Predicting mortality in moderate-severe TBI patients without early withdrawal of life-sustaining treatments including ICU complications: The MYSTIC-score.

PURPOSE: To develop and internally validate the MortalitY in Moderate-Severe TBI plus ICU Complications (MYSTIC)-Score to predict in-hospital mortality of msTBI patients without early (<24 h) withdrawal-of-life-sustaining treatments. METHODS: We analyzed data from a Neuro-Trauma Intensive Care Unit prospectively collected between 11/2009-5/2019. Consecutive adult msTBI patients were included if Glasgow Coma Scale≤12, and neither died nor had withdrawal-of-life-sustaining treatments within 24 h of admission (n = 485). Using univariate and multivariable logistic regression in a random-split cohort approach (2/3 derivation;1/3 validation), we identified independent predictors of in-hospital mortality while adjusting for validated predictors of mortality (IMPACT-variables). We constructed the MYSTIC-Score and examined discrimination and calibration. RESULTS: The MYSTIC-Score included the ICU complications brain edema, herniation, systemic inflammatory response syndrome, sepsis, acute kidney injury, cardiac arrest, and urinary tract infection. In the derivation cohort(n = 324), discrimination and calibration were excellent (area-under-the-receiver-operating-curve [AUC-ROC] = 0.95;Hosmer-Lemeshow p-value = 0.09, with p > 0.05 indicating good calibration). Internal validation revealed an AUC-ROC = 0.93 and Hosmer-Lemeshow-p-value = 0.76 (n = 161). CONCLUSIONS: Certain ICU complications are independent predictors of in-hospital mortality and strengthen outcome prediction in msTBI when combined with validated admission predictors of mortality. However, external validation is needed to determine robustness and practical applicability of our model given the high potential for residual confounders.

Left Ventricular Noncompaction Cardiomyopathy as a Potential Cause of Bilateral Posterior Cerebral Artery Stroke - a Rare and Unique Clinical Occurrence.

BACKGROUND Bilateral posterior cerebral artery (PCA) occlusions are exceedingly rare, and are considered a devastating phenomenon that presents as cortical blindness. Predominant causes of PCA infarcts include cardiac and arterial embolisms. Left ventricular noncompaction (LVNC) cardiomyopathy is also an extremely rare cardiopathology. Several reports describe stroke as a potential manifestation of LVNC, but bilateral PCA infarcts are likely also caused by underlying LVNC cardiomyopathy, although this has not yet been reported. CASE REPORT A 63-year-old man presented to the emergency department of an outside hospital with acute vision loss in both eyes and dysarthria. His neurological examination necessitated an emergent stroke evaluation. His electrocardiogram and telemetry at admission did not reveal arrhythmia. He underwent an emergency endovascular thrombectomy at our facility. During the post-intervention stroke workup, a transthoracic echocardiogram with contrast showed left ventricle dilation, with an ejection fraction (EF) of 29%. Subsequent cardiac magnetic resonance imaging confirmed the presence of LVNC cardiomyopathy. He was started on therapeutic anticoagulation (apixaban) and remained stable neurologically during the 3-month followup, with some residual visual field deficits. His cardiac outcome also improved (stress test was unremarkable for any cardiac ischemia, and an echocardiogram showing improved EF of 40%). CONCLUSIONS Our report is distinct, as it presents 2 exceedingly rare events in a patient: the occurrence of simultaneous bilateral PCA infarcts and LVNC cardiomyopathy. Prompt and accurate diagnosis was pivotal to the successful management of both conditions. Prospective studies are warranted to further knowledge of LVNC pathophysiology and the occurrence of stroke in such patients so that comprehensive management plans can be devised.

