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Aneurysmal subarachnoid hemorrhage (aSAH) is bleeding into the subarachnoid space from a cerebral aneurysm, defined as a thin-walled outpouching on one of the cerebral arteries.1 SAH represents 0.8% to 15% of strokes and has a low incidence of 0.03 to 0.2 per 1000 person-years with a female preponderance.2,3 However, SAH usually occurs at a relatively young age and has a high 1-month case fatality rate (32%), leading to a high loss of potential life years.2 Subsequently, primary prevention of aSAH by identifying and addressing modifiable risk factors has been a focus of research for decades.4 Although the main focus has been on identifying modifiable risk factors, less attention has been given to the underlying pathogenic mechanisms. We, therefore, conducted a literature review to identify recognized modifiable risk factors for aneurysm development and aSAH and examined the pathogenesis by which these individual risk factors are suspected to contribute to aneurysm development and rupture. We conducted MEDLINE searches using the PubMed database for relevant articles published between 1980 and 2012 in English. We used search words such as Cerebral Arteries [Majr], Subarachnoid Hemorrhage [Majr], or Intracranial Aneurysm [Majr] combined with Medical Subject Headings (MeSH) search words for different risk factors such as Alcohol drinking, Ethanol, Estrogens, Menopause, Hypertension, Smoking, Cholesterol, Diabetes Mellitus, and Cocaine. The first search was performed in June 2012 and the last in December 2012. Articles were screened by title and abstract, and if relevant the article was reviewed in its entirety. References lists in key publications were hand-searched to reveal additional relevant studies. Initially, the focus was on epidemiological studies that helped establish the different modifiable risk factors for aSAH. Inclusion criteria comprised: (1) SAH analyzed as a separate stroke entity, although in some studies SAH was part of a hemorrhagic stroke …

Background— Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients. Methods— One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (V MCA ) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale. Results— Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively ( P -logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5–10.9; P =0.006). ADMA or arginine:ADMA had no association to V MCA , but there was an inverse relationship between V MCA and nitrite/nitrate levels ( P NOS3 894G/G genotype was associated with 15% lower V MCA ( P =0.01). ATbG- NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels ( P =0.003). Conclusions— This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.

Background Protein S100B has proven to be a useful biomarker for cerebral damage. The predictive ability of S100B may, however, be affected by extracerebral injuries. The aim of this study was to investigate serum levels of S100B in patients with either isolated head injury (IHI), multi trauma with head injury (MTHI), or no head injury (NHI). The primary aim was to assess if a significant difference in serum levels of S100B could be found between IHI and MTHI patients. Methods Patients (233) were primarily admitted to the trauma centre. Serum samples were drawn on admission and 6 h after trauma and then stored at −80°C until analysed. Variables included Abbreviated Injury Scale (AIS) for head trauma, Injury Severity Score (ISS) and 30-day survival. Results Two patients could not be classified. IHI occurred in 28, MTHI in 102 and NHI was found in 101. The median S100B concentrations on arrival were 0.47, 1.68 and 0.49 μg/l, respectively (p

Hypothermia is shown to be beneficial for the outcome after a transient global brain ischaemia through its neuroprotective effect. Whether this is also the case after focal ischaemia, such as following a severe traumatic brain injury (TBI), has been investigated in numerous studies, some of which have shown a tendency towards an improved outcome, whereas others have not been able to demonstrate any beneficial effect. A Cochrane report concluded that the majority of the trials that have already been published have been of low quality, with unclear allocation concealment. If only high-quality trials are considered, TBI patients treated with active cooling were more likely to die, a conclusion supported by a recent high-quality Canadian trial on children. Still, there is a belief that a modified protocol with a shorter time from the accident to the start of active cooling, longer cooling and rewarming time and better control of blood pressure and intracranial pressure would be beneficial for TBI patients. This belief has led to the instigation of new trials in adults and in children, including these types of protocol adjustments. The present review provides a short summary of our present knowledge of the use of active cooling in TBI patients, and presents some tentative explanations as to why active cooling has not been shown to be effective for outcome after TBI. We focus particularly on the compromised circulation of the penumbra zone, which may be further reduced by the stress caused by the difference in thermostat and body temperature and by the hypothermia-induced more frequent use of vasoconstrictors, and by the increased risk of contusional bleedings under hypothermia. We suggest that high fever should be reduced pharmacologically.

