Resting state EEG relates to short- and long-term cognitive functioning after cardiac arrest.

BACKGROUND: Approximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. METHODS: We analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. RESULTS: Each individual EEG parameter related to MoCA at one week (ßnATR = 7.36; P < 0.01; ßpeak frequency = 1.73, P < 0.01; ßCoG = -9.88, P < 0.01). The nATR also related with the MoCA at three months ((ßnATR = 2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. CONCLUSION: Early resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.

Anakinra in cerebral haemorrhage to target secondary injury resulting from neuroinflammation (ACTION): Study protocol of a phase II randomised clinical trial.

BACKGROUND: Inflammation plays a vital role in the development of secondary brain injury after spontaneous intracerebral haemorrhage (ICH). Interleukin-1 beta is an early pro-inflammatory cytokine and a potential therapeutic target. AIM: To determine the effect of treatment with recombinant human interleukin-1 receptor antagonist anakinra on perihematomal oedema (PHO) formation in patients with spontaneous ICH compared to standard medical management, and investigate whether this effect is dose-dependent. METHODS: ACTION is a phase-II, prospective, randomised, three-armed (1:1:1) trial with open-label treatment and blinded end-point assessment (PROBE) at three hospitals in The Netherlands. We will include 75 patients with a supratentorial spontaneous ICH admitted within 8 h after symptom onset. Participants will receive anakinra in a high dose (loading dose 500 mg intravenously, followed by infusion with 2 mg/kg/h over 72 h; n = 25) or in a low dose (loading dose 100 mg subcutaneously, followed by 100 mg subcutaneous twice daily for 72 h; n = 25), plus standard care. The control group (n = 25) will receive standard medical management. OUTCOMES: Primary outcome is PHO, measured as oedema extension distance on MRI at day 7 ± 1. Secondary outcomes include the safety profile of anakinra, the effect of anakinra on serum inflammation markers, MRI measures of blood brain barrier integrity, and functional outcome at 90 ± 7 days. DISCUSSION: The ACTION trial will provide insight into whether targeting interleukin-1 beta in the early time window after ICH onset could ameliorate secondary brain injury. This may contribute to the development of new treatment options to improve clinical outcome after ICH.

Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke.

PURPOSE: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. METHODS: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). RESULTS: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2-3.2)) and distal occlusion locations (aOR 2.2  (95% CI 1.3-3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23-0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. CONCLUSION: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk.

Degree of differentiation impacts neurobiological signature and resistance to hypoxia of SH-SY5Y cells.

Objective.SH-SY5Y cells are valuable neuronalin vitromodels for studying patho-mechanisms and treatment targets in brain disorders due to their easy maintenance, rapid expansion, and low costs. However, the use of various degrees of differentiation hampers appreciation of results and may limit the translation of findings to neurons or the brain. Here, we studied the neurobiological signatures of SH-SY5Y cells in terms of morphology, expression of neuronal markers, and functionality at various degrees of differentiation, as well as their resistance to hypoxia. We compared these to neurons derived from human induced pluripotent stem cells (hiPSCs), a well-characterized neuronalin vitromodel.Approach.We cultured SH-SY5Y cells and neurons derived from hiPSCs on glass coverslips or micro-electrode arrays. We studied expression of mature neuronal markers, electrophysiological activity, and sensitivity to hypoxia at various degrees of differentiation (one day up to three weeks) in SH-SY5Y cells. We used hiPSC derived neurons as a reference.Main results.Undifferentiated and shortly differentiated SH-SY5Y cells lacked neuronal characteristics. Expression of neuronal markers and formation of synaptic puncta increased during differentiation. Longer differentiation was associated with lower resistance to hypoxia. At three weeks of differentiation, MAP2 expression and vulnerability to hypoxia were similar to hiPSC-derived neurons, while the number of synaptic puncta and detected events were significantly lower. Our results show that at least three weeks of differentiation are necessary to obtain neurobiological signatures that are comparable to those of hiPSC-derived neurons, as well as similar sensitivities to metabolic stress. Significance.This indicates that extended differentiation protocols should be used to study neuronal characteristics and to model brain disorders with SH-SY5Y cells. We provided insights that may offer the basis for the utilization of SH-SY5Y cells as a more relevant neuronal model in the study of brain disorders.

