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Background Specific procedural complications in aneurysm surgery are broadly related to vascular territory compromise and brain/nerve retraction; vascular complications account for about half of this. Intraoperative indocyanine green video angiography (ICG-VA) provides real-time high spatial resolution imaging of the cerebrovascular architecture, allowing immediate quality assurance of aneurysm occlusion and vessel integrity. The aim of this study was to examine whether the routine use of ICG-VA reduced early procedural complications related to vascular compromise or injury during micro-neurosurgical clipping of ruptured cerebral aneurysms. Methods Retrospective comparative observational study of 412 adult good-grade (WFNS 1 or 2) SAH patients who had undergone microsurgical clipping without (n = 200, 2001–2004) or with (n = 212, 2009–2015) ICG-VA in a high-volume neurosurgical centre. Results The ICG-VA group had a significantly lower incidence of procedural vascular complications (7/212; 3.3%) compared with the non-ICG-VA group (19/200; 9.5%) (Fisher’s exact test p = 0.0137). Conclusions ICG-VA is a straightforward, easy-to-use, intraoperative adjunct which significantly reduces avoidable ‘technical error’ related morbidity.

Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.

Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical method affects RCT primary outcome.Methods: Individual patient data for the primary outcome (Glasgow outcome scale [GOS]) of two SAH RCTs were analyzed using 15 statistical methods. For tests requiring outcome dichotomization, multiple cut-points in the 5-level GOS were assessed. Next, a synthetic dataset generated using random sampling with replacement from ten SAH RCTs was assessed using the same statistical tests. A Friedman test (two-way non-parametric analysis of variance) determined which tests produced the highest average absolute Z-values. The number of times each test reported significance of pResults: Bootstrapping with replacement produced the best-ranking results, followed by three χ2-tests: one differentiating excellent (GOS=5) from good (GOS=4), poor (GOS=2-3), or dead (GOS=1) outcomes; one differentiating favorable (GOS=4-5) from poor or dead outcomes; and one differentiating favorable (GOS=4-5) from unfavorable outcomes. Each of these reported statistical significance for both RCTs, as did the following ranked tests, respectively: Wilcoxon median test, Student’s t-test, ordinal logistic regression, median test, and a chi-square dichotomizing excellent (GOS≥4) and inferior outcomes. Statistical significance for one or neither RCT was reported by two Cochrane-Armitage tests and two logistic regressions with alternate versions of bucketing, the Kolmogorov-Smirnov test and chi-square test differentiating surviving from dead patients. The synthetic dataset returned similar results, with the same nine most and six least efficient tests.Conclusions: Bootstrapping produced the most efficient results but is time-and resource-intensive. Chi-square tests grouping outcomes into dichotomous or multiple buckets are also efficient, and their ease of use and popularity make them appropriate candidates for statistical analysis in future SAH RCTs.

Introduction: Subarachnoid hemorrhage (SAH) mortality is decreasing, but data on functional outcomes over time is lacking. Methods: We created trends of good (Glasgow Outcomes Scale [GOS] of 4 or 5) and optimal (GOS of 5) functional outcomes and mortality (GOS of 1) using linear regression in 15 SAH trials and registries from 1982 to 2014. Models adjusted for age, sex, history of hypertension, World Federation of Neurological Surgeons grade, Fisher grade, aneurysm size, location, and repair modality, and whether data was from a clinical trial or registry. Analyses were repeated separately for the clinical trials and registries. Missing data were handled with multiple imputation. Results: Overall, 13,343 SAH patients were included. 9,524 (71%) patients had good functional outcome, while 1,608 (12%) died. There was a 0.6% adjusted improvement (95% confidence interval [CI]: 0.5% to 0.7%; p Conclusions: SAH morbidity and mortality decreased from the 1980s to 2010s. This data can be helpful for researchers planning trials, clinicians discussing expected outcomes with patients and family members, and healthcare administrators planning resource utilization.

Background and Purpose— Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. Methods— The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving β-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. Results— Forty-eight patients were included. Median age was 58 years old (36–76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS ( P =0.007), sedation ( P =0.001), World Federation of Neurosurgery score ( P =0.001), Glasgow score ( P =0.002), Fisher score ( P =0.022), and heart rate ( P =0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048–1.818; P =0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171–0.706; P =0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. Conclusions— In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study.

Microglia, the tissue resident macrophages of the CNS, are implicated in a broad range of neurological pathologies, from acute brain injury to dementia. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single cell and bulk RNA sequencing, we defined distinct cellular populations of acutelyin vivo-activated microglia, and characterised a dramatic switch in microglial population composition in patients suffering from acute brain injury. We mapped expression quantitative trait loci (eQTLs) in human microglia and show that many disease-associated eQTLs in microglia replicate well in a human induced pluripotent stem cell (hIPSC) derived macrophage model system. Using ATAC-seq from 95 individuals in this hIPSC model we fine-map candidate causal variants at risk loci for Alzheimer’s disease, the most prevalent neurodegenerative condition in acute brain injury patients. Our study provides the first population-scale transcriptional map of a critically important cell for neurodegenerative disorders.