Patients with large intracerebral haematomas (ICH) from aneurysm rupture often present in a poor clinical condition and have a poor prognosis. Time delay for preoperative angiography might in some cases be unappealing. We evaluated the outcome after immediate haematoma removal and aneurysm occlusion without preoperative angiography. We retrospectively identified 13 consecutive patients. We recorded clinical data and evaluated mortality and morbidity with the Glasgow Outcome Score (GOS) and Telephone Interview of Cognitive Status (TICS). At follow up seven of thirteen patients had favourable outcome assessed by GOS. Three patients had severe disability and three patients died. None of the survived patients interviewed had impaired cognition. In patients presented in a critical state with aneurysmal ICH, emergency haematoma removal and aneurysm clipping without the delay for diagnostic angiography may be life saving and a satisfactory outcome can be accomplished.

Background and Purpose— Cerebral artery aneurysms rupture when wall tension exceeds the strength of the wall tissue. At present, risk-assessment of unruptured aneurysms does not include evaluation of the lesions shape, yet clinical experience suggests that this is of importance. We aimed to develop a computational model for simulation of fluid-structure interaction in cerebral aneurysms based on patient specific lesion geometry, with special emphasis on wall tension. Methods— An advanced isogeometric fluid-structure analysis model incorporating flexible aneurysm wall based on patient specific computed tomography angiogram images was developed. Variables used in the simulation model were retrieved from a literature review. Results— The simulation results exposed areas of high wall tension and wall displacement located where aneurysms usually rupture. Conclusion— We suggest that analyzing wall tension and wall displacement in cerebral aneurysms by numeric simulation could be developed into a novel method for individualized prediction of rupture risk.

Background and Purpose— Wall shear stress (WSS) and pressure are important factors in the development of cerebral aneurysms. We aimed to develop a computational fluid dynamics simulator for flow in the complete circle of Willis to study the impact of variations in vessel radii and bifurcation angles on WSS and pressure on vessel walls. Methods— Blood flow was modeled with Navier-Stokes equations as an incompressible newtonian fluid within rigid vessel walls. A model of the circle of Willis geometry was approximated as a network of tubes around cubic curves. Pulsatile inlet flow rates and constant outlet pressure were used as boundary conditions. Results— The simulations confirmed that differences in vessel radii and asymmetric branch angles influence WSS magnitude and spatial distribution. High WSS occurred at locations where aneurysms are frequent and in anatomic variants known to be associated with an increased risk for aneurysm development. Conclusions— Computational fluid dynamics analysis can be applied to the complete circle of Willis and should be used to study the pathophysiology of this complex vascular structure, including risk factors for aneurysm development. Further development of the method should include simulations with flexible vessel walls.

Patients with traumatic brain injury (TBI) often show progression of hemorrhagic injuries (PHI) after admission to the hospital. This progression is correlated with poor outcome. In this study, we have investigated if thrombocytopenia was a risk factor for PHI. The study was performed on patients admitted to the hospital with severe TBI during year 2000. In total, 50 patients were admitted with severe TBI. Twenty-seven out of these had complete platelet counts at admission and 24 hours thereafter and were included for further study. We found thrombocytopenia at admission to be a risk factor for PHI (p=0.008). We also found that the platelet count decreased more significantly during the first 24 h after injury in patients with PHI compared to patients without PHI (p=0.009). A trend towards longer periods of mechanical ventilation in patients with PHI compared to patients without PHI was identified. These findings support a causal relationship between thrombocytopenia and PHI. The findings provide a rationale for future studies of hemostatic agents in the treatment of TBI in order to minimise complications caused by PHI.

Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed. Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional 133Xenon) and regional (three-dimensional 99 mTc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml. Isovolemic hemodilution increased global cerebral blood flow from 52.25±10.12 to 58.56±11.73 ml * 100 g−1 * min−1 (p

