Space-occupying Hemispheric Infarction Research Articles

Pupillometry in the follow-up of patients undergoing EVT - prediction of space-occupying hemispheric infarction

BackgroundDespite benefits of endovascular treatment (EVT) for large vessel occlusion (LVO) ischemic stroke, space-occupying brain edema (BE) represents a detrimental complication. In critical-care settings, CT-imaging is needed for monitoring these patients. Yet, bed-side techniques with the potential to predict whether patients develop BE or not would facilitate a time- and cost-efficient patient care. We assessed clinical significance of automated pupillometry in the follow-up of patients undergoing EVT.MethodsFrom 10/2018 to 10/2021, neurocritical-care-unit patients were retrospectively enrolled after EVT of anterior circulation LVO. We monitored parameters of pupillary reactivity [light-reflex-latency (Lat), constriction- and redilation-velocities (CV, DV), percentage-change-of-apertures (per-change); NeurOptics-pupilometer®] up to every hour on day 1–3 of ICU stay. BE was defined as midline shift ≥ 5 mm on follow-up imaging 3–5 days after EVT. We calculated mean values of intra-individual differences between successive pairs of parameters (mean-deltas), determined best discriminative cut-off values for BE development (ROC-analyses), and evaluated prognostic performance of pupillometry for BE development (sensitivity/specificity/positive-/negative-predictive-values).Results3241 pupillary assessments of 122 patients [67 women, 73 years (61.0–85.0)] were included. 13/122 patients developed BE. Patients with BE had significantly lower CVs, DVs, and smaller per-changes than patients without BE. On day 1 after EVT mean-deltas of CV, DV, and per-changes were significantly lower in patients with than without BE. Positive-predictive-values of calculated thresholds to discriminate both groups were considerably low, yet, we found high negative-predictive-values for CV, DV, per-changes, and mean-deltas (max.: 98.4%).ConclusionOur data suggest associations between noninvasively detected changes in pupillary reactivity and BE early after LVO-EVT. Pupillometry may identify patients who are unlikely to develop BE and may not need repetitive follow-up-imaging or rescue-therapy.

Investigational drugs for ischemic stroke: what’s in the clinical development pipeline for acute phase and prevention?

Introduction Stroke is a leading cause of disability and mortality and its burden expected to increase. The only approved drug for acute ischemic stroke is the intravenous thrombolytic alteplase. The risk of bleeding complications is one of the reasons for the undertreatment of eligible patients. Numerous drugs are currently being developed to improve safety-efficacy. Areas covered We reviewed literature from January 1st, 2000, to 15th January 2022 for the development and testing of novel drugs with the aim of targeting treatment at prevention of ischemic stroke: PubMed, MEDLINE, Google Scholar, and ClinicalTrial.gov. Expert opinion The pathophysiology of ischemic stroke involves multiple pathways causing cerebral artery obstruction and brain tissue ischemia. Data suggest that tenecteplase is a more promising fibrinolytic agent with a superior efficacy-safety profile, compared to the currently approved alteplase. Current guidelines consider a short-term cycle of mannitol or hypertonic saline to be advisable in patients with space-occupying hemispheric infarction. Regarding primary and secondary prevention, research is primarily focused on identifying mechanisms to improve the safety-efficacy profile using a “hemostasis-sparing” approach. Further evaluation on those agents that have already shown promise for their risk/benefit profiles, would benefit greatly a neurologist’s capacity to successfully prevent and treat ischemic stroke patients.

European Stroke Organisation (ESO) guidelines on the management of space-occupying brain infarction.

Space-occupying brain oedema is a potentially life-threatening complication in the first days after large hemispheric or cerebellar infarction. Several treatment strategies for this complication are available, but the size and quality of the scientific evidence on which these strategies are based vary considerably. The aim of this Guideline document is to assist physicians in their management decisions when treating patients with space-occupying hemispheric or cerebellar infarction. These Guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A working group identified 13 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. An expert consensus statement was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high-quality evidence to recommend surgical decompression to reduce the risk of death and to increase the chance of a favourable outcome in adult patients aged up to and including 60 years with space-occupying hemispheric infarction who can be treated within 48 hours of stroke onset, and low-quality evidence to support this treatment in older patients. There is continued uncertainty about the benefit and risks of surgical decompression in patients with space-occupying hemispheric infarction if this is done after the first 48 hours. There is also continued uncertainty about the selection of patients with space-occupying cerebellar infarction for surgical decompression or drainage of cerebrospinal fluid. These Guidelines further provide details on the management of specific subgroups of patients with space-occupying hemispheric infarction, on the value of monitoring of intracranial pressure, and on the benefits and risks of medical treatment options. We encourage new high-quality studies assessing the risks and benefits of different treatment strategies for patients with space-occupying brain infarction.