Symptomatic stenosis or occlusion of the cervical (C1) internal carotid artery (ICA) is best addressed surgically with direct endarterectomy or thrombectomy procedures. This strategy is not usually possible for more distal lesions, and restoring brain perfusion requires diversion of blood from the extracranial to intracranial circulation with a variety of indirect and direct bypass techniques. However, despite five decades of experience and technical refinement, extracranial-intracranial (EC-IC) bypass for cerebral ischaemia remains contentious. This chapter looks at the conflicting bodies of evidence and opinion regarding how best to select patients for surgery, and asks whether there is meaningful clinical benefit with the surgical options available.

In the context of traumatic brain injury (TBI), decompressive craniectomy (DC) is used as part of tiered therapeutic protocols for patients with intracranial hypertension (secondary or protocol-driven DC). In addition, the bone flap can be left out when evacuating a mass lesion, usually an acute subdural haematoma (ASDH), in the acute phase (primary DC). Even though, the principle of “opening the skull” in order to control brain oedema and raised intracranial pressure has been practised since the beginning of the 20th century, the last 20 years have been marked by efforts to develop the evidence base with the conduct of randomised trials. This article discusses the merits and challenges of this approach and provides an overview of randomised trials of DC following TBI. An update on the RESCUEicp study, a randomised trial of DC versus advanced medical management (including barbiturates) for severe and refractory post-traumatic intracranial hypertension is provided. In addition, the rationale for the RESCUE-ASDH study, the first randomised trial of primary DC versus craniotomy for adult head-injured patients with an ASDH, is presented.

Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm affects approximately 600 000 patients worldwide1 and 7000 patients within the United Kingdom2 each year. Despite considerable advances in treatment, the condition is associated with a disproportionate (25%) loss of productive life and cost to society affecting a young age group.3 Combined morbidity and mortality reach 50%, with one-third of survivors becoming dependent.4 Late clinical deterioration is associated with morbidity and mortality, the causes of which are multifactorial. The most recognized contributor to clinical deterioration and unfavorable outcome is delayed cerebral ischemia. Although phase II randomized controlled trials suggested a potential role for statin therapy in SAH,5-8 a large placebo-controlled and blinded phase III study showed no benefit for simvastatin 40 mg in either the long-term or short-term outcome of patients with aneurysmal subarachnoid hemorrhage (STASH Trial).9 In addition to delayed cerebral ischemia, there are a number of non-neurological systemic complications that often occur post SAH and which can contribute to poor outcome, including sepsis, anemia, hypertension, hypotension, hyperglycemia, hypernatremia, hyponatremia, hypomagnesemia, and cardiac complications.2,10 Many of these complications could be attributed to poor neurological status on admission. However, there remains a group of patients who present with a good World Federation of Neurological Surgeons (WFNS) grade who unpredictably deteriorate with a poor outcome. In this group there is a need for early recognition and close monitoring, opening up the opportunity to earlier intervention. In a post hoc study of the STASH data, we explored whether biochemical markers sampled soon after the time of initial hemorrhage are predictive of a subsequent poor outcome, hence providing a simple and readily accessible indication of who in the population of good grade SAH patients are likely to worsen.

Cerebral vasospasm has traditionally been regarded as an important cause of delayed cerebral ischaemia (DCI) which occurs after aneurysmal subarachnoid haemorrhage, and often leads to cerebral infarction and poor neurological outcome. However, data from recent studies argue against a pure focus on vasospasm as the cause of delayed ischaemic complications. Findings that marked reduction in the incidence of vasospasm does not translate to a reduction in DCI, or better outcomes has intensified research into other possible mechanisms which may promote ischaemic complications. Early brain injury and cell death, blood-brain barrier disruption and initiation of an inflammatory cascade, microvascular spasm, microthrombosis, cortical spreading depolarisations and failure of cerebral autoregulation, have all been implicated in the pathophysiology of DCI. This review summarises the current knowledge about the mechanisms underlying the development of DCI. Furthermore, it aims to describe and categorise the known pharmacological treatment options with respect to the presumed mechanism of action and its role in DCI.

Background and Purpose— To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. Methods— After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Results— Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Conclusions— Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

A 53-year-old right-handed woman developed left pulsatile tinnitus. One year later she presented with a severe occipital headache with neck stiffness while defecating. On admission to hospital she was normotensive (blood pressure 120/70 mm Hg), with a Glasgow coma scale score of 15/15. Examination showed meningism but no focal features. ### Investigations CT scan of head showed a linear periventricular haemorrhage, centred upon the posterior aspect of the corpus callosum (figure 1A) with intraventricular haemorrhage. An MR scan of the brain 1 year before (when she had presented with left pulsatile tinnitus) had shown left internal carotid artery occlusion (figure 1B) and left hemisphere signal change, consistent with a watershed infarction (figure 1C). The same MR scan also showed extensive collateralisation from the left internal carotid artery occlusion, including prominent vessels in the corpus callosum (figure 1D). Figure 1 (A) Unenhanced axial CT scan of head showing transverse linear haemorrhage in the splenium of corpus callosum. Axial T2 MRI of brain 1 year earlier showing (B) left internal cavernous carotid artery flow void is absent (arrow) implying occlusion, (C) numerous small T2 hyperintense internal watershed zone infarcts and (D) excess flow voids due to collateral vessels (arrow) in region of corpus callosum. A CT …

