Statins for neuroprotection in spontaneous intracerebral hemorrhage.

Statins, a common drug class for treatment of dyslipidemia, may be neuroprotective for spontaneous intracerebral hemorrhage (ICH) by targeting secondary brain injury pathways in the surrounding brain parenchyma. Statin-mediated neuroprotection may stem from downregulation of mevalonate and its derivatives, targeting key cell signaling pathways that control proliferation, adhesion, migration, cytokine production, and reactive oxygen species generation. Preclinical studies have consistently demonstrated the neuroprotective and recovery enhancement effects of statins, including improved neurologic function, reduced cerebral edema, increased angiogenesis and neurogenesis, accelerated hematoma clearance, and decreased inflammatory cell infiltration. Retrospective clinical studies have reported reduced perihematomal edema, lower mortality rates, and improved functional outcomes in patients who were taking statins before ICH. Several clinical studies have also observed lower mortality rates and improved functional outcomes in patients who were continued or initiated on statins after ICH. Subgroup analysis of a previous randomized trial has raised concerns of a potentially elevated risk of recurrent ICH in patients with previous hemorrhagic stroke who are administered statins. However, most statin trials failed to show an association between statin use and increased hemorrhagic stroke risk. Variable statin dosing, statin use in the pre-ICH setting, and selection biases have limited rigorous investigation of the effects of statins on post-ICH outcomes. Future prospective trials are needed to investigate the association between statin use and outcomes in ICH.

Cocaine Use is Associated with More Rapid Clot Formation and Weaker Clot Strength in Acute Stroke Patients.

INTRODUCTION: 1.1.Cocaine use is a known risk factor for stroke and has been associated with worse outcomes. Cocaine may cause an altered coagulable state by a number of different proposed mechanisms, including platelet activation, endothelial injury, and tissue factor expression. This study analyzes the effect of cocaine use on Thrombelastography (TEG) in acute stroke patients. PATIENT AND METHODS: 1.2.Patients presenting with Acute Ischemic Stroke (AIS) and spontaneous Intracerebral Hemorrhage (ICH) to a single academic center between 2009 and 2014 were prospectively enrolled. Blood was collected for TEG analysis at the time of presentation. Patient demographics and baseline TEG values were compared between two groups: cocaine and non-cocaine users. Multivariable Quantile regression models were used to compare the median TEG components between groups after controlling for the effect of confounders. RESULTS: 1.3.91 patients were included, 53 with AIS and 38 with ICH. 8 (8.8%) patients were positive for cocaine, 4 (50%) with AIS, and 4 (50%) with ICH. There were no significant differences in age, blood pressure, platelet count, or PT/PTT between the cocaine positive and cocaine negative group. Following multivariable analysis, and adjusting for factors known to influence TEG including stroke subtype, cocaine use was associated with shortened median R time (time to initiate clotting) of 3.8 minutes compared to 4.8 minutes in non-cocaine users (p=0.04). Delta (thrombin burst) was also earlier among cocaine users (0.4 minutes) compared with non-cocaine users (0.5 min, p=0.04). The median MA and G (measurements of final clot strength) were reduced in cocaine users (MA=62.5 mm, G=7.8 dynes/cm2) compared to non-cocaine users (MA=66.5 mm, G=10.1 dynes/cm2; p=0.047, p=0.04, respectively). CONCLUSION: 1.4.Cocaine users demonstrate more rapid clot formation but reduced overall clot strength based on admission TEG values.

Workflow Optimization for Ischemic Stroke in a Community-Based Stroke Center.

BACKGROUND: We analyzed the effect of specific optimization steps to reduce treatment delays in a nonacademic stroke hospital setting. METHODS: The data from patients with ischemic stroke who had been treated with intravenous tissue plasminogen activator or endovascular therapy, or both, were analyzed. The metrics were divided into 2 periods: preoptimization period (October 1, 2015 to September 30, 2016) and postoptimization period (October 1, 2016 to September 30, 2017). The key interventions were 1) notification by the emergency medical service to the emergency department and stroke team; 2) division of the stroke alert between level 1 (intravenous/intra-arterial candidate) and level 2; 3) direct transportation of level 1 patients to brain computed tomography; 4) limitation of nonessential interventions; 5) stroke orientation; 6) 24-hour, 7-day code stroke response by a vascular neurologist; 7) earlier notification of the interventional radiology team; 8) direct transportation from computed tomography to angiography suite for large vessel occlusion; and 9) multidisciplinary monthly meetings to discuss delayed cases. RESULTS: A total of 279 patients were identified. No significant differences in any of the baseline characteristics were documented. Almost all metrics favored the postoptimization period, with remarkable improvement in the door-to-puncture time (median, 64 minutes; interquartile range, 36-86; vs. 47 minutes; interquartile range, 20-62; P = 0.001). We observed an increased percentage of good clinical outcomes in the postoptimization group (60.1% vs. 54.8%; P = 0.500). We found an 8.4% increase in patients with good clinical outcomes in the postoptimization group compared with our previously reported work. CONCLUSIONS: For acute reperfusion therapies, significant reductions in workflow intervals can be achieved after simple optimization methods in a nonacademic community-based hospital.