Great expectations have been raised about neuroprotection of therapeutic hypothermia in patients with traumatic brain injury (TBI) by analogy with its effects after heart arrest, neonatal asphyxia, and drowning in cold water. The aim of this study is to review our present knowledge of the effect of therapeutic hypothermia on outcome in children and adults with severe TBI. A literature search for relevant articles in English published from year 2000 up to December 2013 found 19 studies. No signs of improvement in outcome from hypothermia were seen in the five pediatric studies. Varied results were reported in 14 studies on adult patients, 2 of which reported a tendency of higher mortality and worse neurological outcome, 4 reported lower mortality, and 9 reported favorable neurological outcome with hypothermia. The quality of several trials was low. The best-performed randomized studies showed no improvement in outcome by hypothermia-some even indicated worse outcome. TBI patients may suffer from hypothermia-induced pulmonary and coagulation side effects, from side effects of vasopressors when re-establishing the hypothermia-induced lowered blood pressure, and from a rebound increase in intracranial pressure (ICP) during and after rewarming. The difference between body temperature and temperature set by the biological thermostat may cause stress-induced worsening of the circulation and oxygenation in injured areas of the brain. These mechanisms may counteract neuroprotective effects of therapeutic hypothermia. We conclude that we still lack scientific support as a first-tier therapy for the use of therapeutic hypothermia in TBI patients for both adults and children, but it may still be an option as a second-tier therapy for refractory intracranial hypertension.

BACKGROUND In 2000, the Scandinavian Neurotrauma Committee (SNC) published evidence-based guidelines for the management of minimal, mild or moderate head injuries. Since then, considerable new evidence has emerged on the clinical use of these guidelines and on the radiation risks associated with computer tomographic (CT) examinations. The SNC has recently published updated Scandinavian guidelines. Here we present the Norwegian version of the updated guidelines with emphasis on the professional recommendations and the reasons the new guidelines were necessary, plus comments from the Norwegian authors.MATERIALS AND METHODS A task force appointed by the SNC compiled recommendations based on a systematic, evidence-based review. These recommendations were revised through consensus in the SNC and through consultation with relevant clinical experts.RESULTS A blood test of the brain injury biomarker S100B is for the first time recommended as an initial diagnostic measure for mild head injury patients with low risk. Of these patients, CT examination is only recommended for those who show a pathologically elevated S100B. CT examination is still the recommended routine for moderate head injury patients and for mild head injury patients with medium to high risk. An updated information sheet on head injuries has also been compiled for patients and their relatives.CONCLUSION The SNC recommends the implementation of these guidelines in Norway.

Endothelial dysfunction might be involved in the development of cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH).This prospective observational study of 48 SAH subjects and 23 control subjects examined associations between reactive hyperaemia index (RHI) measured by peripheral arterial tonometry and plasma concentrations of S-100B protein, nitrite/nitrate, arginine, and asymmetric dimethyl arginine (ADMA). Clinical variables were flow velocity in the middle cerebral artery (VMCA), angiographic vasospasm, delayed neurological deficit, and 30 day survival. Five consecutive measurements were obtained at days 0-2, 3-5, 6-8, 9-11, and 12-15.RHI was 1.67 (0.46) at days 0-2 after SAH but increased at days 3-15 to the same levels as in controls (P0.05 compared with days 0-2). RHI was lower in subjects who died before day 30 (P=0.07), but no trends were observed in relation to angiographic vasospasm or delayed neurological deficit. Both arginine and ADMA increased after SAH compared with days 0-2 (P0.05). S-100B was highest in non-survivors (P0.01) and in subjects with neurological deficit (P0.01). A positive correlation was found between RHI and arginine:ADMA ratio (r=0.43, P0.005), but not with nitrite/nitrate, VMCA, or S-100B.Peripheral flow-mediated vasodilation is attenuated in the first days after SAH indicating acute systemic endothelial dysfunction. Impairment of endothelial function after SAH correlates with imbalance of the arginine/ADMA pathway.

Response: We thank Dr Tsuda for his interest. Asymmetrical dimethylarginine (ADMA) and l-arginine are compounds with significant and well-known biological effects.1 Symmetrical dimethylarginine (SDMA), on the other hand, has long been regarded as a biologically inactive molecule, and as such has been under investigation as a putative marker of renal dysfunction.1 In vitro evidence provides some support for a mechanism by which SDMA through inhibition of transmembrane l-arginine transport theoretically could exert a rate-limiting effect on nitric oxide …

Background Clinical examination of patients with chronic lumbar radiculopathy aims to clarify whether there is nerve root impingement. The aims of this study were to investigate the association between findings at clinical examination and nerve root impingement, to evaluate the accuracy of clinical index tests in a specialised care setting, and to see whether imaging clarifies the cause of chronic radicular pain. Methods A total of 116 patients referred with symptoms of lumbar radiculopathy lasting more than 12 weeks and at least one positive index test were included. The tests were the straight leg raising test, and tests for motor muscle strength, dermatome sensory loss, and reflex impairment. Magnetic resonance imaging (n = 109) or computer tomography (n = 7) were imaging reference standards. Images were analysed at the level of single nerve root(s), and nerve root impingement was classified as present or absent. Sensitivities, specificities, and positive and negative likelihood ratios (LR) for detection of nerve root impingement were calculated for each individual index test. An overall clinical evaluation, concluding on the level and side of the radiculopathy, was performed. Results The prevalence of disc herniation was 77.8%. The diagnostic accuracy of individual index tests was low with no tests reaching positive LR >4.0 or negative LR

