Previous ultrasound-based studies have shown an association between carotid artery atherosclerosis and dementia. Our aim was to investigate this association using postmortem examination.Methods—
Postmortem morphometric measurements of carotid stenosis and intima-media thickness were performed in individuals with dementia (n=112) and control subjects (n=577). Multivariate logistic regression models were applied.Results—
High-grade left internal carotid stenosis (≥70%) was associated with increased odds for dementia (OR, 2.30; 95% CI, 1.14–4.74; P=0.02). Intima-media thickness was not associated with dementia.Conclusions—
The likelihood of dementia is increased with high-grade left internal carotid artery atherosclerosis after adjusting for demographic and cardiovascular risk factors.
Elevated lipoprotein (a) concentration is associated with carotid atherosclerosis in middle-aged and older patients with ischemic stroke. This association has not been explored in young patients with stroke.Methods—
A retrospective analysis of data from patients aged 16 to 54 years consecutively treated for acute ischemic stroke in a tertiary stroke unit during 4.5 years was performed. We graded carotid atherosclerosis using carotid duplex as: no atherosclerosis (A); plaque without stenosis (B); or stenosis ≥50% (C).Results—
One hundred ninety-six patients were included (male/female: 119/77; mean age±SD: 44.3±8.6 years): 115 in Group A; 67 in Group B; and 14 in Group C. Multivariate analysis using polynomial logistic regression showed a graded association of lipoprotein (a) plasma concentration with carotid atherosclerosis (P<0.001).Conclusions—
Our results showed a positive association of lipoprotein (a) plasma concentration with carotid atherosclerosis in young adults with ischemic stroke. This association was strong, graded, and independent of traditional risk factors including cholesterol.
Little was known about the predictive accuracy of the Essen Stroke Risk Score and the Stroke Prognostic Instrument II in Chinese patients with stroke.Methods—
We evaluated the predictive accuracy of both Essen Stroke Risk Score and Stroke Prognostic Instrument II scores for both recurrent stroke and combined vascular events using data from a prospective cohort of 11 384 patients with acute ischemic stroke and transient ischemic attack admitted to 132 urban hospitals throughout China.Results—
The cumulative 1-year event rates were 16% (95% CI, 15%–16%) for recurrent stroke and 18% (95% CI, 18%–19%) for combined vascular events. Both event rates were significantly higher in patients with transient ischemic attack and increased significantly from lower to higher Essen Stroke Risk Score and Stroke Prognostic Instrument II categories. Essen Stroke Risk Score and Stroke Prognostic Instrument II had similar predictive accuracies for each study outcome.Conclusions—
In Chinese patients with ischemic stroke or transient ischemic attack, both Essen Stroke Risk Score and Stroke Prognostic Instrument II scores are equally able to stratify the risk of recurrent stroke and combined vascular events.
Fish consumption has been postulated to reduce the risk of stroke. We conducted a dose–response meta-analysis to summarize the evidence from prospective studies regarding the association between fish consumption and stroke risk.Methods—
Pertinent studies were identified by searching Embase and PubMed through May 2011 and by reviewing the references of retrieved articles. We included prospective studies that reported relative risks with 95% CIs of stroke for ≥3 categories of fish consumption. Results were combined using a random-effects model.Results—
Fifteen prospective studies, with 9360 stroke events among 383 838 participants, were included. An increment of 3 servings/week in fish consumption was associated with a 6% reduction in risk of total stroke (relative risk, 0.94; 95% CI, 0.89–0.99) without heterogeneity among studies (P=0.15, I2=25.7%). Among 9 studies with results for stroke subtypes, the relative risks were 0.90 (95% CI, 0.84–0.97) for ischemic stroke and 0.90 (95% CI, 0.76–1.06) for hemorrhagic stroke.Conclusions—
These findings indicate that fish consumption is weakly inversely associated with the risk of stroke.
