Preoperative antithrombotic treatment in acutely symptomatic carotid artery stenosis.

OBJECTIVES: Early recurrence of cerebral ischemia in acutely symptomatic carotid artery stenosis can precede revascularization. The optimal antithrombotic regimen for this high-risk population is not well established. Although antiplatelet agents are commonly used, there is limited evidence for the use of anticoagulants. We sought to understand the safety and efficacy of short-term preoperative anticoagulants in secondary prevention of recurrent cerebral ischemic events from acutely symptomatic carotid stenosis in patients awaiting carotid endarterectomy (CEA). MATERIALS AND METHODS: A retrospective query of a prospective single institution registry of carotid revascularization was performed. Patients who presented with acute ischemic stroke or transient ischemic attack (TIA) attributable to an ipsilateral internal carotid artery stenosis (ICA) were included. Antiplatelet (AP) only and anticoagulation (AC) treatment arms were compared. The primary outcome was a composite of preoperative recurrent ischemic stroke or TIA. The primary safety outcome was symptomatic intracranial hemorrhage. RESULTS: Out of 443 CEA patients, 342 were in the AC group and 101 in the AP group. Baseline characteristics between groups (AC vs AP) were similar apart from age (71±10.5 vs 73±9.5, p=0.04), premorbid modified Rankin scale (mRS) score (1.0±1.2 vs 1.4±1.3, p=0.03) and stroke as presenting symptom (65.8 vs 53.5%, p=0.02). Patients in the AC group had a lower incidence of recurrent stroke/TIA (3.8 vs 10.9%, p=0.006). One patient had symptomatic intracranial hemorrhage in the AC group, and none in the AP group. In multivariate analysis controlling for age, premorbid mRS, stroke severity, degree of stenosis, presence of intraluminal thrombus (ILT) and time to surgery, AC was protective (OR 0.30, p=0.007). This effect persisted in the cohort exclusively without ILT (OR 0.23, p=0.002). CONCLUSIONS: Short term preoperative anticoagulation in patients with acutely symptomatic carotid stenosis appears safe and effective compared to antiplatelet agents alone in the prevention of recurrent cerebral ischemic events while awaiting CEA.

Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Evidence-Based Management of External Ventricular Drains.

PURPOSE OF REVIEW: The optimal management of external ventricular drains (EVD) in the setting of acute brain injury remains controversial. Therefore, we sought to determine whether there are optimal management approaches based on the current evidence. RECENT FINDINGS: We identified 2 recent retrospective studies on the management of EVDs after subarachnoid hemorrhage (SAH) which showed conflicting results. A multicenter survey revealed discordance between existing evidence from randomized trials and actual practice. A prospective study in a post-traumatic brain injury (TBI) population demonstrated the benefit of EVDs but did not determine the optimal management of the EVD itself. The recent CLEAR trials have suggested that specific positioning of the EVD in the setting of intracerebral hemorrhage with intraventricular hemorrhage may be a promising approach to improve blood clearance. Evidence on the optimal management of EVDs remains limited. Additional multicenter prospective studies are critically needed to guide approaches to the management of the EVD.

Intermittent CSF drainage and rapid EVD weaning approach after subarachnoid hemorrhage: association with fewer VP shunts and shorter length of stay.