Background The management of aneurysmal subarachnoid hemorrhage (aSAH) has changed dramatically in the last few decades with the publication of a few major studies, including ISAT (International Subarachnoid Aneurysm Trial, the International Cooperative Study on the Timing of Aneurysm Surgery Study). The aim of this study is to analyze the outcome of patients with aSAH based on a contemporary series, identify the risk factors for poor outcome, and focus on patients with good-grade aSAH (to match the ISAT cohort). Methods Baseline demographic and outcome data (modified Rankin Scale) were available for the 803 patients recruited from the STASH (Simvastatin in Aneurysmal Subarachnoid Haemorrhage) trial for post hoc analysis, using a χ2 test or 2-sample t test. Logistic regression analysis was performed to assess the risk factors for poor outcome at 6 months. Propensity matched analysis comparing coiling and clipping, and subgroup analysis of good-grade patients (World Federation of Neurosurgical Societies grade I–II) were also performed. Results Logistic regression analysis showed that the treatment modality (i.e., coiling or clipping) was not associated with poor outcome at 6 months (P = 0.839). The risk factors associated with poor outcome at 6 months were poor admission World Federation of Neurosurgical Societies grade (P < 0.0001), Fisher grade on initial computed tomography scan (P = 0.013), and the development of delayed cerebral ischemia (P < 0.0001). Subgroup analysis for good-grade patients only showed that 82% of patients after coiling and 78% of patients after clipping were classed as good outcome at 6 months (P = 0.181). Conclusions In the current era of aSAH management, apart from patients' admission status, SAH blood load and the development of delayed cerebral ischemia, treatment modality with either coiling or clipping was not associated with poor outcome difference at 6 months.

Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([This study tested the efficacy of gallium-68-labeled DOTATATE (We confirmedTarget SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specificWe validated

The main objective of this study was to assess the long-term cost-effectiveness of five alternative diagnostic strategies for identification of severe carotid stenosis in recently symptomatic patients. A decision-analytical model with Markov transition states was constructed. Data sources included a prospective study involving 167 patients who had screening Doppler ultrasound (DUS), confirmatory contrast-enhanced magnetic resonance angiography (CEMRA) and confirmatory digital subtraction angiography (DSA), individual patient data from the European Carotid Surgery Trial and other published clinical and cost data. A “selective” strategy, whereby all patients receive DUS and CEMRA (only proceeding to DSA if the CEMRA is positive and the DUS is negative), was most cost-effective. This was both the cheapest imaging and treatment strategy ($35,205 per patient) and yielded 6.1590 quality-adjusted life years (QALYs), higher than three alternative imaging strategies. Probabilistic sensitivity analysis demonstrated that there was less than a 10% probability that imaging with either DUS or DSA alone are cost-effective at the conventional $50,000/QALY threshold. In conclusion, DSA is not cost-effective in the routine diagnostic workup of most patients. DUS, with additional imaging in the form of CEMRA, is recommended, with a strategy of “CEMRA and selective DUS review” being shown to be the optimal imaging strategy. Ann Neurol 2005;58:506–515

Delayed cerebral ischemia (DCI) is a major contributor to morbidity and mortality after subarachnoid hemorrhage (SAH). Data challenge vasospasm being the sole cause of ischemia and suggest other factors. We tested the hypothesis that early autoregulatory failure might predict DCI.This is a prospective observational study of cerebral autoregulation following SAH in which the primary end point was DCI at 21 days. Cox proportional hazards and multivariate models were used and the benefit of using multiple indices was analyzed.Ninety-eight patients were included in the study. There was an increased risk of DCI with early dysautoregulation (odds ratio [OR]: 7.46, 95% confidence interval [CI]: 3.03-18.40 and OR: 4.52, 95 % CI: 1.84-11.07 for the transcranial Doppler index of autoregulation [Sxa] and near-infrared spectroscopy index of autoregulation [TOxa], respectively), but not vasospasm (OR: 1.36, 95 % CI: 0.56-3.33). Sxa and TOxa remained independent predictors of DCI in the multivariate model (OR: 12.66, 95 % CI: 2.97-54.07 and OR: 5.34, 95 % CI: 1.25-22.84 for Sxa and TOxa, respectively). There was good agreement between different indices. All 13 patients with impaired autoregulation in all three methods developed DCI.Disturbed autoregulation in the first 5 days after SAH is predictive of DCI. Although colinearities exist between the methods assessed, multimodal monitoring of cerebral autoregulation can aid the prediction of DCI.

In patients after subarachnoid hemorrhage (SAH) failure of cerebral autoregulation is associated with delayed cerebral ischemia (DCI). Various methods of assessing autoregulation are available, but their predictive values remain unknown. We characterize the relationship between different indices of autoregulation. Patients with SAH within 5 days were included in a prospective study. The relationship between three indices of autoregulation was analyzed: two indices calculated using spontaneous blood pressure fluctuations, Sxa (based on transcranial Doppler) and TOxa (based on near-infrared spectroscopy); and transient hyperemic response test (THRT) where a brief compression of the common carotid artery is used. The predictive value of indices was assessed using data from the first 5 days. Overall there was only moderate correlation between indices. However, both Sxa and TOxa showed good accuracy in predicting impaired autoregulation evidenced by a negative THRT (area under the curve (AUC): 0.788, 95% CI: 0.723 to 0.854 and AUC: 0.827, 95% CI: 0.769 to 0.885, respectively). All indices proved accurate in predicting DCI when 0- to 5-day data were used (AUC: 0.801, 95% CI: 0.660 to 0.942; AUC: 0.857, 95% CI: 0.731 to 0.984, AUC: 0.796, 95% CI: 0.658 to 0.934 for THRT, Sxa, and TOxa, respectively). Combining all three indices had 100% specificity for predicting DCI. While multiple colinearities exist between the assessed methods, multimodal monitoring of cerebral autoregulation can aid in predicting DCI.

