3-month Poor Outcome Research Articles

Computed Tomography–Estimated Specific Gravity at Hospital Admission Predicts 6-Month Outcome in Mild-to-Moderate Traumatic Brain Injury Patients Admitted to the Intensive Care Unit

It is clear that patients with a severe traumatic brain injury (TBI) develop secondary, potentially lethal neurological deterioration. However, it is difficult to predict which patients with mild-to-moderate TBI (MM-TBI), even after intensive care unit (ICU) admission, will experience poor outcome at 6 months. Standard computed tomography (CT) imaging scans provide information that can be used to estimate specific gravity (eSG). We have previously demonstrated that higher eSG measurements in the standard CT reading were associated with poor outcomes after severe TBI. The aim of this study was to determine whether eSG of the intracranial content predicts 6-month outcome in MM-TBI. We analyzed admission clinical and CT scan data (including eSG) of 66 patients with MM-TBI subsequently admitted to our neurosurgical ICU. Primary outcome was defined as a Glasgow Outcome Scale score of 1 to 3 after 6 months. Discriminating power (area under the receiver operating characteristic curve [ROC-AUC], 95% confidence interval) of eSG to predict 6-month poor outcome was calculated. The correlation of eSG with the main ICU characteristics was then compared. Univariate and stepwise multivariate analyses showed an independent association between eSG and 6-month poor outcome (P = 0.001). ROC-AUC of eSG for the prediction of 6-month outcomes was 0.87 (confidence interval: 0.77-0.96). Admission eSG values were correlated with the main ICU characteristics, specifically 14-day mortality (P = 0.004), length of mechanical ventilation (P = 0.01), length of ICU stay (P = 0.045), and ICU procedures such as intracranial pressure monitoring (P < 0.001). In this MM-TBI cohort admitted to the ICU, eSG of routine CT scans was correlated with mortality, ICU severity, and predicted 6-month poor outcome. An external validation with studies that include the spectrum of TBI severities is warranted to confirm our results.

Abstract 2834: Elevated Blood and Cerebrospinal Fluid Matrix Metalloproteinase-9 is Associated with Poor 3-month Outcome Following Subarachnoid Hemorrhage

Background There is growing evidence supporting the role of inflammation in early brain injury (EBI) and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix Metalloproteinases (MMP) are released by inflammatory cells and can mediate EBI via disruption of the extracellular matrix. MMPs also cleave endothelin-1 (ET-1) into strongly vasoactive fragments and may thereby mediate vasospasm, which can further worsen SAH outcome. We hypothesize that elevated MMP-9 in human cerebrospinal fluid (CSF) is associated with vasospasm and SAH outcome, and therefore a potential clinical biomarker. Methods We prospectively enrolled consecutive SAH subjects, banked serial blood and CSF samples, and evaluated their 3- and 6-month modified Rankins scores (mRS) via telephone follow-up. Angiographic vasospasm was defined as &gt;50% reduction in vessel caliber on angiography on post-SAH day 6-8. Poor outcome was defined as mRS&gt;2. We compared blood and CSF MMP-9 by ELISA on post SAH days 0-1, 2-3, 4-5, 6-8, and 10-14 in a cohort of SAH subjects (N=35) with respect to vasospasm and to 3-month outcome. Continuous variables were compared using student t-test or Wilcoxan rank sum test depending on data normality. Repeated measurements were analyzed using longitudinal regression. Results The study population had a mean age of 53 years and has 54% female. Sixty percent of subjects presented with Hunt and Hess grade of 3 and above. Fifty-four percent developed vasospasm and 32% achieved poor 3-month outcome. Elevation of CSF MMP-9 throughout post SAH days 0-14 was associated with poor 3-month outcome (p=0.008). Specifically, elevated CSF MMP-9 on post SAH day 2-3 (p=0.05) and blood MMP-9 on post SAH day 4-5 (p=0.045) were associated with poor 3-month outcome ( Figure 1 ). Blood MMP-9 correlated strongly with blood leukocyte count (r=0.56, p=0.007). Neither CSF nor blood MMP-9 correlated with vasospasm. Conclusion Early elevation of CSF and blood MMP-9 are associated with poor 3-month outcome but not with vasospasm in SAH. Leukocytes are likely a significant source of blood but not CSF MMP-9. Blood and CSF MMP-9 may mediate neuronal death in SAH via mechanisms independent of angiographic vasospasm. Further studies are necessary to determine the source of CSF MMP-9 and the mechanism by which it mediates poor outcome in SAH. Larger prospective studies are necessary to validate CSF MMP-9 as a predictive biomarker for SAH outcome.

