Term Neurological Outcome Research Articles

Optimization of time for neural stem cells transplantation for brain stroke in rats.

Despite encouraging data in terms of neurological outcome, stem cell based therapy for ischemic stroke in experimental models and human patients is still hampered by multiple as yet un-optimized variables, i.e., time of intervention, that significantly influence the prognosis. The aim of the present study was to delineate the optimum time for neural stem cells (NSCs) transplantation after ischemic stroke. The NSCs were isolated from 14 days embryo rat ganglion eminence and were cultured in NSA medium (neurobasal medium, 2% B27, 1% N2, bFGF 10 ng/mL, EGF 20 ng/mL and 1% pen/strep). The cells were characterized for tri-lineage differentiation by immunocytochemistry for tubulin-III, Olig2 and GFAP expression for neurons, oligodendrocytes and astrocyte respectively. The NSCs at passage 3 were injected intraventricularly in a rodent model of middle-cerebral artery occlusion (MCAO) on stipulated time points of 1 & 12 h, and 1, 3, 5 and 7 days after ischemic stroke. The animals were euthanized on day 28 after their respective treatment. dUTP nick end labeling (TUNEL) assay and Caspase assay showed significantly reduced number of apoptotic cells on day 3 treated animals as compared to the other treatment groups of animals. The neurological outcome showed that the group which received NSCs 3 days after brain ischemia had the best neurological performance. The optimum time for NSCs transplantation was day 3 after ischemic stroke in terms of attenuation of ischemic zone expansion and better preserved neurological performance.

Association of biophysical profile with neonatal outcome: an observational study

Background: Perinatal asphyxia is a common cause of neonatal mortality and morbidity in India. Antenatal surveillance prevents foetal injury and death and improves long term neurological outcome through optimal timing of delivery while avoiding unnecessary interventions such as caesarean delivery or preterm delivery.Methods: After thorough history and physical examination, all patients underwent BPP assessment with USG and electronic foetal heart rate tracing and association between BPP score and various parameters were studied. Results: Low BPP scores were associated with low Apgar score, increased rate of neonatal admissions and increased neonatal deaths. For BPP score of 6 there were 5 deaths constituting 71.4% of the total cases.Conclusions: BPP score was found to be significantly associated with Apgar score and neonatal outcomes.

Early Electroencephalographic Findings Correlate With Neurologic Outcome in Children Following Cardiac Arrest.

To determine the clinical and electroencephalographic findings associated with prognosis in nonneonate children following cardiac arrest. Retrospective observational study. PICU and cardiac ICU. Nonneonate children with a history of cardiac arrest more than 2 minutes. Electroencephalographic monitoring within 72 hours of return of spontaneous circulation. Clinical and features, neurophysiologic data, and Pediatric Cerebral Performance Category scores were collected. Electroencephalographic traces were reviewed in a blinded manner, all seizures and electroencephalographic findings noted, and the electroencephalography was scored at 1 hour, 24 hours, and continuous electroencephalographic end. Discrete data regarding specific characteristics of the electroencephalographic background and seizures were studied. Univariate and multivariate analyses were performed to identify associations between clinical variables, electroencephalographic findings, and Pediatric Cerebral Performance Category score at hospital discharge. Multivariate analysis of 73 children revealed duration of cardiac arrest less than 20 minutes or continuous electroencephalographic background activity within 12 hours postreturn of spontaneous circulation were associated with good short term neurologic outcome. Change in electroencephalographic background score over time and electroencephalographic data collected after the initial hour were not associated with outcome. Following pediatric cardiac arrest, an initially normal electroencephalography or generalized slowing of the electroencephalographic background was associated with good neurologic outcome at hospital discharge.

Introduction of percutaneous-tunneled transfontanellar external ventricular drainage in the management of hydrocephalus in extremely low-birth-weight infants.