Subarachnoid hemorrhage (SAH) pathophysiology involves neurovascular proteolysis and inflammation. How these 2 phenomena are related remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the depletion of anti-inflammatory plasma-type gelsolin (pGSN).Methods—
We enrolled 42 consecutive SAH subjects and sampled cerebrospinal fluid (CSF) and blood on post-SAH Days 2 to 3, 4 to 5, 6 to 7, and 10 to 14. Control subjects were 20 consecutive non-SAH hydrocephalus patients with lumbar drains. Enzyme-linked immunosorbent assay, Western blotting, and zymography were used to quantify pGSN and MMP-9.Results—
In CSF, pGSN was lower in SAH compared with control subjects on post-SAH Days 2 to 3 (P=0.0007), 4 to 5 (P=0.041), and 10 to 14 (P=0.007). In blood, pGSN decreased over time (P=0.001) and was lower in SAH compared with control subjects on post-SAH Days 4 to 5 (P=0.037), 6 to 7 (P=0.006), and 10 to 14 (P=0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and 46 kDa, representing cleaved pGSN fragments. Gelatin zymography showed that CSF MMP-9 was elevated in SAH compared with control subjects. Higher CSF MMP-9 correlated with lower CSF pGSN on post-SAH Day 7 (r=–0.38; P=0.05).Conclusions—
SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN cleavage by MMPs. Because pGSN is known to inhibit inflammatory mediators, these findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH. Further studies are warranted to investigate the mechanisms underlying MMP–pGSN signaling in SAH.
Dynamic cerebral autoregulation is impaired in subjects who develop acute mountain sickness (AMS), a neurological disorder characterized by headache. The present study examined if the normoxic sea-level measurement of dynamic cerebral autoregulation would predict subsequent susceptibility to AMS during rapid ascent to terrestrial high altitude.Methods—
A dynamic cerebral autoregulation index was determined in 18 subjects at sea level from continuous recordings of middle cerebral artery blood flow velocity (Doppler ultrasonography) and arterial blood pressure (finger photoplethysmography) after recovery from transiently induced hypotension. Six hours after passive ascent to 3800 m (Mt Elbrus, Russia), the Lake Louise and Environmental Symptoms Cerebral Symptoms questionnaires were used to assess AMS.Results—
AMS scores increased markedly at high-altitude (Lake Louise: +3±2 points, P=0.001 and Environmental Symptoms Cerebral Symptoms: +0.6±0.9 points, P=0.0003 versus sea level). Inverse relationships were observed between the sea-level autoregulation index score and the high-altitude-induced increases in the Lake Louise (r=–0.62, P=0.007) and Environmental Symptoms Cerebral Symptoms (r=–0.78, P=0.01) scores. One subject with a history of high-altitude pulmonary and cerebral edema presented with the lowest sea-level autoregulation index score (3.7 versus group: 6.2±1.0 points) and later developed high-altitude cerebral edema at 4800 m during the summit bid.Conclusions—
These findings suggest that a lower baseline autoregulation index may be considered a potential risk factor for AMS. This laboratory measurement may prove a useful screening tool for the expedition doctor when considering targeted pharmacological prophylaxis in individuals deemed "AMS-susceptible."
This is the first prospective evaluation of changes in systemic hematologic status following administration of intraventricular recombinant tissue-type plasminogen activator in patients with intraventricular hemorrhage (IVH).Methods—
Laboratory data from subjects enrolled onto the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) Trials were analyzed. We analyzed pre- and post- recombinant tissue-type plasminogen activator dosing coagulation parameters. Longer-term changes in hematologic status were studied in subjects who received the study agent after blood clot in the third/fourth ventricles had resolved radiologically.Results—
Plasma fibrinogen increased significantly in both treatment groups. Dosing did not have a significant impact on any systemic coagulation parameters in either treatment group.Conclusions—
Intraventricular recombinant tissue-type plasminogen activator is unlikely to impact systemic coagulation or to compound the effects of systemic anticoagulation for deep venous thrombosis prophylaxis.Clinical Trial Registration—
URL: http://clinicaltrials.gov. Unique identifier: NCT00650858.