OBJECTIVE: There is variability and uncertainty about the optimal approach to the management and discontinuation of an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH). Evidence from single-center randomized trials suggests that intermittent CSF drainage and rapid EVD weans are safe and associated with shorter ICU length of stay (LOS) and fewer EVD complications. However, a recent survey revealed that most neurocritical care units across the United States employ continuous CSF drainage with a gradual wean strategy. Therefore, the authors sought to determine the optimal EVD management approach at their institution. METHODS: The authors reviewed records of 200 patients admitted to their institution from 2010 to 2016 with aneurysmal SAH requiring an EVD. In 2014, the neurocritical care unit of the authors' institution revised the internal EVD management guidelines from a continuous CSF drainage with gradual wean approach (continuous/gradual) to an intermittent CSF drainage with rapid EVD wean approach (intermittent/rapid). The authors performed a retrospective multivariable analysis to compare outcomes before and after the guideline change. RESULTS: The authors observed a significant reduction in ventriculoperitoneal (VP) shunt rates after changing to an intermittent CSF drainage with rapid EVD wean approach (13% intermittent/rapid vs 35% continuous/gradual, OR 0.21, p = 0.001). There was no increase in delayed VP shunt placement at 3 months (9.3% vs 8.6%, univariate p = 0.41). The intermittent/rapid EVD approach was also associated with a shorter mean EVD duration (10.2 vs 15.6 days, p < 0.001), shorter ICU LOS (14.2 vs 16.9 days, p = 0.001), shorter hospital LOS (18.2 vs 23.7 days, p < 0.0001), and lower incidence of a nonfunctioning EVD (15% vs 30%, OR 0.29, p = 0.006). The authors found no significant differences in the rates of symptomatic vasospasm (24.6% vs 20.2%, p = 0.52) or ventriculostomy-associated infections (1.3% vs 8.8%, OR 0.30, p = 0.315) between the 2 groups. CONCLUSIONS: An intermittent CSF drainage with rapid EVD wean approach is associated with fewer VP shunt placements, fewer complications, and shorter LOS compared to a continuous CSF drainage with gradual EVD wean approach. There is a critical need for prospective multicenter studies to determine if the authors' experience is generalizable to other centers.

External Ventricular Drains After Subarachnoid Hemorrhage: Is Less More?

External ventricular drains (EVD) are essential in the early management of hydrocephalus and elevated intracranial pressure after subarachnoid hemorrhage (SAH). Once in place, management of the EVD is thought to influence long-term patient outcomes, rates of ventriculitis, incidence of delayed cerebral ischemia, need for a ventriculoperitoneal shunt, and intensive care unit (ICU) and hospital length of stay. The available evidence supports adopting early clamp trials and intermittent cerebrospinal fluid (CSF) drainage. However, a recent survey demonstrated that most neurological ICUs employ the opposite approach of continuously open EVDs and gradual weaning. In this article, we review the literature and arguments for and against the different EVD approaches. We conclude that an early clamp trial and intermittent CSF drainage can be safe and result in fewer EVD complications and shorter length of stay. Given the discrepancy between the available evidence and current practice, more studies on the optimal management of EVDs are warranted with the greatest need for multicenter prospective studies.

Cerebrovascular fibromuscular dysplasia: The MGH cohort and literature review.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare noninflammatory, nonatherosclerotic arteriopathy of medium-sized arteries affecting up to 7% of the population. The disease can affect any artery but commonly affects renal, extracranial carotid, and vertebral arteries. The epidemiology and natural course of cerebrovascular FMD is unknown and requires further investigation. METHODS: We present demographic and outcomes data on a case series of 81 patients with cerebrovascular FMD from Massachusetts General Hospital presenting between 2011 and 2015 followed by a review of the peer-reviewed literature. RESULTS: Patients were a median age of 53 years (±12 SD) and the majority were women. Approximately 50% had a history of tobacco use and more than two-thirds had hypertension. Most patients were on monoplatelet therapy with aspirin; during follow-up, 7 of 67 had progressive disease or additional symptoms. One of 67 patients had a cerebrovascular event: TIA. There were 5 of 67 who had noncerebrovascular events or disease progression and 1 death of unclear cause. CONCLUSIONS: Cerebrovascular FMD may present with myriad symptoms. Our data support that patients with FMD with symptomatic disease have a low rate of recurrent symptoms or disease progression and can be managed conservatively with stroke risk modification, antiplatelet agents, surveillance imaging, and counseling.

Management of External Ventricular Drains After Subarachnoid Hemorrhage: A Multi-Institutional Survey.

BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (SAH) often develop hydrocephalus requiring an external ventricular drain (EVD). The best available evidence suggests that a rapid EVD wean and intermittent CSF drainage is safe, reduces complications, and shortens ICU and hospital length of stay as compared to a gradual wean and continuous drainage. However, optimal EVD management remains controversial and the baseline practice among neurological ICUs is unclear. Therefore, we sought to determine current institutional practices of EVD management for patients with aneurysmal SAH. METHODS: An e-mail survey was sent to attending intensivists and neurosurgeons from 72 neurocritical care units that are registered with the Neurocritical Care Research Network or have been previously associated with the existing literature on the management of EVDs in critically ill patients. Only one response was counted per institution. RESULTS: There were 45 out of 72 institutional responses (63%). The majority of responding institutions (80%) had a single predominant EVD management approach. Of these, 78% favored a gradual EVD weaning strategy. For unsecured aneurysms, 81% kept the EVD continuously open and 19% used intermittent drainage. For secured aneurysms, 94% kept the EVD continuously open and 6% used intermittent drainage. Among continuously drained patients, the EVD was leveled at 18 (unsecured) and 11 cm H2O (secured) (p < 0.0001). When accounting for whether the EVD strategy was to enhance or minimize CSF drainage, there was a significant difference in the management of unsecured versus secured aneurysms with 42% using an enhance drainage approach in unsecured patients and 92% using an enhance drainage approach in secured patients (p < 0.0001). CONCLUSION: Most institutions utilize a single predominant EVD management approach, with a consensus toward a continuously open EVD to enhance CSF drainage in secured aneurysm patients coupled with a gradual weaning strategy. This finding is surprising given that the best available evidence suggests that the opposite approach is safe and can reduce ICU and hospital length of stay. We recommend a critical reassessment of the approach to the management of EVDs. Given the potential impact on patient outcomes and length of stay, more research needs to be done to reach a threshold for practice change, ideally via multicenter and randomized trials.

Recanalization and Remarkable Outcome after Subocclusive Thrombus: A Case Report.

Minimal literature exists regarding subocclusive thrombi and their management in acute ischemic stroke, and no randomized trials or guidelines are currently available. We present the case of an 83-year-old man with multiple vascular risk factors and recent cardiac surgery who presented with a severe left middle cerebral artery (MCA) syndrome due to a subocclusive thrombus. Intravenous (IV) tissue plasminogen activator was contraindicated given the patient's recent surgery, and endovascular therapy was deferred given improvement in symptoms. He was placed on IV heparin. His symptoms improved with recanalization of the MCA. Optimal management of subocclusive thrombi, which appear to have better outcomes than occlusive thrombi, has yet to be elucidated. Acute anticoagulation and endovascular therapy may both be reasonable; however, there are minimal data supporting the use of either and further studies are needed to develop the most favorable treatment algorithm. In the meantime, management decisions should be made on a case-by-case basis by multidisciplinary care teams.

Default Mode Network Perfusion in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The etiology of altered consciousness in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH) is not thoroughly understood. We hypothesized that decreased cerebral blood flow (CBF) in brain regions critical to consciousness may contribute. METHODS: We retrospectively evaluated arterial-spin labeled (ASL) perfusion magnetic resonance imaging (MRI) measurements of CBF in 12 patients with aneurysmal SAH admitted to our neurocritical care unit. CBF values were analyzed within gray matter nodes of the default mode network (DMN), whose functional integrity has been shown to be necessary for consciousness. DMN nodes studied were the bilateral medial prefrontal cortices, thalami, and posterior cingulate cortices. Correlations between nodal CBF and admission Glasgow Coma Scale (GCS) score, admission Hunt and Hess (HH) class, and GCS score at the time of MRI (MRI GCS) were tested. RESULTS: Spearman's correlation coefficients were not significant when comparing admission GCS, admission HH, and MRI GCS versus nodal CBF (p > 0.05). However, inter-rater reliability for nodal CBF was high (r = 0.71, p = 0.01). CONCLUSIONS: In this retrospective pilot study, we did not identify significant correlations between CBF and admission GCS, admission HH class, or MRI GCS for any DMN node. Potential explanations for these findings include small sample size, ASL data acquisition at variable times after SAH onset, and CBF analysis in DMN nodes that may not reflect the functional integrity of the entire network. High inter-rater reliability suggests ASL measurements of CBF within DMN nodes are reproducible. Larger prospective studies are needed to elucidate whether decreased cerebral perfusion contributes to altered consciousness in SAH.