OBJECTIVE Hydrocephalus treatment in extremely low-birth-weight (ELBW) infants still represents a challenge for the pediatric neurosurgeon, particularly when the patient weighs far less than 1000 g. In such cases, the benefits in terms of neurological outcome following early treatment do not always outweigh the surgical risks, especially considering the great difference in the surgical risk before patient weight increases. To assess the efficacy and reliability of a percutaneous-tunneled, transfontanellar external ventricular drain (PTTEVD) in ELBW infants, the authors started a new protocol for the early surgical treatment of hydrocephalus. METHODS Ten cases of posthemorrhagic hydrocephalus (PHH) in ELBW infants (5 cases < 700 g, range for all cases 550-1000 g) were treated with a PTTEVD that was implanted at bedside as the first measure in a stepwise approach. RESULTS The average duration of the procedure was 7 minutes, and there was no blood loss. The drain remained in place for an average of 24 days (range 8-45 days). In all cases early control of the hydrocephalus was achieved. One patient had a single episode of CSF leakage (due to insufficient CSF removal). In another patient Enterococcus in the CSF sample was detected the day after abdominal surgery with ileostomy (infection resolved with intrathecal vancomycin). One patient died of Streptococcus sepsis, a systemic infection existing prior to drain placement that never resolved. One patient had Pseudomonas aeruginosa sepsis prior to drain insertion; a PTTEVD was implanted, the infection resolved, and the hydrocephalus was treated in the same way as with a traditional EVD, while the advantages of a quick, minimally invasive, bedside procedure were maintained. Once a patient reached 1 kg in weight, when necessary, a ventriculoperitoneal shunt was implanted and the PTTEVD was removed. CONCLUSIONS The introduction of PTTEVD placement in our standard protocol for the management of PHH has proved to be a wise option for small patients.

Effect of postnatal magnesium therapy on neonatal seizure in infants with moderate to severe hypoxic ischemic encephalopathy: a post- hoc subgroup analysis

Background: Magnesium has got both neuroprotective and anticonvulsant effect on developing human brain. A post hoc subgroup analysis was done to determine the effect of magnesium on neonatal seizures in infants with moderate-severe hypoxic ischemic encephalopathy (HIE) who received postnatal magnesium therapy for perinatal asphyxia. Methods: Term asphyxiated infants were randomly assigned to receive either magnesium sulphate infusion or placebo within 48 hours of life to maintain serum magnesium levels in neuroprotective range. Short term neurological outcome at discharge was evaluated. The post hoc analysis evaluated the effect of magnesium on neonatal seizures in infants with moderate-severe HIE. All statistical analysis was done through SPSS (version 19.0) for windows and p value <0.05 was taken as statistically significant. Results: Sixty infants were included in magnesium and 60 in placebo group. Both groups were similar in baseline characteristics. Of 36 infants in magnesium group with moderate to severe HIE, 25 (69%) had neonatal seizures vs 27 (82%) of 33 infants in placebo group (p value 0.23). Among those with seizures, seizure control was achieved with single anticonvulsant in 24 infants (96%) in magnesium group vs 20 (74%) in placebo (p value 0.02). Seizures got controlled early in magnesium group compared to placebo, 36.5 hours vs 55 hours (p value 0.02). At discharge, anticonvulsant was required for 2 infants in magnesium group and 3 in placebo group. Conclusions: Postnatal magnesium therapy as a neuroprotective agent in moderate-severe HIE may decrease the duration of clinical seizures and need for multiple anticonvulsants during the critical period of neuronal damage.

Evaluation of Short-Term Neurological Outcomes in Children with Brain Abscesses.

To evaluate the neurological outcomes of children diagnosed with brain abscesses in the early post-treatment period. < b > MATERIAL and METHODS: This study was a retrospective analysis of pediatric brain abscess patients between January 2000 and December 2015, during a 16-years period. Patients were divided into two groups according to their outcome at the end of the treatment. The patients with "good outcome" were the ones without any neurological sequelae [Glasgow Outcome Scale (GOS) score 5]. "Unfavorable outcome" was defined as having any kind of neurological deficit (GOS score 1-4). A total number of 31 patients (22 male, 71%) with the median age at diagnosis of 84 months (range, 1-202 months) were enrolled in this study. The most common presenting symptom was fever being encountered in 71% of the patients (n=22), followed by focal neurological deficit (FND)(n=17, 54.8%), vomiting (n=14, 45.2%), headache (n=13, 41.9%), seizure (n=13, 41.9%), change in mental status (n=12, 38.7%) and visual disturbance (n=2, 6.5%). Twenty-four patients (77.4%) had predisposing factors. The most common pathogens were gram-positive cocci (n=9, 29%). Seventeen patients (54.8%) had unfavorable outcome; 2 patients (6.4%) died. All patients were treated with parenteral antibiotherapy with median duration of 73 days (range, 28-540 days). Surgical procedures were performed in 83.9% (n=26) of patients [isolated aspiration (n=19, 61.3%), only resection (n=5, 16.1%), aspiration and resection (n=2, 6.5%)]. Glasgow coma scale score below 12 and the presence of FND on admission were found to be independent risk factors for unfavourable neurological outcome in children with brain abscesses.