Background Cerebrospinal fluid (CSF) infections associated with external ventricular drain (EVD) placement attract major consequences. Silver impregnation of catheters attempts to reduce infection. Objective To assess the efficacy of silver catheters against CSF infection. Methods We performed a randomized, controlled trial involving 2 neurosurgical centers (June 2005 to September 2009). A total of 356 patients requiring an EVD were assessed for eligibility; 325 patients were enrolled and randomized (167 plain, 158 silver); 278 patients were analyzed (140 plain, 138 silver). The primary outcome measure was CSF infection as defined by organisms seen on Gram stain or isolated by culture. Secondary outcome measures included ventriculoperitoneal (VP) shunting. Results There was a significant difference in infection risk between the 2 study arms: 21.4% (30/140) for plain catheters vs 12.3% (17/138) for silver catheters (P = .0427; 95% confidence interval [CI]: 1.015-3.713). Patients who had an EVD infection had more than double the risk of requiring a VP shunt compared with patients without an EVD infection (45.7% [21/46] vs 19.7% [45/229], respectively, P = .0002; 95% CI: 1.766-6.682). There was also a significant difference in VP shunt risk with infection: plain (55.2%; 16/29) vs the silver arm (29.4%; 5/17); P = .0244 (95% CI: 1.144-11.695). A multivariate analysis demonstrated that infection risk was increased by duration of EVD placement (odds ratio: 1.160), spontaneous intracranial hemorrhage (odds ratio 4.958) and decreased by silver catheters (odds ratio: 0.423). Conclusion The study provides Class I evidence that silver-impregnated catheters reduce CSF infection.

Background Acute subdural haematomas (ASDH) occur commonly following traumatic brain injury and may be evacuated by either craniotomy (CR) or decompressive craniectomy (DC). We reviewed a series of consecutive patients undergoing evacuation of a traumatic ASDH at a regional centre, comparing observed clinical outcomes (assessed by Glasgow Outcome Scale at six months) with those predicted by the CRASH-CT prognostic model.

Cerebral autoregulation assessed using transcranial Doppler (TCD) mean flow velocity (FV) in response to various physiological challenges is predictive of outcome after traumatic brain injury (TBI). Systolic and diastolic FV have been explored in other diseases. This study aims to evaluate the systolic, mean and diastolic FV for monitoring autoregulation and predicting outcome after TBI.300 head-injured patients with blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and FV recordings were studied. Autoregulation was calculated as a correlation of slow changes in diastolic, mean and systolic components of FV with CPP (Dx, Mx, Sx, respectively) and ABP (Dxa, Mxa, Sxa, respectively) from 30 consecutive 10 s averaged values. The relationship with age, severity of injury, and dichotomized 6 months outcome was examined.Association with outcome was significant for Mx and Sx. For favorable/unfavorable and death/survival outcomes Sx showed the strongest association (F = 20.11; P = 0.00001 and F = 13.10; P = 0.0003, respectively). Similarly, indices derived from ABP demonstrated the highest discriminatory value when systolic FV was used (F = 12.49; P = 0.0005 and F = 5.32; P = 0.02, respectively). Indices derived from diastolic FV demonstrated significant differences (when calculated using CPP) only when comparing between fatal and non-fatal outcome.Systolic flow indices (Sx and Sxa) demonstrated a stronger association with outcome than the mean flow indices (Mx and Mxa), irrespective of whether CPP or ABP was used for calculation.

Bedside monitoring of cerebral metabolism in traumatic brain injury (TBI) with microdialysis is gaining wider clinical acceptance. The objective of this study was to examine the relationship between the fundamental physiological neuromonitoring modalities intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygen (P(bt)O(2)), and cerebrovascular pressure reactivity index (PRx), and cerebral chemistry assessed with microdialysis, with particular focus on the lactate/pyruvate (LP) ratio as a marker of energy metabolism. Prospectively collected observational neuromonitoring data from 97 patients with TBI, requiring neurointensive care management and invasive cerebral monitoring, were analyzed. A linear mixed model analysis was used to account for individual patient differences. Perilesional tissue chemistry exhibited a significant independent relationship with ICP, P(bt)O(2) and CPP thresholds, with increasing LP ratio in response to decrease in P(bt)O(2) and CPP, and increase in ICP. The relationship between CPP and chemistry depended upon the state of PRx. Within the studied physiological range, tissue chemistry only changed in response to increasing ICP or drop in P(bt)O(2)1.33 kPa (10 mmHg). In agreement with previous studies, significantly higher levels of cerebral lactate (p0.001), glycerol (p=0.013), LP ratio (p0.001) and lactate/glucose (LG) ratio (p=0.003) were found in perilesional tissue, compared to "normal" brain tissue (Mann-Whitney test). These differences remained significant following adjustment for the influences of other important physiological parameters (ICP, CPP, P(bt)O(2), P(bt)CO(2), PRx, and brain temperature; mixed linear model), suggesting that they may reflect inherent tissue properties related to the initial injury. Despite inherent biochemical differences between less-injured brain and "perilesional" cerebral tissue, both tissue types exhibited relationships between established physiological variables and biochemistry. Decreases in perfusion and oxygenation were associated with deteriorating neurochemistry and these effects were more pronounced in perilesional tissue and when cerebrovascular reactivity was impaired.