EEG in a four-electrode frontotemporal montage reliably predicts outcome after cardiac arrest.

AIM: To increase efficiency of continuous EEG monitoring for prognostication of neurological outcome in patients after cardiac arrest, we investigated the reliability of EEG in a four-electrode frontotemporal (4-FT) montage, compared to our standard nine-electrode (9-EL) montage. METHODS: EEG recorded with Ag/AgCl cup-electrodes at 12 and/or 24 h after cardiac arrest of 153 patients was available from a previous study. 220 EEG epochs of 5 minutes were reexamined in a 4-FT montage according to the ACNS criteria. Background classification was compared to the available 9-EL classification using Cohens kappa. Reliability for prognostication was assessed in 151 EEG epochs at 24 h after CA using sensitivity and specificity for prediction of poor (cerebral performance categories (CPC) 3-5) and good (CPC 1-2) neurological outcome. RESULTS: Agreement for EEG background classification between the two montages was substantial with a kappa of 0.85 (95%-CI 0.81-0.90). Specificity for prediction of poor outcome was 100% (95%-CI 95-100) for both montages, sensitivity was 31% (95%-CI 21-43) for the 4-FT montage and 35% (95%-CI 24-47) for the 9-EL montage. Good outcome was predicted with 65% specificity (95%-CI 53-76) and 81% sensitivity (95%-CI 71-89) for the 4-FT montage, similar to the 9-EL montage. CONCLUSION: In this cohort, EEG background patterns determined in a four-electrode frontotemporal montage predict both poor and good outcome after CA with similar reliability. Our results may contribute to decreasing the workload of EEG monitoring in patients after CA without compromising reliability of outcome prediction. However, validation in a larger cohort is necessary, as is a multimodal approach.

Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke.

Background: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. Methods: A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. Results: We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Conclusion: Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.

Dynamic functional connectivity of the EEG in relation to outcome of postanoxic coma.

OBJECTIVE: Early EEG contains reliable information for outcome prediction of comatose patients after cardiac arrest. We introduce dynamic functional connectivity measures and estimate additional predictive values. METHODS: We performed a prospective multicenter cohort study on continuous EEG for outcome prediction of comatose patients after cardiac arrest. We calculated Link Rates (LR) and Link Durations (LD) in the α, δ, and θ band, based on similarity of instantaneous frequencies in five-minute EEG epochs, hourly, during 3 days after cardiac arrest. We studied associations of LR and LD with good (Cerebral Performance Category (CPC) 1-2) or poor outcome (CPC 3-5) with univariate analyses. With random forest classification, we established EEG-based predictive models. We used receiver operating characteristics to estimate additional values of dynamic connectivity measures for outcome prediction. RESULTS: Of 683 patients, 369 (54%) had poor outcome. Patients with poor outcome had significantly lower LR and longer LD, with largest differences 12 h after cardiac arrest (LRθ 1.87 vs. 1.95 Hz and LDα 91 vs. 82 ms). Adding these measures to a model with classical EEG features increased sensitivity for reliable prediction of poor outcome from 34% to 38% at 12 h after cardiac arrest. CONCLUSION: Poor outcome is associated with lower dynamics of connectivity after cardiac arrest. SIGNIFICANCE: Dynamic functional connectivity analysis may improve EEG based outcome prediction.

Brain imaging in comatose survivors of cardiac arrest: Pathophysiological correlates and prognostic properties.