Association of Dexamethasone with Shunt Requirement, Early Disability, and Medical Complications in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Current guidelines do not support the routine use of corticosteroids in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, corticosteroids use in aSAH has been practiced at some centers by convention. The aim of the study was to determine the incidence of hydrocephalus requiring ventriculoperitoneal shunt (VPS) placement as well as functional outcome on discharge and adverse events attributed to corticosteroids in patients with aSAH treated with different dexamethasone (DXM) treatment schemes. METHODS: We retrospectively analyzed 206 patients with aSAH stratified to three groups based on the DXM treatment scheme: no corticosteroids, short course of DXM (S-DXM; 4 mg every 6 h for 1 day followed by a daily total dose reduction by 25% and then by 50% on last day), and long course of DXM (L-DXM; 4 mg every 6 h for 5-7 days followed by reduction by 50% every other day). The primary outcome measure was the placement of a VPS, and the secondary outcome was a good functional outcome [modified Rankin Scale (mRS) 0-3] at hospital discharge. Safety measures were the incidence of infection (pneumonia, urinary tract infection, ventriculitis, meningitis), presence of delirium, and hyperglycemia. RESULTS: There was no difference in the rate of external ventricular drain (EVD) (p = 0.164) and VPS placement (p = 0.792), nor in the rate of good outcome (p = 0.928) among three defined treatment regimens. Moreover, the median duration of treatment with EVD did not differ between subjects treated with no corticosteroids, S-DXM, and L-DXM (p = 0.905), and the probability of EVD removal was similar when stratified according to treatment regimens (log-rank; p = 0.256). Patients who received L-DXM had significantly more complications as compared to patients, who received no corticosteroids or S-DXM (78.4% vs. 58.6%; p = 0.005). After adjustment, L-DXM remained independently associated with increased risk of combined adverse events (OR = 2.72; 95%CI, 1.30-5.72; p = 0.008), infection (OR = 3.45; 95%CI, 1.63-7.30; p = 0.001) and hyperglycemia (OR = 2.05; 95%CI, 1.04-4.04; p = 0.039). CONCLUSIONS: DXM use among patients with aSAH did not relate to the rate of EVD and VPS placement, duration of EVD treatment, and functional disability at discharge but increased the risk of medical complications.

Ultrasound-guided lumbar puncture improves success rate and efficiency in overweight patients.

BACKGROUND: Approximately 400,000 diagnostic lumbar punctures (LPs) are performed by neurologists yearly in the United States. There has been a transition from neurologists performing >40% of LPs 2 decades ago to now <15% of the time. High body mass index (BMI) is one of the key obstacles of LP for neurology residents, and the success rates drop to 58% when BMI is >35 kg/m2. METHODS: A prospective intervention study was conducted from March 2017 to March 2018 at an academic medical center. Patients were divided into ultrasound-guided LP or conventional LP. The primary outcome was the success rate of LP. The secondary outcome was the parameters regarding LP performance, the patients' feedback after procedures, and the residents' feedback about the learning modules. RESULTS: Eighty-two patients were enrolled with inclusion criteria of age >18 years, BMI ≥25 kg/m2, and able to give written informed consent. The ultrasound-guided LP group showed higher success rate (92.7% vs 68.3%, p < 0.05) and less duration of time (17.02 vs 37.63 minutes, p < 0.05) compared with the conventional LP group. It also showed advantages of decreased trials of needle insertions and redirections and reduced pain levels perceived by patients. CONCLUSIONS: This study suggests that using ultrasound to localize before LP could increase the LP success rate and improve other related LP outcomes in the overweight populations. Our study also provides evidence that brief, targeted teaching modules are feasible and effective for ultrasound-guided LP training. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with BMI ≥25 kg/m2 undergoing LP, ultrasound guidance increases the LP success rate.

12 versus 24 h bed rest after acute ischemic stroke thrombolysis: a preliminary experience.

