Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Foreword: National health reform and America\u27s uninsured

For those uninitiated to the intricacies of the U.S. health system, perhaps its single most striking characteristic is its failure to function as a universal benefit in a manner similar to education, Social Security, and essential, population-based community services. This nation enjoys extraordinary and unprecedented wealth; yet it stands alone among industrialized countries in the area of health coverage. Why and how we as a people have chosen this pathway, the human, financial and economic, and social consequences of our choice, and the imperative for reform, are the subject of this special symposium of JLME

Early abnormal transient hyperemic response test can predict delayed ischemic neurologic deficit in subarachnoid hemorrhage

Abstract Background Early detection of vasospasm is crucial to prevent significant delayed ischemic neurological deficit post subarachnoid hemorrhage. The standard methods of detection, including cerebral angiogram and computed tomography are invasive and not safe to be repeated, as is very often indicated clinically. Transient hyperemic response test has been previously used to predict autoregulation failure in traumatic brain injury and subarachnoid hemorrhage. Aims We investigate the usability of transient hyperemic response test as a predictor of clinical vasospasm in a cohort of patients with aneurismal subarachnoid hemorrhage. Methods A retrospective review of all THRT examinations done between January 2011 and July 2012 conducted at Montreal Neurological Institute and Hospital and the Montreal General Hospital. Patients diagnosed with aSAH in which the THRT was performed within the first 24–48 h of admission were included in the study. Two-dimensional transcranial Doppler images were obtained and velocities were recorded. A positive response was one in which the velocity was increased by more than 9% of the baseline systolic velocity, indicating an intact cerebral autoregulation. Lindegaard ratio > 3 is considered abnormal and in the context of elevated systolic velocity of the MCA, is highly suggestive of DIND. Results Fifteen patients met the inclusion criteria. A total of 6 patients developed clinical and radiological vasospasm. Out of these 6 patients, 5 (83%) had an abnormal THRT in the initial TCD assessment (p = 0.0406). We found that abnormal transient hyperemic response test readings are predictive of subsequent vasospasm development. Conclusions The results of this small retrospective study support the notion that transient hyperemic response test has predictive value in vasospasm development and may prove useful in patient monitoring and successful clinical management

CT Perfusion to Guide Placement of Invasive Cerebral Perfusion Monitor in Subarachnoid Hemorrhage Induced Vasospasm

Background. Vasospasm is a challenging component of the subarachnoid hemorrhage “syndrome” that is unpredictable and very difficult to monitor using noninvasive or invasive monitoring technologies in neurocritical units. Methods. We describe the novel use of computerized tomography perfusion (CTP) imaging to choose proper targets for invasive cerebral blood flow monitors. Results. A total of 3 patients are included in this report. CTP parameters were used to generate points of interest to target using invasive cerebral monitoring of the cerebral blood flow and initiate vasodilator therapy and subsequently guide its weaning. Conclusions. CTP can be useful in localizing a specific anatomical target for invasive monitoring in subarachnoid hemorrhage patients suffering from vasospasm

Rabies in a nine-year-old child: The myth of the bite

A nine-year-old boy died from rabies encephalitis caused by a rabies virus variant associated with insectivorous bats. The patient was most likely infected in the Laurentian Mountains of western Quebec, but neither the patient nor his parents remembered any direct contact with an animal. The diagnosis was made seven days after the start of symptoms. After examining the most recent cases of rabies in North America, it is obvious that rabies following bat exposure can occur without history of a documented bite. The present case report emphasizes that the general public and medical care providers need better information about the risks associated with exposure to bats

Effect of ximelagatran and warfarin on stroke subtypes in atrial fibrillation

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND AND PURPOSE: The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke. METHODS: 7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0--3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype. RESULTS: The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant. CONCLUSIONS: In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied

Effect of ximelagatran and warfarin on stroke subtypes in atrial fibrillation

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND AND PURPOSE: The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke. METHODS: 7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0--3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype. RESULTS: The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant. CONCLUSIONS: In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied

Clinical outcome prediction in aneurysmal subarachnoid hemorrhage - Alterations in brain-body interface

Background:Brain–body associations are essential in influencing outcome in patients with ruptured brain aneurysms. Thus far, there is scarce literature on such important relationships. Methods:The multicenter Tirilazad database (3551 patients) was used to create this clinical outcome prediction model in order to elucidate significant brain–body associations. Traditional binary logistic regression models were used. Results:Binary logistic regression main effects model included four statistically significant single prognostic variables, namely, neurological grade, age, stroke, and time to surgery. Logistic regression models demonstrated the significance of hypertension and liver disease in development of brain swelling, as well as the negative consequences of seizures in patients with a history of myocardial infarction and post-admission fever worsening neurological outcome. Conclusions:Using the aforementioned results generated from binary logistic regression models, we can identify potential patients who are in the high risk group of neurological deterioration. Specific therapies can be tailored to prevent these detriments, including treatment of hypertension, seizures, early detection and treatment of myocardial infarction, and prevention of hepatic encephalopathy