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Objective The present study was conducted to validate S-100 protein as a marker of brain damage after minor head injury. Methods We studied 50 patients with minor head injuries and Glasgow Coma Scale scores of 13 to 15 in whom computed tomographic scans of the brain revealed no abnormalities. Serum levels of S-100 protein were measured at admittance and hourly thereafter until 12 hours after injury. Magnetic resonance imaging and baseline neuropsychological examinations were performed within 48 hours, and neuropsychological follow-up was conducted at 3 months postinjury. Results Fourteen patients (28%) had detectable serum levels of S-100 protein (mean peak value, 0.4 microg/L [standard deviation, +/- 0.3]). The S-100 protein levels were highest immediately after the trauma, and they declined each hour thereafter. At 6 hours postinjury, the serum level was below the detection limit (0.2 microg/L) in five (36%) of the patients with initially detectable levels. Magnetic resonance imaging revealed brain contusions in five patients, four of whom demonstrated detectable levels of S-100 protein in serum. The proportion of patients with detectable serum levels was significantly higher when magnetic resonance imaging revealed a brain contusion. In patients with detectable serum levels, we observed a trend toward impaired neuropsychological functioning on measures of attention, memory, and information processing speed. Conclusion Determination of S-100 protein levels in serum provides a valid measure of the presence and severity of traumatic brain damage if performed within the first hours after minor head injury.

This retrospective population-based survey describes the epidemiology of head injury in a defined population in Northern Norway. It includes all 247 patients with head injury referred to the University Hospital of Tromsø, Norway, during 1993. Head injury was defined as physical damage to the brain or skull caused by external force. The annual incidence rate of hospital-referred head injury was 229/100,000 population with a male preponderance of 1.7:1.0. The cause was a fall in 62%, road traffic accident in 21% and assault in 7% of the cases. The observed incidence rate is low despite the use of wide inclusion criteria, probably due to a decrease in road traffic accidents. A further decrease in the number of head injuries in our region may be achieved by preventing falls.

Computed tomography (CT) scan was performed within 6 h in 91 patients with minor head injury (MHI). Eight patients (9%) demonstrated intracranial lesions on CT scan (6 brain contusions, 1 brain edema and 1 extradural hematoma). No patient required craniotomy. In patients with normal CT scan, no complications to the head injury were observed. Patients with intracranial lesions were hospitalized significantly longer (mean 9.4 days) than patients without (mean 1.6 days). In a subgroup of 50 patients with normal CT scan, serum S-100 protein was measured on admission. Elevated S-100 levels were seen in 10 of 50 patients (0.5–2.4 μg/L, mean 1.1). These patients were hospitalized significantly longer (mean 3.4 days) compared to patients with normal CT scan and normal S-100 levels (mean 1.1 days). MHI patients with GCS 14–15 without neurological deficits can safely be discharged when CT scan is normal. Serum protein S-100 measurements appear to provide information about diffuse brain injury after MHI.

Protein S100B is today the most promising biomarker for cerebral injury. A welcomed area for the use of such a marker is in the early stages of head trauma and diagnosis of brain injury, in particular epidural haematomas. We report five consecutive cases of epidural haematoma where serum samples for S100B were drawn at admission. Three of the patients showed low levels of S100B (< or =0.2 microg/l). One patient with a large epidural haematoma with radiological signs of cerebral herniation displayed normal levels (0.14 microg/l) of S100B 3.5 h after the initial head trauma. Normal S100B levels in serum do not predict normal intracranial findings. S100B may be unreliable as a marker for epidural haematomas after closed head injury.

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.

Elevated intracranial pressure (ICP) is an important cause of secondary brain injury, and a measurement of ICP is often of crucial value in neurosurgical and neurological patients. The gold standard for ICP monitoring is through an intraventricular catheter, but this invasive technique is associated with certain risks. Intraparenchymal ICP monitoring methods are considered to be a safer alternative but can, in certain conditions, be imprecise due to zero drift and still require an invasive procedure. An accurate noninvasive method to measure elevated ICP would therefore be desirable. This article is a review of the current literature on noninvasive methods for measuring and evaluating elevated ICP. The main focus is on studies that compare noninvasively measured ICP with invasively measured ICP. The aim is to provide an overview of the current state of the most common noninvasive techniques available. Several methods for noninvasive measuring of elevated ICP have been proposed: radiologic methods including computed tomography and magnetic resonance imaging, transcranial Doppler, electroencephalography power spectrum analysis, and the audiological and ophthalmological techniques. The noninvasive methods have many advantages, but remain less accurate compared with the invasive techniques. None of the noninvasive techniques available today are suitable for continuous monitoring, and they cannot be used as a substitute for invasive monitoring. They can, however, provide a reliable measurement of the ICP and be useful as screening methods in select patients, especially when invasive monitoring is contraindicated or unavailable.

S100B is a calcium-binding protein most abundant in neuronal tissue. It is expressed in glia cells and Schwann cells and exerts both intra- and extracellular effects. Depending on the concentration, secreted S100B exerts either trophic or toxic effects. Its functions have been extensively studied but are still not fully understood. It can be measured in cerebrospinal fluid and blood, and increased S100B level in blood can be seen after, e.g., traumatic brain injury, certain neurodegenerative disorders and malignant melanoma. This chapter provides a short background of protein S100B, commercially available methods of analysis, and its clinical use.