BACKGROUND: The practice of ≥24 h of bed rest after acute ischemic stroke thrombolysis is common among hospitals, but its value compared to shorter periods of bed rest is unknown. METHODS: Consecutive adult patients with a diagnosis of ischemic stroke who had received intravenous thrombolysis treatment from 1/1/2010 until 4/13/2016, identified from the local ischemic stroke registry, were included. Standard practice bed rest for ≥24 h, the protocol prior to 1/27/2014, was retrospectively compared with standard practice bed rest for ≥12 h, the protocol after that date. The primary outcome was favorable discharge location (defined as home, home with services, or acute rehabilitation). Secondary outcome measures included incidence of pneumonia, NIHSS at discharge, and length of stay. RESULTS: 392 patients were identified (203 in the ≥24 h group, 189 in the ≥12 h group). There was no significant difference in favorable discharge outcome in the ≥24 h bed rest protocol compared with the ≥12 h bed rest protocol in multivariable logistic regression analysis (76.2% vs. 70.9%, adjusted OR 1.20 CI 0.71-2.03). Compared with the ≥24 h bed rest group, pneumonia rates (8.3% versus 1.6%, adjusted OR 0.12 CI 0.03-0.55), median discharge NIHSS (3 versus 2, adjusted p = .034), and mean length of stay (5.4 versus 3.5 days, adjusted p = .006) were lower in the ≥12 h bed rest group. CONCLUSION: Compared with ≥24 h bed rest, ≥12 h bed rest after acute ischemic stroke reperfusion therapy appeared to be similar. A non-inferiority randomized trial is needed to verify these findings.

Concordance of angiography and cerebral biopsy results for suspected primary central nervous system vasculitis: A multi-center retrospective review.

OBJECTIVE: Primary CNS Vasculitis (PCNSV) is a rare disease that is often challenging to diagnose. Cerebral angiography and biopsy have been utilized in the diagnostic workup for several decades but limited literature reports on the concordance of findings of angiography and biopsy. The primary objective of this work was to examine how cerebral angiography corresponded with biopsy findings in patients with suspected PCNSV. PATIENTS AND METHODS: A total of 128 patients who underwent workup for PCNSV between years 2005-2016 were identified by query of existing neurological surgery and angiography databases at University Hospitals Cleveland Medical Center (UHCMC) and the Cleveland Clinic Foundation (CCF). The primary outcome was to examine the concordance of results between angiography and cerebral biopsy. Secondary outcomes included examining concordance between results of biopsy and other commonly performed tests for diagnosis of PCNSV including Magnetic Resonance Imaging (MRI), cerebrospinal fluid white blood cell count (CSF WBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP). RESULTS: 128 patients underwent cerebral biopsy for diagnosis of suspected PCNSV. 93 (73%) of these patients also underwent angiography. Of the 34 patients with positive biopsy findings, only 5 also had positive angiography. Positive angiography was not found to be correlated with positive biopsy in our analysis. The only test that was significantly associated with biopsy proven vasculitis was increased CSF WBC count (P = 0.0114). CONCLUSIONS: PCNSV is a rare disease and often requires multiple tests or procedures to obtain definitive diagnosis. These results suggest that cerebral angiography findings are not associated with biopsy findings and should be used cautiously in the diagnostic work-up of PCNSV.

Nitric Oxide and Mitochondrial Function in Neurological Diseases.

Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology. Moreover, excess NO or the formation of reactive NO species (RNS), e.g., peroxynitrite (ONOO-), impairs mitochondrial functioning and this, in conjunction with nuclear events, eventually affects neuronal cell metabolism and survival, contributing to the pathogenesis of several neurodegenerative diseases. In this review we highlight the possible mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial function including (i) negative effects on electron transport chain (ETC); (ii) ONOO--mediated alteration in mitochondrial permeability transition; (iii) enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key proteins involved in this process such as dynamin-related protein 1 (DRP-1) and Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex; (iv) alterations in the mitochondrial metabolic pathways including Krebs cycle, glycolysis, fatty acid metabolism, and urea cycle; and finally (v) mitochondrial ONOO--induced nuclear toxicity and subsequent release of apoptosis-inducing factor (AIF) from mitochondria, causing neuronal cell death. These proposed mechanisms highlight the multidimensional nature of NO and its signaling in the mitochondrial function. Understanding the mechanisms by which NO mediates mitochondrial (dys)function can provide new insights into the treatment of neurodegenerative diseases.

"Don't lose hope early": Hemorrhagic diffuse axonal injury on head computed tomography is not associated with poor outcome in moderate to severe traumatic brain injury patients.