Abstract 2900: Fasting Glucose On 14 Day After Onset predicts One-year poor Outcome In Aneurysmal Subarachnoid Hemorrhage

Background and purpose: Admission hyperglycemia is associated with 3-month and/or 6-month poor outcomes after aneurysmal subarachnoid hemorrhage, but the effect of prolonged hyperglycemia on long-term outcomes is not very clear. We studied the relationship between 14 th day fasting glucose and 1-year outcome after aneurysmal subarachnoid hemorrhage. Methods: A prospective study of aneurysmal subarachnoid hemorrhage from August 2007 to August 2010 was used to analyze the effect of fasting glucose on admission and 14 th day respectively on 1-year outcome assessed with the modified Rankin scale. Onset to admission longer than 14 days were excluded from analysis, as well as patients died within the first 14 days post-onset. A total of 322 patients (female 54.7%, average age: 53.9±11.6 yr, 310 patients admitted within 7 days) were used to assess the relationship between poor outcomes and fasting glucose, and medical history, Fisher scale, Hunt and Hess grade, Glasgow Coma Scores. Poor outcome (death and dependency) was defined as modified Rankin scale 3-6 at 1 year. Multivariate Cox regression analysis was performed to assess risk factors for 1-year outcome. Results: The mean fasting glucose on 14 th day of poor outcome patients was higher than that of good outcome patients [(7.11±3.35) vs. (5.43±1.55) mmol/L, p &lt;0.001]. Fasting glucose at admission in poor outcome patients was also higher than that of good outcome ones[(6.90±2.61) vs. (5.92±1.74) mmol/L, p =0.005]. After adjusting for Hunt and Hess grade, history of hypertension and Fisher scale, fasting glucose on 14 th day was an independent predictor of poor outcome (odds ratio, 1.278; 95% CI, 1.098 to 1.487; P =0.0016). Meanwhile, glucose level on 14 th day was found to be associated with 1-year death (adjusted HR, 1.183; 95%CI, 1.087 to 1.288) after adjusting for Fisher scale, Glasgow Coma Scale and treatment methods. However, fasting glucose at admission wasn’t independent predictor of 1-year death and dependency in Logistic regression and death in Cox regression. Conclusions: After aneurysmal subarachnoid hemorrhage, the fasting glucose levels on 14 th day are associated with an increased risk of 1-year death and dependency. Further studies are needed to confirm these results.

Blood Pressure Variability after Intravenous Thrombolysis in Acute Stroke Does Not Predict Intracerebral Hemorrhage but Poor Outcome

Background: The relevance of blood pressure variability (BPV) in the development of intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) in acute stroke still remains uncertain. Methods: 427 consecutive patients treated with IVT in the years 2007–2009 were studied. Blood pressure (BP) values were analyzed from admission to follow-up imaging scan and described as mean, maximum, minimum, standard deviation (SD), difference between maximum and minimum, successive variation (SV) and maximum SV. ICH was categorized based on radiologic criteria and symptomatic ICH (sICH) was defined as ICH plus worsening of the National Institute of Health Stroke Scale by ≧4 points or leading to death. Three-month outcome was described by means of the modified Rankin Scale. Results: We observed any ICH in 51 (11.9%) and sICH in 10 (2.3%) patients. Systolic and diastolic BP profiles, including mean, maximum, minimum, SD, difference between maximum and minimum, SV and maximum SV, did not differ between ICH-negative, ICH-positive and sICH patients. In univariate analysis, high systolic BPV was associated with sICH (p = 0.03). A logistic regression model to predict ICH only found early CT findings (OR = 2.74, 95% CI = 1.47–5.11, p < 0.01) as independently associated with ICH. Poor 3-month outcome was independently predicted by age (OR = 0.96, 95% CI = 0.94–0.97, p < 0.001), NIHSS on admission (OR = 0.84, 95% CI = 0.80–0.87, p < 0.001), ICH (OR = 0.29, 95% CI = 0.13–0.66, p < 0.01) and high systolic BPV (OR = 1.68, 95% CI = 1.05–2.69, p < 0.05). Conclusions: We demonstrate that high BPV in patients receiving IVT leads to poor outcome but does not increase the risk of ICH/sICH.

