In patients with refractory traumatic intracranial hypertension, decompressive craniectomy resulted in lower mortality but higher proportions of vegetative state and severe neurological impairment compared to ongoing medical management. Level of evidence: 1B (CEBM, Individual RCT of good quality)

Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.

Background-Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque.Current imaging techniques provide anatomic data but no indication of plaque inflammation. The current "gold standard" imaging technique for atherosclerosis is x-ray contrast angiography, which provides high-resolution definition of the site and severity of luminal stenoses, but no information about plaque inflammation.There is a need to quantify plaque inflammation to predict the risk of plaque rupture and to monitor the effects of atheroma-modifying therapies. This is important because recent experimental and clinical studies strongly suggest that hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) promote plaque stability by decreasing plaque macrophage content and activity without substantially reducing plaque size and therefore angiographic appearance. 4 [ 18 F]-fluorodeoxyglucose ( 18 FDG) is a glucose analogue that is taken up by cells in proportion to their metabolic activity. 5 We tested the hypothesis that plaque inflammation could be visualized and quantified non-invasively using 18 FDG-PET in patients with symptomatic carotid artery disease. Methods Patient RecruitmentWe recruited 8 patients who had experienced a recent carotidterritory transient ischemic attack and had an internal carotid artery stenosis of at least 70%. Patients were excluded if they had either carotid artery occlusion or diabetes. The study protocol was approved by the local ethics committee and the UK Administration of Radioactive Substances Advisory Committee. All patients gave written informed consent. PET ProtocolPET was carried out using a GE Advance PET scanner (GE Medical Systems). We administered 370 MBq 18 FDG intravenously over 60 seconds. PET images (as 4ϫ5 minute frames) were acquired in 3D mode, at 190 (Ϯ6) minutes after 18 FDG administration. This timepoint was chosen after preliminary dynamic studies indicated that late imaging provided optimal contrast between the 18 FDG concentration in plaque and the main background region, namely blood.A stiff cervical collar was worn to minimize patient movement. PET images were reconstructed using the 3D reprojection algorithm, 6 with corrections applied for attenuation, dead time, scatter, and random coincidences. Rigid body co-registration with CT was performed, using a combination of fiducial markers and internal anatomical landmarks (spinal cord and muscles of the jaw and neck). This resulted in co-registration typically to within 1 mm in each dimension around the stenosis. To estimate plaque 18 FDG concentration, three-dimensional volumes of interest (VOI) were drawn CT ProtocolUsing a GE Hispeed Advantage CT scanner (GE Medical Systems), helical contrast CT angiograms were acquired from skull base to 3 cm below the level of the carotid bifurcation. Plaque HistologyAfter imaging, carotid endarterectomy samples from all 8 patients imaged were fixed and stained with hematoxylin and eosin. Immunohistochemistry was performed using anti-macr...

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Background and Purpose-Statins may improve cerebral vasomotor reactivity through cholesterol-dependent and -independent mechanisms. A phase II randomized controlled trial was conducted to examine the hypothesis that acute pravastatin treatment could improve cerebrovascular autoregulation and reduce vasospasm-related complications after aneurysmal subarachnoid hemorrhage (SAH). Methods-A total of 80 aneurysmal SAH (aSAH) patients (18 to 84 years of age) within 72 hours from the ictus were randomized equally to receive either oral pravastatin (40 mg) or placebo daily for up to 14 days. Primary end points were the incidence, duration, and severity of cerebral vasospasm, and duration of impaired autoregulation estimated from transcranial Doppler ultrasonography. Secondary end points were the incidence of vasospasm-related delayed ischemic deficits (DIDs) and disability at discharge. Results-Prerandomization characteristics were balanced between the 2 groups. No treatment-related complication was observed. The incidences of vasospasm and severe vasospasm were reduced by 32% (Pϭ0.006) and 42% (Pϭ0.044), respectively, and the duration of severe vasospasm was shortened by 0.8 days (Pϭ0.068) in the pravastatin group. These measurements were maximal on the ipsilateral side of ruptured aneurysms. The duration of impaired autoregulation was shortened bilaterally (PՅ0.01), and the incidence of vasospasm-related DIDs and mortality were decreased by 83% (PϽ0.001) and 75% (Pϭ0.037), respectively, in the pravastatin group. Conclusion-Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID. Unfavorable outcome at discharge was reduced primarily because of a reduction in overall mortality. This is the first demonstration of clinical benefits with immediate statin therapy for an acute cerebrovascular disorder. (Stroke. 2005;36:1627-1632.)

Secondary insults can adversely influence outcome following severe traumatic brain injury. Monitoring of cerebral extracellular chemistry with microdialysis has the potential for early detection of metabolic derangements associated with such events. The objective of this study was to determine the relationship between the fundamental biochemical markers and neurological outcome in a large cohort of patients with traumatic brain injury. Prospectively collected observational neuromonitoring data from 223 patients were analysed. Monitoring modalities included digitally recorded intracranial pressure, cerebral perfusion pressure, cerebrovascular pressure reactivity index and microdialysis markers glucose, lactate, pyruvate, glutamate, glycerol and the lactate/pyruvate ratio. Outcome was assessed using the Glasgow Outcome Scale at 6 months post-injury. Patient-averaged values of parameters were used in statistical analysis, which included univariate non-parametric methods and multivariate logistic regression. Monitoring with microdialysis commenced on median (interquartile range) Day 1 (1-2) from injury and median (interquartile range) duration of monitoring was 4 (2-7) days. Averaged over the total monitoring period levels of glutamate (P = 0.048), lactate/pyruvate ratio (P = 0.044), intracranial pressure (P = 0.006) and cerebrovascular pressure reactivity index (P = 0.01) were significantly higher in patients who died. During the initial 72 h of monitoring, median glycerol levels were also higher in the mortality group (P = 0.014) and median lactate/pyruvate ratio (P = 0.026) and lactate (P = 0.033) levels were significantly lower in patients with favourable outcome. In a multivariate logistic regression model (P < 0.0001), which employed data averaged over the whole monitoring period, significant independent positive predictors of mortality were glucose (P = 0.024), lactate/pyruvate ratio (P = 0.016), intracranial pressure (P = 0.029), cerebrovascular pressure reactivity index (P = 0.036) and age (P = 0.003), while pyruvate was a significant independent negative predictor of mortality (P = 0.004). The results of this study suggest that extracellular metabolic markers are independently associated with outcome following traumatic brain injury. Whether treatment-related improvement in biochemistry translates into better outcome remains to be established.

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BackgroundInflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.ObjectivesThis study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation.MethodsWe confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis.ResultsTarget SSTR2 gene expression occurred exclusively in “proinflammatory” M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients.ConclusionsWe validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188)