Subcortical Sparing Associated with Ambulatory Independence after Hemicraniectomy for Malignant Infarction

Decompressive hemicraniectomy (DHC) is a life-saving 1 Vahedi K. Hofmeijer J. Juettler E. et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007; 6: 215-222 Abstract Full Text Full Text PDF PubMed Scopus (1209) Google Scholar and function-sparing 2 Reinink H. Juttler E. Hacke W. et al. Surgical decompression for space-occupying hemispheric infarction: a systematic review and individual patient meta-analysis of randomized clinical trials. JAMA Neurol. 2020; Google Scholar procedure for patients with malignant middle cerebral artery (MCA) infarction. Pooled estimates suggest that approximately 40% of patients achieve ambulatory independence after DHC, 1 Vahedi K. Hofmeijer J. Juettler E. et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007; 6: 215-222 Abstract Full Text Full Text PDF PubMed Scopus (1209) Google Scholar ,2 Reinink H. Juttler E. Hacke W. et al. Surgical decompression for space-occupying hemispheric infarction: a systematic review and individual patient meta-analysis of randomized clinical trials. JAMA Neurol. 2020; Google Scholar with age 3 Juttler E. Unterberg A. Woitzik J. et al. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. N Engl J Med. 2014; 370: 1091-1100 Crossref PubMed Scopus (360) Google Scholar being the only clinical or radiologic feature found to influence the likelihood of achieving this outcome. 2 Reinink H. Juttler E. Hacke W. et al. Surgical decompression for space-occupying hemispheric infarction: a systematic review and individual patient meta-analysis of randomized clinical trials. JAMA Neurol. 2020; Google Scholar Subcortical infarctions have been shown to impair motor recovery and gait, 4 Jones P.S. Pomeroy V.M. Wang J. et al. Does stroke location predict walk speed response to gait rehabilitation?. Hum Brain Mapp. 2016; 37: 689-703 Crossref PubMed Scopus (36) Google Scholar ,5 Zhu L.L. Lindenberg R. Alexander M.P. Schlaug G. Lesion load of the corticospinal tract predicts motor impairment in chronic stroke. Stroke. 2010; 41: 910-915 Crossref PubMed Scopus (194) Google Scholar but whether the presence of a subcortical infarction affects functional outcome following DHC remains unknown. Our aim was to determine if subcortical involvement in malignant MCA infarction is associated with independent ambulation one year following DHC.

European Stroke Organisation (ESO) guidelines on the management of space-occupying brain infarction.

Space-occupying brain oedema is a potentially life-threatening complication in the first days after large hemispheric or cerebellar infarction. Several treatment strategies for this complication are available, but the size and quality of the scientific evidence on which these strategies are based vary considerably. The aim of this Guideline document is to assist physicians in their management decisions when treating patients with space-occupying hemispheric or cerebellar infarction. These Guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A working group identified 13 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. An expert consensus statement was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high-quality evidence to recommend surgical decompression to reduce the risk of death and to increase the chance of a favourable outcome in adult patients aged up to and including 60 years with space-occupying hemispheric infarction who can be treated within 48 hours of stroke onset, and low-quality evidence to support this treatment in older patients. There is continued uncertainty about the benefit and risks of surgical decompression in patients with space-occupying hemispheric infarction if this is done after the first 48 hours. There is also continued uncertainty about the selection of patients with space-occupying cerebellar infarction for surgical decompression or drainage of cerebrospinal fluid. These Guidelines further provide details on the management of specific subgroups of patients with space-occupying hemispheric infarction, on the value of monitoring of intracranial pressure, and on the benefits and risks of medical treatment options. We encourage new high-quality studies assessing the risks and benefits of different treatment strategies for patients with space-occupying brain infarction.

Surgical decompression for space-occupying hemispheric infarction.

Surgical decompression for space-occupying hemispheric infarction.