The role of ICP monitoring in meningitis.

Intracranial pressure (ICP) monitoring has been widely accepted in the management of traumatic brain injury. However, its use in other pathologies that affect ICP has not been advocated as strongly, especially in CNS infections. Despite the most aggressive and novel antimicrobial therapies for meningitis, the mortality rate associated with this disease is far from satisfactory. Although intracranial hypertension and subsequent death have long been known to complicate meningitis, no specific guidelines targeting ICP monitoring are available. A review of the literature was performed to understand the pathophysiology of elevated ICP in meningitis, diagnostic challenges, and clinical outcomes in the use of ICP monitoring.

Hemodynamic and neuro-monitoring for neurocritically ill patients: An international survey of intensivists.

PURPOSE: To investigate multimodality systemic and neuro-monitoring practices in acute brain injury (ABI) and to analyze differences among "neurointensivists" (NI; clinical practice comprised >1/3 by neurocritical care), and other intensivists (OI). METHODS: Anonymous 22-question Web-based survey among physician members of SCCM and ESICM. RESULTS: Six hundred fifty-five responded (66% completion rate); 422 (65%) were OI, and 226 (35%) were NI. More NI follow hemodynamic protocols for TBI (44.5% vs 33%, P=.007) and SAH (38% vs 21%, P<.001). For CPP optimization, NI use more arterial-waveform-analysis (AWA) (45% vs 35%, P=.019), and ultrasound (37.5% vs 28%, P=.023); NI use more PbtO2 (28% vs 10%, P<.001). In the case scenario of raised ICP/low PbtO2, most employ analgesia and/or sedation (47%) and osmotherapy (38%). More NI use pressure reactivity (vasopressor use OI 23% vs NI 34.5%, P=.014). For DCI, more NI target cardiac index (CI) (35% vs 21%, P<.001), and fluid responsiveness (62.5% vs 53%, P=.03). Also, NI use more angiography (57% vs 43.5%, P=.004), TCD (56.5% vs 38%, P<.001), CTP (32% vs16%, P<.001), and PbtO2 (18% vs 7.5%, P=.001). CONCLUSIONS: Intensivists with exposure to ABI patients employ more neuro- and hemodynamic monitoring. We found large heterogeneity and low overall use of advanced brain-physiology parameters.

Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Seizures are relatively common after aneurysmal subarachnoid hemorrhage (aSAH). Seizure prophylaxis is controversial and is often based on risk stratification; middle cerebral artery (MCA) aneurysms, associated intracerebral hemorrhage (ICH), poor neurological grade, increased clot thickness, and cerebral infarction are considered highest risk for seizures. The purpose of this study was to evaluate the impact of recent cocaine use on seizure incidence following aSAH. METHODS: Prospectively collected data from aSAH patients admitted to 2 institutional neuroscience critical care units between 1991 and 2009 were reviewed. The authors analyzed factors that potentially affected the incidence of seizures, including patient demographic characteristics, poor clinical grade (Hunt and Hess Grade IV or V), medical comorbidities, associated ICH, intraventricular hemorrhage (IVH), hydrocephalus, aneurysm location, surgical clipping and cocaine use. They further studied the impact of these factors on "early" and "late" seizures (defined, respectively, as occurring before and after clipping/coiling). RESULTS: Of 1134 aSAH patients studied, 182 (16%) had seizures; 81 patients (7.1%) had early and 127 (11.2%) late seizures, with 26 having both. The seizure rate was significantly higher in cocaine users (37 [26%] of 142 patients) than in non-cocaine users (151 [15.2%] of 992 patients, p = 0.001). Eighteen cocaine-positive patients (12.7%) had early seizures compared with 6.6% of cocaine-negative patients (p = 0.003); 27 cocaine users (19%) had late seizures compared with 10.5% non-cocaine users (p = 0.001). Factors that showed a significant association with increased risk for seizure (early or late) on univariate analysis included younger age (< 40 years) (p = 0.009), poor clinical grade (p = 0.029), associated ICH (p = 0.007), and MCA aneurysm location (p < 0.001); surgical clipping was associated with late seizures (p = 0.004). Following multivariate analysis, age < 40 years (OR 2.04, 95% CI 1.355-3.058, p = 0.001), poor clinical grade (OR 1.62, 95% CI 1.124-2.336, p = 0.01), ICH (OR 1.95, 95% CI 1.164-3.273, p = 0.011), MCA aneurysm location (OR 3.3, 95% CI 2.237-4.854, p < 0.001), and cocaine use (OR 2.06, 95% CI 1.330-3.175, p = 0.001) independently predicted seizures. CONCLUSIONS: Cocaine use confers a higher seizure risk following aSAH and should be considered during risk stratification for seizure prophylaxis and close neuromonitoring.