BACKGROUND: Diffuse axonal injury (DAI) on magnetic resonance imaging has been associated with poor functional outcome after moderate-severe traumatic brain injury (msTBI). Yet, DAI assessment with highly sensitive magnetic resonance imaging techniques is unfeasible in the acute trauma setting, and computed tomography (CT) remains the key diagnostic modality despite its lower sensitivity. We sought to determine whether CT-defined hemorrhagic DAI (hDAI) is associated with discharge and favorable 3- and 12-month functional outcome (Glasgow Coma Scale score ≥4) after msTBI. METHODS: We analyzed 361 msTBI patients from the single-center longitudinal Outcome Prognostication in Traumatic Brain Injury study collected over 6 years (November 2009 to November 2015) with prospective outcome assessments at 3 months and 12 months. Patients with microhemorrhages on CT were designated "CT-hDAI-positive" and those without as "CT-hDAI-negative." For secondary analyses "CT-hDAI-positive" was stratified into two phenotypes according to presence ("associated") versus absence ("predominant") of concomitant large acute traumatic lesions to determine whether presence versus absence of additional focal mass lesions portends a different prognosis. RESULTS: Seventy (19%) patients were CT-hDAI-positive (n = 36 predominant; n = 34 associated hDAI). In univariate analyses, CT-hDAI-positive status was associated with discharge survival (p = 0.004) and favorable outcome at 3 months (p = 0.003) and 12 months (p = 0.005). After multivariable adjustment, CT-hDAI positivity was no longer associated with discharge survival and functional outcome (all ps > 0.05). Stratified by hDAI phenotype, predominant hDAI patients had worse trauma severity, longer intensive care unit stays, and more systemic medical complications. Predominant hDAI, but not associated hDAI, was an independent predictor of discharge survival (adjusted odds ratio, 24.7; 95% confidence interval [CI], 3.2-192.6; p = 0.002) and favorable 12-month outcome (adjusted odds ratio, 4.7; 95% CI, 1.5-15.2; p = 0.01). Sensitivity analyses using Cox regression confirmed this finding for 1-year survival (adjusted hazard ratio, 5.6; 95% CI, 1.3-23; p = 0.048). CONCLUSION: The CT-defined hDAI was not an independent predictor of unfavorable short- and long-term outcomes and should not be used for acute prognostication in msTBI patients. Predominant hDAI patients had good clinical outcomes when supported to intensive care unit discharge and beyond. LEVEL OF EVIDENCE: Prognostic study, level III.

The Estimated Verbal GCS Subscore in Intubated Traumatic Brain Injury Patients: Is it Really Better?

The Glasgow Coma Scale (GCS) has limited utility in intubated patients due to the inability to assign verbal subscores. The verbal subscore can be derived from the eye and motor subscores using a mathematical model, but the advantage of this method and its use in outcome prognostication in traumatic brain injury (TBI) patients remains unknown. We compared the validated "Core+CT"-IMPACT-model performance in 251 intubated TBI patients prospectively enrolled in the longitudinal OPTIMISM study between November 2009 and May 2015 when substituting the original motor GCS (mGCS) with the total estimated GCS (teGCS; with estimated verbal subscore). We hypothesized that model performance would improve with teGCS. Glasgow Outcome Scale (GOS) scores were assessed at 3 and 12 months by trained interviewers. In the complete case analysis, there was no statistically or clinically significant difference in the discrimination (C-statistic) at either time-point using the mGCS versus the teGCS (3 months: 0.893 vs. 0.871;12 months: 0.926 vs. 0.92). At 3 months, IMPACT-model calibration was excellent with mGCS and teGCS (Hosmer-Lemeshow "goodness-of-fit" chi square p value 0.9293 and 0.9934, respectively); it was adequate at 12 months with teGCS (0.5893) but low with mGCS (0.0158), possibly related to diminished power at 12 months. At both time-points, motor GCS contributed more to the variability of outcome (Nagelkerke ΔR2) than teGCS (3 months: 5.8% vs. 0.4%; 12 months: 5% vs. 2.6%). The sensitivity analysis with imputed missing outcomes yielded similar results, with improved calibration for both GCS variants. In our cohort of intubated TBI patients, there was no statistically or clinically meaningful improvement in the IMPACT-model performance by substituting the original mGCS with teGCS.

