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Background Aneurysmal subarachnoid haemorrhage is a major cause of haemorrhagic stroke. The incidence is ≈ 80 per million population per year; it peaks in the 40–60 years age range and often has a poor prognosis with the outcome linked to severity of the initial haemorrhage. Aneurysmal subarachnoid haemorrhage accounts for 5% of strokes, but 20% of quality-adjusted life-years are lost to stroke and much of that loss is concentrated in World Federation of Neurosurgical Societies grade 4–5 (or poor-grade) aneurysmal subarachnoid haemorrhage patients. Before endovascular coiling was available, the conventional management strategy for poor-grade aneurysmal subarachnoid haemorrhage patients was to treat the ruptured aneurysm on neurological improvement. That incurs a risk of aneurysm rebleeding, which is highest soon after the first bleed; if rebleed occurs prior to aneurysm treatment, prognosis is dismal. Reducing rebleeding with early treatment might improve outcome. Therefore, an early coiling strategy in grade 4–5 patients is appealing, but not robustly evidenced. Early treatment in all grade 4–5 patients might prevent death from rebleeding but possibly at the expense of creating severely disabled survivors, with attendant societal costs. Many neuroclinicians have expressed genuine uncertainty regarding whether or not to treat all grade 4–5 aneurysmal subarachnoid haemorrhage patients emergently (as soon as possible regardless of neurological status). A pilot trial, the treatment of poor-grade subarachnoid haemorrhage trial 1 (TOPSAT1), indicated that recruitment to a randomised trial to address this uncertainty was feasible. Methods We investigated a management policy in aneurysmal subarachnoid haemorrhage World Federation of Neurosurgical Societies grades 4 or 5 of securing the ruptured aneurysm emergently (within 24 hours of randomisation) compared with the strategy to treat the aneurysm on neurological improvement (to World Federation of Neurosurgical Societies grades 1–3), irrespective of when that improvement occurred. The treatment of poor-grade subarachnoid haemorrhage trial 2 (TOPSAT2) was a pragmatic, randomised, open-blinded, end-point design trial aiming to recruit 346 adult patients (aged 18–80 years) in 30 UK and European neuroscience centres. Randomisation was web based, with minimisation criteria relating to age, grade, presence of hydrocephalus and UK location (vs. non-UK). Fifteen sites were opened to recruitment, 12 of which were in the UK. Standard institutional procedures for securing aneurysms were followed. An exploratory magnetic resonance biomarker substudy of 100 UK participants was planned but not opened. The primary end point was functional outcome at 12 months, determined by analysis of the modified Rankin Scale score. The secondary end points relating to safety were assessed. Results Of the 305 World Federation of Neurosurgical Societies grade 4–5 patients screened, 23 were randomised: 11 to the emergent treatment arm and 12 to the treatment on neurological improvement (control) arm. Trial recruitment was suspended when it was judged to have failed a feasibility assessment. The median time from ictus to treatment (where aneurysm was treated) was 26 hours in the emergent treatment arm and 163 hours in the treatment on neurological improvement arm. There were no statistically significant differences between arms in mortality (p = 0.4) or functional outcome at 365 days [modified Rankin Scale score 0–3 vs. 4–6 (p = 0.32)]. Sensitivity analysis was performed to examine the effect of missing data but differences remained non-significant. Limitations A limitation was the failure to recruit to time/target. Conclusions The randomised trial approach to investigating whether poor-grade aneurysmal subarachnoid haemorrhage patients should receive emergent treatment or be treated on neurological improvement proved unfeasible. No statistically significant differences were identified between the trial arms in mortality or functional outcome, but the small number of patients enrolled limits drawing firm conclusions. Future work No future work is currently planned. Trial registration Current Controlled Trials ISRCTN15960635. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 8. See the NIHR Journals Library website for further project information.

[Purpose] We have previously shown inversion therapy to be effective in a small prospective randomised controlled trial of patients with lumbar disc protrusions. Our purpose now was to measure symptoms and to compare the surgery rate following inversion for 85 participants with the surgery rate in 3 control groups. [Participants and Methods] Each of the 85 inverted participants acted as their own control for the "symptomatic" part of the study. In the "Need for surgery" part of the study, one control group was made up of similar patients with leg pain and sciatica who were referred to the same clinic in the same year. Two additional control groups were examined: the original control group from the pilot trial and the lumbar disc surgery waiting list patients. [Results] Inversion therapy relieved symptoms: there were improvements in the Visual Analogue Score, Roland Morris and Oswestry Disease indices and Health Utility Score compared with their pre-treatment status. Also, the 2 year surgery rate in the inversion participants in the registry (21%) was significantly lower than in the matched control group (39% at two years and 43% at four years). It was also lower than the surgery rate in the other 2 control groups. [Conclusion] Inversion therapy relieved symptoms and avoided surgery.

Background Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. Objective To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications. Methods We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials. Results Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence. Conclusions Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation.

Background Study was a PROBE design phase II randomized controlled trial (RCT). We assessed trial feasibility and technical efficacy and safety of two novel thrombectomy devices – ERIC (a retriever device) and SOFIA (a distal access catheter) – used alone or in combination depending on operator preference. Methods Four UK neuroscience centers enrolled adults with proximal large artery occlusion (LAO) stroke on imaging where arterial puncture was achievable within 5.5 hours (8.5 hours for posterior circulation) of symptom onset; National Institutes of Health Stroke Scale (NIHSS) ≥6 with limited ischemic change on CT imaging. Randomization was 2:1 into intervention arm (ERIC and/or SOFIA). Patients and core lab were blinded to allocation. Primary outcome was independent core lab adjudication of reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) scale). Secondary outcomes were modified Rankin score (mRS) at 90 and 365 days (independence and shift analysis), 30-day mortality, symptomatic intracranial hemorrhage (sICH), procedural complications and NIHSS change. Results Sixty-six patients were enrolled. TICI 2B/3 reperfusion was achieved in 72% in intervention compared with 90% in control arm on intention to treat (ITT) analysis (P=0.2) and 78% compared with 86% on per protocol analysis (P=0.7). Functional independence at 90 days was 40% (intervention) compared with 43% (control) on ITT analysis (P=1.0). sICH rates were low at 0% and 5%, respectively (P=0.3). The 30-day mortality was 9% intervention compared with 14% control (P=0.7). Conclusions Study indicated feasibility of a phase II RCT trial approach for assessing new thrombectomy devices. In a broad LAO stroke population ERIC and SOFIA were not statistically different from control devices. Larger trials are needed.