Surgical Decompression for Space-Occupying Hemispheric Infarction

In patients with space-occupying hemispheric infarction, surgical decompression reduces the risk of death and increases the chance of a favorable outcome. Uncertainties, however, still remain about the benefit of this treatment for specific patient groups. To assess whether surgical decompression for space-occupying hemispheric infarction is associated with a reduced risk of death and an increased chance of favorable outcomes, as well as whether this association is modified by patient characteristics. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Stroke Trials Registry were searched from database inception to October 9, 2019, for English-language articles that reported on the results of randomized clinical trials of surgical decompression vs conservative treatment in patients with space-occupying hemispheric infarction. Published and unpublished randomized clinical trials comparing surgical decompression with medical treatment alone were selected. Patient-level data were extracted from the trial databases according to a predefined protocol and statistical analysis plan. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and the Cochrane Collaboration's tool for assessing risk of bias were used. One-stage, mixed-effect logistic regression modeling was used for all analyses. The primary outcome was a favorable outcome (modified Rankin Scale [mRS] score ≤3) at 1 year after stroke. Secondary outcomes included death, reasonable (mRS score ≤4) and excellent (mRS score ≤2) outcomes at 6 months and 1 year, and an ordinal shift analysis across all levels of the mRS. Variables for subgroup analyses were age, sex, presence of aphasia, stroke severity, time to randomization, and involved vascular territories. Data from 488 patients from 7 trials from 6 countries were available for analysis. The risk of bias was considered low to moderate for 6 studies. Surgical decompression was associated with a decreased chance of death (adjusted odds ratio, 0.16; 95% CI, 0.10-0.24) and increased chance of a favorable outcome (adjusted odds ratio, 2.95; 95% CI, 1.55-5.60), without evidence of heterogeneity of treatment effect across any of the prespecified subgroups. Too few patients were treated later than 48 hours after stroke onset to allow reliable conclusions in this subgroup, and the reported proportions of elderly patients reaching a favorable outcome differed considerably among studies. The results suggest that the benefit of surgical decompression for space-occupying hemispheric infarction is consistent across a wide range of patients. The benefit of surgery after day 2 and in elderly patients remains uncertain.

Treatment for Large Cerebral Infarction: Past, Present, and Future

As Cushing wrote, decompressive hemicraniectomy (DHC) has been used to palliate increased intracranial pressure from brain tumors whose localization was not detected with available neurologic or radiologic diagnostic techniques or those from head injury. After World War II, experimental studies showed that removing a bone flap over the site of acute closed cerebral lesion characterized by hemorrhage, necrosis, and edema was of definite benefit, even after the onset of symptoms indicating impending death (18), and internal and external decompressive surgeries were performed for mass effect in patients with cerebral or cerebellar infarctions, which was diagnosed as a brain tumor by radiographical examinations before the operations. Several reports have shown the effectiveness of surgical decompression in treating edema secondary to cerebral and cerebellar infarctions (7, 12). In the first prospective, nonrandomized, control trial, Rieke et al. (13) reported that DHC decreased rates of mortality to less than 35% in patients with space-occupying hemispheric infarction. Early DHC after such an infarction leads to a significant reduction in the length of time in which critical care therapy is necessary and trends toward a better outcome (15). Walz et al. (21) reported that survivors were significantly younger than nonsurvivors after DHC and that younger patients had a significantly better outcome than older patients in survivors. Based on previously reported promising

Cost-Effectiveness of Surgical Decompression for Space-Occupying Hemispheric Infarction

Surgical decompression reduces mortality and increases the probability of a favorable functional outcome after space-occupying hemispheric infarction. Its cost-effectiveness is uncertain. We assessed clinical outcomes, costs, and cost-effectiveness for the first 3 years in patients who were randomized to surgical decompression or best medical treatment within 48 hours after symptom onset in the Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema Trial (HAMLET). Data on medical consumption were derived from case record files, hospital charts, and general practitioners. We calculated costs per quality-adjusted life year (QALY). Uncertainty was assessed with bootstrapping. A Markov model was constructed to estimate costs and health outcomes after 3 years. Of 39 patients enrolled within 48 hours, 21 were randomized to surgical decompression. After 3 years, 5 surgical (24%) and 14 medical patients (78%) had died. In the first 3 years after enrollment, operated patients had more QALYs than medically treated patients (mean difference, 1.0 QALY [95% confidence interval, 0.6-1.4]), but at higher costs (mean difference, €127,000 [95% confidence interval, 73,100-181,000]), indicating incremental costs of €127,000 per QALY gained. Ninety-eight percent of incremental cost-effectiveness ratios replicated by bootstrapping were >€80,000 per QALY gained. Markov modeling suggested costs of ≈€60,000 per QALY gained for a patient's lifetime. Surgical decompression for space-occupying infarction results in an increase in QALYs, but at very high costs. http://www.controlled-trials.com. Unique identifier: ISRCTN94237756.