Background: Protein S100B has proven to be a useful biomarker for cerebral damages. Increased levels of serum and CSF S100B have been shown in patients suffering subarachnoid hemorrhage, severe head injury and stroke. In patients with subarachnoid hemorrhage, the course of S100B levels has been correlated with neurological deficits and outcome. Cerebral vasospasm is a major contributor to morbidity and mortality. The primary aim of this study was to investigate the potential of S100B protein as a predictor of cerebral vasospasm in patients with severe subarachnoid hemorrhage. Methods: Patients with SAH, Fisher grade 3 and 4, were included in the study. Five samples of CSF and serum S100B were collected from each patient. The first sample (baseline sample) was drawn within the first three days following ictus and the following four samples, once a day on days 5 to 8, with day of ictus defined as day 1. Clinical suspicion of cerebral vasospasm confirmed by computed tomography angiography was used to diagnose cerebral vasospasm. Results: A total of 18 patients were included. Five patients (28 %) developed cerebral vasospasm, two (11 %) developed ventriculitis. There were no significant differences between S100B for those with and without vasospasm. Serum S100B levels in patients with vasospasm were slightly lower within the first 5 days following ictus, compared to patients without vasospasm. Two out of 5 patients had elevated and increasing serum S100B prior to vasospasm. Only one showed a peak level of S100B one day before vasospasm could be diagnosed. Due to the low number of patients in the study, statistical significance could not be reached. Conclusion: Neither serum nor CSF S100B can be used as predictor of cerebral vasospasm in patients suffering from subarachnoid hemorrhage.

Background Erythropoietin (EPO) and its covalently modified analogs are neuroprotective in various models of brain damage and disease. We investigated the effect on brain damage and memory performance, of a continuous 3-day intravenous infusion of EPO, starting 20 min after a transient 10 minute period of global cerebral ischemia in the rat. Results We found no effect on selective neuronal damage in the CA1 region of the hippocampus, neocortical damage and damage to the striatum assessed at 7 days after ischemia. Also, no differences were observed in sensori-motor scores between EPO treated and saline treated ischemic animals. In contrast, memory performance was significantly improved in the EPO treated group. Saline treated injured animals (n = 7) failed in a test assessing recovery of spatial memory (6/6 and 5/6), while EPO treated animals had few and none failures (0/7 and 1/7). Conclusion We conclude that although post-ischemic treatment with EPO is not neuroprotective in a model of cardiac arrest brain ischemia, its markedly positive effect on brain plasticity and recovery of memory function warrants consideration as treatment of cardiac arrest patients.

Background. Transcranial Doppler measurements of the middle cerebral artery flow velocity are widely used as an indicator of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). We investigated inter- and intraoperator agreement in SAH patients and healthy volunteers using colour-coded transcranial Doppler (TCCD), with the secondary aim of describing prediction of angiographic vasospasm and mortality. Methods. Sixty patients and 70 healthy controls were each examined in duplicate by alternating operators. A total of 939 measurements divided on 201 examination sets were conducted by four observers. The Bland –Altman limits of agreement (LoA) were calculated using a variance components analysis. Angiography was performed on clinical indication and survival recorded at 30 days. Results. Differences between measurements increased with increasing average, and therefore, we analysed log-transformed values. Thus, LoA are given as ratios between measurements. There were no systematic intra- or interobserver differences (bias). The intraobserver LoA was 0.62 –1.61 in patients and 0.67 –1.50 in controls. However, they were 0.55 –1.82 in patients with angiographic vasospasm, whereas in patients without, they were 0.66 –1.52. The interobserver LoA was 0.55–1.81 in patients and 0.65 –1.55 in controls, while in patients with and without angiographic vasospasm, they were 0.45 – 2.22 and 0.60 –1.67, respectively. Flow velocity measurements day 6– 10 were positively associated with 30 day mortality risk (P¼0.02, logistic regression). Conclusions. TCCD measurement variability is wider in patient measurements than in controls. This discrepancy can largely be explained by a higher degree of error in patients with angiographic vasospasm. Despite the considerable measurement variability in TCCD, values are predictive of outcome in SAH.