ROLE OF MAGNESIUM SULPHATE IN SHORT TERM NEUROLOGICAL OUTCOME OF PERINATAL ASPHYXIA

Background: Perinatal asphyxia or Hypoxic Ischemic Encephalopathy (HIE) is a condition of impaired blood gas exchange during the intrapartum period that leads to progressive hypoxemia and hypercapnea with a metabolic acidosis resulting ischemic encephalopathy. Now a days many therapeutic interventions are tried to reduce the morbidity and mortality in Hypoxic ischemic encephalopathy. Magnesium sulphate is one of them. Reduced morbidity with such an inexpensive and easy to administered drug is appreciable especially for resource limited countries. Objective: To compare Magnesium sulphate to placebo in short term neurological outcome of the full term newborns presented with perinatal asphyxia. Study design: It was a randomised control trial. Methodology: 200 term neonates with moderate to severe perinatal asphyxia admitted in NNU were studied in a prospective, longitudinal placebo control trial. Patients were randomly assigned in two groups. One group received 3 doses of Mgso4 infusion at 250 mg/kg per dose 24 hr apart ( treatment group A) and second group received 3 doses of normal saline infusion 1 ml/kg per dose 24 hr apart ( placebo group B) . Both groups received same supportive care according to unit protocol. Results: Showed a significant difference in short term outcome in the form of early discharge and oral feeding. 71% of the patient in treatment group were discharged on oral feeding up to 2 weeks comparative to 23% patients in placebo group. Mortality in treatment group(A) was 13% and in placebo(B) 23%. Conclusion: The study concluded that the Magnesium sulphate is an effective drug for the management of morbidity in perinatal asphyxia.

Limited effect of mild therapeutic hypothermia on outcome after prolonged resuscitation

BackgroundMild therapeutic hypothermia interferes with multiple cascades of the ischaemia/reperfusion injury that is known as primary mechanism for brain damage after cardiac arrest. First resuscitation attempts and the duration of resuscitation efforts will initiate and aggravate this pathophysiology. Therefore we investigated the interaction between the duration of basic and advanced life support and outcome after cardiac arrest in patients treated with or without mild therapeutic hypothermia. MethodsThis retrospective cohort study included patients 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with presumed cardiac cause, which remained comatose after restoration of spontaneous circulation. The basic and advanced life support ‘low-flow’ time, categorized into four quartiles (0–11, 12–17, 18–28, ≥29min), was correlated with neurological outcome. ResultsOut of 1103 patients 613 were cooled to a target temperature of 33±1°C for 24h. In the three quartiles with ‘low-flow’ time up to 28min cooling was associated with >2-fold odds of favourable neurological outcome. In the fourth quartile with ‘low-flow’ time of ≥29min cooling had no influence on neurological outcome (OR: 0.73; 95% CI: 0.38–1.4, test for interaction p<0.01). ConclusionThe duration of resuscitation efforts, defined as ‘low-flow’ time, influences the effectiveness of mild therapeutic hypothermia in terms of neurologic outcome. Patients with low to moderate ‘low-flow’ time benefit most from this treatment.

TCT-686 Impact of Aortic Valve Type on Cerebral Ischemic Lesions in DW-MRI after TAVR

Subclinical cerebral ischemic lesions are detected by diffusion- weighted magnetic resonance imaging (DW-MRI) in the majority of patients after TAVR which may be associated with impaired short term neurological outcome. The impact of the TAVR device on cerebral ischemic lesions is not well defined.

Diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch is associated with better neurologic response to intravenous thrombolytic therapy in acute ischemic stroke patients.