Development of translational functional imaging modalities for atherosclerosis risk stratification is sought for stroke prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP-CEUS) to quantify microbubble contrast retention within carotid atherosclerosis and shown it to separate asymptomatic plaques from those responsible for recent cerebrovascular events. We hypothesized that microbubbles are retained in areas of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque biology.Methods—
Subjects awaiting carotid endarterectomy (n=31) underwent axial LP-CEUS and diseased intimal segments were symmetrically divided in the long axis. Half-specimens underwent quantitative immunohistochemical analysis for CD68 (macrophages) and CD31 (angiogenesis). Half-specimens were processed for atheroma cell culture and supernatant collected at 24 hours for multianalyte profiling for 34 analytes.Results—
Percentage area immunopositivity was significantly higher in subjects in which normalized plaque late-phase intensity was ≥0 versus <0 (CD68 mean 11.8 versus 6.68, P=0.004; CD31 mean 9.45 versus 4.82, P=0.025). Interleukin-6, matrix metalloproteinase-1, and matrix metalloproteinase-3 were significantly higher by multianalyte profiling when LP-CEUS was ≥0.Conclusions—
LP-CEUS reflects biological features of inflammation and angiogenesis, key features predisposing to plaque rupture. Further investigation of LP-CEUS as a tissue-specific marker of inflammation for risk stratification of carotid atherosclerosis is warranted.
The Carotid Occlusion Surgery Study (COSS) was an improvement over the Extracranial–Intracranial Bypass Study, which did not utilize physiological selection. To assess possible reasons for early closure of the COSS trial, we reviewed COSS methods used to identify high-risk patients and compared results with separate quantitative data.Methods—
Increased oxygen extraction fraction (OEF) by positron emission tomography is a gold standard for ischemia, but the specific thresholds and equivalency of the semiquantitative OEF ratio utilized in COSS and quantitative OEF are at issue.Results—
The semiquantitative hemispheric OEF ratio used in COSS did not identify the same group of patients as did quantitative OEF using a threshold of 50%.Conclusions—
The failure of COSS is likely caused by a failure of the semiquantitative, hemispheric OEF ratio method rather than by the selection for bypass based on hemodynamic compromise.
Although corticosteroid use in acute hemorrhagic stroke is not widely adopted, management with intravenous dexamethasone has been standard of care at the University Hospital of Heraklion, Crete with observed outcomes superior to those reported in the literature. To explore this further, we conducted a retrospective, multivariable-adjusted 2-center study.Methods—
We studied 391 acute hemorrhagic stroke cases admitted to the University Hospital of Heraklion, Crete between January 1997 and July 2010 and compared them with 510 acute hemorrhagic stroke cases admitted to Massachusetts General Hospital, Boston, from January 2003 to September 2009. Of the Cretan cases, 340 received a tapering scheme of intravenous dexamethasone, starting with 16 to 32 mg/day, whereas the Boston patients were managed without steroids.Results—
The 2 cohorts had comparable demographics and stroke severity on admission, although anticoagulation was more frequent in Boston. The in-hospital mortality was significantly lower on Crete (23.8%, n=340) than in Boston (38.0%, n=510; P<0.001) as was the 30-day mortality (Crete: 25.4%, n=307; Boston: 39.4%, n=510; P<0.001). Exclusion of patients on anticoagulants showed even greater differences (30-day mortality: Crete 20.8%; n=259; Boston 37.0%; n=359; P<0.001). The improved survival on Crete was observed 3 days after initiation of intravenous dexamethasone and was pronounced for deep-seated hemorrhages. After adjusting for acute hemorrhagic stroke volume/location, Glasgow Coma Scale, hypertension, diabetes mellitus, smoking, coronary artery disease and statin, antiplatelet, and anticoagulant use, intravenous dexamethasone treatment was associated with better functional outcomes and significantly lower risk of death at 30 days (OR, 0.357; 95% CI, 0.174–0.732).Conclusions—
This study suggests that intravenous dexamethasone improves outcome in acute hemorrhagic stroke and supports a randomized clinical trial using this approach.