Background A new adjustable valve, the Codman CertasTM valve for treatment of hydrocephalus was introduced into clinical practice in January 2011. It has 8 different settings with an opening pressure varying from 36 to over 400 mm H2O at a flow rate of 20 mL/h. The 8th setting is designed to provide a "virtual off" function. The objective of this report is to describe the initial clinical experience with the CertasTM valve and evaluate clinical usage with the main focus on the portable adjustment device - Therapeutic Management System (TMS), the “virtual off” setting and compatibility with magnetic resonance imaging (MRI). Findings Forty-two patients with hydrocephalus from different etiologies were treated with the CertasTM adjustable shunt system. Data regarding implantation procedures, the use of the TMS system, x-ray imaging, and MRI procedures were recorded prospectively. All patients had clinical follow-up at four weeks after implantation and every three months until a stable clinical condition was obtained. The mean time for follow-up was 8.6 months (1–16.6). Seventy-one adjustments were performed with the TMS, 12 were problematic. Twenty-nine MRI procedures were performed and did not cause accidental resetting. Five patients were treated with the "virtual off" function for a period. Conclusions We found the CertasTM valve valuable in the treatment of hydrocephalus, usability of the TMS was high because it is small and portable, but in some cases we experienced adjustment problems with the first procedures performed by a surgeon, indicating that there is a learning curve. The "virtual off" function provided a possibility of treating over-drainage without the need for shunt ligation or other invasive procedures.

Background One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In vitro models have shown a relaxing effect of prostacyclin after induced contraction in cerebral arteries, and a recent pilot trial showed a positive effect on cerebral vasospasm in a clinical setting. No randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. Methods This trial is a single-centre, randomised, placebo-controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of three intervention arms: epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. The primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months. Trial registration Clinicaltrials.gov NCT01447095.

Monitoring of intracranial pressure (ICP) has been used for decades in the fields of neurosurgery and neurology. There are multiple techniques: invasive as well as noninvasive. This paper aims to provide an overview of the advantages and disadvantages of the most common and well-known methods as well as assess whether noninvasive techniques (transcranial Doppler, tympanic membrane displacement, optic nerve sheath diameter, CT scan/MRI and fundoscopy) can be used as reliable alternatives to the invasive techniques (ventriculostomy and microtransducers). Ventriculostomy is considered the gold standard in terms of accurate measurement of pressure, although microtransducers generally are just as accurate. Both invasive techniques are associated with a minor risk of complications such as hemorrhage and infection. Furthermore, zero drift is a problem with selected microtransducers. The non-invasive techniques are without the invasive methods' risk of complication, but fail to measure ICP accurately enough to be used as routine alternatives to invasive measurement. We conclude that invasive measurement is currently the only option for accurate measurement of ICP.

Background: Protein S100B is soon in clinical use as a sensitive marker after mild traumatic head injury in adults. Initial studies of S100B in pediatric head injury have shown promising results. Venous sampling can be challenging in children and capillary samples are often a preferred option. The aim of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples in severely brain-injured patients. Methods: Venous, arterial and capillary blood samples for S100B were collected simultaneously once a day for a maximum of 6 days. Patients were >= 18 years old and admitted to neurointensive care due to severe brain pathology. Results: Capillary S100B samples were on average 0.08 mu g/L higher than venous S100B samples. Prediction of venous concentration from capillary samples yielded a prediction error of 0.07 mu g/L. The mean difference between venous and arterial samples was 0.01 mu g/L. The mean prediction error was 0.03 mu g/L. Conclusions: Capillary and venous serum S100B are not interchangeable, and should be considered as two separate, although related, variables. Arterial measurements of S100B can successfully predict the corresponding venous concentration. (Less)