Background: A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO2. Methods: We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO2 inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. Results: At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = −0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO2, was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. Conclusions: The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Object In a previous randomized controlled trial, the authors demonstrated that acute erythropoietin (EPO) therapy reduced severe vasospasm and delayed ischemic deficits (DIDs) following aneurysmal subarachnoid hemorrhage. In this study, the authors aimed to investigate the potential interaction of neurovascular protection by EPO with age, sepsis, and concurrent statin therapy. Methods The clinical events of 80 adults older than 18 years and with < 72 hours of aneurysmal subarachnoid hemorrhage, who were randomized to receive 30,000 U of intravenous EPO-β or placebo every 48 hours for a total of 3 doses, were analyzed by stratification according to age (< or ≥ 60 years), sepsis, or concomitant statin therapy. End points in the trial included cerebral vasospasm and impaired autoregulation on transcranial Doppler ultrasonography, DIDs, and unfavorable outcome at discharge and at 6 months measured with the modified Rankin Scale and Glasgow Outcome Scale. Analyses were performed using the t-test and/or ANOVA for repeated measurements. Results Younger patients (< 60 years old) or those without sepsis obtained benefits from EPO by a reduction in vasospasm, impaired autoregulation, and unfavorable outcome at discharge. Compared with nonseptic patients taking EPO, those with sepsis taking EPO had a lower absolute reticulocyte count (nonsepsis vs sepsis, 143.5 vs. 105.8 × 109/L on Day 6; p = 0.01), suggesting sepsis impaired both hematopoiesis and neurovascular protection by EPO. In the EPO group, none of the statin users suffered DIDs (p = 0.078), implying statins may potentiate neuroprotection by EPO. Conclusions Erythropoietin-related neurovascular protection appears to be attenuated by old age and sepsis and enhanced by statins, an important finding for designing Phase III trials.

We compared autoregulation monitored with cortical laser Doppler flowmetry (LDF) and autoregulation monitored with transcranial Doppler (TCD) in the middle cerebral artery (MCA) to verify the hypothesis that, following brain trauma, cortical vessel autoregulation to intracranial hypertension is different than assessed in the MCA.Data collected from 29 head injured patients were analysed retrospectively. Arterial blood pressure (ABP), intracranial pressure (ICP), flow velocity (FV) of the MCA and cortical flux (LDF) were monitored. Indices of cortical autoregulation (Lx) and autoregulation of cerebral blood flow in the MCA (Mx) were calculated as a moving correlation coefficient between slow waves of LDF and cerebral perfusion pressure (CPP) (Lx) or FV and CPP (Mx), respectively. Intact autoregulation was indicated by negative values for Lx and Mx; disturbed autoregulation was reflected by positive values.FV and LDF showed a high coherence in the slow wave spectrum of 1-4 cycles/min (mean: 0.79 +/- 0.12), indicating that similar information regarding autoregulation is carried by both signals. Mx and Lx correlated in all patients (R=0.43, p=0.02). On average, Lx was significantly higher than Mx; the mean difference was 0.13 +/- 0.38 (p=0.032), potentially due to severe intracranial hypertension above 40 mmHg, driving CPP values below 60 mmHg.After traumatic brain injury, cortical autoregulation appears to be worse than autoregulation assessed in the MCA during rising ICP and falling CPP. When CPP is above 60 mmHg, cortical assessed autoregulation is similar to autoregulation assessed in the MCA.

Research has shown that knowing the morphology of carotid atheroma improves current risk stratification for predicting subsequent thrombo-embolic events. Previous magnetic resonance (MR) ex vivo studies have shown that diffusion-weighted imaging (DWI) can detect lipid-rich necrotic core (LR/NC) and fibrous cap. This study aims to establish if this is achievable in vivo.Twenty-six patients (mean age 73 years, range 54-87 years) with moderate to severe carotid stenosis confirmed on ultrasound were imaged. An echo-planar DWI sequence was performed along with standard high-resolution MR imaging. Apparent diffusion coefficient (ADC) maps were evaluated. Two independent readers reported the mean ADC values from regions of interest defining LR/NCs and fibrous caps. For subjects undergoing carotid endarterectomy (n = 19), carotid specimens were obtained and stained using Nile red.The mean ADC values were 1.0 × 10(-3) mm(2)/s (±SD 0.3 × 10(-3) mm(2)/s) and 0.7 × 10(-3) mm(2)/s (±SD 0.2 × 10(-3) mm(2)/s) for fibrous cap and LR/NC, respectively; the difference was significant (p 0.0001). The intra-class correlation coefficients summarising the agreement between the two independent readers were 0.84 and 0.60 for fibrous cap and LR/NC, respectively. Comparison of quantitative ADC values and histology (by subjective grading of lipid content) showed a significant correlation: heavier lipid staining matched lower ADC values (r = -0.435, p = 0.005).This study indicates that DWI can be used to distinguish LR/NC and the fibrous cap. The study also suggests that the mean ADC value may be linearly related to subjective graded LR/NC content determined by histology.