INTRODUCTION: Hypoxic-ischemic brain injury is the main cause of death and disability of comatose patients after cardiac arrest. Early and reliable prognostication is challenging. Common prognostic tools include clinical neurological examination and electrophysiological measures. Brain imaging is well established for diagnosis of focal cerebral ischemia but has so far not found worldwide application in this patient group. OBJECTIVE: To review the value of Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) for early prediction of neurological outcome of comatose survivors of cardiac arrest. METHODS: A literature search was performed to identify publications on CT, MRI or PET in comatose patients after cardiac arrest. RESULTS: We included evidence from 51 articles, 21 on CT, 27 on MRI, 1 on CT and MRI, and 2 on PET imaging. Studies varied regarding timing of measurements, choice of determinants, and cut-off values predicting poor outcome. Most studies were small (n = 6-398) and retrospective (60%). In general, cytotoxic oedema, defined by a grey-white matter ratio <1.10, derived from CT, or MRI-diffusion weighted imaging <650 × 10-6 mm2/s in >10% of the brain could differentiate between patients with favourable and unfavourable outcomes on a group level within 1-3 days after cardiac arrest. Advanced imaging techniques such as functional MRI or diffusion tensor imaging show promising results, but need further evaluation. CONCLUSION: CT derived grey-white matter ratio and MRI based measures of diffusivity and connectivity hold promise to improve outcome prediction after cardiac arrest. Prospective validation studies in a multivariable approach are needed to determine the additional value for the individual patient.

Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A computational study.

OBJECTIVE: In postanoxic coma, EEG patterns indicate the severity of encephalopathy and typically evolve in time. We aim to improve the understanding of pathophysiological mechanisms underlying these EEG abnormalities. METHODS: We used a mean field model comprising excitatory and inhibitory neurons, local synaptic connections, and input from thalamic afferents. Anoxic damage is modeled as aggravated short-term synaptic depression, with gradual recovery over many hours. Additionally, excitatory neurotransmission is potentiated, scaling with the severity of anoxic encephalopathy. Simulations were compared with continuous EEG recordings of 155 comatose patients after cardiac arrest. RESULTS: The simulations agree well with six common categories of EEG rhythms in postanoxic encephalopathy, including typical transitions in time. Plausible results were only obtained if excitatory synapses were more severely affected by short-term synaptic depression than inhibitory synapses. CONCLUSIONS: In postanoxic encephalopathy, the evolution of EEG patterns presumably results from gradual improvement of complete synaptic failure, where excitatory synapses are more severely affected than inhibitory synapses. The range of EEG patterns depends on the excitation-inhibition imbalance, probably resulting from long-term potentiation of excitatory neurotransmission. SIGNIFICANCE: Our study is the first to relate microscopic synaptic dynamics in anoxic brain injury to both typical EEG observations and their evolution in time.

EEG in postanoxic coma: Prognostic and diagnostic value.

Evolution of the EEG background pattern is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest. At 24h, persistent isoelectricity, low voltage activity, or burst-suppression with identical bursts predicts a poor outcome without false positives. Rapid recovery toward continuous patterns within 12h is strongly associated with a good neurological outcome. Predictive values are highest in the first 24h, despite the use of mild therapeutic hypothermia and sedative medication. Studies on reactivity or mismatch negativity have not included the EEG background pattern. Therefore, the additional predictive value of reactivity parameters remains unclear. Whether or not treatment of electrographic status epilepticus improves outcome is studied in the randomized multicenter Treatment of Electroencephalographic STatus epilepticus After cardiopulmonary Resuscitation (TELSTAR) trial (NCT02056236).

Imaging Findings Associated with Space-Occupying Edema in Patients with Large Middle Cerebral Artery Infarcts.