ObjectiveTo investigate differences in the effect of intravenous (IV) thrombolysis regarding the mismatch of diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) among acute ischemic stroke patients who visited the emergency department (ED) within 3 hours from the onset of symptoms.MethodsAmong ED patients presenting with an acute ischemic stroke between January 2011 and May 2013 at a tertiary hospital, those who underwent magnetic resonance imaging before IV thrombolytic therapy were included in this retrospective study. Patients were divided into DWI-FLAIR mismatch and match groups. National Institutes of Health Stroke Scale (NIHSS) scores obtained initially, 24 hours after thrombolytic therapy, and on discharge, and early neurologic improvement (ENI) and major neurologic improvement (MNI) were compared.ResultsDuring the study period, 50 of the 213 acute ischemic stroke patients who presented to the ED were included. The DWI-FLAIR mismatch group showed a statistically significantly greater reduction in NIHSS both at 24 hours after thrombolytic therapy and upon discharge than did the match group (5.5 vs. 1.2, P<0.001; 6.0 vs. 2.3, P<0.01, respectively). Moreover, ENI and MNI were significantly greater for the DWI-FLAIR mismatch group than for the match group (27/36 vs. 2/14, P<0.001; 12/36 vs. 0/14, P=0.012, respectively).ConclusionAmong acute ischemic stroke patients who visited the ED within 3 hours from the onset of symptoms, patients who showed DWI-FLAIR mismatch showed a significantly better response to IV thrombolytic therapy than did the DWI-FLAIR match group in terms of neurologic outcome.

Early and late operation of cleft lip and intelligence quotient and psychosocial development in 3–7 years

BackgroundEarly and late operations of the cleft lip represent exposure to general anesthesia during the first year of life. The early exposure to the anesthetics may influence long term neurological outcome. Timing of the operation may also influence the quality of life as babies with early repair might be accepted better by their families. AimsThe aim of the study was to compare outcomes between two groups of patients operated on for the cleft lip in the first year of life. Study designObservational cohort study. SubjectsEarly repair group included patients operated on in the first eight days of life and late repair group those operated on between 3 and 10months. Outcome measuresIntelligence quotient (IQ) and psychosocial development of children who were operated on for cleft lip were compared at the age of 3–7years. ResultsNo differences were found between early (n=15) and late (n=17) repair group in terms of IQ. In both IQ was within the normal range: 100.00 (SD 13.867), 98.76 (SD 10.109), respectively. Significantly better results in physical functioning (P=0.042) and self-esteem (P=0.014) concepts in early repair group were found. ConclusionsWe compared outcomes of two groups of patients operated on for cleft lip in the first year of life. The earlier anesthesia did not show a negative impact on intelligence quotient in 3–7years compared to later anesthesia. The earlier repair of the cleft lip showed a significant positive impact on psychosocial development in 2 out of 13 concepts tested.

Subaxial cervical spine injury classification system: is it most appropriate for classifying cervical injury?

Subaxial cervical spine injury classification system: is it most appropriate for classifying cervical injury?

Neurological Study of Radial Nerve Conduction During Endoscopic Radial Artery Harvesting:An Intra‐Operative Evaluation

Endoscopic radial artery harvesting (ERAH) is a feasible and attractive minimally invasive approach for conduit procurement, however there have been concerns about a potential neurological damage occurring at the harvest limb site secondary to injury of the radial nerve during endoscopic harvesting. We present a case of ERAH in which we evaluated intraoperatively the characteristics of radial nerve conduction by means of electroneuromyography (ENM) during harvesting. No pathological changes of nerve conduction were detected at the harvest limb site during surgery and postoperatively, thereby supporting the benefits of the endoscopic approach in terms of neurological outcomes following radial artery procurements with a less invasive approach.

The impact of general anaesthesia for elective adenotonsillectomy in children aged 6-12 years on biomarkers of cerebral injury S100B and NSE

Background and Goal of Study: S100B protein and NSE (neuron specific enolase) can be considered as early markers of cerebral injury. The impact of general anesthesia for elective noncardiac surgery in children on these markers has not been studied before. The goal was to find out whether these markers can be used to access the short term neurological outcome after general anesthesia. The secondary goal was to determine whether different types of anesthesia influence the levels of S100B and NSE. Materials and methods: Prospective study was conducted at the University Hospital on 64 children (aged 6-12, ASA I-II) undergoing elective adenotonsillectomy. The children were randomized into 2 groups:TIVA (n=32) and sevoflurane(S) (n=32). In TIVA group anesthesia was induced with propofol, fentanyl and vecuronium and maintained with continuous infusion of propofol. In S group, anesthesia was induced with fentanyl, sevoflurane and vecuronium and maintained with sevoflurane. S100B and NSE were measured before and after the surgery. S100B and NSE assays were performed using the electrochemiluminiscence immunoassay “ECLIA” used on Roche Cobas e601 immunoassay analyzer (Roche Diagnostics GmbH, Mannheim, Germany). Statistical significance of the differences was accessed by two-tailed asymptotic Wilcoxon Signed Rank test. The 95% CI for median difference was calculated by bootstrapping on 1000 samples in IBM SPSS Statistics version 21. Results and discussion: There was statistically significant increase of S100B median value after surgery with regard to preoperative values (P< 0.001). Median(interquartile range) values of S100B before and after surgery were 0.08 (0.064-0.102) and 0.1 (0.072-0.179), respectively. There was no statistically significant change of NSE median value af ter surgery regarding preoperative values (P=0.567). The prevalence of elevated S100B (≥0.105 ug/l) after the surgery was statistically significantly higher than before (McNemar test, two sided exact P=0.003). There were 12/60 children (20.0% ; 95% CI=(10.5%-29.8%)) with elevated S100 B before and 28/60 (46.7% ; 95% CI=33.3%-59.6%)) after surgery. Conclusion(s): The values of neurological biomarker S100B, but not of NSE, were significantly increased af ter general anesthesia for elective adenotonsillectomy in children, indicating possible cerebral injury.There were no differences regarding 2 types of anaesthesia, TIVA or inhalational.

Dietary Treatments and New Therapeutic Perspective in GLUT1 Deficiency Syndrome

GLUT1 deficiency syndrome (GLUT1DS) results from impaired glucose transport into the brain: awareness of its wide phenotypic spectrum is a prerequisite in order to ensure an early diagnosis, treating the patients is the subsequent challenge to allow prompt compensation for the brain's lack of fuel. The ketogenic diet (KD) plays a primary role in the treatment of GLUT1DS because it provides ketone bodies as an alternative source to meet the demands of energy of the brain. Therefore, we recommend early initiation of the KD based on the assumption that early diagnosis and treatment improves the long term neurological outcome: the classic KD (4:1 or 3:1) at the present time is the most proven and effective in GLUT1DS. A KD should be continued at least until adolescence, although there are reports of good tolerability even in adulthood, possibly with a less rigorous ratio; in our experience seizure and movement disorder control can be achieved by a 2:1 ketogenic ratio but the relationship between ketosis and neurodevelopmental outcome remains undetermined. Other types of KDs can, therefore, be considered. The Modified Atkins diet, for example, is also well tolerated and provides effective symptom control; furthermore, this diet has the advantage of being easy to prepare and more palatable, which are important requirements for good compliance. Nevertheless, about 20% of these patients have compliance trouble or the same diet loses its effectiveness over time; for these reasons, new therapeutic strategies are currently under investigation but further studies on pathophysiological mechanisms and potential effects of novel "diets" or "therapies" are needed for this new pathology.

A Systematic Review and Meta-analysis of the Timing of Early Intraventricular Hemorrhage in Preterm Neonates: Clinical and Research Implications.

A considerable number of intraventricular hemorrhages (IVH) occur within the first hours of life (HOL). Temporality between IVH and its antecedents as well as a consistent definition of “early IVH” is lacking in a large and growing body of literature. We performed a systematic review of prospective studies that reported onset of IVH in preterm neonates within the first HOL and afterwards. The English literature was searched using three databases up to March 2013. Four timing periods of IVH can be compared in 16 identified studies: 0-6; 7-12; 13-24; after 24 HOL. The 0-6 and after 24 HOL were the major modes of IVH timing. Pooled IVH proportions were estimated through a meta-analysis of studies that were conducted after antenatal steroid and surfactant era. In neonates weighing ≤1500 g at birth: 48% of IVH (95% CI: 42-58%, 5 studies, 279 IVH cases) occurred during 0-6 HOL and 38% (95% CI: 19-57%, 4 studies, 241 IVH cases) after 24 HOL. The 0-6 HOL is the shortest, most vulnerable period for IVH, thus, an early IVH is an IVH occurs in it. Such early IVH had prognostic, etiological/preventive and medicolegal implications. Accordingly, preterm neonates at risk of IVH should have their first routine screening head ultrasound at about 6 HOL. Future research exploring the antecedents of IVH should guaranty the temporality between these antecedents and IVH. Additional research will be required to determine whether the long term neurological outcomes of early and late IVH are the same.