Background The Scandinavian guidelines for management of minimal, mild and moderate head injuries were developed to provide safe and cost effective assessment of head injured patients. In a previous study conducted one year after publication and implementation of the guidelines (2003), we showed low compliance, involving over-triage with computed tomography (CT) and hospital admissions. The aim of the present study was to investigate guideline compliance after an educational intervention. Methods We evaluated guideline compliance in the management of head injured patients referred to the University Hospital of Stavanger, Norway. The findings from the previous study in 2003 were communicated to the hospitals physicians, and a feed-back loop training program for guideline implementation was conducted. All patients managed during the months January through June in the years 2005, 2007 and 2009 were then identified with an electronic search in the hospitals patient administrative database, and the patient files were reviewed. Patients were classified according to the Head Injury Severity Scale, and the management was classified as compliant or not with the guideline. Results The 1 180 patients were 759 (64%) males and 421 (36%) females with a mean age of 31.5 (range 0-97) years. Over all, 738 (63%) patients were managed in accordance with the guidelines and 442 (37%) were not. Compliance was not significantly different between minimal (56%) and mild (59%) injuries, while most moderate (93%) injuries were managed in accordance with the guidelines (p < 0.05). Noncompliance was caused by overtriage in 362 cases (30%) and undertriage in 80 (7%). Guideline compliance was 54% in 2005, 71% in 2007, and 64% in 2009. Conclusions This study shows higher guideline compliance after an educational intervention involving feed-back on performance. A substantial number of patients are exposed to over-triage, involving unnecessary radiation from CT examinations, and unnecessary costs from hospital admissions.

Introduction: Induced hypothermia has been shown to improve outcome after cardiac arrest, but early prognostication is hampered by the need for sedation. Here we tested whether a biomarker for neurodegeneration, the neurofilament heavy chain (NfH), may improve diagnostic accuracy in the first days after cardiac arrest. Methods: This prospective study included 90 consecutive patients treated with hypothermia after cardiac arrest. Plasma levels of phosphorylated NfH (SMI35) were quantified using standard ELISA over a period of 72 h after cardiac arrest. The primary outcome was the dichotomized Cerebral Performance Categories scale (CPC). A best CPC 1-2 during 6 months follow-up was considered a good outcome, a best CPC of 3-4 a poor outcome. Receiver operator characteristics and area under the curve were calculated. Results: The median age of the patients was 65 years, and 63 (70%) were male. A cardiac aetiology was identified in 62 cases (69%). 77 patients (86%) had out-of-hospital cardiac arrest. The outcome was good in 48 and poor in 42 patients. Plasma NfH levels were significantly higher 2 and 36 hours after cardiac arrest in patients with poor outcome (median 0.28 ng/mL and 0.5 ng/mL, respectively) compared to those with good outcome (0 ng/mL, p = 0.016, p < 0.005, respectively). The respective AUC were 0.72 and 0.71. Conclusions: Plasma NfH levels correlate to neurological prognosis following cardiac arrest. In this study, 15 patients had neurological co-morbidities and there was a considerable overlap of data. As such, neurofilament should not be used for routine neuroprognostication until more data are available.

Retrospectively 93 consecutive patients operated on for lumbar disc herniation were studied in order to evaluate the prognostic value of symptoms (lumbar pain and sciatica) and sick-leave. Surgical results were evaluated 1-3 years postoperatively by a questionaire. The duration of the present attack of sciatica and sick-leave prior to surgery was significantly longer in the group with unsatisfactory outcome compared to the group with satisfactory outcome. Patients with duration of the present attack of sciatica of less than 6 months had a significantly better result concerning outcome compared to patients with duration of 6-12 months and more than 12 months. Patients who returned to the same type of work had a preoperatively statistically significant shorter duration of present sick-leave, compared to the patients who had changed the type of work and the patients who did not return to work. The patients with duration of their present sick-leave of less than 6 months had a significantly higher percentage of returning to the same type of work compared to patients with duration of their present sick-leave of 6-12 months and more than 12 months. We conclude that the duration of sciatica and sick-leave before the operation has value as predictive factors concerning the over-all result after surgery for lumbar disc herniation.