Elevated Peripheral Neutrophils and Matrix Metalloproteinase 9 as Biomarkers of Functional Outcome Following Subarachnoid Hemorrhage

There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix metalloproteinases (MMPs) are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects (N = 55), banked serial blood and cerebrospinal fluid (CSF) samples, and evaluated their 3-month modified Rankin scores (mRS). Vasospasm was defined as >50% vessel caliber reduction on angiography 6–8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0–14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects (N = 35), we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay (ELISA) on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte (p = 0.0003) and neutrophil (p = 0.0002) counts during post-SAH days 0–14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count (post-SAH days 2–3, p = 0.018), blood MMP-9 (post-SAH days 4–5, p = 0.045), and CSF MMP-9 (post-SAH days 2–3, p = 0.05) are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 (post-SAH days 6–8, R = 0.39; p = 0.055; post-SAH days 10–14, R = 0.79; p < 0.0001), and blood MMP-9 correlates with CSF MMP-9 (post-SAH days 4–5, R = 0.72; p = 0.0002). Elevation of CSF MMP-9 during post-SAH days 0–14 is associated with poor 3-month outcome (p = 0.0078). Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.

Tissue at risk in the deep middle cerebral artery territory is critical to stroke outcome

The clinical efficacy of thrombolysis in stroke patients is explained by the increased rate of recanalization, which limits infarct growth. However, the efficacy could also be explained by the protection of specific sites of the brain. Here, we investigate where is this outcome-related tissue at risk using voxel-based analysis. We included 68 acute stroke patients with middle cerebral artery (MCA) occlusion on the admission MRI performed within 6h of symptoms onset (H6) and 16 controls. MCA recanalization was assessed using the magnetic resonance angiography performed at day1 (D1). Apparent diffusion coefficient (ADC) changes were analyzed using a voxel-based method between patients vs. controls group at admission (H6) in non-recanalized vs. recanalized and in 3-month poor vs. good outcome patients at D1. Complete or partial MCA recanalization was observed in 52 of 68 patients. Good outcome at 3months occurred in 40 patients (59%). In non-recanalized patients, ADC was decreased in the deep MCA and watershed arterial territory (the lenticular nucleus, internal capsule, and the overlying periventricular white matter). This decrease was not observed in recanalized patients at D1 or patients at H6. Fiber tracking suggested that the area is crossed by the cortico-spinal, cerebellar, and intra-hemispheric association tracts. Finally, this area almost co-localized with the area associated with poor outcome. A clinically relevant area of tissue at risk may occur in patients with MCA infarcts at the level of deep white matter fiber tracts. These findings suggest that neuroprotection research should be refocused on white matter.

Patient outcomes from symptomatic intracerebral hemorrhage after stroke thrombolysis

To assess the impact of symptomatic intracerebral hemorrhage (sICH) on outcome of thrombolysis-treated ischemic stroke patients, as additional to recognized prognosticators. The study cohort included 985 ischemic stroke patients treated with IV thrombolysis at the Helsinki University Central Hospital (1995-2008). In a multivariable model adjusted for baseline stroke severity, age, onset-to-treatment time, baseline glucose, hyperdense cerebral artery sign, and early infarct signs on baseline imaging, and prior modified Rankin Scale (mRS), we calculated risk ratios (RRs) of patients with sICH (separately per Safe Implementation of Thrombolysis in Stroke[SITS]-Monitoring Study, European Cooperative Acute Stroke Study II [ECASS-II], and National Institute of Neurological Disorders and Stroke [NINDS] definitions) for poor 3-month outcome (mRS 3-6) and mortality. Receiver operating characteristic (ROC) curve and integrated discrimination improvement (IDI) evaluated impact of sICH on outcome. Internal cross-validation of the model was done with bootstrap statistics. The frequency of sICH was 2.1% (SITS), 7.0% (ECASS-II), and 9.4% (NINDS). RRs for poor and fatal outcome, respectively, were 1.7 and 4.8 (SITS), 1.6 and 3.8 (ECASS-II), and 1.6 and 3.4 (NINDS). In IDI analyses, sICH improved prediction model for 3-month mRS of 3-6 and 4-6, respectively, by 1.4% and 3.0% (SITS), 4.0% and 5.9% (ECASS-II), and 4.7% and 6.1% (NINDS). In case of 3-month mRS 5-6 and mortality, it was 6.1% and 5.3% (SITS), 11.3% and 9.3% (ECASS-II), and 10.3% and 8.0% (NINDS). ROC analysis revealed similar results. Patients with sICH have increased risk of poor and fatal outcome. Compared with recognized stroke prognosticators, contribution of sICH is smaller. Definition-wise, ECASS-II- and NINDS-based sICH contribute relatively more; ECASS-II has the largest contribution to worst outcomes.