Fractionated external beam radiotherapy of skull base metastases with cranial nerve involvement

Skull base metastases frequently appear in a late stage of various tumor entities and cause pain and neurological disorders which strongly impair patient quality of life. This study retrospectively analyzed fractionated external beam radiotherapy (EBRT) as a palliative treatment approach with special respect to neurological outcome, feasibility and acute toxicity. A total of 30 patients with skull base metastases and cranial nerve disorders underwent EBRT with a mean total dose of 31.6Gy. Neurological status was assessed before radiotherapy, during radiotherapy and 2 weeks afterwards categorizing orbital, parasellar, middle fossa, jugular foramen and occipital condyle involvement and associated clinical syndromes. Neurological outcome was scored as persistence of symptoms, partial response, good response and complete remission. Treatment-related toxicity and overall survival were assessed. Before EBRT 37 skull base involvement syndromes were determined with 4 patients showing more than 1 syndrome. Of the patients 81.1 % responded to radiotherapy with 10.8 % in complete remission, 48.6 % with good response and 21.6 % with partial response. Grade 1 toxicity of the skin occurred in two patients and grade 1 hematological toxicity in 1 patient under concurrent chemoradiotherapy. Median overall survival was 3.9 months with a median follow-up of 45 months. The use of EBRT for skull base metastases with symptomatic involvement of cranial nerves is marked by good therapeutic success in terms of neurological outcome, high feasibility and low toxicity rates. These findings underline EBRT as the standard therapeutic approach in the palliative setting.

Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes

Our previous ecological studies of autism spectrum disorder (ASD) has demonstrated a correlation between increasing ASD rates and aluminium (Al) adjuvants in common use in paediatric vaccines in several Western countries. The correlation between ASD rate and Al adjuvant amounts appears to be dose-dependent and satisfies 8 of 9 Hill criteria for causality. We have now sought to provide an animal model to explore potential behavioural phenotypes and central nervous system (CNS) alterations using s.c. injections of Al hydroxide in early postnatal CD-1 mice of both sexes. Injections of a “high” and “low” Al adjuvant levels were designed to correlate to either the U.S. or Scandinavian paediatric vaccine schedules vs. control saline-injected mice. Both male and female mice in the “high Al” group showed significant weight gains following treatment up to sacrifice at 6months of age. Male mice in the “high Al” group showed significant changes in light–dark box tests and in various measures of behaviour in an open field. Female mice showed significant changes in the light–dark box at both doses, but no significant changes in open field behaviours. These current data implicate Al injected in early postnatal life in some CNS alterations that may be relevant for a better understanding of the aetiology of ASD.

PF.71 We Have Diagnosed Ventriculomegaly – What Happens Next?

Ventriculomegaly is defined as dilatation ≥10 mm of the fetal cerebral lateral ventricles on ultrasound at 20 weeks gestation1 2.AimTo assess the aetiology and neurological outcomes of ventriculomegaly at a...

High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage

Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage. However, no clinical data are available to answer whether a high-dose regimen is more effective than a normal-dose regimen, even though the biochemical actions and related neuroprotective mechanisms are thought to be dose related. To determine whether 80 mg simvastatin daily (high dose) over 3 weeks initiated within 96 hours of the ictus will reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with 40 mg simvastatin daily (normal dose), leading to improvements in clinical outcomes and thus cost-effectiveness. The study design is a randomized, controlled, double-blind clinical trial (www.ClinicalTrials.gov; identifier: NCT01077206). Two hundred forty patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers are being recruited over 3 years. The primary outcome measure is the presence of delayed ischemic deficits. Secondary outcome measures include modified Rankin Disability Score at 3 months and cost-effectiveness analysis. This will be the first study to clarify whether high-dose simvastatin is better than normal-dose simvastatin for patients with acute aneurysmal subarachnoid hemorrhage in terms of neurological outcomes and cost-effectiveness. In the present trial, we compare high-dose and normal-dose simvastatin; we know that another ongoing phase III multicenter trial (Simvastatin in Aneurysmal Subarachnoid Haemorrhage; http://www.stashtrial.com/home.html) is comparing normal-dose and no simvastatin. When the results are interpreted together, the research question of a possible beneficial effect of high-dose simvastatin in acute aneurysmal subarachnoid hemorrhage could be answered.