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Background The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. Objective To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. Methods Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. Results End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. Conclusion Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.

Introduction: The Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation Phase III trial (MISTIE III) concluded that the extent of hematoma reduction confers a mortality and functional benefit. It is unclear if a minimum extent of evacuation is needed for mortality and functional outcome benefit in lobar cases with MISTIE and with open surgical interventions. Objective: We analyzed the effect of extent of lobar ICH evacuation on clinical outcome at 180 days after undergoing the MISTIE procedure and open craniotomy, in the context of the MISTIE III and STICH II clinical trials, respectively. Methods: Patients randomized to the surgical arm with lobar ICH, who underwent the procedure in the MISTIE III trial (n=84) and the STICH II trial (n=266) were analyzed, excluding cases crossing over to surgery. We assessed end of treatment ICH volume on post procedure CT scans and % hematoma evacuation, in relation to survival and likelihood of mRS 0-3. Cubic spline modeling with dichotomized outcome was used to compare the extent of hematoma evacuation on clinical outcome. Results: End of treatment volume of < 28 mL in lobar ICH MISTIE III patients and < 30 mL in STICH II trial patients showed a significantly increased probability of achieving an mRS of 0-3 at 180 days (p Conclusion: This analysis confirms that extent of hematoma evacuation is important in attaining the benefits of both minimally invasive and open surgical interventions in non-herniating lobar ICH patients randomized in clinical trials. Extent of ICH evacuation must be considered in the analysis of comparative effectiveness of various techniques and in the design of future trials.

Introduction: Completion of the MISTIE procedure requires a period of hematoma stability before and during hematoma removal and, if necessary, dosing of rtPA which can take days to complete. Early surgery was intended in the STICH I and II trials, yet was performed after varying delays. No previous analysis has evaluated the timing for hematoma removal on outcomes in these trials. Objective: Determine if time from ictus to completion of hematoma removal may have affected patient outcome in three large surgical clinical trials of ICH evacuation. Methods: Patients randomized to surgery in the MISTIE III (n=242), STICH I (n=464) and STICH II (n=266) trials who received the procedure were analyzed, excluding cases crossing over to surgery. Time from ictus to end of treatment, defined as 24 hours after last dose in (MISTIE III) or time to craniotomy (STICH I and II), was analyzed in relation to likelihood of survival and functional outcome at 180 days. Cubic spline models with dichotomized outcomes were used. Results: The probability of achieving an mRS 0-3 increased significantly with longer time until completion of the procedure, up to 83 hours post-ictus, and worsened with longer delays thereafter (p=0.05). Better mRS was also achieved in STICH I patients with longer time until surgical removal, up to 60 hours post-ictus (p=0.0002), but not with longer delays (p=0.49). In STICH II (lobar cases), there was greater likelihood of mRS 0-3 with longer delay after 22 hours post-ictus (p=0.004), but not with earlier surgery (p=0.19). There was no significant benefit in survival, with earlier intervention across modalities and trials. Adjustment by initial hematoma volume further validated that early procedures do not favor survival or achieving a mRS 0-3. Conclusion: Early hematoma evacuation up to 60-80 hours post-ictus does not increase the probability of survival nor a good functional outcome in non-herniating ICH patients included in clinical trials, likely in view of bleeding instability. This was true in minimally invasive intervention as well as open surgeries.

Background and Purpose— The ABC/2 method for calculating intracerebral hemorrhage (ICH) volume has been well validated. However, the formula, derived from the volume of an ellipse, assumes the shape of ICH is elliptical. We sought to compare the agreement of the ABC/2 formula with other methods through retrospective analysis of a selection of the STICH II cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas). Methods— From 390 patients, 739 scans were selected from the STICH II image archive based on the availability of a CT scan compatible with OsiriX DICOM viewer. ICH volumes were calculated by the reference standard semiautomatic segmentation in OsiriX software and compared with calculated arithmetic methods (ABC/2, ABC/2.4, ABC/3, and 2/3SC) volumes. Volumes were compared by difference plots for specific groups: randomization ICH (n=374), 3- to 7-day postsurgical ICH (n=206), antithrombotic-associated ICH (n=79), irregular-shape ICH (n=703) and irregular-density ICH (n=650). Density and shape were measured by the Barras ordinal shape and density groups (1–5). Results— The ABC/2.4 method had the closest agreement to the semiautomatic segmentation volume in all groups, except for the 3- to 7-day postsurgical ICH group where the ABC/3 method was superior. Conclusions— Although the ABC/2 formula for calculating elliptical ICH is well validated, it must be used with caution in ICH scans where the elliptical shape of ICH is a false assumption. We validated the adjustment of the ABC/2.4 method in randomization, antithrombotic-associated, heterogeneous-density, and irregular-shape ICH. Clinical Trial Registration— URL: http://www.isrctn.com/ISRCTN22153967 . Unique identifier: ISRCTN22153967.