Cerebral revascularisation with extracranial - intracranial (EC-IC) bypass is generally indicated in patients with complex anterior circulation aneurysms who have failed parent artery occlusion. We report on the process and outcome of our early experience of performing high flow bypass in patients with complex anterior circulation aneurysms. We have reviewed patients who have undergone an EC-IC bypass for treatment of complex anterior circulation aneurysms, and report our outcome on graft patency, surgical complications, discharge destination, and obliteration rates. Nine patients that underwent 11 bypasses are described. Seven patients had a giant saccular aneurysm of the carotid, and these were all obliterated on post-operative imaging. Two patients presenting with an intracranial carotid dissection required trapping of the diseased segment following the bypass. The overall graft patency rate was 88%. One patient developed a post operative subdural collection (managed conservatively), and one patient required early graft revision. Discharge destination was home in 8/9 patients. There was no mortality. Although EC-IC bypass is a technically challenging procedure, it provides a valuable treatment option for patients with complex anterior circulation aneurysms. Good graft patency rates can be achieved with low surgical morbidity in patients with a disease process that otherwise attracts a highly unfavourable natural history.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

Objectives The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy. Background Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation. Methods Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (ΔSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks. Results Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (ΔSI 0.13; p = 0.0003) and at 12 weeks (ΔSI 0.20; p Conclusions Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to “anti-inflammatory” interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589 )

Cerebral microdialysis is a monitoring technique with expanding clinical and research utility following traumatic brain injury. This study's aim was to determine the relative recovery for 12 cytokines using both crystalloid (CNS perfusion fluid) and colloid (CNS perfusion fluid supplemented with 3.5% human serum albumin) perfusate. Six CMA71 microdialysis catheters (nominal molecular weight cut-off 100 kDa) were perfused in vitro with either crystalloid or colloid and the relative recovery (%) determined for the cytokines as follows (crystalloid/colloid perfusate): IL-1alpha (50.6/48), IL-1beta (34.6/38.4), IL-1ra (21.9/38.4), IL-2 (17.1/52.8), IL-4 (26/56.7), IL-6 (9.8/25.5), IL-8 (47.7/73.4), IL-10 (2.9/8.7), IL-17 (14.4/43.7), TNF-alpha (4.4/31.2), MIP-1alpha (31.8/55.6), and MIP-1beta (31.9/50.1). The colloid perfusate significantly improved relative recovery for nine of these cytokines ( p0.05), but not for IL-1alpha, IL-1beta, and IL-8. Relative recovery was related to apparent molecular weight of cytokine and to isoelectric point (pI), a surrogate marker of hydrophilicity. The mean fluid recovery for crystalloid and colloid perfusate was 92% and 145%, respectively. Scanning electron microscopy was utilized to investigate the ultrastructure of microdialysis membranes: (1) 20-kDa membrane, (2) 100-kDa membrane, and (3) ex vivo 100-kDa membrane. The 100-kDa membranes possessed multiple large cavities and the catheter examined after use in human brain clearly demonstrated cellular debris within the pores of the membrane. While colloid perfusate improves relative recovery, it causes a net influx of fluid into the microdialysis catheter, potentially dehydrating the extracellular space. This study is the first to systematically determine relative recovery in vitro for a wide range of cytokines. The two forms of perfusion fluid require direct comparison in vivo.

Critical closing pressure (CCP) is an arterial pressure threshold below which small arterial vessels collapse. Our aim was to compare different methods to estimate CCP in the cerebrovascular circulation using the relationships between transcranial Doppler flow velocity (FV), laser-Doppler flux (LDF), and arterial blood pressure (ABP). A total of 116 experiments in rabbits were analyzed retrospectively. At the end of each recording, cardiac arrest (CA) was induced. Arterial blood pressure in femoral artery, basilar artery FV, cortical blood LDF, intracranial pressure (ICP) was recorded. Critical closing pressure was estimated using linear regression between decreasing mean ABP values, FV, and LDF during CA. In addition, CCP was calculated from FV waveform just before CA. The correlation between CCP evaluated using LDF and FV during CA was 0.98 ( P < 0.0001). The correlation between CCP measured during CA and CCP estimated from the transcranial Doppler ultrasonography (TCD) waveform was weaker ( R=0.39; P

Decompressive Craniectomy (DC) continues to be widely practiced but remains controversial. The procedure has its origins thousands of years ago, with early trepanation performed for a range of medical and religious reasons. We summarize the history, techniques, complications and pathophysiology and then explore in detail the recent evidence base for the most common indications for DC; Traumatic brain injury (TBI) and Cerebral infarction. An important consideration from the outset is the often forgotten issue of cranioplasty and we summarize advances in materials, technology and discuss the optimum timing. Outcomes of ongoing randomized trials in TBI are awaited with interest but the trend in the nonrandomized literature suggests timely intervention reduces mortality with acceptable morbidity. Level 1 evidence for early DC in young patients with malignant middle cerebral artery infarction has arrived and has implications for neurosurgical practice and rehabilitation services. Current European and North American practice recommends the judicious use of DC in traumatic brain injury and malignant middle cerebral artery infarction in select patients.