The Modified Apnea Test During Brain Death Determination: An Alternative in Patients With Hypoxia.

INTRODUCTION: Conventional apnea testing in patients with severe hypoxemia or hemodynamic instability with removal from the ventilator support is unsafe. We describe an alternative approach to apnea testing, which may be used in patients with hypoxia unable to undergo conventional apnea testing. METHODS: Case Report. A 42-year-old man had a severe traumatic brain injury resulting in diffuse cerebral edema and subarachnoid hemorrhage with herniation. His presentation was complicated by hypoxic respiratory failure from pulmonary contusions and hemorrhagic shock. On hospital day 2, the patient lost brain stem reflexes. Brain death testing with conventional apnea testing was attempted but aborted due to hypoxia. RESULTS: A modified apnea test was applied, which had been approved by appropriate hospital committees including critical care operations, ethics, and the brain death protocol council. Minute ventilation was gradually decreased by ≥50% to attain a PaCo2 level ≥20 mm Hg above baseline. The ventilation mode was then switched from volume control to continuous positive airway pressure while observing the patient for signs of respiration for a duration of 60 seconds. CONCLUSION: The modified apnea test does not require circuit disconnection and can be successfully applied to determine brain death without compromising safety in high-risk patients having severe hypoxia.

Prevalence of Pelvic Vein Pathology in Patients with Cryptogenic Stroke and Patent Foramen Ovale Undergoing MRV Pelvis.

BACKGROUND: A substantial proportion of ischemic strokes has no any identified underlying cause. Notably, the prevalence of a patent foramen ovale (PFO) is increased in cryptogenic stroke (CS) populations, which may serve as a conduit for paradoxical emboli originating from deep vein thrombosis (DVT) including the pelvic veins. Yet, there are no published guidelines for the assessment of pelvic veins as part of the stroke workup and few studies have systematically investigated pelvic veins as a potential source for paradoxical emboli in CS patients. Further, there is a relative paucity of data regarding pelvic DVT in CS and results have been conflicting. Hence, we sought to determine the prevalence of pelvic DVT in select CS patients with PFO who underwent magnetic resonance venography (MRV). METHODS: We retrospectively identified patients (n = 50) who underwent contrast-enhanced pelvic MRV at the discretion of the treating physician for the evaluation of CS in the presence of a PFO during hospitalization at a single academic stroke center between January 2011 through December 2013. Multivariable logistic regression analyses were used to assess for factors independently associated with the presence of an abnormal MRV pelvis. RESULTS: Patients (47 ± 13 years of age) had MRV performed 4 ± 3 days after their incident stroke. Nine patients had an abnormal MRV (18%). Of these, four (8%) had pelvic vein thrombosis and 5 (10%) a May-Thurner anatomic variant. All patients with pelvic DVT were subsequently anticoagulated with warfarin (none had abnormal hypercoagulability testing). Clinical clues suggesting paradoxical embolism were present in as many as 40% of patients. On multivariable logistic regression, a history of any risk factors predisposing to DVT (OR 6.7; coefficient 1.9; BCa 95% CI 0.08-20.2; p = 0.014) as well as the number of predisposing risk factors (OR 3.9; coefficient 1.4; BCa 95% CI 0.25-4.2; p = 0.005) predicted the presence of pelvic vein pathology on MRV. CONCLUSION: We demonstrate a relatively high prevalence of pelvic DVT among select CS patients emphasizing the importance of considering the pelvic veins as a potential source for emboli particularly in the presence of risk factors known to predispose DVT. Because patients were included at the treating physician's discretion, our results reflect 'real-life' practice. Our results may be of clinical importance as inclusion of pelvic vein imaging in CS patients with PFO had impactful therapeutic and nosologic implications. Further study is needed to define patients most likely to benefit from pelvic vein imaging.