Dehydroepiandrosterone sulphate: diabolical hormone or epiphenomenon in aneurysmal subarachnoid hemorrhage?

Inflammation is purported to play an important role in the clinical course of subarachnoid hemorrhage. The current study by Höllig et al. entails using dehydroepiandrosterone sulfate, a hormone that inhibits key inflammatory pathways, as a predictor of functional outcome in these patients.

Impact of case volume on aneurysmal subarachnoid hemorrhage outcomes.

PURPOSE: To compare aneurysmal subarachnoid hemorrhage (aSAH) outcomes between high- and low-volume referral centers with dedicated neurosciences critical care units (NCCUs) and shared neurosurgical, endovascular, and neurocritical care practitioners. MATERIALS AND METHODS: Prospectively collected data of aSAH patients admitted to 2 institutional NCCUs were reviewed. NCCU A is a 22-bed unit staffed 24/7 with overnight in-house NCCU fellow and resident coverage. NCCU B is a 14-bed unit with home call by NCCU attending/fellow and in-house residents. RESULTS: A total of 161 aSAH patients (27%) were admitted to NCCU B compared with 447 at NCCU A (73%). Among factors that independently impacted hospital mortality, there were no differences in baseline characteristics: mean age (A: 53.5 ± 14.1 years, B: 53.1 ± 13.6 years), poor grade Hunt and Hess (A: 28.2%, B: 26.7%), presence of multiple medical comorbidities (A: 28%, B: 31.1%), and associated cocaine use (A: 11.6%, B: 14.3%). There was no significant difference in hospital mortality (A: 17.9%, B: 18%), poor functional outcome (A: 30%, B: 25.4%), aneurysm rerupture (A: 2.8%, B: 2.4%), or delayed cerebral ischemia (A: 14.1%, B: 16.1%). CONCLUSIONS: The noninferior outcomes at the lower SAH volume center suggests that provider expertise, not patient volume, is critical to providing high-quality specialized care.

In-hospital outcomes of aneurysmal subarachnoid hemorrhage associated with cocaine use in the USA.

Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007-2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 ± 9.8 versus 58.4 ± 15.8, p<0.001), predominantly male (53.3% versus 38.5%, p<0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p<0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p<0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p<0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27-1.61, p<0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69-0.87, p<0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted.

The SAH Score: a comprehensive communication tool.

BACKGROUND: The Hunt and Hess grade and World Federation of Neurological Surgeons (WFNS) scale are commonly used to predict mortality after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to improve the accuracy of mortality prediction compared with the aforementioned scales by creating the "SAH score." METHODS: The aSAH database at our institution was analyzed for factors affecting in-hospital mortality using multiple logistic regression analysis. Scores were weighted based on relative risk of mortality after stratification of each of these variables. Glasgow Coma Scale (GCS) was subdivided into groups of 3-4 (score = 1), 5-8 (score = 2), 9-13 (score = 3), and 14-15 (score = 4). Age was categorized into 4 subgroups: 18-49 (score = 1), 50-69 (score = 2), 70-79 (score = 3), and 80 years or more (score = 4). Medical comorbidities were subdivided into none (score = 1), 1 (score = 2), or 2 or more (score = 3). RESULTS: In total, 1134 patients were included; all-cause SAH hospital mortality was 18.3%. Admission GCS, age, and medical comorbidities significantly affected mortality after multivariate analysis (P < .05). Summated scores ranged from 0 to 8 with escalating mortality at higher scores (0 = 2%, 1 = 6%, 2 = 8%, 3 = 15%, 4 = 30%, 5 = 58%, 6 = 79%, 7 = 87%, and 8 = 100%). Positive predictive value (PPV) for scores in the range 7-8 was 88.5%, whereas 6-8 was 83%. Negative predictive value (NPV) was 94% for range 0-2 and 92% for 0-3. The area under the curve (AUC) for the SAH score was .821 (good accuracy), compared with the WFNS scale (AUC .777, fair accuracy) and the Hunt and Hess grade (AUC .771, fair accuracy). CONCLUSIONS: The SAH score was found to be more accurate in predicting aSAH mortality compared with the Hunt and Hess grade and WFNS scale.