Background and Purpose— Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The study explores the relationship between the degree of Magnetic Resonance (MR)–defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles and the severity of luminal stenosis in asymptomatic carotid plaques. Methods— Seventy-one patients with an asymptomatic carotid stenosis of ≥40% underwent multi-sequence USPIO-enhanced MR imaging. Stenosis severity was measured according to the NASCET and ECST methods. Results— No demonstrable relationship between inflammation as measured by USPIO-enhanced signal change and the degree of luminal stenosis was found. Conclusions— Inflammation and stenosis are likely to be independent risk factors, although this needs to be further validated.

A wide range of treatment modalities are employed in the treatment of chronic subdural haematoma (CSDH). A rational and evidence-based treatment strategy has the potential to optimise treatment for the individual patient and save resources. The aim of this study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest.

Atherosclerotic disease of the carotid arteries has been identified as a major cause of stroke and thromboembolism from ruptured atheroma plaques within the walls of these vessels, has been proposed as the putative pathophysiological event underlying cerebral ischaemia. Carotid endarterectomy has been shown to be superior to pharmacotherapy in reducing the likelihood of further disabling stroke or death, in selected individuals. It is, therefore, necessary to identify those individuals at highest risk of stroke, for whom the risks of aggressive intervention may be worthwhile. Our understanding of atherosclerosis suggests that plaque rupture is precipitated by inflammation that causes alteration in the morphological composition and functional activity within the plaque resulting in exposure of thrombogenic material to the circulation. Identification of this in vivo biological process or surrogate markers suggesting 'vulnerability' to plaque rupture could, therefore, aid the selection of individuals for whom the risks of aggressive intervention may be warranted. This review outlines the imaging modalities that have been evaluated for in vivo structural assessment of carotid plaques and risk stratification for selection for aggressive interventions. More recent strategies appear to be moving toward a combination of morphological and functional imaging in order to visualize the pathophysiological mechanisms that underlie plaque rupture.

BACKGROUND\ud The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear.\ud \ud METHODS\ud From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to “upper good recovery” [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively.\ud \ud RESULTS\ud The GOS-E distribution differed between the two groups (P

Introduction: Delayed cerebral ischemia (DCI) is a major contributor to morbidity and mortality after subarachnoid hemorrhage (SAH). Data challenge vasospasm being the sole cause of ischemia and suggest other factors. We tested the hypothesis that early autoregulatory failure might predict DCI. Methods: This is a prospective observational study of cerebral autoregulation following SAH in which the primary end point was DCI at 21 days. Cox proportional hazards and multivariate models were used and the benefit of using multiple indices was analyzed. Results: Ninety-eight patients were included in the study. There was an increased risk of DCI with early dysautoregulation (odds ratio [OR]: 7.46, 95% confidence interval [CI]: 3.03–18.40 and OR: 4.52, 95 % CI: 1.84–11.07 for the transcranial Doppler index of autoregulation [Sxa] and near-infrared spectroscopy index of autoregulation [TOxa], respectively), but not vasospasm (OR: 1.36, 95 % CI: 0.56–3.33). Sxa and TOxa remained independent predictors of DCI in the multivariate model (OR: 12.66, 95 % CI: 2.97–54.07 and OR: 5.34, 95 % CI: 1.25–22.84 for Sxa and TOxa, respectively). There was good agreement between different indices. All 13 patients with impaired autoregulation in all three methods developed DCI. Conclusions: Disturbed autoregulation in the first 5 days after SAH is predictive of DCI. Although colinearities exist between the methods assessed, multimodal monitoring of cerebral autoregulation can aid the prediction of DCI.

Background: Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance (MR) defined inflammation using ultra small superparamagnetic iron oxide (USPIO) particles within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis contralateral to the symptomatic side. Methods: 20 symptomatic patients with contralateral disease and 20 completely asymptomatic patients underwent multi-sequence MR imaging before and 36 h after USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change was compared across all quadrants in the two groups. Results: The mean percentage of quadrants showing signal loss was 53% in the contralateral group compared with 31% in completely asymptomatic individuals (p = 0.025). The mean percentages showing enhancement were 44% and 65%, respectively (p = 0.024). The mean signal difference between the two groups was 8.6% (95% CI 1.6% to 15.6%; p = 0.017). Conclusions: Truly asymptomatic plaques seem to demonstrate inflammation but not to the extent of the contralateral asymptomatic stenosis to the symptomatic side. Inflammatory activity may be a significant risk factor in asymptomatic disease.

The Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure (RESCUEicp) study was undertaken to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure. The study compares maximal medical management and decompressive craniectomy, the two approaches used when all other interventions have failed to control intracranial hypertension. Neither of these therapies has grade one evidence to support its use, but both are regularly used as a final escalation of treatment in this vulnerable client group. The pilot phase of the study has been completed and the main study is now underway, having recruited over 100 patients to date. Nurses caring for patients enrolled in research studies have a duty to be involved in the research process, as well as to understand the evidence obtained and apply it to practice. In this article, the authors draw on their experience of involvement in the RESCUEicp study to highlight possible areas where nurses can become more involved in the process of research so that research findings can be used to improve the care that their patients receive when they are at their most vulnerable. Such an approach has great potential to shape the development of nursing as a profession.

