We conclude that ICH volume can be accurately estimated in less than 1 minute with the simple formula ABC/2.

Purpose-The aim of this statement is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage. Methods-A formal literature search of Medline was performed through the end date of August 2006. The results of this search were complemented by additional articles on related issues known to the writing committee. Data were synthesized with the use of evidence tables. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 5 expert peer reviewers and by the members of the Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years' time. Results-Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intracerebral hemorrhage, and the prevention of recurrent intracerebral hemorrhage. Recent trials of recombinant factor VII to slow initial bleeding are discussed. Recommendations for various surgical approaches for treatment of spontaneous intracerebral hemorrhage are presented. Finally, withdrawal-of-care and end-of-life issues in patients with intracerebral hemorrhage are examined.

Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

SUMMARY Background Craniotomy, when evaluated in trials, does not improve outcome after intracerebral haemorrhage (ICH). Whether minimally invasive catheter evacuation followed by thrombolysis is safe and can achieve a good functional outcome by removing clot is unknown. We investigated safety and efficacy of alteplase with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. Methods MISTIE was an international, randomized, open-label study and was done in 26 hospitals in the USA, Canada, the UK, and Germany. Patients (aged 18–80 years), with non-traumatic (spontaneous) ICH ≥20 mL were randomly allocated, centrally, to medical care or image-guided MIS plus rt-PA (0.3 mg or 1.0 mg every 8 hours for up to 9 doses) to remove clot using surgical aspiration followed with alteplase clot irrigation. The primary efficacy outcome was the adjusted dichotomized modified Rankin Scale (mRS) 0–3 vs 4–6 assessed at day 180 after symptom onset. Analysis was by intention to treat. (ClinicalTrials.gov number NCT00224770). Findings Between February 2, 2006 and April 8, 2013, 96 subjects were randomized and completed follow-up: 54 received treatment and 42 medical care. Primary safety outcomes: mortality, symptomatic bleeding, brain infections, as well as withdrawal of care, did not differ between groups. Asymptomatic hemorrhages were more common in the surgical group (3 (7%) vs. 12 (22%) p= 0.05) producing a difference of 15.1% (95% CI: 1.5% to 28.6%). The estimated absolute benefit, i.e., the unadjusted difference in observed proportions of all subjects with mRS 0–3 (33% vs 21%) at 180 days comparing MISPA vs. medical control, is 0.109 [95%CI: −0.088, 0.294; p=0.26], and is 0.162 [95%CI: 0.003, 0.323; p=0.05] after adjustment for potential imbalances in baseline severity between study arms (primary efficacy outcome). Interpretation MIS+rt-PA appears safe with an apparent advantage of better functional outcome at 180 days. Increased asymptomatic bleeding is a major cautionary finding. The MISTIE trial results, if replicable, could produce a meaningful functional benefit adding surgical management as a therapeutic strategy for ICH. Funding National Institute of Neurologic Disorders and Stroke, Genentech, and Codman.

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.

The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter.

Background and Purpose Perihematomal edema (PHE) can worsen outcomes following ICH. Reports suggest that blood degradation products lead to PHE. We hypothesized that hematoma evacuation will reduce PHE volume and that treatment with rt-PA will not exacerbate it. Methods MISTIE II tested safety and efficacy of hematoma evacuation after ICH. We conducted a semi-automated, computerized volumetric analysis on CT to assess impact of hematoma removal on PHE and 2) effects of rt-PA on PHE. Volumetric analyses were performed on Baseline Stability (BLS) and End of Treatment (EOT) scans. Results Seventy-nine surgical and 39 medical patients from MISTIE II were analyzed. Mean hematoma volume at EOT was 19.6±14.5 cc for the surgical cohort and 40.7±13.9 cc for the medical cohort (p<0.001). Edema volume at EOT was lower for the surgical cohort: 27.7±13.3 cc than medical cohort: 41.7±14.6 cc (p<0.001). Graded effect of clot removal on PHE was observed when patients with >65%, 20-65%, and <20% ICH removed were analyzed (p<0.001). Positive correlation between PHE reduction and percent of ICH removed was identified (ρ=0.658; p<0.001). In the surgical cohort, 69 patients underwent surgical aspiration and rt-PA (S+rt-PA) while 10 underwent surgical aspiration only (SO). Both cohorts achieved similar clot reduction: S+rt-PA, 18.9±14.5 cc; and SO, 24.5±14.0 cc (p=0.26). Edema at EOT in S+rt-PA was 28.1±13.8 cc and 24.4±8.6 cc in SO (p=0.41). Conclusions Hematoma evacuation is associated with significant reduction in PHE. Furthermore, PHE does not appear to be exacerbated by rt-PA, making such neurotoxic effects unlikely when the drug is delivered to intracranial clot. Clinical Trial Registration Information URL: http://clinicaltrials.gov/ct2/show/NCT00224770?term=MISTIE&rank=1 Clinicaltrials.gov ID: NCT00224770

Background and Purpose-The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH. Methods-Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume Ͼ10 cm 3 on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score Ͼ4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score Ͼ3. Results-Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes.