Neurological Outcome In Survivors Research Articles

Erythropoietin attenuates hyperoxia-induced oxidative stress in the developing rat brain

Oxygen toxicity contributes to the pathogenesis of adverse neurological outcome in survivors of preterm birth in clinical studies. In infant rodent brains, hyperoxia triggers widespread apoptotic neurodegeneration, induces pro-inflammatory cytokines and inhibits growth factor signaling cascades. Since a tissue-protective effect has been observed for recombinant erythropoietin (rEpo), we hypothesized that rEpo would influence hyperoxia-induced oxidative stress in the developing rat brain. The aim of this study was to investigate the level of glutathione (reduced and oxidized), lipid peroxidation and the expression of heme oxygenase-1 (HO-1) and acetylcholinesterase (AChE) after hyperoxia and rEpo treatment. Six-day-old Wistar rats were exposed to 80% oxygen for 2–48 h and received 20,000 IU/kg rEpo intraperitoneally (i.p.). Sex-matched littermates kept under room air and injected with normal saline or rEpo served as controls. Treatment with rEpo significantly reduced hyperoxia-induced upregulation of oxidized glutathione (GSSG) and malondialdehyde, a product of lipid breakdown, whereas reduced glutathione (GSH) was upregulated by rEpo. In parallel, hyperoxia-treated immature rat brains revealed rEpo-suppressible upregulation of synaptic AChE-S as well as of the stress-inducible AChE-R variant, together predicting rEpo-protected cholinergic signaling and restrained inflammatory reactions. Furthermore, treatment with rEpo induced upregulation of HO-1 on mRNA, protein and activity level in the developing rat brain. Our results suggest that rEpo generates its protective effect against oxygen toxicity by a reduction of diverse oxidative stress parameters and by limiting the stressor-inducible changes in both HO-1 and cholinergic functions.

Erythropoietin Attenuates Hyperoxia-Induced Cell Death by Modulation of Inflammatory Mediators and Matrix Metalloproteinases

Oxygen toxicity appears to contribute to the pathogenesis of adverse neurological outcome in survivors of preterm birth. In infant rodent brains, hyperoxia triggers widespread apoptotic neurodegeneration, induces proinflammatory cytokines and inhibits growth factor signaling cascades. Since a tissue-protective effect has been observed for recombinant erythropoietin (rEpo), we hypothesized that rEpo would influence the expression of proinflammatory cytokines and matrix metalloproteinase (MMP)-2 and MMP-9. Six-day-old Wistar rats were exposed to 80% oxygen for 2–48 h and received 20,000 IU rEpo i.p. Sex-matched littermates kept in room air and injected with normal saline or rEpo served as controls. Treatment with rEpo significantly reduced hyperoxia-induced upregulation of the proinflammatory cytokines IL-1β and IL-18 in infant rodent brains on the mRNA and protein levels. In parallel, gelatin zymography in hyperoxia-treated immature rat brains revealed an upregulation of active MMP-2 which was reduced by concomitant rEpo treatment. Furthermore, hyperoxia induced upregulation of MMP-9 following 12 h of oxygen exposure and this was attenuated by rEpo treatment. Our results suggest that rEpo generates its protective effect against oxygen toxicity through a reduction of proinflammatory mediator levels.

Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis*

Accurate prediction of neurological outcome in survivors of cardiac arrest may be difficult. We report the case of a 44-year-old survivor of a hypoxic cardiac arrest who repeatedly developed relentless myoclonic jerks on attempted discontinuation of his propofol infusion. These were initially thought to represent myoclonic status epilepticus before the correct diagnosis of Lance-Adams syndrome was made. Lance-Adams syndrome is a rare disorder seen in survivors of profound hypoxic episodes. It is characterised by intention myoclonus but preserved intellect. Accurate distinction between myoclonic status epilepticus and Lance-Adams syndrome is vital as they have very different prognoses. The different pathophysiology and distinguishing clinical features of these two conditions are highlighted.

Erythropoietin protects the developing brain from hyperoxia‐induced cell death and proteome changes

Oxygen toxicity has been identified as a risk factor for adverse neurological outcome in survivors of preterm birth. In infant rodent brains, hyperoxia induces disseminated apoptotic neurodegeneration. Because a tissue-protective effect has been observed for recombinant erythropoietin (rEpo), widely used in neonatal medicine for its hematopoietic effect, we examined the effect of rEpo on hyperoxia-induced brain damage. Six-day-old C57Bl/6 mice or Wistar rats were exposed to hyperoxia (80% O(2)) or normoxia for 24 hours and received rEpo or normal saline injections intraperitoneally. The amount of degenerating cells in their brains was determined by DeOlmos cupric silver staining. Changes of their brain proteome were determined through two-dimensional electrophoresis and mass spectrometry. Western blot, enzyme activity assays and real-time polymerase chain reaction were performed for further analysis of candidate proteins. Systemic treatment with 20,000 IE/kg rEpo significantly reduced hyperoxia-induced apoptosis and caspase-2, -3, and -8 activity in the brains of infant rodents. In parallel, rEpo inhibited most brain proteome changes observed in infant mice when hyperoxia was applied exclusively. Furthermore, brain proteome changes after a single systemic rEpo treatment point toward a number of mechanisms through which rEpo may generate its protective effect against oxygen toxicity. These include reduction of oxidative stress and restoration of hyperoxia-induced increased levels of proapoptotic factors, as well as decreased levels of neurotrophins. These findings are highly relevant from a clinical perspective because oxygen administration to neonates is often inevitable, and rEpo may serve as an adjunctive neuroprotective therapy.

Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury

Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 microM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin lead to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.

Protein nitration and poly-ADP-ribosylation in brain after rapid exsanguination cardiac arrest in a rat model of emergency preservation and resuscitation

Emergency preservation and resuscitation (EPR) of 60 min in rats is achievable with favorable outcome, while 75 min is associated with substantial mortality and impaired neurological outcome in survivors. We hypothesized that 75 min but not 60 min of EPR would be associated with activation of two potential secondary injury cascades in brain as reflected by protein nitration and poly (ADP-ribose) polymerase (PARP) activation. Rats were rapidly exsanguinated over 5 min. After 1 min of cardiac arrest (CA), rats were cooled to a target tympanic temperature of 15 degrees C. After either 60 min or 75 min of CA, resuscitation was achieved via cardiopulmonary bypass (CPB). Rats subjected to CPB only served as controls. Overall performance category (OPC) and neurologic deficit score (NDS) were assessed at 24 h. Protein nitration and poly-ADP-ribosylation were assessed by Western blotting and immunohistochemistry for 3-nitrotyrosine and poly-ADP ribose polymers, respectively, in multiple brain regions. Neurologic outcome was better in the 60 min vs. the 75 min EPR group (OPC, P<0.001; NDS, P=0.001). Densitometric analysis of the major 64 kD band showed that nitration and PARP activation were significantly increased in hippocampus, cortex and striatum in the 75 min EPR group vs. other groups. However, there were no differences in cerebellum. Analysis of the full protein spectrum showed significantly increased PARP activation only in hippocampus in the 75 min EPR group vs. other groups. Extending the duration of EPR beyond the limit that can yield favorable recovery in rats was associated with increased nitration and ribosylation of selected proteins in selectively vulnerable brain regions. The impact of these mechanisms on the outcome remains to be determined.

Vasopressin or Epinephrine for Out-of-Hospital Cardiac Arrest

The use of vasopressin in patients with cardiac arrest presenting with specific rhythms is controversial. We performed an evidence-based emergency medicine review of evidence comparing vasopressin to epinephrine in structured cardiac arrest protocols. We searched MEDLINE, EMBASE, the Cochrane Library, and other databases for randomized trials or systematic reviews comparing vasopressin to epinephrine for adults with cardiac arrest and measuring survival to hospital discharge and neurologic function in survivors. We used standard criteria to appraise the quality of published trials and systematic reviews. We used the random effects model in supplementary analyses to summarize results and to test for significant differences across subgroups of patients presenting with different arrest rhythms. We found 3 high-quality well-reported randomized trials and 1 rigorous meta-analysis. The evidence does not confirm a consistent benefit of vasopressin over epinephrine in increasing survival or improving neurologic outcome in survivors. Subgroup analysis reveals a large difference in effect of vasopressin over epinephrine in cardiac arrest patients with asystole, compared to other arrest rhythms, coming from within-trial comparisons. The difference is not consistent across otherwise similar trials, is not statistically significant, may reflect the application of multiple unplanned subgroup analyses, and is not supported by a plausible biological hypothesis. Evidence from randomized trials does not establish a benefit of vasopressin over epinephrine in increasing survival to discharge or improving neurologic outcomes in adult patients with nontraumatic cardiac arrest.

Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest

Therapeutic hypothermia can improve survival after cardiopulmonary resuscitation (CPR). Coenzyme Q10 (CoQ10) has shown a protective effect in neurodegenerative disorders. We investigated whether combining mild hypothermia with CoQ10 after out-of-hospital cardiac arrest provides additional benefit. Forty-nine patients were randomly assigned to either hypothermia plus CoQ10 or hypothermia plus placebo after CPR. Hypothermia with a core temperature of 35 degrees C was instituted for 24 hours. Liquid CoQ10 250 mg followed by 150 mg TID for 5 days or placebo was administered through nasogastric tube. Age, sex, premorbidity, cause of arrest, conditions of CPR, and degree of hypoxia were similar in both groups; no side effects of CoQ10 were identified. Three-month survival in the CoQ10 group was 68% (17 of 25) and 29% (7 of 24) in the placebo group (P=0.0413). Nine CoQ10 patients versus 5 placebo patients survived with a Glasgow Outcome Scale of 4 or 5. Mean serum S100 protein 24 hours after CPR was significantly lower in the CoQ10 group (0.47 versus 3.5 ng/mL). Combining CoQ10 with mild hypothermia immediately after CPR appears to improve survival and may improve neurological outcome in survivors.

The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury.

The purpose of this study was to determine the incidence of acute lung injury (ALI) in trauma patients with severe traumatic brain injury (TBI), to evaluate the impact of ALI on mortality and neurologic outcome after severe traumatic brain injury (TBI), and to identify whether the development of ALI correlates with the severity of TBI. Clinical data were collected prospectively over a 4-year period in a Level I trauma center. Patients included in the study met the following criteria: mechanical ventilation > 24 hours, head Abbreviated Injury Scale score >or= 3, no other body region Abbreviated Injury Scale score >or= 3, and age between 18 and 54 years. ALI was defined using international consensus criteria. Glasgow Outcome Scale scores were assessed at 3 and 12 months. Bivariate comparisons were made between ALI and non-ALI groups. Multivariate analysis with stepwise logistical regression was used to assess independent factors on mortality. The patient's admission head computed tomographic (CT) scan was graded using the Marshall system, and the presence and size of specific intracranial abnormality was noted. Glasgow Coma Scale (GCS) score, Marshall CT scan score, and intracranial abnormality were correlated with the development of ALI. One hundred thirty-seven patients with isolated head trauma were enrolled in the study over a 4-year period. Thirty-one percent of patients with severe TBI developed ALI. Head trauma patients with ALI had a significantly higher ISS, a greater number of days on the ventilator, and a worse neurologic outcome for those who survived their hospitalization. Mortality was 38% in the ALI group and 15% in the non-ALI group (p = 0.004). Only 3 of 16 (19%) of the deaths within the ALI group were directly related to ALI. By multivariate analysis, only the presence of ALI, older age, and lower initial GCS score were associated with higher mortality. There was no association between ISS, the presence of arterial hypotension (arterial systolic pressure < 90 mm Hg) at admission to the hospital, or the amount of blood transfused and mortality. No correlation was found between the severity of head injury (GCS score, Marshall score, or intracranial abnormality) and development of ALI. The development of ALI is a critical independent factor affecting mortality in patients suffering traumatic brain injury and is associated with a worse long-term neurologic outcome in survivors. The risk of developing ALI is not associated with specific anatomic lesions diagnosed by cranial CT scanning.

Cesarean section is not protective against adverse neurological outcome in survivors of preterm delivery due to overt chorioamnionitis

Cesarean section is not protective against adverse neurological outcome in survivors of preterm delivery due to overt chorioamnionitis

Cesarean section is not protective against adverse neurological outcome in survivors of preterm delivery due to overt chorioamnionitis

Objective: To determine whether the mode of delivery has a protective value on the immediate adverse neonatal neurological outcome of infants born from pregnancies complicated by preterm chorioamnionitis.Methods: A comparison of the immediate and long-term neurological outcome of preterm neonates (24-34 weeks' gestation) of pregnancies complicated by chorioamnionitis, was made between those bornby Cesarean section and by vaginal delivery.Results: Of the 73 newborns, 54 (74%) survived the neonatal period; two (2.7%) had incomplete records, leaving 71 for analysis. Thirty (42.2%) weredelivered by Cesarean section and 41 (57.7%) vaginally. The obstetric and neonatal characteristics were comparable. Twenty-four (80%) survived in the Cesarean group and 30 (73.2%) in the vaginal deliverygroup (NS). There was no significant difference in the immediate adverse neonatal neurological outcome between Cesarean and vaginal deliveries.Conclusions: The mode of delivery did not significantlyaffect the immediate neurological status of preterm infants exposed to antenatal intrauterine infection.

Clinical course and medical management of neonates with severe cardiac failure related to vein of Galen malformation

Background: Neonatal presentation of vein of Galen aneurysmal malformations (VGAMs) with intractable cardiac failure is considered a poor prognostic sign. Interventional neuroradiology with embolisation has been shown to control cardiac...

Shaken baby syndrome

Purpose To examine the comprehensive ophthalmologic experience with the shaken baby syndrome at one medical center, including clinical findings, autopsy findings, and the outcome of survivors. Design Retrospective, noncomparative case series. Participants One hundred twenty-three children admitted from January 1987 through December 1998 for subdural hematomas of the brain secondary to abuse were included. Methods Clinical features of eye examinations of the patients during their admission and after discharge and histopathologic observations for patients who died were retrieved from medical records and statistically analyzed. Main outcome measures Visual response and pupillary response on initial examination, fundus findings, final vision, neurologic outcome of survivors, and death. Results Ninety percent of the patients had ophthalmologic assessments. Retinal hemorrhages were detected in 83% of the examined children. The retinal hemorrhages were bilateral in 85% of affected children and varied in type and location. Nonophthalmologists missed the hemorrhages in 29% of affected patients. Poor visual response, poor pupillary response, and retinal hemorrhage correlated strongly with the demise of the child. One child who died had pigmented retinal scars from previous abuse, a condition not previously observed histopathologically to our knowledge. One fifth of the survivors had poor vision, largely the result of cerebral visual impairment. Severe neurologic impairment correlated highly with loss of vision. Conclusions Shaken baby syndrome causes devastating injury to the brain and thus to vision. Retinal hemorrhages are extremely common, but vision loss is most often the result of brain injury. The patient’s visual reaction and pupillary response on presentation showed a high correlation with survival. Good initial visual reaction was highly correlated with good final vision and neurologic outcome. According to the literature, when retinal hemorrhages are found in young children, the likelihood that abuse occurred is very high. Nonophthalmologists’ difficulty in detecting retinal hemorrhages may be an important limiting factor in identifying shaken babies so they can be protected from further abuse.

Neurologic Outcome in Survivors of Childhood Arterial Ischemic Stroke and Sinovenous Thrombosis

Ischemic stroke during infancy and childhood has the potential for life-long morbidity. Information on the neurologic outcome of children who survive ischemic stroke is lacking. Children surviving ischemic stroke between January 1, 1995 and July 1, 1999 were prospectively followed. Neurologic deficit severity was based on the Pediatric Stroke Outcome Measure (PSOM) developed in this study and parental response to two recovery questions. Predictor variables for poor outcome were tested. One-hundred twenty-three children with arterial ischemic stroke and 38 with sinovenous thrombosis were followed for a mean of 2.1 years (range, 0.8 to 6.6 years). The primary outcome based on PSOM assessment was: normal, 37%; mild deficit, 20%; moderate deficit, 26%; and severe deficit, 16%. The secondary outcome was full recovery in 45% of patients, based on parental response. The primary and secondary outcome measures were moderately correlated (P < .001; K = 0.5). In bivariate analysis, arterial stroke type, male gender, age of at least 28 days, presence of associated neurologic disorders, and need for rehabilitation therapy after stroke were predictors of poor outcome (P < .05). Multivariate analysis showed that only arterial ischemic stroke, associated neurologic disorders, and presence of rehabilitation therapy were independent predictors of poor outcome (P < .02). Poor outcome in children after ischemic stroke is therefore frequent and more likely in the presence of arterial stroke, rehabilitation therapy, and associated neurologic disorders, which justifies clinical trials of treatment strategies in childhood ischemic stroke.

Outcome at 2 years of children 23–27 weeks' gestation born in Victoria in 1991–92

Objective:To determine the survival and sensorineural disability rates in very preterm infants born in 1991–92, and to compare the results with contemporaneous normal birthweight controls and with preterm infants born in 1985–87.Methodology:This was a geographically determined cohort study in the state of Victoria, Australia of consecutive livebirths 23–27 weeks' gestational age born during 1991–92, and randomly selected contemporaneous normal birthweight (NBW) controls born during 1991–92 in the three level‐III perinatal centres in the State. Consecutive livebirths 24–26 weeks gestational age born in the State during 1985–87 comprised another comparison group. The main outcome measures were survival and sensorineural disability rates at 2 years of age.Results:Of the 401 livebirths 23–27 weeks in 1991–92, 225 (56.1%) survived to 2 years of age. The survival rate for those 24–26 weeks was 57.4% (143/249), a statistically significant increase on the regional survival rate of 30.1% (95/316) in 1985–87. In 1991–92 births, the survival rate rose significantly with increasing gestational age, and was significantly higher than in 1985–87 at each of 24, 25, and 26 weeks. Of sensorineural impairments in preterm survivors at 2 years of age, the rate of blindness was significantly lower in 1991–92 (2.3%) compared with 1985–87 (8.4%), and the overall rates of sensorineural disability were not statistically different in 1991–92 compared with 1985–87. In 1991–92 preterm survivors, the survival rate free of disability rose significantly with increasing gestational age, and as a percentage of survivors the rate of disability overall fell with increasing gestational age. However, the rate of disability overall was much higher in preterm infants than NBW controls.Conclusions:Survival rates of very preterm infants in this regional cohort have improved in the 1990s after the introduction of exogenous surfactant. Blindness at 2 years of age was significantly lower than in an earlier preterm cohort, but the rates of sensorineural disability still remain higher in very preterm survivors than for NBW controls. Although survival rates are lower and disability rates are higher with diminishing maturity, there is no obvious gestational age below which adverse neurological outcome in survivors would preclude active management on the basis of gestational age alone.

Emergency department echocardiography improves outcome in penetrating cardiac injury

To determine the effect of immediate two-dimensional echocardiography on the time to diagnosis, survival rate, and neurologic outcome of patients with penetrating cardiac injury. A ten-year retrospective review. Regional trauma center serving a population base of 1.25 million with 85,000 visits yearly. All patients presenting to the emergency department with penetrating cardiac injury. The records of 49 patients with penetrating cardiac injury were reviewed. Of these, 28 received immediate two-dimensional echocardiography in the ED (echo group) and 21 did not (nonecho group). The probability of survival was derived using TRISS methodology. Differences between groups were determined using either the two sample t-test for parametric data or the Mann-Whitney test for nonparametric data. The overall probability of survival was 33.2%, and the actual survival rate was 81.6%. The probability of survival was 34.2% and 31.8% for the echo group and nonecho group, respectively. The actual survival was 100% in the echo group and 57.1% in the nonecho group. The average time to diagnosis and disposition for surgical intervention was 15.5 +/- 11.4 minutes for the echo group and 42.4 +/- 21.7 minutes for the nonecho group (P less than .001). The Glasgow Outcome Score was 5.0 for the echo group and 4.2 for the nonecho group (P = .007). Since the introduction of immediate ED two-dimensional echocardiography, the time to diagnosis of penetrating cardiac injury has decreased and both the survival rate and neurologic outcome of survivors has improved.

Update on Calcium Antagonists in Cerebrovascular Diseases

Clinical management of patients affected by subarachnoid hemorrhage has been modified by the use of nimodipine. Although no differences in overall neurologic outcome and rates of symptomatic spasm have been observed between nimodipine and control patients, severity of permanent neurologic deficits consequent to cerebral vasospasm is reduced in the former. On the other hand, clinical trials with nimodipine in ischemic stroke did not substantiate the expected neurologic benefits. A meta-analysis of the two phase IV studies published thus far shows that of 350 patients examined, mortality rate was 11.5% and 19% in subjects given nimodipine and placebo, respectively (n.s.). Cerebral death accounted for 30% of cases in both groups, whereas a lower percentage of cardiac and pulmonary fatal events were observed among nimodipine-treated subjects. Moreover, neurologic outcome of survivors was not significantly different. These results may be associated with the notion that the voltage-operated channel blockade exerted by calcium antagonists is only a part of the complex events leading to the enhancement of calcium ion intracellular concentration as a "common final pathway." However, difficulties encountered in planning clinical trials in acute ischemic stroke also might explain the lack of conclusive results. The feasibility of randomization of an adequate sample of patients and of very early therapeutic intervention after stroke onset are discussed.

The effect of bystander CPR on neurologic outcome in survivors of prehospital cardiac arrests

The efficacy of CPR has been questioned. A major criticism is that neurologic outcomes have not been adequately studied. For a 26-month period, 138 patients from six major receiving hospitals were discharged alive following prehospital cardiac arrests. For 65/138 (47.1%) patients, either the patient or a direct family member was contacted for information concerning neurologic outcome. For 63/138 (45.7%) patients, contact with patient or family was unsuccessful, consequently neurologic outcome at time of discharge was obtained from the medical record. For 10/138 (7.2%) patients, no data on neurologic outcome was obtainable. Neurologic outcome was rated by a 5-point Cerebral Performance Categories Scale (CPC); (1) Minimal Disability; (2) Moderate; (3) Severe; (4) Vegetative; and (5) Brain Dead. The bystander/first responder CPR group had 55.1% CPC-1; 24.4% CPC-2; 16.7% CPC-3; and 3.8% CPC-4 outcomes. The bystander/first responder NO CPR group had 58.0% CPC-1; 18.0% CPC-2; 16.0% CPC-3; and 8.0% CPC-4 outcomes. There was no significant difference at any CPC level (P not significant). Furthermore, there was no statistical difference between either group when compared for age, response time, resuscitation time, witnessing of arrest or distribution of presenting rhythms. In conclusion, no significant effect in neurologic outcome among saved cardiac arrest victims was found between bystander/first responder CPR and bystander/first responder NO CPR groups in the paramedic program studied.

Multicenter trial of hemodilution in acute ischemic stroke. Results of subgroup analyses. Scandinavian Stroke Study Group.

In a multicenter trial, 183 patients with acute ischemic stroke of less than 48 hours' duration and hematocrits of 38-50% were randomized to standardized hemodilution treatment (venesection and dextran 40 administration) and 190 to a control group. We have previously reported that there were no beneficial effects of hemodilution in the total patient population. In this report, the case fatality rates and neurologic outcome in survivors (3 months' follow-up) in subsets of patients have been analyzed. The patients were subgrouped by sex, age, medical history, smoking habits, delay from the onset of symptoms to the start of treatment, hematocrit at entry, venesection volume, neurologic score at entry into the study, blood pressure changes in the acute phase, presence of atrial fibrillation, location of brain lesion by computed tomography, type of diagnostic procedures, and hospital setting. No subset in which hemodilution reduced mortality or improved neurologic outcome could be identified. Case fatality rate was apparently higher in hemodiluted patients with infarction affecting deep brain structures than in control patients with such lesions. By simple clinical criteria, we have been unable to define subsets of stroke patients who benefit from the present standardized regimen of moderate hemodilution. The sample sizes are, however, too small to refute the possibility that a modest clinical effect of hemodilution may be present in some patients with stroke.

The effect of bystander CPR on neurological outcome in survivors of pre-hospital cardiac arrests : John Masaryk, Philip Troiano, Harlan Stveren, David Olson, Denis Tonsfeldt, Eugene Kasterson, Dennis Birchall, Edward Barthell. Medical College of Wisconsin, Milwaukee, WI 53226

The effect of bystander CPR on neurological outcome in survivors of pre-hospital cardiac arrests : John Masaryk, Philip Troiano, Harlan Stveren, David Olson, Denis Tonsfeldt, Eugene Kasterson, Dennis Birchall, Edward Barthell. Medical College of Wisconsin, Milwaukee, WI 53226