The Effect of Spontaneous Alterations in Brain Temperature on Outcome: A Prospective Observational Cohort Study in Patients with Severe Traumatic Brain Injury

There are few prospective studies reporting the effect of spontaneous temperature changes on outcome after severe traumatic brain injury (TBI). Where studies have been conducted, results are based on systemic rather than brain temperature per se. However, body temperature is not a reliable surrogate for brain temperature. Consequently, the effect of brain temperature changes on outcome in the acute phase after TBI is not clear. Continuous intraparenchymal brain temperature was measured in consecutive admissions of severe TBI patients during the course of the first 5 days of admission to the intensive care unit (ICU). Patients received minimal temperature altering therapy during their ICU stay. Logistic regression was used to explore the relationship between the initial, the 24-h mean, and the 48-h mean brain temperature with outcome for mortality at 30 days and outcome at 3 months. Multifactorial analysis was performed to account for potential confounders. At the 24-h time point, brain temperature within the range of 36.5°C to 38°C was associated with a lower probability of death (10-20%). Brain temperature outside of this range was associated with a higher probability of death and poor 3-month neurological outcome. After adjusting for other predictors of outcome, low brain temperature was independently associated with a worse outcome. Lower brain temperatures (below 37°C) are independently associated with a higher mortality rate after severe TBI. The results suggest that, contrary to current opinion, temperatures within the normal to moderate fever range during the acute post-TBI period do not impose an additional risk for a poor outcome after severe TBI.

Intensive Versus Conventional Insulin Therapy in Critically Ill Neurologic Patients

Previous studies of glycemic control in non-neurologic ICU patients have shown conflicting results. The purpose was to investigate whether intensive insulin therapy (IIT) to keep blood glucose levels from 80 to 110 mg/dl or conventional treatment to keep levels less than 151 mg/dl was associated with a reduction of mortality and improved functional outcome in critically ill neurologic patients. Within 24 h of ICU admission, mechanically ventilated adult neurologic patients were enrolled after written informed consent and randomized to intensive or conventional control of blood glucose levels with insulin. Primary outcome measure was death within 3 months. Secondary outcome measures included 90-day modified Rankin scale (mRS) score, ICU, and hospital LOS. 81 patients were enrolled. The proportion of deaths was higher among IIT patients but this was not statistically significant (36 vs. 25%, P = 0.34). When good versus poor outcome at 3 months was dichotomized to mRS score 0-2 versus 3-6, respectively, there was no difference in outcome between the two groups (76.2 vs. 75% had a poor 3-month outcome, P = 1.0). There was also no difference in ICU or hospital LOS. Hypoglycemia (<60 mg/dl) and severe hypoglycemia (<40 mg/dl) were more common in the intensive arm (48 vs. 11%, P = 0.0006; and 4 vs. 0%, P = 0.5, respectively). There was no benefit to IIT in this small critically ill neurologic population. This is the first glycemic control study to specifically examine both critically ill stroke and traumatic brain injury (TBI) patients and functional outcome. Given these results, IIT cannot be recommended over conventional control.

Effect of Systolic Blood Pressure Reduction on Hematoma Expansion, Perihematomal Edema, and 3-Month Outcome Among Patients With Intracerebral Hemorrhage