Objective: To assess the efficacy of caudal epidural steroid or saline injection in chronic lumbar radiculopathy in the short (6 weeks), intermediate (12 weeks), and long term (52 weeks). Design: Multicentre, blinded, randomised controlled trial. Setting: Outpatient multidisciplinary back clinics of five Norwegian hospitals. Participants: Between October 2005 and February 2009, 461 patients assessed for inclusion (presenting with lumbar radiculopathy >12 weeks). 328 patients excluded for cauda equina syndrome, severe paresis, severe pain, previous spinal injection or surgery, deformity, pregnancy, ongoing breast feeding, warfarin therapy, ongoing treatment with non-steroidal anti-inflammatory drugs, body mass index >30, poorly controlled psychiatric conditions with possible secondary gain, and severe comorbidity. Interventions: Subcutaneous sham injections of 2 mL 0.9% saline, caudal epidural injections of 30 mL 0.9% saline, and caudal epidural injections of 40 mg triamcinolone acetonide in 29 mL 0.9% saline. Participants received two injections with a two week interval. Main outcome measures: Primary: Oswestry disability index scores. Secondary: European quality of life measure, visual analogue scale scores for low back pain and for leg pain. Results: Power calculations required the inclusion of 41 patients per group. We did not allocate 17 of 133 eligible patients because their symptoms improved before randomisation. All groups improved after the interventions, but we found no statistical or clinical differences between the groups over time. For the sham group (n=40), estimated change in the Oswestry disability index from the adjusted baseline value was -4.7 (95% confidence intervals -0.6 to -8.8) at 6 weeks, -11.4 (-6.3 to -14.5) at 12 weeks, and -14.3 (-10.0 to -18.7) at 52 weeks. For the epidural saline intervention group (n=39) compared with the sham group, differences in primary outcome were -0.5 (-6.3 to 5.4) at 6 weeks, 1.4 (-4.5 to 7.2) at 12 weeks, and -1.9 (-8.0 to 4.3) at 52 weeks; for the epidural steroid group (n=37), corresponding differences were -2.9 (-8.7 to 3.0), 4.0 (-1.9 to 9.9), and 1.9 (-4.2 to 8.0). Analysis adjusted for duration of leg pain, back pain, and sick leave did not change this trend. Conclusions: Caudal epidural steroid or saline injections are not recommended for chronic lumbar radiculopathy. Trial registration: Current Controlled Trials ISRCTN No 12574253.

Tetracykline is a first-line treatment of the common skin disorder acne vulgaris. A rare side effect of tetracycline treatment is intracranial hypertension also called pseudotumor cerebri (PTC). We report a severe case of PTC with cranial nerve palsy and visual loss in a 16 year old girl following acne vulgaris treatment with tetracycline.

Background In three previous Norwegian studies conducted between 1974 and 1993, the annual incidence rates of hospital admitted head injuries were 236, 200 and 169 per 100,000 population. The aim of this study was to describe the incidence of head injury in the Stavanger region and to compare it with previous Norwegian studies. Methods All head injured patients referred to Stavanger University Hospital during a one-year period (2003) were registered in a partly prospective and partly retrospective study. The catchment area for the hospital is strictly defined to a local population of 283,317 inhabitants (2003). Results The annual incidence rate was 207/100,000 population for hospital referred head injury and 157/100,000 population for hospital admitted head injury. High age- and sex specific incidence rates were observed among the oldest, and the highest rate (882/100,000) among men above 90 years. More than 50% of the injuries were caused by falls. Conclusion Comparison with previous Norwegian studies indicates decreasing annual incidence rates for hospital admitted head injury during the last 30 years.

Head trauma is the cause the death for many young persons. The number of fatalities can be reduced through systematic management. Prevention of secondary brain injury combined with the fastest possible transport to a neurosurgical unit, have been shown to effectively reduce mortality and morbidity. Evidence-based guidelines already exist that focus on all steps in the process. In the present article members of the Scandinavian Neurotrauma Committee present recommendations on prehospital management of traumatic brain injury adapted to the infrastructure of the Nordic region.

Conventional treatments for severe head injury : are they effective, ineffective, or even harmful?

Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI) or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg) significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI.

A national survey in 1996 showed insufficient routines for management of patients with mild head injuries in Norwegian hospitals. Since then, the Scandinavian guidelines for management of mild head injuries have been published.A cross-sectional questionnaire survey of management practice was performed in all 59 hospitals in 2002. We compared the results with figures from 1996 and evaluated guideline compliance.The proportion of noncompliant hospitals was reduced (p = 0.02) from 52% to 31%. The proportion assessing patient consciousness according to the Glasgow Coma Scale increased (p = 0.001) from 49% to 80%. The proportion requiring a normal computed tomographic scan if a patient with a history of loss of consciousness was to be discharged from the emergency department increased (p0.001) from 2% to 19%.The Scandinavian guidelines have had a significant impact on management practice in Norwegian hospitals.