Supplemental Digital Content is available in the text., Background and Purpose— The STICH (Surgical Trial in Lobar Intracerebral Haemorrhage) I and II trials randomized patients with spontaneous intracerebral hemorrhage (ICH) to early surgery or initial conservative treatment. Both were nonsignificant; possibly because surgery has minimal effect on recovery, or because surgery benefits some and harms others. We introduce a new nonparametric method of analysis. The method is then applied to data from a third trial, STITCH(Trauma) (Surgical Trial in Traumatic Intracerebral Haemorrhage), which addressed a similar surgical question in head-injured patients. Methods— Data from 1541 patients from the STICH trials were analyzed using (1) standard meta-analysis of prognosis-based dichotomized outcome and prespecified standard subgroups of Glasgow Coma Scale (GCS): 3–8, 9–12, and 13–15; (2) new nonparametric regression of ranked Extended Glasgow Outcome Scale against ranked GCS and ranked volume; and (3) analysis (1) repeated using categories identified by analysis (2). Results— Standard meta-analysis showed more favorable outcomes, although nonsignificant, with surgery if presenting GCS was 9–12 (spontaneous ICH odds ratio, 0.70 [95% CI, 0.48–1.03; P=0.07]; traumatic odds ratio, 0.48 [95% CI, 0.18–1.26; P=0.14]). Ranked analysis showed a similar pattern of results for both spontaneous and traumatic ICH. Surgery was harmful for small lesions with increasing benefit for larger volumes. With GCS, surgery had little effect at either ends of the spectrum but suggested a beneficial effect in the range 10 to 13 (identified graphically). Repeating the meta-analysis with this categorization showed significant benefit for surgery (spontaneous odds ratio, 0.71 [95% CI, 0.51–1.00; P=0.05]; traumatic odds ratio, 0.16 [95% CI, 0.05–0.51; P=0.002]). Conclusions— The nonsignificant results observed in the STICH trials are because of mixing patients who benefit from surgery with those who are harmed. Patients with a GCS 10–13 or a large ICH are likely to benefit from surgery. Our analysis showed a similar effect on traumatic ICH/contusion data and promises to be a valuable tool. Clinical Trial Registration— URL: http://www.isrctn.com/. Unique identifiers: ISRCTN19976990 (STITCH), ISRCTN22153967 (STICH II), and ISRCTN19321911 (STITCH[Trauma]).

On 7 February 2019, the results of the efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III) trial were announced at the Internati...

Summary Background Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18–80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770. Findings Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7–22.6] vs eight [14·8%, 6·6–27·1], p=0·542), 7 day mortality (zero [0%, 0–8·4] vs one [1·9%, 0·1–9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1–12·6] vs five [9·3%, 3·1–20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1–12·6] vs zero [0%, 0–6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0–35·6] vs three [7·1%; 1·5–19·5]; p=0·051). Interpretation MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. Funding National Institute of Neurological Disorders and Stroke, Genentech, and Codman.

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.

External ventricular drainage (EVD) may be used for therapeutic cerebrospinal fluid (CSF) drainage to control intracranial pressure (ICP) after traumatic brain injury (TBI). However, there is currently uncertainty regarding the optimal timing for EVD insertion. This study aims to compare patient outcomes for patients with early and late EVD insertion. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, MEDLINE/EMBASE/Scopus/Web of Science/Cochrane Central Register of Controlled Trials were searched for published literature involving at least 10 severe TBI (sTBI) patients from their inception date to December 2019. Outcomes assessed were mortality, functional outcome, ICP control, length of stay, therapy intensity level, and complications. Twenty-one studies comprising 4542 sTBI patients with an EVD were included; 19 of the studies included patients with an early EVD, and two studies had late EVD placements. The limited number of studies, small sample sizes, imbalance in baseline characteristics between the groups and poor methodological quality have limited the scope of our analysis. We present the descriptive statistics highlighting the current conflicting data and the overall lack of reliable research into the optimal timing of EVD. There is a clear need for high quality comparisons of early vs. late EVD insertion on patient outcomes in sTBI.

In undertaking international neurosurgical trials it is useful to understand international patient demographics and potential patient populations that study results will apply to. The STITCH(Trauma) trial included 59 centres from 20 countries, which were requested to screen all patients with traumatic intracerebral haemorrhage. This paper reviews these data.Demographic, clinical and exclusion reason data were analysed. Comparisons were made between patients who were included in the trial and patients who were potentially eligible (but not included in the trial) and patients who were not potentially eligible.Screening evidence was returned for 1735 patients, 11% of these may potentially have been eligible, of whom 52% were not included because consent could not be gained. By country, median age per centre ranged from 26 years (Egypt) to 67 years (Germany), median time from injury to screening ranged from 5 h (Germany and Nepal) to 16 h (India), median intracerebral haemorrhage (ICH) volume ranged from 5 ml (Germany) to 30 ml (China), the proportion of male patients ranged from 56% (Egypt) to 91% (Canada) and the proportion of patients with both pupils reactive ranged from 68% (China) to 98% (Nepal). The most common exclusion reasons were ICH volume10 ml (49%) and presence of subdural haemorrhage/extradural haemorrhage or SDH/EDH requiring surgery (20%).Data presented here including international patient demographics and reasons for patient ineligibility will be useful for future traumatic ICH studies.