Rapid unexpected brain herniation in association with renal replacement therapy in acute brain injury: caution in the neurocritical care unit.

INTRODUCTION: We aim to raise awareness for the potential for rapid brain edema and herniation in acutely brain-injured patients undergoing renal replacement therapy (RRT), including one case undergoing continuous veno-venous hemofiltration. Dialysis disequilibrium syndrome (DDS) may have been a possible cause for the brain edema. METHODS: We retrospectively reviewed four consecutive neurocritically ill patients in acute renal failure undergoing RRT between 2011 and 2013. Imaging, blood pressure, and laboratory data pre-, during, and post-RRT are presented in graphical form. We performed an extensive literature review. RESULTS: All patients suffered rapidly progressive herniation and death from global brain edema closely related in time to RRT, without other identifiable causes even after detailed review by three neurointensivists. Common clinical symptoms included sudden onset fixed and dilated pupils with apnea, consistent with brain stem compression. Herniation was not reversed by high-dose osmotherapy, and all patients died. Our detailed literature review provides plausible mechanisms for DDS as the most likely cause for our patients' brain edema. CONCLUSIONS: Even today, sudden brain edema and herniation may occur in association with RRT in neurocritically ill patients. We call for the establishment of RRT guidelines in patients with acute neurological injuries.

Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial.

BACKGROUND: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH. METHODS: In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed. RESULTS: Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy. CONCLUSIONS: In this small trial, IV-D after aSAH was feasible, tolerable and safe. TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov NCT01024972.

Severe leukoaraiosis portends a poor outcome after traumatic brain injury.

BACKGROUND AND PURPOSE: It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI. METHODS: We retrospectively analyzed consecutive, prospectively enrolled patients of ≥50 years (n = 136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0-4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12 months, respectively. RESULTS: After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12 months defined as mRS 3-6 and GOS 1-3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3 months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) ≤12; p = 0.001], or had mild TBI (GCS 13-15; p = 0.002), respectively. CONCLUSION: We provide first evidence that preexisting cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization.

Self-fulfilling prophecies through withdrawal of care: do they exist in traumatic brain injury, too?

OBJECTIVE: We examined factors associated with withdrawal of care (WOC) in moderate-severe traumatic brain injury (msTBI) patients, and how WOC may affect short-term mortality and receipt of neurosurgery. Variability in msTBI-related outcome prognostication by clinicians from different specialties was also assessed. METHODS: Rates of WOC, factors associated with WOC, and the relation between WOC and in-hospital case-fatality rate (CFR) and neurosurgery were determined in 232 prospectively enrolled msTBI patients in the ongoing OPTIMISM Study at a level-1 trauma center. In a concomitant web-based survey with clinical vignettes, outcome prognostication comfort, treatment aggressiveness, and WOC recommendations were examined among 106 respondents from neurology, neurocritical care, neurosurgery, trauma and anesthesia/critical care. RESULTS: The average age of the study sample was 53 years, with a median Glasgow Coma Scale of 6. The in-hospital CFR was 36 and 68 % of patients had WOC. Factors independently associated with WOC were advanced age, pupillary reactivity, lower intensive care unit-length-of-stay, pre- and in-hospital cardiac arrest, herniation, intracranial pressure crisis, and pre-existing endocrine disease. Inclusion of WOC in our multivariable regression model predicting in-hospital CFRs negated all other variables. Survey results suggested that in younger patients, some clinicians prognosticated overly pessimistically based upon data available at the time of presentation. CONCLUSION: In our msTBI cohort, WOC was the most important predictor of in-hospital mortality. We identified several important independent predictors of WOC. Large within-center variability in msTBI outcome prognostication with varying levels of possible clinical nihilism exists, which may form the basis of self-fulfilling prophecies.

Frequency and impact of intensive care unit complications on moderate-severe traumatic brain injury: early results of the Outcome Prognostication in Traumatic Brain Injury (OPTIMISM) Study.