BACKGROUND AND PURPOSE: Prominent space-occupying cerebral edema is a devastating complication occurring in some but not all patients with large MCA infarcts. It is unclear why differences in the extent of edema exist. Better knowledge of factors related to prominent edema formation could aid treatment strategies. This study aimed to identify variables associated with the development of prominent edema in patients with large MCA infarcts. MATERIALS AND METHODS: From the Dutch Acute Stroke Study (DUST), 137 patients were selected with large MCA infarcts on follow-up NCCT (3 ± 2 days after stroke onset), defined as ASPECTS ≤4. Prominent edema was defined as a midline shift of ≥5 mm on follow-up. Admission patient and treatment characteristics were collected. Admission CT parameters used were ASPECTS on NCCT and CBV and MTT maps, and occlusion site, clot burden, and collaterals on CTA. Permeability on admission CTP, and day 3 recanalization and reperfusion statuses were obtained if available. Unadjusted and adjusted (age and NIHSS) odds ratios were calculated for all variables in relation to prominent edema. RESULTS: Prominent edema developed in 51 patients (37%). Adjusted odds ratios for prominent edema were higher with lower ASPECTS on NCCT (adjusted odds ratio, 1.32; 95% CI, 1.13-1.55) and CBV (adjusted odds ratio, 1.26; 95% CI, 1.07-1.49), higher permeability (adjusted odds ratio, 2.35; 95% CI, 1.30-4.24), more proximal thrombus location (adjusted odds ratio, 3.40; 95% CI, 1.57-7.37), higher clot burden (adjusted odds ratio, 2.88; 95% CI, 1.11-7.45), and poor collaterals (adjusted odds ratio, 3.93; 95% CI, 1.78-8.69). CONCLUSIONS: Extensive proximal occlusion, poor collaterals, and larger ischemic deficits with higher permeability play a role in the development of prominent edema in large MCA infarcts.

Antithrombotic treatment and intracerebral haemorrhage: between Scylla and Charybdis.

In patients who have intracerebral haemorrhage while on antithrombotic treatment, there is no evidence from randomised clinical trials to support decisions with regard to antithrombotic medication. In the acute phase, we advise stopping all antithrombotic treatment with rapid reversal of antithrombotic effects of oral anticoagulants. After the acute phase, we discourage restarting oral anticoagulants in patients with a lobar haematoma caused by cerebral amyloid angiopathy because of the high risk of recurrent bleeding. In these patients, even treatment with platelet inhibitors needs careful weighing of the risks of bleeding and ischaemic stroke. In patients with non-lobar intracerebral haemorrhage, we suggest considering restarting optimal antithrombotic treatment. This includes treatment with oral anticoagulants for patients with atrial fibrillation and/or mechanical valve prosthesis. After intracerebral haemorrhage during oral anticoagulant therapy in patients with atrial fibrillation, direct anticoagulants may be better than vitamin K antagonists, but we await confirmation of this from ongoing trials.

New algorithm for treatment allocation reduced selection bias and loss of power in small trials.

OBJECTIVE: In clinical trials, patients become available for treatment sequentially. Especially in trials with a small number of patients, loss of power may become an important issue, if treatments are not allocated equally or if prognostic factors differ between the treatment groups. We present a new algorithm for sequential allocation of two treatments in small clinical trials, which is concerned with the reduction of both selection bias and imbalance. STUDY DESIGN AND SETTING: With the algorithm, an element of chance is added to the treatment as allocated by minimization. The amount of chance depends on the actual amount of imbalance of treatment allocations of the patients already enrolled. The sensitivity to imbalance may be tuned. We performed trial simulations with different numbers of patients and prognostic factors, in which we quantified loss of power and selection bias. RESULTS: With our method, selection bias is smaller than with minimization, and loss of power is lower than with pure randomization or treatment allocation according to a biased coin principle. CONCLUSION: Our method combines the conflicting aims of reduction of bias by predictability and reduction of loss of power, as a result of imbalance. The method may be of use in small trials.

Appreciation of the informed consent procedure in a randomised trial of decompressive surgery for space occupying hemispheric infarction.