Background and Purpose— Increased sympathetic drive after stroke is involved in the pathophysiology of several complications including poststroke immunudepression. β-Blocker (BB) therapy has been suggested to have neuroprotective properties and to decrease infectious complications after stroke. We aimed to examine the effects of random pre- and on-stroke BB exposure on mortality, functional outcome, and occurrence of pneumonia after ischemic stroke. Methods— Data including standard demographic and clinical variables as well as prestroke and on-stroke antihypertensive medication, incidence of pneumonia, functional outcome defined using modified Rankin Scale and mortality at 3 months were extracted from the Virtual International Stroke Trials Archive. For statistical analysis multivariable Poisson regression was used. Results— In total, 5212 patients were analyzed. A total of 1155 (22.2%) patients were treated with BB before stroke onset and 244 (4.7%) patients were newly started with BB in the acute phase of stroke. Mortality was 17.5%, favorable outcome (defined as modified Rankin Scale, 0–2) occurred in 58.2% and pneumonia in 8.2% of patients. Prestroke BB showed no association with mortality. On-stroke BB was associated with reduced mortality (adjusted risk ratio, 0.63; 95% confidence interval, 0.42–0.96). Neither prestroke BB nor on-stroke BB showed an association with functional outcome. Both prestroke and on-stroke BB were associated with reduced frequency of pneumonia (adjusted risk ratio, 0.77; 95% confidence interval, 0.6–0.98 and risk ratio, 0.49; 95% confidence interval, 0.25–0.95). Conclusions— In this large nonrandomized comparison, on-stroke BB was associated with reduced mortality. Prestroke and on-stroke BB were inversely associated with incidence of nosocomial pneumonia. Randomized trials investigating the potential of β-blockade in acute stroke may be warranted.

Background and Purpose— National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed may prove useful both clinically and for research studies. We aimed to validate the NIHSS item profiles in an acute cohort. Methods— We conducted a retrospective analysis on pooled data from randomized clinical trials. We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping, a -NIHSS item profiles. We implemented an independent latent class analysis to derive secondary symptom grouping, b -NIHSS item profiles. Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles’ discrimination and calibration to the data. The outcomes evaluated included modified Rankin Scale (mRS; using the full distribution and dichotomized, mRS, 0–1) at day 90 and mortality by 90 days. Results— We identified 10 271 patients. Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner, adjusted for age and thrombolysis treatment, for each set of NIHSS item profiles. Similar patterns were observed for mRS 0 to 1, and inverse patterns were seen for mortality. The c -statistics of a -NIHSS and b -NIHSS item profiles for mRS 0 to 1 were similar at 0.71 (95% confidence interval, 0.70–0.72) and for mortality, 0.74 (0.73–0.75) and 0.75 (0.73–0.76), respectively. Calibration was good. Conclusions— These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke. This approach has the potential to enhance the clinical value of the overall NIHSS score.

The aim of this study was to find the relationships between the degree of cord compression as seen on MRIs with persisting cord atrophy after decompression and patient outcomes in spinal meningiomas.We undertook a retrospective analysis of 31 patients' pre- and postoperative MRIs, preoperative functional status and their outcomes at follow-up. The following metrics were analysed; percentage cord area at maximum compression, percentage tumour occupancy and percentage cord occupancy. These were then compared with outcome as measured by the Nurick scale.Of the 31 patients, 27 (87%) had thoracic meningiomas, 3 (10%) cervical and 1 (3%) cervicothoracic. The meningiomas were pathologically classified as grade 1 (29) or grade 2 (2) according to the WHO classification. The average remaining cord cross-sectional area was 61% of the estimated original value. The average tumour occupancy of the canal was 72%. The average cord occupancy of the spinal canal at maximum compression was 20%. No correlation between cord cross-section area and Nurick Scale was seen. On the postoperative scan, the average cord area had increased to 84%. No correlation was seen between this value and outcome.We found that cross-section area measurements on MRI scans have no obvious relationship with function before or after surgery. This is a base for future research into the mechanism of cord recovery and other compressive cord conditions.

OBJECTIVE Symptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH. METHODS Data on management and outcomes for patients with CSDH referred to UK and Ireland NSUs were collected prospectively over an 8-month period and audited against criteria predefined from the literature: NSU mortality5%, NSU morbidity10%, symptomatic recurrence within 60 days requiring repeat surgery20%, and unfavorable functional status (modified Rankin Scale score of 4-6) at NSU discharge30%. RESULTS Data from 1205 patients in 26 NSUs were collected. Bur-hole craniostomy was the most common procedure (89%), and symptomatic recurrence requiring repeat surgery within 60 days was observed in 9% of patients. Criteria on mortality (2%), rate of recurrence (9%), and unfavorable functional outcome (22%) were met, but morbidity was greater than expected (14%). Multivariate analysis demonstrated that failure to insert a drain intraoperatively independently predicted recurrence and unfavorable functional outcome (p = 0.011 and p = 0.048, respectively). Increasing patient age (p0.00001), postoperative bed rest (p = 0.019), and use of a single bur hole (p = 0.020) independently predicted unfavorable functional outcomes, but prescription of high-flow oxygen or preoperative use of antiplatelet medications did not. CONCLUSIONS This is the largest prospective CSDH study and helps establish national standards. It has confirmed in a real-world setting the effectiveness of placing a subdural drain. This study identified a number of modifiable prognostic factors but questions the necessity of some common aspects of CSDH management, such as enforced postoperative bed rest. Future studies should seek to establish how practitioners can optimize perioperative care of patients with CSDH to reduce morbidity as well as minimize CSDH recurrence. The BNTRC is unique worldwide, conducting multicenter trainee-led research and audits. This study demonstrates that collaborative research networks are powerful tools to interrogate clinical research questions.

Introduction: As large clinical trials for spontaneous intracerebral hemorrhage (ICH) increasingly influence management, recruitment of diverse populations must be ensured to fully understand the disease process and benefit of interventions to the general public. There is little data on sex, race and outcomes in ICH trials. We hypothesize that women and geographic minorities are underrepresented in ICH clinical trials and that there exist population specific differences in mortality, functional outcomes and response to interventions. Methods: Pooled analysis of 5456 subjects from the following clinical trials: VISTA (985), INTERACT I (404) and II (2829), STICH II (597), MISTIE II (141) and CLEAR III (500). Patients were grouped by sex, race, and geographic location. Modified Rankin Scale [mRS] was obtained at 30 days and 3 months. Results: More men than women participated in ICH trials (61.9% vs. 38.1%); women were older and more likely to have hypertension; men had more coronary artery disease. Women presented with lower Glasgow Coma scale, higher ICH score and more intraventricular hemorrhage. Day 90 mortality was 13.9% in women and 16.6 % in men (p=0.01); 90 day poor outcome (mRS 3-5) was 57.2% in women and 51.0% in men (p Conclusions: Sex and race representation in ICH clinical trials only partially equate to current understanding of epidemiology of ICH. There is a lack of trial evidence from Africa and South America and under-representation of women, Hispanics and blacks. Despite higher ICH severity, Hispanics had lower adjusted mortality risk while males had higher risk and Arabics and blacks had worse adjusted poor outcomes.