Children undergoing selective dorsal rhizotomy (SDR) experience severe pain postoperatively; a pain related to both the extensive surgical exposure with multilevel laminectomy and nerve root manipulation. We sought to define an optimal dose of continuous intrathecal (IT) morphine and bupivacaine to treat this severe pain. The aim of this study was to compare two different concentrations of morphine in a fixed dose of bupivacaine with regard to the analgesic effect and survey if they differed in side effects.Twenty-six children, aged 2.7-7.4 years undergoing SDR were included in this study. Postoperatively 11 children received a continuous infusion of morphine 0.4 microg x kg(-1) x h(-1) and bupivacaine 40 microg x kg(-1) x h(-1) (low-dose group) and 15, a continuous infusion of morphine 0.6 microg x kg(-1) x h(-1) and bupivacaine 40 microg x kg(-1) x h(-1) (high-dose group). The Behavioral Observational Pain Scale (BOPS) was used to evaluate pain.Better pain relief was obtained in the high-dose group seen in lower BOPS score compared with the low-dose group [P = 0.03, Fisher's permutation test and P = 0.06 Wilcoxon-Mann-Whitney (WMW) test]. The low-dose group received seven times as much ketobemidone 0.43 +/- 0.54 mg x kg(-1) 48 h(-1) compared with 0.06 +/- 0.09 mg x kg(-1) 48 h(-1) in the high-dose group (P = 0.0005 Fisher's permutation test, P = 0.0017 WMW test). There was no statistical difference in pruritus and postoperative nausea and vomiting between the groups. Respiratory and hemodynamic depression was not found.This study shows that, compared with low-dose, the higher dose of continuous IT morphine combined with bupivacaine, significantly reduce pain score and postoperative intravenous analgesic requirements without increasing adverse effects.

S-100 is a calcium-binding protein synthesized in astroglial cells in all parts of the central nervous system (CNS). It is present in the body in different subchains, of which the beta form (96%) predominates in the brain (1). S-100 protein is normally not detectable in serum (1), but previous studies have demonstrated that increased S-100 concentrations in cerebrospinal fluid (CSF) are an index of the active phase of cell injury in patients with acute multiple sclerosis exacerbations, intracranial tumors, acute encephalomyelitis, and spinal cord compression (2). High CSF concentrations of the S-100 protein have also been demonstrated in patients with glioblastoma, cervical compression, polyneuropathy, hydrocephalus, subarachnoid hemorrhage, encephalitis, meningitis, and cerebral infarction (3)(4)(5)(6)(7)(8). A previous study demonstrated age-related reference values for S-100 protein in CSF in children and adults with distinct neurological disorders (9). We sampled serum and CSF from 75 men and 35 women undergoing various surgical procedures in spinal anesthesia.The patients had no actual or previous history of neurological disease. The study was performed to establish reference intervals of S-100 protein in CSF and serum. From August 1995 to June 1996, serum and CSF samples were obtained from 110 patients undergoing surgery in spinal anesthesia. Before inclusion in the study, the patients answered a questionnaire concerning known neurological symptoms or diseases, and their hospital records were investigated. The inclusion criteria were as follows: no history of previous neurological symptoms or disease, no previous investigation in a neurological department, no present symptoms indicating any neurological disease, no evidence of malignant disease, …

Purpose To evaluate artifact sizes at 3 T compared to at 1.5 T, and to evaluate the influence of scanning parameters with respect to artifact size on a 3-T magnetic resonance imaging (MRI) system. Materials and Methods Two aneurysm clips and five shunt valves were imaged in a water phantom at 1.5 and 3 T. At 3 T the influence of bandwidth (spin echo (SE) images) and echo time (gradient echo (GRE) images) on artifact size (area and extension in two orthogonal directions) was investigated. Results Artifact sizes increased substantially (typically 5–10 mm) at 3 T, compared to at 1.5 T, for implants entirely made of metallic materials, whereas the increase was the size less prominent (0–5 mm) for implants only partly containing metal. Artifact areas could be altered by changing the bandwidth or the echo time to about the same extent as it was affected by the increased field strength. Conclusion Artifact sizes increase at 3 T, compared to at 1.5 T, depending on the type and composition of the implant, but can be substantially reduced by altering the imaging parameters. Optimization of imaging protocols to minimize artifacts is therefore important at higher field strengths. J. Magn. Reson. Imaging 2005. © 2005 Wiley-Liss, Inc.

A randomized study has indicated that continuous monitoring of intracranial pressure (ICP) in patients with traumatic brain injury does not improve outcome compared with care based on imaging and clinical examination. The results do not, however, justify elimination of continuous ICP measurement from standard care in patients with head injury.