BACKGROUND: Known predictors of adverse outcomes in patients with moderate-severe TBI (msTBI) explain only a relatively small proportion of patient-related outcomes. The frequency and impact of intensive care unit complications (ICU-COMPL) on msTBI-associated outcomes are poorly understood. METHODS: In 213 consecutive msTBI patients admitted to a Level I Trauma Center neuro trauma ICU, twenty-eight ICU-COMPL (21 medical and 7 neurological) were prospectively collected and adjudicated by group consensus, using pre-defined criteria. We determined frequencies, and explored associations of ICU-COMPL and hospital discharge outcomes using multivariable logistic regression. RESULTS: The average age of the study sample was 53 years, and the median presenting Glasgow Coma Scale and Injury Severity Scores were 5 and 27, respectively. Hyperglycemia (79%), fever (62%), systemic inflammatory response syndrome (60%), and hypotension requiring vasopressors (42%) were the four most common medical ICU-COMPL. Herniation (39%), intracranial rebleed (39%), and brain edema requiring osmotherapy (37%) were the three most common neurological ICU-COMPL. After adjusting for admission variables, duration of ventilation, and ICU length-of-stay, patients with brain edema (OR 5.8; 95% CI 2, 16.7) had a significantly increased odds for dying during hospitalization whereas patients with hospital-acquired urinary tract infection (UTI) had a decreased odds (OR 0.05; 95% CI 0.005, 0.6). Sensitivity analysis revealed that UTI occurred later, suggesting a non-causal association with survival. Brain herniation (OR 15.7; 95% CI 2.6, 95.4) was associated with an unfavorable functional status (GOS 1-3). CONCLUSION: ICU-COMPL are very common after msTBI, have a considerable impact on short-term outcomes, and should be considered in the prognostication of these high risk patients. Survival associations of time-dependent complications warrant cautious interpretation.

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.

Cortical Vein Thrombosis as a Mimic for Isolated Cortical Subarachnoid Hemorrhage and Transient Ischemic Attack.

Isolated cortical subarachnoid hemorrhage is rare and poorly understood. Differential diagnoses and proposed pathophysiology vary widely and the diagnostic work-up for these patients who present with transient ischemic attack-like episodes and characteristic imaging findings is still unclear. We report a case of isolated subarachnoid hemorrhage and transient neurologic deficits due to isolated cortical vein thrombosis that was not detected by noninvasive tests. A 75-year-old woman with a history of a lobar intracerebral hemorrhage presented to the Academic Medical Center with sudden-onset transient left upper extremity weakness. Head CT showed a linear hyperdensity in the right precentral gyrus suggestive of isolated subarachnoid hemorrhage. MRI showed susceptibility in the corresponding area. CT angiogram and MRV showed no evidence of a venous thrombosis. The main outcome measures were results of computerized tomography and CT angiogram, magnetic resonance parenchymal and vascular imaging, angiography findings and clinical follow-up at 3 months. Cortical vein thrombosis was detected on conventional angiography. MRI was negative for microhemorrhages. The patient was anticoagulated and had no recurrences of her symptoms. We conclude that cortical vein thrombosis can present as isolated subarachnoid hemorrhage and transient ischemic attack-like episodes and may require angiography for definitive diagnosis.

Decompressive hemicraniectomy and durotomy for malignant middle cerebral artery infarction.

The high early case fatality among patients with massive hemispheric strokes calls for effective treatments. Release of the restriction created by the dura mater and bony skull to allow the infarcted brain tissue to swell has been successfully adopted by some while considered controversial by others. A recent pooled analysis provides estimates for the efficacy of decompressive surgery. Further analyses of current trial data suggest that in particular patient age and timing of surgery determine outcome. Nonetheless, in order to guide the management of individual patients, carefully adjusted medical care, ongoing futility analysis, and simultaneous caregiver meetings should be conducted to reach a joint decision addressing any ethical concerns. In conclusion, decompressive surgery increases the probability of survival but produces patients with moderate or moderately severe disability (albeit not severe disability). Currently, the decision to perform decompressive surgery should remain an individual one in each and every patient.