Summary Background Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. Funding National Institute of Neurological Disorders and Stroke.

BACKGROUND AND PURPOSE: Management of poor-grade subarachnoid hemorrhage is based on limited evidence from small single-center retrospective observational studies. The purpose of this study was to undertake a single-center randomized controlled feasibility trial comparing a strategy of early endovascular aneurysm treatment with treatment after neurologic recovery in this group of patients. MATERIALS AND METHODS: Patients with poor-grade SAH were randomized within 24 hours of admission to early treatment or treatment after neurologic recovery. If a patient was randomized to early treatment, the aneurysm was treated endovascularly within 24 hours of randomization. Recruitment rate, safety profile, and functional outcome at the time of discharge and at 6 months were assessed. RESULTS: Fourteen of 51 patients screened were eligible for the trial. Of these 14, 8 patients were randomized (57%). All patients in the early coiling arm received treatment within 24 hours of randomization. There was no treatment-related complication. Overall, good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in the early treatment arm ( n = 5) had a good outcome rate of 20%, while those in treatment after neurologic recovery arm ( n = 3) had a good outcome rate of 33.3%. CONCLUSIONS: This was a feasibility study that demonstrated that recruitment and randomization for comparing management strategies in poor-grade SAH are feasible. The recruitment rate among eligible patients was encouraging (57%), though a number of patients had to be excluded due to ineligibility. A multicenter study is necessary to recruit the numbers required to compare the clinical outcomes of these management strategies.

Background and purpose. When undertaking multicentre randomised controlled trials some obstacles cause a slower than required recruitment rate. This article discusses factors that affected the completion of the international neurosurgical trial STICH II, which took almost 6 years. Methods. We reviewed the following factors: recruitment of participating sites, patient recruitment, patient screening, trial fatigue and maintenance of profile and maintenance of quality and standards. We discuss the practical strategies employed by the STICH II team to address these factors and optimise patient recruitment. Conclusion. Although STICH II attained its final recruitment target, it took longer to complete than anticipated. Publishing and sharing the experiences of the STICH II trial team is an important step towards ensuring that other potential neurosurgical triallists are aware of the issues that can slow patient recruitment and strategies that can help to overcome them.

Objective Subarachnoid haemorrhage (SAH) may present with coma and this is known to be associated with aneurysmal origin and blood load. Aneurysmal origin is associated with increased blood load and existing data do not allow us to determine if the association between coma and aneurysmal SAH is wholly due to blood load or if aneurysmal origin has an additional independent effect. The objective of our study is to find if an aneurysmal origin is a predictor of acute onset of coma independent of blood load. Methods A series of consecutive patients with spontaneous SAH were divided into two groups: aneurysmal (aSAH) and non-aneurysmal – angiographically negative SAH (naSAH). Blood load was quantified so that the effect of aneurysmal origin could be resolved from the effect of the amount of blood spilled. Non-parametric regression was used to relate blood load to coma and poor outcome rates for aneurysmal bleeds. Results We analysed a total of 421 patients presenting during the period 2009–2011. Ninety aneurysmal cases presented with coma, seventy immediately in the early phase and seven shortly after rebleeding. None of the naSAH cases presented with immediate coma and 1 developed delayed coma. Delayed coma was associated with acute hydrocephalus in both groups. Aneurysmal origin was found to be an independent determinant of immediate coma (p = 0.02) and poor outcome (p Conclusion Immediate coma and poor outcome in SAH are associated with an aneurysmal origin and do not characterize naSAH.

Introduction: Recent research has been equivocal regarding the usefulness of intracranial pressure (ICP) monitoring for traumatic intracerebral haemorrhage (ICH). We aimed to investigate attitudes of clinicians from as wide an international audience as possible. Materials and Methods: A SurveyMonkey® questionnaire was distributed to individuals, including members of the Society of British Neurological Surgeons, the European Brain Injury Consortium, the Euroacademia Multidisciplinaria Neurotraumatologica and the neurotrauma committee of the World Federation of Neurosurgical Societies. Results: Ninety-eight participants from at least 25 different countries completed the survey (86 surgeons). ICP was routinely monitored by 76 % and would be monitored by 5 % more if they had equipment. ICP monitoring was valued (0 = not at all important, 10 = critically important) as 10 by 21 % (median = 8; Q1 = 7, Q3 = 9). Responders were aware of 16 trials that investigated the value of ICP monitoring in neurotrauma, including BEST TRIP (n = 35), Rescue ICP (n = 13) and DECRA (n = 8). Other results are discussed. Discussion: Despite equivocation in the literature, we found that ICP monitoring continues to be routinely performed and is highly valued. Interestingly, only 36 % of responders were aware of the BEST TRIP trial, which found no difference in outcome between patients with a head injury managed with or without ICP monitoring.

Objective The literature regarding surgical treatment of brain abscess was reviewed from 1990 to (and including) 2008 to supplement a previous literature review from 1930 to 1990. Methods The Ovid Medline database 1950–2009 with the year range limited to 1990–2009 was used to identify all articles relating to brain abscess. The results were compared with a previously published review from 1930–1990 by the senior author. Results The original finding was confirmed that the high mortality from aspiration in the pre-computer tomography era decreased dramatically after computer tomographic scanning became available. In the present review, the mean mortality for aspiration post-1990 was 6.6% for publications with more than five patients. With surgical excision by craniotomy, the mean mortality in the same period was 12.7%. Conclusions The present review suggests that aspiration may be the first surgical choice in patients with supratentorial parenchymal brain abscesses.