Evidence indicates that systolic blood pressure (SBP) reduction may reduce hematoma expansion in patients with intracerebral hemorrhage (ICH) who are initially seen with acute hypertensive response. To explore the relationship between different variables of SBP reduction and hematoma expansion, perihematomal edema, and 3-month outcome among patients with ICH. Post hoc analysis of a traditional phase 1 dose-escalation multicenter prospective study. Emergency departments and intensive care units. Patients having ICH with an elevated SBP of at least 170 mm Hg who were seen within 6 hours of symptom onset. Systolic blood pressure reduction using intravenous nicardipine hydrochloride targeting 3 tiers of sequentially escalating SBP reduction goals (170-199, 140-169, or 110-139 mm Hg). We evaluated the effect of SBP reduction (relative to initial SBP) on the following: hematoma expansion (defined as an increased intraparenchymal hemorrhage volume >33% on 24-hour vs baseline computed tomographic [CT] images), higher perihematomal edema ratio (defined as a >40% increased ratio of edema volume to hematoma volume on 24-hour vs baseline CT images), and poor 3-month outcome (defined as a modified Rankin scale score of 4-6). Sixty patients (mean [SD] age, 62.0 [15.1] years; 34 men) were recruited (18, 20, and 22 patients in each of the 3 SBP reduction goal tiers). The median area under the curve (AUC) (calculated as the area between the hourly SBP measurements over 24 hours and the baseline SBP) was 1360 (minimum, 3643; maximum, 45) U. Comparing patients having less vs more aggressive SBP reduction based on 24-hour AUC analysis, frequencies were 32% vs 17% for hematoma expansion, 61% vs 40% for higher perihematomal edema ratio, and 46% vs 38% for poor 3-month outcome (P > .05 for all). The median SBP reductions were 54 mm Hg at 6 hours and 62 mm Hg at 6 hours from treatment initiation. Comparing patients having equal to or less vs more than the median SBP reduction at 2 hours, frequencies were 21% vs 31% for hematoma expansion, 42% vs 57% for higher perihematomal edema ratio, and 35% vs 48% for poor 3-month outcome (P > .05 for all). We found no significant relationship between SBP reduction and any of the outcomes measured herein; however, the Antihypertensive Treatment of Acute Cerebral Hemorrhage study was primarily a safety study and was not powered for such end points. The consistent favorable direction of these associations supports further studies with an adequately powered randomized controlled design to evaluate the efficacy of aggressive pharmacologic SBP reduction.

Role of High Augmentation Index in Spontaneous Intracerebral Haemorrhage

Intracerebral haemorrhage (ICH) is the most disabling and least treatable form of stroke. Its risk factors include old age, hypertension, diabetes mellitus, hypercholesterolaemia, smoking and high alcohol intake, which are also associated with arterial stiffness. The aim of the present study was to determine the prognostic value of high augmentation index (AI), which is a surrogate marker of arterial stiffness, in patients with spontaneous ICH. A prospective study of 60 patients with spontaneous supratentorial ICH was conducted. Outcome was assessed using the Modified Rankin Scale at 3 months follow-up. Data were collected on age and sex, risk factors for ICH, clinical parameters, laboratory parameters, radiological findings and hospital management. Logistic regression analysis was carried out to identify independent predictors of 3-month outcome and mortality. Admission Glasgow Coma Scale score (OR, 0.7; 95% CI, 0.450-0.971; p = 0.035), total leukocyte count (OR,1.2; 95% CI, 1.028-1.453; p = 0.023) and haematoma volume (OR, 1.1; 95% CI, 1.024-1.204; p = 0.011) were found to be statistically significant in multivariate analysis of 3-month poor outcome. Factors independently associated with mortality were high AI (OR, 8.6; 95%CI, 1.748-40.940; p = 0.007) and midline shift (OR, 7.5; 95%CI, 1.809-31.004; p = 0.005). Admission Glasgow Coma Scale score, total leukocyte count and haematoma volume were significant predictors for 3-month poor outcome; high AI and midline shift were significant predictors for 3-month mortality.

Renal Dysfunction as an Independent Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage

Acute kidney injury occurs in 1% to 25% of critically ill patients with small increases in creatinine adversely affecting outcome. We sought to determine the burden of acute kidney injury in patients with aneurysmal subarachnoid hemorrhage and whether this dysfunction affects outcome. Between 1996 and 2008, 787 consecutive patients with aneurysmal subarachnoid hemorrhage were enrolled in our prospective database. Demographics, serum creatinine levels, and discharge modified Rankin scores were recorded, and changes in creatinine clearance were calculated. A multiple logistic regression was performed using known predictors for poor outcome after aneurysmal subarachnoid hemorrhage in addition to burden of contrast-enhanced imaging and change in creatinine clearance. One hundred seventy-nine (23.1%) patients were at risk for renal failure during their hospitalization. In a multivariate model, those patients who developed risk for renal failure were twice as likely to have a poor 3-month outcome (OR, 2.01; P=0.021). Survival curves comparing those not at risk, those at risk (increasing severity classes Risk, Injury, and Failure, and the 2 outcome classes Loss and End-Stage Kidney Disease [RIFLE] R), and those with renal injury or failure (RIFLE I and F) demonstrated that risk of death increases significantly as one progresses through the RIFLE classes (log rank, P<0.0001). In a large, consecutive series of prospectively enrolled patients with aneurysmal subarachnoid hemorrhage, we demonstrate, using the newly defined RIFLE classification for risk of renal failure, that even seemingly insignificant decreases in creatinine clearance are associated with significantly worse 3-month outcomes. This study highlights the importance of close surveillance of renal function and stresses the value of renal hygiene in the aneurysmal subarachnoid hemorrhage population.