Outcomes after Early Anticonvulsant Discontinuation in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Empiric use of anticonvulsant (AED) for seizure prophylaxis in aneurysmal subarachnoid hemorrhage (SAH) remains controversial and may be associated with worse SAH outcome. We determined the safety and feasibility of early discontinuation of empiric AED in a select cohort of SAH patients. METHODS: In a cohort of 166 consecutive SAH patients, a subset underwent early AED discontinuation if they were awake and following commands after aneurysm treatment. We examined the effect of AED discontinuation on seizure incidence, mortality and functional outcome at discharge using logistic regression and validated results using 70%-30% data partition. RESULTS: Seventy-three subjects underwent AED discontinuation. Patient groups had similar gender, age, Fisher grade, incidence of craniotomy, vasospasm, ischemic infarct, intraventricular and intraparenchymal hemorrhages. Hunt-Hess (HH) grade were lower in AED-discontinuation group. Clinical or electrographic seizure occurred in 1/93 (1%) patients on AED and 0/73 patient in AED-discontinuation group. Crude mortality was 24% in patients on AED and 2.7% off AED. After adjusting for age, HH grade, vasospasm, ischemic infarct, intracerebral, and intraventricular hemorrhage, AED discontinuation remains independently associated with lower mortality and higher odds of discharge to home (p=0.0002). AED use is not associated with angiographic vasospasm on exploratory analysis. CONCLUSION: AED discontinuation in SAH patients who are awake and following commands post aneurysm treatment is safe, feasible, and associated with better outcome at hospital discharge. A larger, prospective study is necessary to determine if empiric AED use in SAH leads to poorer functional status.

Risk adjustment for case mix and the effect of surgeon volume on morbidity.

IMPORTANCE: Retrospective studies of large administrative databases have shown higher mortality for procedures performed by low-volume surgeons, but the adequacy of risk adjustment in those studies is in doubt. OBJECTIVE: To determine whether the relationship between surgeon volume and outcomes is an artifact of case mix using a prospective sample of carotid endarterectomy cases. DESIGN: Observational cohort study from January 1, 2008, through December 31, 2010, with preoperative, immediate postoperative, and 30-day postoperative assessments acquired by independent monitors. SETTING: Urban, tertiary academic medical center. PATIENTS: All 841 patients who underwent carotid endarterectomy performed by a vascular surgeon or cerebrovascular neurosurgeon at the institution. INTERVENTION: Carotid endarterectomy without another concurrent surgery. MAIN OUTCOME MEASURES: Stroke, death, and other surgical complications occurring within 30 days of surgery along with other case data. A low-volume surgeon performed 40 or fewer cases per year. Variables used in a comparison administrative database study, as well as variables identified by our univariate analysis, were used for adjusted analyses to assess for an association between low-volume surgeons and the rate of stroke and death as well as other complications. RESULTS The rate of stroke and death was 6.9% for low-volume surgeons and 2.0% for high-volume surgeons (P = .001). Complications were similarly higher (13.4% vs 7.2%, P = .008). Low-volume surgeons performed more nonelective cases. Low-volume surgeons were significantly associated with stroke and death in the unadjusted analysis as well as after adjustment with variables used in the administrative database study (odds ratio, 3.61; 95% CI, 1.70-7.67, and odds ratio, 3.68; 95% CI, 1.72-7.89, respectively). However, adjusting for the significant disparity of American Society of Anesthesiologists Physical Status classification in case mix eliminated the effect of surgeon volume on the rate of stroke and death (odds ratio, 1.65; 95% CI, 0.59-4.64) and other complications. CONCLUSIONS AND RELEVANCE: Variables selected for risk adjustment in studies using administrative databases appear to be inadequate to control for case mix bias between low-volume and high-volume surgeons. Risk adjustment should empirically analyze for case mix imbalances between surgeons to identify meaningful risk modifiers in clinical practice such as the American Society of Anesthesiologists Physical Status classification. A true relationship between surgeon volume and outcomes remains uncertain, and caution is advised in developing policies based on these findings.