BACKGROUND AND AIM: As non-randomised studies have suggested that surgical decompression may reduce mortality in patients with space occupying hemispheric infarction, randomisation may be considered unethical in controlled trials testing this treatment strategy. We studied differences in recall of information and in appreciation of the informed consent procedure between representatives included in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET) and representatives of patients participating in the randomised trial of Paracetamol (Acetaminophen) In Stroke (PAIS). METHODS: 1 year after study inclusion, we contacted 30 consecutive representatives who had given informed consent for participation of their relative in HAMLET, and 30 for PAIS. Recall of trial details and appreciation of the informed consent procedure were investigated using standardised questionnaires and compared between the two groups. RESULTS: All 30 PAIS representatives and 28 HAMLET representatives were interviewed. Participation of their relative in a clinical trial was remembered by 86% of HAMLET and 40% of PAIS representatives (p<0.001). HAMLET representatives remembered more trial details (effect of the treatment under study (61% vs 3%, p<0.001); randomised treatment allocation (71% vs 0%, p<0.001)). With respect to appreciation of the informed consent procedure, we found no differences between the groups: in each trial, four representatives (14% vs 13%) had considered the question of randomisation unacceptable. CONCLUSIONS: Participation of patients in a randomised controlled trial of surgical decompression for space occupying infarction is generally considered acceptable by their representatives, and recall of trial details is better than in a trial in which less vital issues are at stake.

Comparison of perfusion MRI by flow-sensitive alternating inversion recovery and dynamic susceptibility contrast in rats with permanent middle cerebral artery occlusion.

We compared cerebral blood flow (CBF) parameters obtained by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with those obtained by flow-sensitive alternating inversion recovery (FAIR) in brain regions with different perfusion levels in rats with permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed in 19 rats. T2-weighted MRI, FAIR and DSC-MRI were performed within 48 h after occlusion. CBF parameters were analyzed in regions of interest with either prolonged or less prolonged mean transit time (MTT). Ratios of ipsi- vs contralateral CBF values were calculated and tested for correlation and differences between FAIR and DSC-MRI. FAIR-aCBF ratios correlated significantly with DSC-rCBF ratios. The mean FAIR-aCBF ratio was significantly lower than mean DSC-rCBF ratio in the area with prolonged MTT. In the area with less prolonged MTT, the mean FAIR-aCBF ratio and mean DSC-rCBF values did not differ significantly. We conclude that FAIR correlates with DSC-MRI if perfusion is preserved. FAIR provides lower CBF values than DSC-MRI if perfusion is reduced and MTT is prolonged. This probable underestimation of perfusion may be caused by transit delays. Care should be taken when quantifying CBF with FAIR and when comparing the results of FAIR- and DSC-MRI in areas with hypoperfusion.

The time course of ischemic damage and cerebral perfusion in a rat model of space-occupying cerebral infarction.

We aimed to establish a rat model of space-occupying hemispheric infarction to evaluate potential treatment strategies. For adequate timing of therapy in future experiments, we studied the development of tissue damage, edema formation, and perfusion over time with different MRI techniques. Permanent middle cerebral artery (MCA) occlusion was performed in 32 Fisher-344 rats. Forty-six MRI experiments including diffusion weighted (DW), T2-weighted (T2W), flow-sensitive alternating inversion recovery (FAIR) perfusion-weighted, and T1-weighted (T1W) imaging before and after gadolinium were performed at 1, 3, 8, 16, 24, and 48 h of ischemia. MCA occlusion consistently led to infarction of the complete MCA territory. Mortality was 75%. Lesion volumes as derived from apparent diffusion coefficient (ADC) and T2 maps increased to maximum values of 400+/-48 mm3 at 24 h and 420+/-54 mm3 at 48 h of ischemia, respectively. Midline shift peaked at 24 h. The area with diffusion-perfusion deficit decreased to a minimum at 24 h after onset of ischemia and perfusion of the contralateral hemisphere dropped at the same time point. Leakage of gadolinium through the blood-brain barrier in the entire infarct occurred within 3 h of ischemia. Permanent intraluminal MCA occlusion in Fisher-344 rats is an adequate model for space-occupying cerebral infarction. Rats may benefit from intervention aimed at reducing tissue shift and intracranial pressure (ICP), and at improving cerebral blood flow, if initiated before 24 h after MCA occlusion. The value of treatment modalities depending on an intact blood-brain barrier should be questioned.

