustment for confounding factors, subjects with severe obstructive sleep apnea hypopnea (defined as apnea-hypopnea index ≥30) at baseline had an increased risk of developing a stroke (hazard ratio=2.52, 95% CI=1.04 to 6.01, P =0.04). Conclusions— This study shows that severe obstructive sleep apnea hypopnea (defined as apnea-hypopnea index ≥30) increases the risk of ischemic stroke in the elderly population, independent of known confounding factors.

Background: Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim: To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods: Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0–2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results: The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08–34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06–226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions: Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.

Thrombotic material retrieved from acute ischemic stroke (AIS) patients represents a valuable source of biological information. In this study, we have developed a clinical proteomics workflow to characterize the protein cargo of thrombi derived from AIS patients. To analyze the thrombus proteome in a large-scale format, we developed a workflow that combines the isolation of thrombus by endovascular thrombectomy and peptide chromatographic fractionation coupled to mass-spectrometry. Using this workflow, we have characterized a specific proteomic expression profile derived from four AIS patients included in this study. Around 1600 protein species were unambiguously identified in the analyzed material. Functional bioinformatics analyses were performed, emphasizing a clustering of proteins with immunological functions as well as cardiopathy-related proteins with blood-cell dependent functions and peripheral vascular processes. In addition, we established a reference proteomic fingerprint of 341 proteins commonly detected in all patients. Protein interactome network of this subproteome revealed protein clusters involved in the interaction of fibronectin with 14-3-3 proteins, TGFβ signaling, and TCP complex network. Taken together, our data contributes to the repertoire of the human thrombus proteome, serving as a reference library to increase our knowledge about the molecular basis of thrombus derived from AIS patients, paving the way toward the establishment of a quantitative approach necessary to detect and characterize potential novel biomarkers in the stroke field.

The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological examination of her offspring showed thalamic and olivary degeneration with isolated focal cortical spongiosis. Genetic examination could only be performed in the contemporary patients and both harboured the prion protein (PrP) 178Asn mutation and homozygous 129 Met/Met genotype.

Muñoz R, Durán-Cantolla J, Martinez-Vila E, Gállego J, Rubio R, Aizpuru F, De La Torre G, Barbé F. Central sleep apnea and risk of stroke in the elderly. Acta Neurol Scand: 2012: 126: 183–188. © 2011 John Wiley & Sons A/S. Objectives – Sleep apnea/hypopnea syndrome is a well-recognized independent risk factor for stroke in middle-aged population, but controversy remains in older subjects. We examined the possible association between different respiratory parameters and risk of stroke in a prospective population-based cohort of 394 stroke-free elderly subjects. Material and Methods – Fully overnight polysomnography was performed at baseline. Over the 6 year follow-up period, 20 ischemic strokes occurred. Differences in stroke-free survival between subjects according to central apnea index (CAI) were assessed. Results – We just observed association with incident ischemic stroke on central sleep apnea (CSA) episodes. Obstructive sleep apnea, time passed under 90% oxygen saturation, or arousal index were not associated. The event-free survival was lowest in the highest CAI group. This association was independent of any other vascular risk factors. Conclusions – CSA is the specific respiratory event associated with stroke in the elderly. Additionally, CSA could be a marker of silent brain ischemia, as a sign of disturbed regulation of central respiratory mechanisms, tentatively of ischemic origin.