Clinical risk predictors for cerebral hyperperfusion syndrome after carotid endarterectomy.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is an important complication of carotid endarterectomy (CEA), yet prior research has been limited to small cohorts and retrospective analyses, or studies using radiographic rather than clinical definitions. METHODS: A prospective monitoring system was implemented to monitor CEA outcomes at a major academic medical centre. Independent, trained monitors from the neurology department examined all patients undergoing CEA preoperatively and postoperatively at 24 h and 30 days. Clinical variables were analysed to identify risk factors for CHS, which was defined as cases with postoperative development of a severe headache, new neurological deficits without infarction, seizure or intracerebral haemorrhage. RESULTS: Between 2008 and 2010, 841 CEAs were monitored and CHS occurred in 14 (1.7%) subjects, including seizures in 5 (0.6%) and intracerebral haemorrhage in 4 (0.5%). Univariate analysis identified a history of dyslipidaemia, coronary artery disease, diastolic blood pressure, intraoperative shunt use and non-elective CEA (performed during hospitalisation for a symptomatic ipsilateral stroke, transient ischaemic attack or amaurosis fugax) as potential risks for CHS (all p≤0.15); other variables-including the degree of ipsilateral and contralateral stenosis, operative time, intraoperative EEG slowing, history of prior CEA or carotid stent and time from prior carotid interventions- were not significant. Logistic regression confirmed the risk association between non-elective CEA and CHS (p=0.046). CONCLUSIONS: Independent, prospective monitoring of a large cohort of CEA cases identified a brief time interval between ischaemic symptoms and endarterectomy as the clearest risk factor for CHS.

Predictors of clamp-induced electroencephalographic changes during carotid endarterectomies.

OBJECTIVE: Electroencephalograms (EEGs) detect clamp-induced cerebral ischemia during carotid endarterectomy (CEA) and thus impact management and minimize the risk of perioperative stroke. We hypothesized that age, preoperative neurologic symptoms, ≥70% contralateral carotid and bilateral vertebral stenosis increase the probability of clamp-induced EEG changes, whereas ≥70% unilateral carotid stenosis does not. METHODS: This is an observational cohort study of 299 patients who underwent CEA with EEG monitoring at a single large urban academic medical center in 2009. Univariate and multivariate logistic regression were used. RESULTS: Seventy percent or greater ipsilateral carotid stenosis decreases the odds of clamp-induced neurophysiologic dysfunction (odds ratio [OR] = 0.43, 95% confidence interval [CI] [0.18, 0.99], P = 0.04) after adjustment for symptomatic status, degree contralateral carotid or vertebral stenosis, and age. Preoperative neurologic symptoms, ≥70% contralateral carotid stenosis, and bilateral extracranial vertebral stenosis independently increase these odds (OR 2.62, 95% CI [1.32, 5.18], P = 0.005; OR 2.84, 95% CI [1.27, 6.34], P = 0.01; and OR 3.58, 95% CI [1.02, 12.53], P = 0.04, respectively), after adjustment for the other factors. Age ≥70 years has no significant impact. CONCLUSIONS: Preoperative neurologic symptoms, ≥70% contralateral carotid, and bilateral vertebral stenosis increase the probability of clamp-induced ischemia as detected by intraoperative EEG, while ≥70% ipsilateral carotid stenosis decreases it.

Nicotine replacement therapy after subarachnoid hemorrhage is not associated with increased vasospasm.

