Spontaneous Intracerebral and Intraventricular Hemorrhage: Advances in Minimally Invasive Surgery and Thrombolytic Evacuation, and Lessons Learned in Recent Trials

ACUTE HEMORRHAGIC AND ISCHEMIC STROKE ACUTE HEMORRHAGIC AND ISCHEMIC STROKE TOPIC Spontaneous Intracerebral and Intraventricular Hemorrhage: Advances in Minimally Invasive Surgery and Thrombolytic Evacuation, and Lessons Learned in Recent Trials Mahua Dey, MD Agnieszka Stadnik, MSc Issam A. Awad, MD Hemorrhagic Stroke Research Unit, Section of Neurosurgery and the Neurovascular Surgery Program, University of Chicago Medicine and Biological Sciences, Chicago, Illinois Correspondence: Issam Awad MD, University of Chicago Medicine and Biological Sciences, 5841 South Maryland Ave, MC 3026, Room J341, Chicago, IL 60637. E-mail: Received, June 10, 2013. Accepted, October 11, 2013. Copyright © 2014 by the Congress of Neurological Surgeons Optimal management of spontaneous intracerebral hemorrhage (ICH) remains one of the highly debated areas in the field of neurosurgery. Earlier studies comparing open surgical intervention with best medical management failed to show a clear benefit. More recent experience with minimally invasive techniques has shown greater promise. Well-designed phase II trials have confirmed the safety and preliminary treatment effect of thrombolytic aspiration and clearance of spontaneous ICH and associated intraventricular obstructive hemorrhage. Those trials are reviewed, including respective protocols and technical nuances, and lessons learned regarding patient selection, the concept of hemorrhage stabilization, optimization of the surgical procedure, and thrombolytic dosing decisions. These concepts have been incorporated in the design of ongoing definite phase III randomized trials (MISTIE and CLEAR) funded by the National Institutes of Health. These are presented including the role of surgical leadership in the training and monitoring of the surgical task and quality assurance. The impact of these techniques on neurosurgical practice is discussed. KEY WORDS: Intracerebral hemorrhage, Intracranial hemorrhage, Intraventricular hemorrhage, Minimally invasive surgery, Thrombolysis Neurosurgery 74:S142–S150, 2014 DOI: 10.1227/NEU.0000000000000221 T he spontaneous, nontraumatic rupture of blood vessels in the brain parenchyma, in the absence of any underlying structural vascular lesion, can lead to the accumulation of the blood within the brain substance. This is known as spontaneous intracerebral hemorrhage (ICH) or primary intracerebral hemorrhage (ICH) (Figure 1). Worldwide clinical management of spontaneous ICH varies significantly along the spectrum of this illness and lacks a consensus-based standard of care. EPIDEMIOLOGY AND SCOPE OF THE PROBLEM Only 10% to 15% of all strokes are hemorrhagic in nature; however, 30-day mortality rates ABBREVIATIONS: AVM, arteriovenous malformation; EVD, external ventricular drain; ICH, intracerebral hemorrhage; IVH, intraventricular hemorrhage; mRS, modified Rankin Score; NIH, National Institutes of Health; rtPA, recombinant tissue plasminogen activator S142 | VOLUME 74 | NUMBER 2 | FEBRUARY 2014 SUPPLEMENT www.neurosurgery-online.com associated with this devastating illness range from 35% to 52%, with half of those deaths occurring in the first 2 days.1-6 Several factors influence the extremely poor outcome associated with spontaneous ICH, such as the level of consciousness at presentation, volume of parenchymal hemorrhage, volume of intraventricular hemorrhage (IVH), and the extent of cerebral damage. Critical care treatment alone, aiming at intracranial pressure control and multisystem support, is often ineffective in these patients and does not prevent death or disability. The outcome of patients who have this devastating illness depends on age, severity of ICH, presenting Glasgow Coma Scale score, and extent of IVH. Volume of ICH has consistently been shown to be a powerful predictor of poor outcome.7-13 IVH is a frequent complication of spontaneous ICH. The extension of ICH into the ventricles has been consistently shown to be an independent predictor of poor outcome.14-19 Of all the www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited. MINIMALLY INVASIVE INTRACRANIAL HEMATOMA EVACUATION FIGURE 1. CT of head demonstrating large ICH with surrounding edema and significant midline shift. ICH, intracerebral hemorrhage. recent studies that have attempted to grade the extent of IVH in relation to patient outcome,14,18-20 the “Graeb score,” which takes into account the extent of involvement of the respective ventricles and associated ventriculomegaly, has been extensively validated in outcomes studies.18,21,22 Using new data emerging from the CLEAR IVH trial, Morgan et al23 developed and validated a modification of the original Graeb scale to facilitate rapid assessment of IVH over time, and found that it is a reliable measure with prognostic validity suitable for rapid use in clinical practice and in research. BEST MEDICAL MANAGEMENT AND OPEN SURGICAL INTERVENTION Modern stroke care systems have contributed to the recognition of symptoms, rapid transport, and earlier imaging and diagnosis of hemorrhagic stroke, including spontaneous ICH. Advances in acute resuscitation and critical care support have been deployed in this disease, aimed at preventing hematoma growth (blood pressure control and reversal of coagulopathy), optimizing brain perfusion (including control of intracranial pressure), and multisystem homeostasis (including the management of secondary sequelae such as aspiration and deep vein thrombosis). These interventions are outside the scope of this review and are summarized in evidencebased guidelines by the American Stroke Association.24 There is a broad consensus about the role of surgery in cases with cerebellar hematoma greater than 3 cm in diameter, and possibly in younger patients with larger spontaneous ICH and impending herniation.24 But there remains wide controversy about the potential role of surgery in the majority of spontaneous ICH cases where the hematoma has stabilized, and the patients progress nevertheless to a poor outcome with high rates of mortality and disability. Despite modern protocolized management, the outcome in this disease remains sobering, especially in cases with larger ICH volume.13 Several clinical trials comparing surgical intervention with best medical management, published between 1961 and 2004, failed to show clear benefit of surgical evacuation of hematoma over best medical management.25-34 A meta-analysis of all 12 trials of surgical interventions in the setting of ICH published before 2006 provided an odds ratio of 0.85 (confidence interval, 0.71-1.02) in favor of surgical treatment.35 Based on the encouraging results from these earlier studies, a larger international multicenter prospectively randomized clinical trial, Surgical Treatment of ICH (STICH), was designed to compare early surgery with initial conservative treatment for patients with ICH. The trial enrolled (...truncated)