Withdrawal of technological life support following subarachnoid hemorrhage.

BACKGROUND: Prognostication of mortality or severe disability often prompts withdrawal of technological life support in patients following aneurysmal subarachnoid hemorrhage (aSAH). We assessed admission factors impacting decisions to withdraw treatment after aSAH. METHODS: Prospectively collected data of aSAH patients admitted to our institution between 1991 and 2009 were reviewed. Patients given comfort care measures were identified, including early withdrawal of treatment (<72 h after admission). Independent predictors of treatment withdrawal were assessed with multivariable analysis. RESULTS: The study included 1,134 patients, of whom 72 % were female, 58 % white, and 38 % black or African-American. Mean age was 52.5 ± 14.0 years. In-hospital mortality was 18.3 %. Of the 207 patients who died, treatment was withdrawn in 72 (35 %) and comfort measures instituted early in 31 (15 %). Among patients who died, WOLST was associated with older age (63.6 ± 14.2 years, WOLST vs. 55.6 ± 13.7 years, no WOLST, p < 0.001); GCS score <8 (62 % of WOLST vs. 44 % with no WOLST, p = 0.010); HH >3 (72 % of WOLST vs. 53 % with no WOLST, p = 0.008); and hydrocephalus (81 % of WOLST vs. 63 % with no WOLST, p = 0.009). Independent predictors of WOLST were poorer Hunt and Hess grade (AOR 1.520, 95 % CI 1.160-1.992, p = 0.002) and older age (AOR 1.045, 95 % CI 1.022-1.068, p < 0.001) with the latter also impacting early WOLST decisions. CONCLUSIONS: Older age and poor clinical grade on presentation predicted WOLST, and age predicted decisions to withdraw treatment earlier following aSAH. While based on prognosis, and in some cases patient wishes, this may also constitute a self-fulfilling prophecy in others.

Impact of acute cocaine use on aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Acute cocaine use has been temporally associated with aneurysmal subarachnoid hemorrhage (aSAH). This study analyzes the impact of cocaine use on patient presentation, complications, and outcomes. METHODS: Data of patients admitted with aSAH between 1991 and 2009 were reviewed to determine impact of acute cocaine use (C). These patients were compared with aSAH patients without recent cocaine exposure (NC) in relation to their presentation, complications such as aneurysmal rerupture and delayed cerebral ischemia, and outcomes including hospital mortality and functional outcome. RESULTS: Data of 1134 aSAH patients were reviewed; 142 patients (12.5%) had associated cocaine use. Cocaine users were more likely to be younger (mean age: C, 49±11; NC, 53±14; P<0.001). There were no differences in rates of poor-grade Hunt and Hess (4-5); (C, 21%; NC, 26%; P>0.05), associated intraventricular hemorrhage (C, 56%; NC, 51%; P>0.05), or hydrocephalus on admission Head CT (C, 49%; NC, 52%; P>0.05). Aneurysm rerupture incidence was higher among cocaine users (C, 7.7%; NC, 2.7%; P<0.05). The association of cocaine use with higher risk of delayed cerebral ischemia (C, 22%; NC, 16%; P<0.05) was not significant after correcting for other factors. Cocaine users were less likely to survive hospitalization compared with nonusers (mortality: C, 26%; NC, 17%; P<0.05); the adjusted odds of hospital mortality were 2.9 times higher among cocaine users (P<0.001). There were no differences in functional outcomes between the 2 groups. CONCLUSIONS: Acute cocaine use was associated with a higher risk of aneurysm rerupture and hospital mortality after aSAH.