BACKGROUND AND PURPOSE: A significant number of patients with aneurysmal subarachnoid hemorrhage are active smokers and at risk for acute nicotine withdrawal. There is conflicting literature regarding the vascular effects of nicotine and theoretical concern that it may worsen vasospasm. The literature on the safety of nicotine replacement therapy and its effects on vasospasm is limited. METHODS: A retrospective analysis was conducted of a prospectively collected database of aneurysmal subarachnoid hemorrhage patients admitted to the neurointensive care unit from 1994 to 2008. Paired control subjects matched for age, sex, Fisher score, aneurysm size and number, hypertension, and current medication were analyzed. The primary outcome was clinical and angiographic vasospasm and the secondary outcome was Glasgow Outcome Score on discharge. Conditional logistic models were used to investigate univariate and multivariate relationships between predictors and outcome. RESULTS: Two hundred fifty-eight active smoking patients were included of which 87 were treated with transdermal nicotine replacement therapy. Patients were well matched for age, sex, gender, Fisher score, aneurysm size and number, hypertension, and current medications, but patients who received nicotine replacement therapy had less severe Hunt-Hess scores and Glasgow coma scores. There was no difference in angiographic vasospasm, but patients who received nicotine replacement therapy were less likely to have clinical vasospasm (19.5 versus 32.8%; P=0.026) and a Glasgow Outcome Score <4 on discharge (62.6% versus 81.6%; P=0.005) on multivariate analysis. CONCLUSIONS: Nicotine replacement therapy was not associated with increased angiographic vasospasm and was associated with less clinical vasospasm and better Glasgow Outcome Score scores on discharge.

Effects of a single dose of dantrolene in patients with cerebral vasospasm after subarachnoid hemorrhage: a prospective pilot study.

BACKGROUND AND PURPOSE: New therapies for cerebral vasospasm after subarachnoid hemorrhage are needed because of its high morbidity and mortality rates. We investigated the feasibility and safety of a single dose of intravenous dantrolene and its effect on transcranial Doppler in cerebral vasospasm after subarachnoid hemorrhage. METHODS: In a prospective, open-label, single-dose ascending safety trial, 5 patients received intravenous dantrolene 1.25 mg/kg and the next 5 patients received 2.5 mg/kg over the course of 60 minutes. All other infusions were kept steady and hemodynamic parameters were recorded. Transcranial Doppler was performed at 0, 45, 90, and 135 minutes relative to infusion start. Basic chemistries, serum osmolality, arterial blood gas, and liver enzymes were measured before and after. RESULTS: Laboratory values and hemodynamic parameters remained unchanged except for a decrease in the systolic blood pressure in the low-dose group (-8 mm Hg; 95% CI, -26 to 10 mm Hg; P=0.027). After correcting for this decrease in blood pressure, peak systolic transcranial Doppler velocities decreased significantly (-26 cm/s; 95% CI, -47 to -5 cm/s; P=0.02), with a borderline change in mean velocities in the low-dose group (-16 cm/s; 95% CI, -36 to 4 cm/s; P=0.07) and peak systolic transcranial Doppler velocity in the high-dose group (-26 cm/s; 95% CI, -56 to 5 cm/s; P=0.05). CONCLUSIONS: In this pilot study, a single dose of intravenous dantrolene in cerebral vasospasm after subarachnoid hemorrhage appears feasible while inhibiting vasoconstriction in the low-dose group, but it may lower blood pressure. Our study provides useful data for the design of larger future studies. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00964548.

Risk of thrombolytic therapy for acute ischemic stroke in patients with current malignancy.

Little is known about the risk of thrombolysis in patients with malignancy, because these patients have been excluded from most clinical trials. We reviewed our acute ischemic stroke (AIS) database for clinical outcomes and complications in patients with current malignancy (CM) who received thrombolytic therapy. Consecutive AIS patients receiving thrombolysis between January 2003 and December 2006 were retrospectively abstracted in accordance with the American Stroke Association's Get With the Guidelines-Stroke definitions and charts were reviewed for history of malignancy. Patients with brain metastases did not receive tissue plasminogen activator (tPA). Stepwise logistic regression was used to identify independent predictors of in-hospital mortality. Of 308 AIS patients treated with thrombolytic therapy, 210 (68%) received intravenous (IV) tPA only, 41 (13%) received IV tPA plus intra-arterial therapy (IAT), and 57 (18%) received IAT only. Eighteen patients (5.8%) had a CM, and 26 patients (8.4%) had a remote history of malignancy. Patients with CM had a higher in-hospital mortality (38.9% vs 19.7 %; P=.05) and were more likely to have died due to worsening medical comorbidity (71.4% vs 9.6%; P < .001). The rate of symptomatic intracranial hemorrhage (ICH) was similar in the 2 groups (5.6% vs 2.7%; P=.47). In multivariate analysis, the only independent predictors of mortality were National Institutes of Health Stroke Scale score, history of hypertension, and smoking. CM was not independently associated with increased in-hospital mortality following thrombolysis. Mortality was attributable largely to medical comorbidities, not to symptomatic ICH. Our data suggest that thrombolysis may be a reasonable option for patients with malignancy who have acceptable medical comorbidities and performance status. Further research is warranted.