Surgical Decompression for Space-Occupying Cerebral Infarction

We assessed whether the effects of surgical decompression for space-occupying hemispheric infarction, observed at 1 year, are sustained at 3 years. Patients with space-occupying hemispheric infarction, who were enrolled in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial within 4 days after stroke onset, were followed up at 3 years. Outcome measures included functional outcome (modified Rankin Scale), death, quality of life, and place of residence. Poor functional outcome was defined as modified Rankin Scale >3. Of 64 included patients, 32 were randomized to decompressive surgery and 32 to best medical treatment. Just as at 1 year, surgery had no effect on the risk of poor functional outcome at 3 years (absolute risk reduction, 1%; 95% confidence interval, -21 to 22), but it reduced case fatality (absolute risk reduction, 37%; 95% confidence interval, 14-60). Sixteen surgically treated patients and 8 controls lived at home (absolute risk reduction, 27%; 95% confidence interval, 4-50). Quality of life improved between 1 and 3 years in patients treated with surgery. In patients with space-occupying hemispheric infarction, the effects of decompressive surgery on case fatality and functional outcome observed at 1 year are sustained at 3 years. http://www.controlled-trials.com. Unique identifier: ISRCTN94237756.

Cognitive outcome of survivors of space-occupying hemispheric infarction

In patients with space-occupying hemispheric infarction, surgical decompression within 48 h after stroke onset increases the chance of a good functional outcome, but also the chance of survival with severe disability. Until now, cognitive outcome in these patients has not been reported in a consecutive series. Participants of the hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial (HAMLET; ISRCTN94237756) underwent detailed neuropsychological examination at a median of 14.5 months after stroke onset. 'Global cognitive impairment' was defined as a score on the Cambridge cognitive examination (CAMCOG) ≤ 83. Impairment on an individual neuropsychological task was defined as a score below the 2.5th percentile or more than two standard deviations below standard norms. The association between cognitive and functional outcome was analysed with linear regression. Twenty patients were tested. Fifteen (75 %) had global cognitive impairment or such poor performance that assessment of global cognitive performance by the CAMCOG was not feasible. Five had only focal cognitive deficits. Still, detailed neuropsychological examination was feasible in 18 patients. Patients with aphasia performed worse than those without on both verbal and non-verbal tasks. Poorer cognitive performance was associated with worse functional outcome as assessed with the modified Rankin scale (β -0.4, 95 % CI -0.6 to -0.1). No differences were observed between operated and non-operated patients. The majority of survivors of space-occupying hemispheric infarction suffered from long-term global cognitive impairment. Isolated focal neuropsychological deficits were found in only a quarter. Impaired cognitive outcome was associated with worse functional outcome.

Direct observation of human microcirculation during decompressive craniectomy after stroke*

Most knowledge related to the pathophysiology of microcirculation in ischemic stroke comes from experimental research. Unfortunately, data on microcirculation in the human brain are limited, partially as a result of the lack of appropriate investigational techniques. The objective of our study was to test the hypothesis that cortical microcirculatory alterations in the brain, in terms of blood flow and vessel density, occur in patients with stroke who require surgical decompression compared with a control group. Prospective and observational study. Third-level university hospital. Six patients who had undergone decompressive surgery as a result of a space-occupying hemispheric infarction. These patients were compared with five patients who had undergone craniotomy for a disease not affecting the cortex. Cortical microcirculation in the brain was directly observed using sidestream dark-field imaging. All images were analyzed offline. In patients with stroke with a space-occupying hemispheric infarction, 18 good-quality movie images were compared with 25 control group images. In the control group, cortical vessels showed a continuous flow in small, medium, and large vessels compared with patients with stroke who presented intermittent or no flow in all vessels. The proportion of perfused vessels was near 100% in control subjects and 63.44% in patients with stroke. The perfused vessel density index was also higher in control subjects (6.16 1/mm; interquartile range, 5.65-7.56) than in patients with stroke (2.77 1/mm; interquartile range, 1.75-3.86). Sidestream dark-field imaging allowed direct visualization of cerebral microcirculatory alterations in the operating room. This technique allowed the documentation of a significant blood flow reduction in the cortical microvascular and a decreased vascular density in patients with stroke compared with control subjects.

Surviving space-occupying cerebral infarction

Patients with space-occupying hemispheric infarction have a poor prognosis, with case fatality rates of up to 78% if treated conservatively.1 The only treatment option of proven benefit is surgical decompression through removal of a large part of the skull ipsilateral to the infarct, followed by a duraplasty—a hemicraniectomy. A pooled analysis of 3 small randomized controlled trials2–4 showed a large reduction in case fatality (71% vs 21%; absolute risk reduction, 50%; 95% confidence interval 34%–66%) after surgical decompression within 48 hours of stroke onset, compared to medical treatment. The chance of a favorable functional outcome at 12 months, defined as a score on the modified Rankin scale (mRS) ≤3, increased from 24% to 40%. Unfortunately, this large reduction in case fatality came at the expense of an increase in severe disability (mRS 4–5) at 12 months,4 from 6% to 40%. Because of the increase in severely disabled survivors, many have expressed concern about decompressive surgery on long-term quality of life. In randomized trials, this issue has received far less attention than that of death or dependency. Quality of life was assessed among survivors in 2 …

