Ricky Medel

Angiographic Vasospasm Is Strongly Correlated With Cerebral Infarction After Subarachnoid Hemorrhage

Background and Purpose— The long-standing concept that delayed cerebral infarction after aneurysmal subarachnoid hemorrhage results exclusively from large artery vasospasm recently has been challenged. We used data from the CONSCIOUS-1 trial to determine the relationship between angiographic vasospasm and cerebral infarction after subarachnoid hemorrhage. Methods— We performed a post hoc exploratory analysis of the CONSCIOUS-1 data. All patients underwent catheter angiography before treatment and 9±2 days after subarachnoid hemorrhage. CT was performed before and after aneurysm treatment, and 6 weeks after subarachnoid hemorrhage. Angiograms and CT scans were assessed by centralized blinded review. Angiographic vasospasm was classified as none/mild (0%–33% decrease in arterial diameter), moderate (34%–66%), or severe (≥67%). Infarctions were categorized as secondary to angiographic vasospasm, other, or unknown causes. Logistic regression was conducted to determine factors associated with infarction. Results— Complete data were available for 381 of 413 patients (92%). Angiographic vasospasm was none/mild in 209 (55%) patients, moderate in 118 (31%), and severe in 54 (14%). Infarcts developed in 6 (3%) of 209 with no/mild, 12 (10%) of 118 patients with moderate, and 25 (46%) of 54 patients with severe vasospasm. Multivariate analysis found a strong association between angiographic vasospasm and cerebral infarction (OR, 9.3; 95% CI, 3.7–23.4). The significant association persisted after adjusting for admission neurological grade and aneurysm size. Method of aneurysm treatment was not associated with a significant difference in frequency of infarction. Conclusions— A strong association exists between angiographic vasospasm and cerebral infarction. Efforts directed at further reducing angiographic vasospasm are warranted.

High-intensity focused ultrasound surgery of the brain: part 1--A historical perspective with modern applications.

THE FIELD OF magnetic resonance imaging-guided high-intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one, with many potential applications in neurosurgery. The first of 3 articles on MRgFUS, this article focuses on the historical development of the technology and its potential applications in modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery, and the 2 seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940s and 1950s demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as the lack of sophisticated imaging technology, resulted in limited growth of high-intensity focused ultrasound for neurosurgery. More recently, technological advances have permitted the combination of high-intensity focused ultrasound along with magnetic resonance imaging guidance to provide an opportunity to effectively treat a variety of central nervous system disorders. Although challenges remain, high-intensity focused ultrasound-mediated neurosurgery may offer the ability to target and treat central nervous system conditions that were previously extremely difficult to address. The remaining 2 articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation.

Influence of Weekend Hospital Admission on Short-Term Mortality After Intracerebral Hemorrhage

Background and Purpose— There is expanding literature to show that certain patients admitted during the weekend have worse outcomes than similar patients admitted during the week. Although many clinicians have hypothesized the presence of this “weekend effect” with patients with intracerebral hemorrhage, there is a paucity of studies validating this conjecture. Methods— We performed a retrospective cohort study of patients with intracerebral hemorrhage (International Classification of Diseases, 9th Revision, Clinical Modification=431) extracted from the 2004 Nationwide Inpatient Sample. Multivariable logistic regression analyses and Cox proportional hazards regression were conducted to calculate the odds of death (within 7, 14, and 30 days) and the hazard ratio of death for patients with weekend intracerebral hemorrhage admissions compared with weekday intracerebral hemorrhage admissions. All analyses were adjusted for concurrent differences in length of stay, patient demographics, and comorbid disease. Results— Weekend hospital admissions accounted for 26.8% of the 13 821 patients with a diagnosis of intracerebral hemorrhage in the National Inpatient Sample. Admission during the weekend was a statistically significant independent predictor of death within 7 days (OR, 1.14; 95% CI, 1.05 to 1.25), within 14 days (OR, 1.15; 95% CI, 1.05 to 1.25), and within 30 days (OR, 1.15; 95% CI, 1.05 to 1.25). The adjusted hazard of in-hospital death (hazard ratio, 1.12; CI, 1.05 to 1.20) indicates that the overall risk of in-hospital death with intracerebral hemorrhage is 12% higher with weekend admission. Conclusion— Weekend admission for intracerebral hemorrhage was associated with increased risk-adjusted mortality when compared with admission during the remainder of the week.