Delayed decompressive surgery increases apparent diffusion coefficient and improves peri-infarct perfusion in rats with space-occupying cerebral infarction.

BACKGROUND AND PURPOSE: There is no conclusive experimental support that decompressive surgery in late stages of space-occupying cerebral infarction will improve outcome. We studied the effects of delayed decompressive surgery on the development of tissue damage, edema formation, and cerebral perfusion with different MRI techniques in a rat model of space-occupying cerebral infarction. METHODS: Permanent middle cerebral artery (MCA) occlusion was performed in 6 Fisher 344 rats. Decompressive surgery was performed 17 hours after the occlusion. Each animal was assessed before surgery and 2 and 4 hours after surgery by means, of diffusion-weighted T2-weighted, and flow-sensitive alternating inversion recovery perfusion-weighted MRI. Ischemic damage was also evaluated in hematoxylin-eosin-stained brain sections. RESULTS: Lesion volume as derived from apparent diffusion coefficient (ADC) maps decreased from 522+/-98 mm3 before to 405+/-100 mm3 (P=0.016) 4 hours after decompressive surgery, whereas lesion volume from T2 maps increased from 420+/-66 mm3 before to 510+/-92 mm3 (P=0.048) 4 hours after decompressive surgery. Midline shift decreased from 1.4+/-0.1 mm to 0.5+/-0.2 mm (P=0.001). Blood flow in the noninfarcted area of the ipsilateral hemisphere improved from 25+/-9 mL/min/100 g of tissue to 38+/-9 mL/min/100 g of tissue (P=0.035). Despite the pseudonormalization of ADC, irreversible damage was found in the entire MCA territory on histological evaluation. CONCLUSIONS: In rats with space-occupying cerebral infarction, delayed decompressive surgery leads to a decrease in lesion volume derived from ADC maps, which is probably because of an increase of extracellular water formation. There are no signs that this reflects rescue of ischemic tissue.

[Surgical decompression in space-occupying cerebral infarct; notification of a randomized trial]. / Chirurgische decompressie bij het ruimte-innemende herseninfarct; aanmelding voor een gerandomiseerde trial.

Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite intensive conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery substantially reduces mortality and improves the functional outcome of survivors. The 'Hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial' (HAMLET) is a newly-conceived randomised multi-centre clinical trial that compares the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction.

Collateral circulation via the ophthalmic artery or leptomeningeal vessels is associated with impaired cerebral vasoreactivity in patients with symptomatic carotid artery occlusion.

BACKGROUND AND PURPOSE: In patients with carotid artery occlusion (CAO), collateral flow may reduce the risk of ischemic stroke. Collateral flow via the ophthalmic artery (OphthA) and flow via leptomeningeal vessels have been considered secondary collaterals, which are recruited only if the primary collateral circulation via the circle of Willis is insufficient. The aim of this study was to investigate whether patients with symptomatic CAO who have secondary in addition to primary collaterals have a worse flow state of the brain than those without secondary collaterals, as measured by vascular reactivity testing. METHODS: We studied 70 patients with symptomatic CAO who were independent for their daily activities. In all patients, collateral circulation through the circle of Willis was present. Vascular reactivity, measured by means of transcranial Doppler sonography with carbogen inhalation, was compared between patients with and without secondary collaterals. RESULTS: CO2 reactivity was lower in 64 patients with (mean +/- standard deviation 8 +/- 14%) than in 6 patients without secondary collaterals (33 +/- 18%) resulting in a mean difference of 24% (95% confidence interval 12-37%; p < 0.01). CONCLUSIONS: Patients with symptomatic CAO with collateral circulation through the OphthA or through leptomeningeal vessels in addition to collaterals via the circle of Willis have a worse hemodynamic status of the brain than those with Willisian collaterals only. Therefore the presence of these collaterals may indicate insufficiency of collateral blood flow via the circle of Willis.