Cerebral Hemodynamic Predictors of Poor 6-Month Glasgow Outcome Score in Severe Pediatric Traumatic Brain Injury

Little is known regarding the cerebral autoregulation in pediatric traumatic brain injury (TBI). We examined the relationship between cerebral hemodynamic predictors, including cerebral autoregulation, and long-term outcome after severe pediatric TBI. After Institutional Review Board (IRB) approval, a retrospective analysis of prospectively collected data (May 2002 to October 2007) for children age < or =16 years with severe TBI (admission Glasgow Coma Scale [GCS] score <9) was performed. Cerebral autoregulation was assessed within 72 h after TBI. Cerebral hemodynamic predictors (intracranial pressure [ICP], systolic blood pressure [SBP], and cerebral perfusion pressure [CPP]) through the first 72 h after TBI were abstracted. Univariate and multivariate analyses examined the relationship between impaired cerebral autoregulation (autoregulatory index <0.4), intracranial hypertension (ICP >20 mm Hg), and hypotension (SBP <5th percentile and CPP <40 mm Hg). Six-month Glasgow Outcome Scale (GOS) score of <4 defined poor outcome. Ten (28%) of the 36 children examined (9.1 +/- 5.3 [0.8-16] years; 74% male) had poor outcome. Univariate factors associated with poor outcome were impaired cerebral autoregulation (p = 0.005), SBP <5(th) percentile for age and gender (p = 0.02), and low middle cerebral artery flow velocity (<2 SD for age and gender; p = 0.04). Independent risk factors for poor 6-month GOS were impaired cerebral autoregulation (adjusted odds ratio [aOR] 12.0; 95% confidence interval [CI] 1.4-99.4) and hypotension (SBP <5th percentile; aOR 8.8; 95% CI 1.1-70.5), respectively. Previous studies of TBI describing poor outcome with hemodynamics did not consider the status of cerebral autoregulation. In this study, both impaired cerebral autoregulation and SBP <5th percentile were independent risk factors for poor 6-month GOS.

Microdialysis patterns in subarachnoid hemorrhage patients with focus on ischemic events and brain interstitial glutamine levels

This observational microdialysis (MD) study of 33 subarachnoid hemorrhage patients explores brain interstitial levels of glutamine, glutamate, lactate and pyruvate, and their relationship to clinical status and clinical course at the neurointensive care unit. The focus was on ischemic events, defined by clinical criteria or by radiology, and the significance of brain interstitial glutamine levels and lactate/pyruvate (L/P) ratio. Eleven out of 12 periods with an ischemic MD pattern, defined as lactate/pyruvate (L/P) ratios exceeding 40, were either related to delayed ischemic neurological deficits (DIND) or CT-verified infarcts, confirming that L/P above 40 is a specific ischemic and pathological MD measure. Poor admittance WFNS grade (WFNS 4-5) patients had lower glutamine at the onset of monitoring than what good admittance WFNS grade (WFNS 1-3) patients had (P < 0.05). Interstitial glutamine increased over time in most patients. A "glutamine surge" was defined as a period where the interstitial glutamine concentration increased at least 150 microM over 12 h. Fifteen patients had a DIND and associated MD patterns were glutamine surges (n = 12) and/or L/P>40 (n = 6). Seven patients received vasospasm treatment; in five of these the only DIND-associated MD pattern was a glutamine surge. Seventy percent of the glutamine surges occurred during ongoing propofol sedation, and there was no association between extubations and glutamine surges. There was no difference in mean glutamine levels during the monitoring period between patients with favorable 6-month outcome and patients with poor 6-month outcome. We suggest that an increasing interstitial glutamine trend is a dynamic sign of augmented astrocytic metabolism with accelerated glutamate uptake and glutamine synthesis. This pattern is presumably present in metabolically challenged, but yet not overt ischemic tissue.