Effective glycemic control with aggressive hyperglycemia management is associated with improved outcome in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hyperglycemia strongly predicts poor outcome in patients with aneurysmal subarachnoid hemorrhage, but the effect of hyperglycemia management on outcome is unclear. We studied the impact of glycemic control on outcome of patients with aneurysmal subarachnoid hemorrhage. METHODS: A prospective intensive care unit database was used to identify 332 patients with hyperglycemic aneurysmal subarachnoid hemorrhage admitted between January 2000 and December 2006. Patients treated with an aggressive hyperglycemia management (AHM) protocol after 2003 (N=166) were compared with 166 patients treated using a standard hyperglycemia management before 2003. Within the AHM group, outcome was compared between patients who achieved good (mean glucose burden <1.1 mmol/L) and poor (mean glucose burden >or=1.1 mmol/L) glycemic control. Poor outcome was defined as modified Rankin scale >or=4 at 3 to 6 months. Multivariable logistic regression models correcting for temporal trend were used to quantify the effect of AHM on poor outcome. RESULTS: Poor outcome in AHM-treated patients was lower (28.31% versus 40.36%) but was not statistically significant after correcting for temporal trend. However, good glycemic control significantly reduced the incidence of poor outcome (OR, 0.25; 95% CI, 0.08 to 0.80; P=0.02) compared with patients with poor glycemic control within the AHM group. No difference in the rate of clinical vasospasm or the development of delayed ischemic neurological deficit was seen before and after AHM protocol implementation. CONCLUSIONS: AHM results in good glucose control and significantly reduces the odds for poor outcome after aneurysmal subarachnoid hemorrhage in glucose-controlled patients. Further studies are needed to confirm these results.

Dantrolene mediates vasorelaxation in cerebral vasoconstriction: a case series.

INTRODUCTION: Cerebral vasoconstriction syndromes such as vasospasm after subarachnoid hemorrhage (SAH) and trauma, or Call-Fleming syndrome are difficult to treat, and can lead to substantial disability and death. Dantrolene, a ryanodine receptor antagonist, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We examined the effect of dantrolene on middle cerebral artery (MCA) blood flow velocities as measured by transcranial Doppler (TCD). METHODS: Three consecutive patients with elevated MCA TCD velocities receiving dantrolene (2.5 mg/kg i.v. q6h) were retrospectively reviewed. Average MCA peak systolic, mean flow velocities, and the pulsatility index (PI) before and after the dantrolene infusion were compared within patients. Systemic physiological parameters (blood pressure, heart rate, central venous pressure, intracranial pressure, body temperature, and cooling water temperature) were retrospectively collected 6 h before and after the dantrolene infusion. RESULTS: MCA peak systolic velocities (mean +/- SE) for the three patients were 297 +/- 3, 248 +/- 8, and 268 +/- 19 cm/s before dantrolene and 159 +/- 9, 169 +/- 8, and 216 +/- 12 cm/s after dantrolene. Average mean flow velocities showed the same trend. Interestingly, the PI increased slightly from 0.6, 0.52, and 0.67 before dantrolene, to 1.17, 0.71, and 0.77 after dantrolene. Systemic physiological parameters remained stable in all three patients. CONCLUSION: Dantrolene attenuated cerebral vasoconstriction as measured by TCD without altering systemic physiological parameters. This suggests that intracellular calcium release from ryanodine channels in smooth muscle might play a role in vasospasm. A prospective study is underway to test this hypothesis.