Object Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses. Methods Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted. Results There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition. Conclusions Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging–based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.

To prospectively determine, for both digital subtraction angiography (DSA) and contrast material-enhanced magnetic resonance (MR) angiography, the accuracy of subjective visual impression (SVI) in the evaluation of internal carotid artery (ICA) stenosis, with objective caliper measurements serving as the reference standard.Local ethics committee approval and written informed patient consent were obtained. A total of 142 symptomatic patients (41 women, 101 men; mean age, 70 years; age range, 44-89 years) suspected of having ICA stenosis on the basis of Doppler ultrasonographic findings underwent both DSA and contrast-enhanced MR angiography. With each modality, three independent neuroradiologists who were blinded to other test results first visually estimated and subsequently objectively measured stenoses. Diagnostic accuracy and percentage misclassification for correct categorization of 70%-99% stenosis were calculated for SVI, with objective measurements serving as the reference standard. Interobserver variability was determined with kappa statistics.After exclusion of arteries that were unsuitable for measurement, 180 vessels remained for analysis with DSA and 159 vessels remained for analysis with contrast-enhanced MR angiography. With respect to 70%-99% stenosis, SVI was associated with average misclassification of 8.9% for DSA (8.9%, 7.8%, and 10.0% for readers A, B, and C, respectively) and of 11.7% for contrast-enhanced MR angiography (11.3%, 8.8%, and 15.1% for readers A, B, and C, respectively). Negative predictive values were excellent (92.3%-100%). Interobserver variability was higher for SVI (DSA, kappa = 0.62-0.71; contrast-enhanced MR angiography, kappa = 0.57-0.69) than for objective measurements (DSA, kappa = 0.75-0.80; contrast-enhanced MR angiography, kappa = 0.66-0.72).SVI alone is not recommended for evaluation of ICA stenosis with both DSA and contrast-enhanced MR angiography. SVI may be acceptable as an initial screening tool to exclude the presence of 70%-99% stenosis, but caliper measurements are warranted to confirm the presence of such stenosis.

✓Brain edema is a common pathophysiological process seen in many neurosurgical conditions. It can be localized in relation to focal lesions or generalized in diffuse types of brain injury. In addition to local adverse effects occurring at a cellular level, brain edema is associated with raised intracranial pressure (ICP), and both phenomena contribute to poor outcome in patients. One of the goals in treating patients with acute neurosurgical conditions in intensive care is to control brain edema and maintain ICP below target levels. The mainstay of treatment is medical therapy to reduce edema, but in certain patients—for example, those with diffuse severe traumatic brain injury (TBI) and malignant middle cerebral artery infarction—such treatment is not effective. In these patients, opening the skull (decompressive craniecto-my) to reduce ICP is a potential option. In this review the authors discuss the role of decompressive craniectomy as a surgical option in patients with brain edema in the context of a variety of pathological entities. They also address the current evidence for the technique (predominantly observational series) and the ongoing randomized studies of decompressive craniectomy in TBI and ischemic stroke.

We examined the predictive value of initial clinical status, mean arterial blood pressure (MABP), intracranial pressure (ICP) and transcranial Doppler (TCD)-derived pulsatility and resistance indices for outcome and quality of life one year following aneurysmal subarachnoid haemorrhage (SAH).Neuromonitoring was performed in 29 patients following clipping or coiling of an aneurysm. Mean arterial blood pressure was measured in the radial artery and intracranial pressure was assessed via a closed external ventricular drainage. Based on transcranial Doppler-recordings of the middle cerebral artery, Gosling's pulsatility (PI) and Pourcelot's resistance (RI) index were calculated. Glasgow outcome score (GOS) and short form-36 (SF-36) scores were determined one year after SAH.An unfavourable outcome (GOS 1-3) was observed in 34% of patients and correlated significantly (p0.05) with a poor initial clinical status, as determined by Glasgow Coma Scale (r = 0.55), Hunt and Hess (r = -0.62), World Federation of Neurosurgical Societies (WFNS) (r = -0.48) and Fisher (r = -0.58) score. Poor outcome was significantly associated with high mean arterial blood pressure (r = -0.44) and intracranial pressure (r = -0.48) as well as increased pulsatility (r = -0.46) and resistance (r = -0.43) indices. Hunt and Hess gradeor = 4 (OR 12.4, 5-95% CI: 1.9-82.3), mean arterial blood pressure95 mmHg (19.5, 2.9-132.3), Gosling's pulsatility0.8 (6.5, 1.6-27.1) and Pourcelot's resistance0.57 (15.4, 2.3-103.4) were predictive for unfavourable outcome in logistic regression, however TCD-diagnosed vasospasm was not. Except for mental health, significantly reduced scores were observed in all short form-36 domains. Initial clinical status correlated significantly with the physical functioning, role physical, bodily pain, social functioning and physical component summary of short form-36.Mortality and morbidity following SAH remains high, especially in poor-grade patients. Outcome is mainly correlated with initial clinical status, mean arterial blood pressure, intracranial pressure, pulsatility and resistance indices. Those factors seem to be stronger than the influence of vasospasm.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding.

Object The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow. Methods In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 ± 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0–5, 132 measurements in 32 patients). There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation. Conclusions The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.

Background and Purpose— It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. Methods— Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. Results— There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side ( P =0.007). Conclusions— This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.