Intracerebral haemorrhage (ICH) accounts for 15 to 20% of strokes. The condition carries a higher morbidity and mortality than occlusive stroke. Despite considerable research effort, no therapeutic modality either medical or surgical has emerged with clear evidence of benefit other than in rare aneurysmal cases. Intracerebral haemorrhages can be divided into those that arise from pre-existing macroscopic vascular lesions - so called "ictohaemorrhagic lesions", and those that do not; the latter being the commoner. Most of the research that has been done on the benefits of surgery has been in this latter group. Trial data available to date precludes a major benefit from surgical evacuation in a large proportion of cases however there are hypotheses of benefit still under investigation, specifically superficial lobar ICH treated by open surgical evacuation, deeper ICH treated with minimally invasive surgical techniques, and decompressive craniectomy. When an ICH arises from an ictohaemorrhagic lesion, therapy has two goals: to treat the effects of the acute haemorrhage and to prevent a recurrence. Three modalities are available for treating lesions to prevent recurrence: stereotactic radiosurgery, endovascular embolisation, and open surgical resection. As with ICH without an underlying lesion there is no evidence to support surgical removal of the haemorrhage in most cases. An important exception is ICHs arising from intracranial aneurysms where there is good evidence to support evacuation of the haematoma as well as repair of the aneurysm.

The summed Alberta Stroke Program Early CT Score (ASPECTS) is useful for predicting stroke outcome. The anatomical information in the CT template is rarely used for this purpose because traditional regression methods are not adept at handling collinearity (relatedness) among brain regions. While penalized logistic regression (PLR) can handle collinearity, it does not provide an intuitive understanding of the interaction among network structures in a way that eigenvector method such as PageRank can (used in Google search engine). In this exploratory analysis we applied graph theoretical analysis to explore the relationship among ASPECTS regions with respect to disability outcome. The Virtual International Stroke Trials Archive (VISTA) was searched for patients who had infarct in at least one ASPECTS region (ASPECTS ≤ 9, ASPECTS = 10 were excluded), and disability (modified Rankin score/mRS). A directed graph was created from a cross correlation matrix (thresholded at false discovery rate of 0.01) of the ASPECTS regions and demographic variables and disability (mRS > 2). We estimated the network-based importance of each ASPECTS region by comparing PageRank and node strength measures. These results were compared with those from PLR. There were 185 subjects, average age 67.5 ± 12.8 years (55% Males). Model 1: demographic variables having no direct connection with disability, the highest PageRank was M2 (0.225, bootstrap 95% CI 0.215-0.347). Model 2: demographic variables having direct connection with disability, the highest PageRank were M2 (0.205, bootstrap 95% CI 0.194-0.367) and M5 (0.125, bootstrap 95% CI 0.096-0.204). Both models illustrate the importance of M2 region to disability. The PageRank method reveals complex interaction among ASPECTS regions with respects to disability. This approach may help to understand the infarcted brain network involved in stroke disability.

S-100B protein is a promising marker of injury severity and outcome after head injury. We examined the relationship between serum S-100B concentrations and injury severity, clinical course, survival, and treatment efficacy after severe traumatic brain injury (TBI).Prospective observational study in a neurosurgical intensive care unit.102 adult patients with severe TBI, admitted between June 2001 and November 2003 (30 months).Serum S-100B levels were measured by immunoluminometric technique on admission and every 24 h thereafter for a maximum of 7 days.Initial S-100B levels were significantly related to pupillary status, computed tomography severity 1, and 1-month survival. Cox's proportional hazard regression analysis showed that initial S-100B was an independent predictor of 1-month survival, in the presence of dilated pupils, and with increased age. Subjects with initial levels above 1 microg/l had a nearly threefold increased probability of death within 1 month. Serum S-100B alteration indicated neurological improvement or deterioration. Finally, surgical treatment reduced S-100B levels.Serum S-100B protein reflects injury severity and improves prediction of outcome after severe TBI. S-100B may also have a role in assessing the efficacy of treatment after severe TBI.

Surgeons are increasingly placed under pressure to accept publication of their results and to abide by recommendations to change practice which others derive. Considerable concern exists about misinterpretation of such data. The issue is well illustrated by this study.Data on outcome following treatment for subarachnoid haemorrhage were prospectively collected from 1993-1998 in two centres in the British Isles: Newcastle and Nottingham.Initial examination of this data suggest a substantial difference in the performance favouring Nottingham over Newcastle. The odds of a poor outcome was 1:1.86 in Newcastle compared with 1:4.26 in Nottingham giving an odds ratio of 2.3 in favour of Nottingham and this difference was highly significant with p0.00001. On a more detailed examination taking account of confounding variables, this difference disappeared entirely. Newcastle was able to operate a less selective admissions policy than Nottingham because of the deficiency of beds at the latter unit. A summary of these results has been published elsewhere.These results illustrate the dangers of applying statistical tools developed for simpler situations such as industrial process control to complex medical problems. We conclude that comprehensive and accurate data on all factors likely to influence the outcome for a particular treatment should be collected as an absolute prerequisite to any judgments being made on apparent statistical differences between the performances of differing units.