Decompressive Hemicraniectomy for Space-occupying Cerebral Infarction

The development of a space-occupying hemispheric infarction occurs in a subset of patients with ischaemic cerebrovascular stroke. It is a life-threatening condition with a high mortality rate of up to 80% with medical therapy alone. Previous retrospective and uncontrolled case series have suggested that decompressive hemicraniectomy can significantly reduce mortality to 20-30% compared to conservative treatment. This evidence has now been confirmed by the data of prospective randomised studies. The data also indicate that the reduction of mortality is not accompanied by an increase in the number of completely disabled patients. However, the number of disabled patients depending on the assistance of others increases significantly, and the patients and their caregivers need to be comprehensively informed about the long-term consequences prior to surgery. Furthermore, questions concerning the optimal time point for decompression and the upper age limit at which patients still benefit from surgery remain unanswered. Thus the indication for surgery is to a great extent still dependent on the individual situation of the patient and the experience of the treating physicians. This review covers the indications, the surgical technique, the prognostic factors and the clinical outcome with this procedure based on the data of retrospective series and the results of the recently published prospective randomised trials.

Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial

Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66). Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.

Antiedema Therapy in Ischemic Stroke

Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive.

The role of surgery in ischemic stroke: decompressive surgery

This review gives an integrated view on the current status of decompressive surgery in space-occupying hemispheric brain infarction with a focus on new developments based on the available data of recent clinical trials, also including preliminary data from randomized trials reported at international stroke conferences in 2006. The treatment of ischemic brain infarction with life-threatening space-occupying edema is, because of a lack of prospective studies, one of the major controversial issues within neurocritical care medicine today. Only a few years ago, massive cerebral infarctions were regarded an untreatable disease with fatal outcome. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view. Most of the reports, however, are retrospective with low numbers of patients. There are only few prospective trials that suggest a substantial benefit of decompressive surgery to significantly reduce mortality as compared to maximal conservative treatment alone. The control groups in these studies, however, consist of patients with higher age and higher rates of co-morbidities. Also, in most studies information on long-term outcome is insufficient. In 2006 long expected preliminary data from randomized trials of hemicraniectomy have been reported at international stroke conferences. They yield very positive results. Decompressive surgery appears to be a promising treatment option for patients with space-occupying hemispheric brain infarction.

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction

BackgroundPatients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal 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 reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarctionMethodsThe study design is that of a multi-centre, randomised clinical trial, which will include 112 patients aged between 18 and 60 years with a large hemispheric infarct with space-occupying oedema that leads to a decrease in consciousness. Patients will be randomised to receive either decompressive surgery in combination with medical treatment or best medical treatment alone. Randomisation will be stratified for the intended mode of conservative treatment (intensive care or stroke unit care). The primary outcome measure will be functional outcome, as determined by the score on the modified Rankin Scale, at one year.

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), T 2-weighted (T 2W), flow-sensitive alternating inversion recovery (FAIR) perfusion-weighted, and T 1-weighted (T 1W) 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 T 2 maps increased to maximum values of 400±48 mm 3 at 24 h and 420±54 mm 3 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.

Treatment of space-occupying cerebral infarction.

Patients with a hemispheric infarct accompanied by massive edema have a poor prognosis; the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Various treatment strategies have been proposed to limit brain tissue shifts and to reduce intracranial pressure, but their use is controversial. We performed a systematic search of the literature to review the evidence of efficacy of these therapeutic modalities. Literature searches were carried out on MEDLINE and PubMed. Studies were included if they were published in English between 1966 and February 2002 and addressed the effect of osmotherapy, hyperventilation, barbiturates, steroids, hypothermia, or decompressive surgery in supratentorial infarction with edema in animals or humans. Animal studies of medical treatment strategies in focal cerebral ischemia produced conflicting results. If any, experimental support for these strategies is derived from studies with animal models of moderately severe focal ischemia instead of severe space-occupying infarction. None of the treatment options have improved outcome in randomized clinical trials. Two large nonrandomized studies of decompressive surgery yielded promising results in terms of reduction of mortality and improvement of functional outcome. There is no treatment modality of proven efficacy for patients with space-occupying hemispheric infarction. Decompressive surgery might be the most promising therapeutic option. For decisive answers, randomized, controlled clinical trials are needed.