New insights into the causes and therapy of cerebral vasospasm following subarachnoid hemorrhage

Cerebral vasospasm lingers as the leading preventable cause of death and disability in patients who experience aneurysmal subarachnoid hemorrhage. Despite the potentially devastating consequences of cerebral vasospasm, the mechanisms behind it are incompletely understood. Nitric oxide, endothelin-1, bilirubin oxidation products and inflammation appear to figure prominently in its pathogenesis. Therapies directed at many of these mechanisms are currently under investigation and hold significant promise for an ultimate solution to this substantial problem.

Potential intracranial applications of magnetic resonance–guided focused ultrasound surgery

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

SONOTHROMBOLYSIS: AN EMERGING MODALITY FOR THE MANAGEMENT OF STROKE

OBJECTIVEIschemic stroke and intracranial hemorrhage remain a persistent scourge in Western civilization. Therefore, novel therapeutic modalities are desperately needed to expand the current limitations of treatment. Sonothrombolysis possesses the potential to fill this void because it has experienced a dramatic evolution from the time of early conceptualization in the 1960s. This process began in the realm of peripheral and cardiovascular disease and has since progressed to encompass intracranial pathologies. Our purpose is to provide a comprehensive review of the historical progression and existing state of knowledge, including underlying mechanisms as well as evidence for clinical application of ultrasound thrombolysis. METHODSUsing MEDLINE, in addition to cross-referencing existing publications, a meticulous appraisal of the literature was conducted. Additionally, personal communications were used as appropriate. RESULTSThis appraisal revealed several different technologies close to broad clinical use. However, fundamental questions remain, especially in regard to transcranial high-intensity focused ultrasound. Currently, the evidence supporting low intensity ultrasounds potential in isolation, without tissue plasminogen, remains uncertain; however, possibilities exist in the form of microbubbles to allow for focal augmentation with minimal systemic consequences. Alternatively, the literature clearly demonstrates, the efficacy of high-intensity focused ultrasound for independent thrombolysis. CONCLUSIONSonothrombolysis exists as a promising modality for the noninvasive or minimally invasive management of stroke, both ischemic and hemorrhagic. Further research facilitating clinical application is warranted.

Endovascular obliteration of an intracranial pseudoaneurysm: the utility of Onyx.

Pseudoaneurysms are rare lesions with a multitude of causes, including infectious, traumatic, and iatrogenic origins. In addition, there are a number of potential treatment options, all of which require consideration to determine the most appropriate management. Historically, surgical intervention has been the method of choice, but because the histopathological features of these lesions make them largely unsuitable for clipping, trapping or excision is often required. More recently endovascular methods have been used, including coil embolization, stent reconstruction, or parent artery occlusion. Although these methods are often successful, situations arise in which they are not technically feasible. The authors describe such a case in a pediatric patient with an iatrogenic pseudoaneurysm. Onyx was used to embolize the lesion and the results were excellent.

Vascular Smooth Muscle Cells in Cerebral Aneurysm Pathogenesis

Vascular smooth muscle cells (SMC) maintain significant plasticity. Following environmental stimulation, SMC can alter their phenotype from one primarily concerned with contraction to a pro-inflammatory and matrix remodeling phenotype. This is a critical process behind peripheral vascular disease and atherosclerosis, a key element of cerebral aneurysm pathology. Evolving evidence demonstrates that SMCs and phenotypic modulation play a significant role in cerebral aneurysm formation and rupture. Pharmacological alteration of smooth muscle cell function and phenotypic modulation could provide a promising medical therapy to inhibit cerebral aneurysm progression. This study reviews vascular SMC function and its contribution to cerebral aneurysm pathophysiology.

Tumor Necrosis Factor-α Modulates Cerebral Aneurysm Formation and Rupture

Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment of macrophages, activation of chemotactic cytokines, upregulation of matrix remodeling genes, production of free radicals leading to oxidative stress, and ultimately cellular apoptosis. Recent studies have indicated that TNF-α may be a potential target for the development of novel medical therapies, but additional experimental data is needed to clarify the intricacies of TNF-α activation and its critical downstream targets in cerebral aneurysms. This review provides an update on the mechanisms underlying TNF-α-induced molecular modulation in cerebral aneurysms.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound.

OBJECT Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. METHODS AND RESULTS In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. CONCLUSIONS The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.