Recurrence of Primary Headache Disorders After Emergency Department Discharge: Frequency and Predictors of Poor Pain and Functional Outcomes

We determine the frequency of moderate or severe headache during the first 24 hours after an emergency department (ED) visit for a primary headache disorder (such as migraine or tension-type headache), determine the burden of headache during the 3 months after the ED visit, and identify predictors of poor pain and functional outcomes after ED discharge for each of these periods. In this prospective cohort study, we enrolled headache patients during their initial ED visit, interviewed them by using a standardized questionnaire, and followed them by telephone 24 hours and 3 months after ED discharge. Two emergency physicians classified all headaches according to criteria established by the International Headache Society, using a valid questionnaire and a reproducible technique. During an 18-month period, we enrolled 309 primary headache disorder patients in the cohort. The most common primary headache diagnoses assigned to patients were migraine, tension-type headache, and unclassifiable recurrent headache disorder. We successfully obtained follow-up in 94% of patients 24 hours after ED discharge and in 94% 3 months after ED discharge. Moderate or severe headache was present within 24 hours of ED discharge in 31% (95% confidence interval [CI] 25% to 38%) of migraine patients, 19% (95% CI 9% to 36%) of tension-type headache patients, and 27% (95% CI 18% to 38%) of the unclassifiable headache patients. Multiple functionally impairing headaches occurred during the 3 months after ED discharge in 37% of migraine patients (95% CI 30% to 44%), 38% of tension-type headache patients (95% CI 23% to 54%), and 26% of the unclassifiable headache patients (95% CI 17% to 37). After multivariate adjustment, independent predictors of poor 24-hour outcomes were severe baseline pain, baseline nausea, screening positive for depression, and longer duration of headache; the independent predictor of poor 3-month outcomes was Medicaid insurance. Regardless of type of primary headache disorder, ED headache patients frequently experience pain and functional impairment during the hours and months after discharge.

Serum lipid levels and 3-month prognosis in Chinese patients with acute stroke

The possible correlation between serum lipid levels and outcome after stroke is still controversial. Therefore we examined whether serum lipid levels at admission had any prognostic value in the 3-month outcome after stroke. We performed a prospective, observational study of 649 patients with acute ischaemic stroke and intracerebral haemorrhagic stroke (ICH). Information on age, sex, history of arterial hypertension, diabetes mellitus, drinking, current smoking status, stroke type, Glasgow Coma Scale and Scandinavian Stroke Scale score, time from stroke onset, and presence of atrial fibrillation was obtained. Serum lipid levels were measured in blood samples taken from fasting patients 12 to 48 hours following ictus. Death and poor neurological outcome (Modified Rankin Scale score of > or =3 points) were defined as outcome events. A logistic regression model was performed to estimate the effect of the above variables on outcome after stroke. We found that the median levels of serum total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in good outcome patients with acute stroke were significantly higher (P<0.005) than those of poor outcome patients. The low levels of serum TC, TG and HDL-C (P<0.05) were independently related to increased 3-month poor outcome after acute ischaemic stroke and ICH. However, there was no significant relationship between LDL-C levels and 3-month outcome. The data from this study show that low levels of serum TC, TG and HDL-C are strong independent predictors of 3-month poor outcome in patients with acute ischaemic stroke and ICH.

Predictors of survival and functional outcome in acute stroke patients admitted to the stroke intensive care unit

Multivariate models have not been widely used to predict the outcome of acute stroke patients admitted to the intensive care unit (ICU). The purpose of this study was to determine potential measures observed in the first 12 h post-stroke that predict early mortality and functional outcomes in ICU-admitted stroke patients. Eight hundred and fifty acute stroke patients (ischemic stroke, 508; intracerebral hemorrhage, 342) were included in this analysis between November 2002 and December 2006. Measures of interest were obtained in the first 12 h after onset of stroke were analyzed for three types of outcome: 3-month mortality, 3-month mortality or institutional care, and poor functional outcomes at discharge. Poor functional outcomes were defined as a Barthel index <80 or a Rankin scale >2. Multivariate regression models were used to determine the predictive value of the observed measures. After 3 months, 17% of patients had died; 21% were alive but being cared for in institutional settings; and 62% were alive and living at home. Functional status at discharge indicated 16% of patients had died, poor function in 50%, and good function in 34% of patients. Initial stroke severity, measured by National Institute of Health Stroke Scale, and dependence on a ventilator predicts 3-month mortality and poor outcome in all stroke patients. In addition, old age, previous stroke, and total anterior circulatory infarct were associated with poor outcome in ischemic stroke patients; old age, low body mass index and the presence of intraventricular hemorrhage were associated with poor outcomes in intracerebral hemorrhage patients. In conclusion, early stroke mortality and outcome at discharge can be predicted in the first few hours following an acute stroke for moderate to severe ICU-admitted stroke patients.