Object. The authors reviewed the management protocols for young adults who presented with subarachnoid hemorrhage (SAH) at the Regional Neurosurgery Unit in Newcastle during a study period of 9 years. Aneurysmal SAH is uncommon in the age group selected (18–39 years) and, therefore, the performance of these patients has not been extensively reported in the literature. The authors also evaluated the good-grade rebleed rate (an index of management efficiency) in this cohort of patients. Methods. The Newcastle neurosurgical unit serves a population of close to 3 million people, and an average of 180 patients with SAH are seen each year. The majority of patients are transferred from other hospitals in the region. This study includes patients admitted between January 1990 and December 1998. A total of 1609 patients were admitted during this period, of whom 295 (18.4%) between the ages of 18 and 39 years constituted the study population of young adults. Two hundred ninety-five young adults presented with SAH; 181 (61.4%) were women and 114 (38.6%) were men, a ratio of 3:2. Of 246 patients in whom this value was recorded, 15 (6.1%) presented with a history of hypertension, and there was an association between hypertension and the occurrence of multiple aneurysms (Fisher two-tailed exact test, p = 0.008). Thirty-five patients (11.9%) presented with a hematoma on computerized tomography scans; of these, 20 (57%) were women and 15 were men. In six patients the lesion had rebled before treatment. The good-grade rebleed rate was three (1.7%) of 178. The overall favorable outcome rate was 83.8% (Glasgow Outcome Scale [GOS] 4 and 5) and unfavorable outcome occurred in 16.2% (GOS 1–3), with a total of 40 deaths in this group (13%). Age had no influence on outcome in young adults. Comparing the outcome at discharge with the follow-up evaluation at 6 months revealed that patients in the moderate and severe disability groups continued to improve and many achieved good recovery. Conclusions. In this report the authors detail the outcome of a large number of young adults with SAH. The incidence of SAH was higher in the female population, although the ratio was not as high as previously reported. The authors have also demonstrated a progressive increase in the incidence of aneurysmal SAH with age, even in young adults. Hypertension but not age influenced the occurrence of multiple aneurysms. The good-grade rebleed rate is low, although it is not zero. Generally, a satisfactory outcome was obtained and significant continuing improvements were noted between discharge and follow-up evaluation. This reflects the power of recovery in young adults. These are people whose economic productivity and fertility are at peak levels and therefore the financial and social burden occasioned by less-than-perfect outcomes is large.

Object. Spontaneous intracerebral hemorrhage (SICH) and traumatic intracerebral hemorrhage (TICH) are common disorders. The authors planned to study how these two types of hemorrhage behave pathologically and clinically to gain further insight into their causes, pathogeneses, indications for surgical intervention, and prognoses. Methods. Prospectively filled databases of demographic, clinical, radiological, and outcome details have been maintained for all patients admitted to the Regional Neurosciences Centre with head injury since 1987 and with SICH since 1993. Of the 5686 patients whose case information was included in the head-injury database, 90 were found to suffer from an isolated intracerebral hemorrhage (ICH) as the only major abnormality observed on computerized tomography scans (subdural and extradural hematomas were excluded). Case details on these 90 patients and the 440 patients from the SICH database were extracted and analyzed using a statistical software program. The median age of patients with TICH was lower than the median age of patients with SICH (51 years compared with 65 years, respectively), but it was much higher than the median age of the entire head-injury group (21 years). Among patients younger than 45 years of age, 0.8% of patients who experienced trauma suffered from an ICH compared with 4.3% of patients older than 45 years of age. Irrespective of intervention, much better outcomes were achieved by patients with TICH compared with those with SICH (67% favorable outcomes compared with 24% in patients with SICH). Following trauma, there was no significant relationship between the severity of injury and the development of ICH. At presentation the median Glasgow Coma Scale (GCS) score for both groups was 13. Younger age and higher GCS score at presentation were strongly related to a favorable outcome for both types of hemorrhage. There was no significant difference in patient age, presenting GCS score, or outcomes of patients who underwent surgery compared with those who did not for either type of hemorrhage. No conclusions can be drawn about the efficacy of surgery from such observational studies. Conclusions. On the basis of these data the authors suggest that TICH and SICH have different features: TICH affects a slightly younger age group and carries a much better prognosis compared with SICH. In addition, indications for surgical intervention are not well defined for either type of hemorrhage. Practice is subjective and inconsistent. The International Surgical Trial in Intracerebral Haemorrhage may resolve the dilemma for SICH. A similar trial in which surgery is compared with conservative management should be considered for cases of TICH.

Recent research has been equivocal regarding the usefulness of intracranial pressure (ICP) monitoring for traumatic intracerebral haemorrhage (ICH). We aimed to investigate attitudes of clinicians from as wide an international audience as possible.A SurveyMonkey(®) questionnaire was distributed to individuals, including members of the Society of British Neurological Surgeons, the European Brain Injury Consortium, the neurotrauma committee of the Euroacademia Multidisciplinaria Neurotraumatologica and the World Federation of Neurosurgical Societies.N = 98 completed the survey (surgeons n = 86) from at least 25 different countries. ICP was routinely monitored by 76% and would be monitored by 5% more if they had equipment. ICP monitoring was valued (0 = not at all important, 10 = critically important) as 10 by 21% (median = 8, Q1 = 7, Q3 = 9). Triggers to begin ICP monitoring included midline shift (n = 48), contusion (n = 47), ICH (n = 46), subdural haemorrhage (n = 42), Glasgow coma scale reduction of median 2 for eye, verbal or motor, and one reactive pupil (30%). Responders stated that intervention would begin for adults with an ICP median of 25 mmHg and for children 20 mmHg. Most favourable treatments of raised ICP included Mannitol and ventriculostomy, which were ranked as most favourable (out of 10) by n = 31 each. Responders claimed to be aware of 16 different trials that investigated the value of ICP monitoring in neurotrauma, including BEST TRIP (n = 35), Rescue ICP (n = 13) and DECRA (n = 8).ICP monitoring continues to be a highly valued and clinically desirable technique for managing traumatic ICH patients.