Preadmission beta-blockers are associated with decreased incidence of neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Neurogenic stunned myocardium (NSM) is a frequent complication of aneurysmal subarachnoid hemorrhage (aSAH), with a significant impact on disease course. The presumed cause is catecholamine surge at the time of aneurysm rupture. Beta-blockers, which reduce the impact of the catecholamine surge, may decrease the risk of developing NSM. METHODS: A chart review of 234 consecutive patients admitted to the Oregon Health and Science University Neurosurgery service between March 6, 2008 and June 23, 2010 with a diagnosis of aneurysmal SAH was performed. This group was further subdivided by patients who received echocardiograms on admission, by gender, and by the prehospital administration of ß-blockers. RESULTS: One hundred thirty of 234 patients had echocardiograms on or shortly after admission, and 18 of these developed NSM (13.8%). None of the 22 patients taking prehospital ß-blockers developed NSM. Using the Fisher exact test to compare the 2 groups, patients who were administered prehospital ß-blockers were significantly less likely to develop stunning compared to those who were not (P = .04). After correcting for other variables using multiple logistic regression analysis, the previous use of ß-blockers was still found to be significantly associated with a decreased incidence of NSM after SAH (P = .049). There was no significant difference in hospital length of stay, peribleed stroke, vasospasm, or death. Of the 18 patients with stunning, 15 were women, 5 of whom were on estrogen supplementation. The mean peak troponin elevation of women who developed NSM on estrogen supplementation was significantly higher than for those who were not (mean peak troponin 9.97 ± 2.01 mg/dL; P < .001). CONCLUSION: Prehospital ß-blockers are associated with decreased risk of developing NSM in patients with aSAH. Estrogen may play an additional role in shaping the degree of NSM in women.

Improved aneurysmal subarachnoid hemorrhage outcomes: a comparison of 2 decades at an academic center.

OBJECTIVE: Management of aneurysmal subarachnoid hemorrhage (aSAH) has evolved over the past 2 decades, including refinement of neurosurgical techniques, availability of endovascular options, and evolution of neurocritical care; their impact on SAH outcomes is unclear. DESIGN/METHODS: Prospectively collected data of patients with aSAH admitted to Johns Hopkins Medical Institutions between 1991 and 2009 were analyzed. We compared survival to discharge and functional outcomes at initial clinic appointment postdischarge (30-120 days) in patients admitted between 1991 and 2000 (phase 1 [P1]) and 2000 and 2009 (phase 2 [P2]), respectively, using dichotomized Glasgow Outcome Scale (good outcome: Glasgow Outcome Scale 4-5). RESULTS: A total of 1134 consecutive patients with aSAH were included in the analysis (P1 46.4%, P2 53.6%). There were higher rates of poor grade Hunt and Hess (P1 23%, P2 28%; P < .05), admission Glasgow Coma Scale score lower than 8 (P1 14%, P2 21%; P < .005), known medical comorbidites (P1 54%, P2 64%; P = .005), associated intraventricular hemorrhage (P1 47%, P2 55%; P < .05), and older population (P1 51.5%, P2 53.5%; P < .05) in P2. Good outcomes were more common in P2 (71.5%) compared with P1 (65.2%), with 2-fold adjusted odds of good outcomes after correction for various confounding factors (P < .001). CONCLUSIONS: Our institutional experience over 2 decades confirms that patients with aSAH have shown significant outcome improvements over time.

Controversies in neurosciences critical care.

Neurocritical care is an evolving subspecialty with many controversial topics. The focus of this review is (1) transfusion thresholds in patients with acute intracranial bleeding, including packed red blood cell transfusion, platelet transfusion, and reversal of coagulopathy; (2) indications for seizure prophylaxis and choice of antiepileptic agent; and (3) the role of specialized neurocritical care units and specialists in the care of critically ill neurology and neurosurgery patients.

Impact of pattern of admission on outcomes after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Patients with aneurysmal subarachnoid hemorrhage (aSAH) require management in centers with neurosurgical expertise necessitating emergent interhospital transfer (IHT). Our objective was to compare outcomes in aSAH IHTs to our institution with aSAH admissions from our institutional emergency department (ED). METHODS: Data for consecutive patients with aSAH admitted to Johns Hopkins Medical Institutions between 1991 and 2009 were analyzed from a prospectively obtained database. We compared in-hospital mortality and functional outcomes at first clinical appointment post-aSAH (30-120 days) using dichotomized Glasgow Outcome Scale (good outcome: Glasgow Outcome Scale 4-5) in ED admissions with IHTs. RESULTS: A total of 1134 consecutive patients with aSAH were included in analysis (ED 40.1%, IHT 59.9%). Direct ED admissions had a higher incidence of poor Hunt and Hess grade (4/5) and major medical comorbidities, with no significant differences between the 2 groups in age, intraventricular hemorrhage, and hydrocephalus. In-hospital mortality for ED admissions (14.9%) was significantly lower than that for IHTs (20.5%), with 1.8 times greater adjusted odds of survival after multivariate analysis (P = .001). Emergency department admissions had nearly 2-fold greater odds of good outcomes (odds ratio, 1.89; P < .001) after multivariate analysis. CONCLUSIONS: Our institutional ED SAH admissions had significantly better outcomes than did IHTs, suggesting that delays in optimizing care before transfer could deleteriously impact outcomes.