Intravenous Thrombolysis with rt-PA in Acute Ischemic Stroke Patients Aged Older than 80 Years in Italy

Background: Intravenous (i.v.) thrombolysis with rt-PA within 3 h from symptom onset is the only approved treatment of pharmacological revascularization in acute ischemic stroke. However, little information exists on its use in elderly patients, in particular those aged >80 years, who at present are excluded from treatment. Methods: In a multicenter Italian study on i.v. thrombolysis, patients aged >80 years (n = 41) were compared with those aged ≤80 years (n = 207) regarding the percentage of symptomatic (nonfatal and fatal) intracerebral hemorrhage (SICH), favorable 3-month functional outcome (modified Rankin Scale score 0–2) and poor outcome (death or dependence, i.e. modified Rankin Scale score 3–5). Results: The percentage of SICH (nonfatal and fatal) was comparable between older (2.4%, 2.4%) and younger (2.4%, 2.4%) patient groups (p = 1.0). At 3 months, favorable outcome occurred in 44% and dependence in 22% of the older, and respectively in 58.5 and in 30.9% of the younger patients (p = 0.897). Patients aged >80 years had a higher mortality (34.1%) as compared to those aged ≤80 years (10.6%) (p < 0.001). Baseline National Institute of Health Stroke Scale score was the only statistically significant predictor of both mortality (OR = 1.26; 95% CI = 1.07–1.50) and poor outcome (OR = 1.39; 95% CI = 1.14–1.68) in the >80-year-old group. Conclusions: Acute ischemic stroke patients aged >80 years treated with i.v. rt-PA have a higher mortality than younger patients, but there are no differences for SICH nor for favorable outcome. Our data suggest that thrombolytic therapy should not be a priori denied for appropriately selected >80-year-old patients but randomized controlled clinical trials are necessary before definite recommendations can be given.

Temperature Rhythm in Aneurysmal Subarachnoid Hemorrhage

In the acute phase following brain injury, alterations in temperature regulation occur commonly and are associated with poorer outcome. However, few studies have examined temperature rhythm following brain insult, such as rupture and surgical management of ruptured cerebral aneurysms, and its association with clinical factors and outcome. This study describes diurnal temperature patterns in patients hospitalized for acute management of cerebral aneurysms (n = 86). Temperature mesor, amplitude, and acrophase were estimated from recorded temperature measurements using cosinor analysis. The association of these patterns with clinical condition, mortality, and 6-month functional outcome was examined. Changes in the temperature cosinor parameters were varied and individual. Most patients experienced elevated mesors (Mean +/- SD, 37.8 +/- 0.4 degrees C) and blunted amplitudes (0.27 +/- 0.14 degrees C). Acrophases were widely dispersed, with only 27% in the normative 12 noon to 6 PM quadrant. Cosinor parameters (particularly the mesor) showed greater alteration in patients with worse initial condition (e.g. Hunt and Hess score > or = 2: P = 0.001, Glasgow Coma Scale < 15: P = 0.001) and poorer 6-month outcome (e.g. mortality: P = 0.013, Extended Glasgow Outcome Scale < 5: P = 0.018). Abnormal cosinor parameters provided additional predictive information in relation to outcome, beyond the impact of initial neurologic condition. Further research is needed to understand the pathophysiology of temperature regulation following cerebral aneurysm rupture and to determine if temperature management strategies can alter outcome.

Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial.

We examined the relation of maximal in-hospital diuretic dose to weight loss, changes in renal function, and mortality in hospitalised heart failure (HF) patients. In ESCAPE, 395 patients received diuretics in-hospital. Weight was measured at baseline, discharge, and every other day before discharge. Weight loss was defined as the difference between baseline and last in-hospital weight. Mortality was assessed using a log-logistic model with non-zero background. Median weight loss: 2.8 kg (0.7, 6.1); mean: 3.7 kg (22% of values <0). Weight loss and maximum in-hospital dose were correlated (p=0.0007). Baseline weight, length of stay, and baseline brain natriuretic peptide were significant predictors of weight loss. After adjusting for these, dose was not a significant predictor of weight loss. A strong relation between dose and mortality was seen (p=0.003), especially at >300 mg/day. Dose remained a significant predictor of mortality after adjusting for baseline variables that significantly predicted mortality. Correlation between maximal dose and creatinine level change was not significant (r=0.043; p=0.412) High diuretic doses during HF hospitalisation are associated with increased mortality and poor 6-month outcome.