Background: STICH II was an international multicentre pragmatic randomised parallel group trial to establish whether a policy of early surgery (ES) improved outcome compared to a policy of initial conservative treatment (ICT) for patients with superficial lobar intracerebral haemorrhage (ICH). The results of the “intention to treat analysis” have been published and showed a non-significant trend in favour of early surgery. However, as observed in other surgical trials, there was a substantial crossover of patients from the ICT group with 21% having surgery within 14 days of randomisation. This paper investigates these patients and their effect on outcome. Methods: Patients from the ICT group who underwent surgery within 14 days were identified and compared with patients who continued to receive conservative treatment and with patients randomised to ES. The protocol defined “early surgery” as within 12 hours of randomisation so analyses were also conducted using this definition. Per protocol and treatment received analyses were conducted. Results: For this analysis there are 285 ICT patients with outcome assessed, 233 had no surgery and 62 patients had surgery within 2 weeks: 23 within 12 hours. Of 297 patients randomised to ES, 278 had surgery within 12 hours. Surgical ICT patients had lower GCS (13 v 14) and larger volumes (54ml v 32ml) of haematoma at randomisation (p Death rates were highest in ICT patients having surgery within 12 hours (48%) compared with later surgery (31%), non-surgical ICT patients (20%) and ES patients (17%). Conclusions: Patients randomised to conservative treatment who deteriorate and have surgery differ considerably from those that do not deteriorate and from those who are randomised to early surgery. Further work is needed to develop ways of analysing these data.

OBJECTIVES Adhesion molecules are involved in the pathogenesis of cerebral ischaemia and may play a part in the pathophysiology of delayed ischaemic neurological deficit (DIND) after aneurysmal subarachnoid haemorrhage. It was hypothesised that after aneurysmal subarachnoid haemorrhage, adhesion molecules may play a part in the pathophysiology of DIND as reflected by significantly altered serum concentrations in patients with and without DIND. METHODS In a prospective study, mean serum concentrations of ICAM-1, VCAM-1, PECAM, and E, P, and L-selectin were compared between patients without (n=23) and with (n=13) DIND in patients with World Federation of Neurological Surgeons (WFNS) grades 1 or 2 subarachnoid haemorrhage. Serum was sampled from patients within 2 days of haemorrhage and on alternate days until discharge. Concentrations of adhesion molecules were measured by standard procedures using commercially available enzyme linked immunoabsorbent assays. RESULTS There were non-significant differences in serum concentrations of ICAM-1 (290.8 ng/ml v 238.4 ng/ml, p=0.0525), VCAM-1 (553.2 ng/ml v 425.8 ng/ml, p=0.053), and PECAM (22.0 ng/ml v 21.0 ng/ml, p=0.56) between patients without and with DIND respectively. The E-selectin concentration between the two patient groups (44.0 ng/ml v 37.4 ng/ml, p=0.33) was similar. The P-selectin concentration, however, was significantly higher in patients with DIND compared with those patients without DIND (149.5 ng/ml v 112.9 ng/ml, p=0.039). By contrast, serum L-selectin concentrations were significantly lower in patients with DIND (633.8 ng/ml v 897.9 ng/ml, p=0.013). CONCLUSIONS Of all the adhesion molecules examined in this study, P and L-selectin are involved in the pathophysiology of DIND after aneurysmal subarachnoid haemorrhage.

Objective: to review the UK literature relating to community-based maternity care. Design: all UK research studies published between 1970 and 1998 relating to community-based maternity care were included. Searches were made via a number of electronic databases using defined search terms. All papers included were independently reviewed by a minimum of two researchers. Study findings were tabulated using a pro-forma. Findings are summarised in this paper. Findings: a total of 241 papers were deemed to meet all inclusion criteria. The majority of studies used descriptive methods with only 11 papers reporting findings from randomised controlled trials. Findings are reported relating to clinical outcomes, the care process and the views of women and health professionals. Conclusion and policy implications: the overall quality of the evidence in the papers reviewed was very mixed. What limited evidence there is suggests that, for the majority of women, care in community settings is as safe and as acceptable to women as care provided in hospital. Despite a large volume of literature, the amount that is known about midwives' contribution to care, and what women think about it, is limited. There is a need for controlled studies to compare outcomes for different patterns of care and for well-designed observational studies to provide information on the care process.

Background and Purpose —Primary intracerebral hemorrhage (ICH) accounts for 10% to 20% of stroke but carries the highest rates of mortality and morbidity of all stroke subtypes. Current treatment, however, is varied and haphazard. The most recent Cochrane systematic review refers to 4 prospective, randomized controlled trials. We present a further meta-analysis to include 3 new trials. In addition, we review the trials of Chen et al and McKissock et al and discuss aspects of their quality that, we believe, prevent their inclusion in modern day meta-analysis. Methods —Literature databases and articles were searched from 1966 to October 1999. Using the end points of death and dependency, the results of the 7 identified randomized trials were expressed as odds ratios. All available data were then analyzed with meta-analysis techniques. Analysis of relevant subsets of trials was also carried out. Results —Meta-analysis of all 7 trials shows a trend toward a higher chance of death and dependency after surgery (OR 1.20; 95% CI 0.83 to 1.74). Meta-analysis was also carried out after exclusion of the Chen and McKissock trials for reasons discussed in the text. This meta-analysis suggests a benefit from surgery, with a reduction in the chances of death and dependency after surgical treatment by a factor of 0.63 (OR 0.63; 95% CI 0.35 to 1.14). Conclusions —When meta-analysis is restricted to modern-day, post-CT, well-constructed, balanced trials, a trend for surgery to reduce the chances of death and dependency is found. Perhaps, then, in the modern era of CT, good neuroanesthesia, intensive care, and the operating microscope, surgery has a role in the treatment of supratentorial intracerebral hemorrhage. The results of a large, multicenter, randomized controlled trial are urgently needed, and the ongoing International Surgical Trial of Intracerebral Hemorrhage should fulfill this objective.