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.

Transcranial Doppler (TCD) examination was performed in 109 patients with aneurysmal subarachnoid haemorrhage. Fifty-seven demonstrated flow velocities exceeding 120 cm/s in the middle cerebral artery. Of these, 23 developed delayed ischaemic deficit (DID). Mean flow velocity in this group was 170, SD 12.8 cm/s, in comparison with 155, SD 11.2 cm/s in the 34 patients without late signs of cerebral ischaemia. This difference is significant (p = 0.0269). In the 34 patients without DID, but TCD120 cm/s, 17 received anti-ischaemic therapy based on TCD values only, while 17 were given no additional treatment. The mean TCD values and the neurological outcome in the two groups were similar. A rapid increase in flow velocities of 50 cm/s or more during a 24-h period seemed to be a strong predictor of symptomatic vasospasm as seven out of 12 patients developed DID, five with permanent neurological sequelae. The study confirms results from other centres, that a strict correlation between high TCD flow velocities and occurrence of DID does not exist.

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.

S100B is a calcium-binding protein most abundant in neuronal tissue. It is expressed in glia cells and Schwann cells and exerts both intra- and extracellular effects. Depending on the concentration, secreted S100B exerts either trophic or toxic effects. Its functions have been extensively studied but are still not fully understood. It can be measured in cerebrospinal fluid and blood, and increased S100B level in blood can be seen after, e.g., traumatic brain injury, certain neurodegenerative disorders and malignant melanoma. This chapter provides a short background of protein S100B, commercially available methods of analysis, and its clinical use.

Despite the fact that it has been used since the 1960s in diseases associated with brain edema and has been investigated in >150 publications on head injury, very little has been published on the outcome of osmotherapy. We can only speculate whether osmotherapy improves outcome, has no effect on outcome, or leads to worse outcome. Here we describe the action and potentially beneficial and adverse effects of the 2 most commonly used osmotic solutions, mannitol and hypertonic saline, and present some critical aspects of their use. There is a well-documented transient intracranial pressure (ICP)-reducing effect of osmotherapy, but an adverse rebound increase in ICP after its withdrawal has been discussed extensively in the literature and is an expected pathophysiological phenomenon. From side effects related to renal and pulmonary failure, electrolyte disturbances, and a rebound increase in ICP, osmotherapy can be negative for outcome, which may explain why we lack scientific support for its use. These drawbacks, and the fact that the most recent Cochrane meta-analyses of osmotherapy in brain edema and stroke could not find any beneficial effects on outcome, make routine use of osmotherapy in brain edema doubtful. Nevertheless, the use of osmotherapy as a temporary measure may be justified to acutely prevent brain stem compression until other measures, such as evacuation of space-occupying lesions or decompressive craniotomy, can be performed. This article is the Con part in a Pro-Con debate in the present journal on the general routine use of osmotherapy in brain edema.

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.

Objective Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy. Methods We conducted a retrospective review of 239 patients undergoing surgery for CSDH over a period of six years (2006–2011). Risk factors such as age, head trauma, anticoagulant and/or antiplatelet agent therapy and co-morbidity were investigated along with gender, coagulation status, laterality, surgical method and recurrence. Results Seventy-two percent of the patients were male and the mean age was 71.8 years (range 28–97 years). Previous fall with head trauma was reported in 60% of the patients while 16% were certain of no previous head trauma. The majority of patients (63%) in the non-trauma group were receiving anticoagulants and/or antiplatelet agent therapy prior to CSDH presentation, compared to 42% in the trauma group. Twenty-four percent experienced recurrence of the CSDH. There was no association between recurrence and anticoagulant and/or antiplatelet agent therapy. Conclusion Anticoagulant and/or antiplatelet aggregation agent therapy is more prevalent among non-traumatic CSDH patients but does not seem to influence the rate of CSDH recurrence.

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.

Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI.CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia.Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.

By using a 1–2-MHz pulsed Transcranial Doppler (TCD), it is possible to penetrate the skull bone at special sites (windows) and register the flow velocity (FV) in the insonated artery at well-defined depts. In this way, the FV can be registered in the central arteries as well as in some of the veins. A normal FV in an artery normally indicates an adequate circulation to the territory it supplies. High and low FV does not necessarily have correlations to the CBF since the diameter of the measured vessel is unknown. If the FV is high, a differentiation between hyperaemia and vasospasm can be obtained by performing a Lindegaard Index (LI) which is the correlation between the FV in the middle cerebral artery and the internal carotid artery.

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.

Based on experimental and clinical studies, there is a general view that fever is detrimental to TBI patients (Thompson et al. 2003). An important goal in the treatment of these patients has therefore been to prevent or reduce fever. So far, we lack evidence-based consensus regarding how to reduce temperature in TBI patients. Fever can be reduced pharmacologically by affecting the thermostat or by active cooling of the patient. During the last 10–15 years, it has also been suggested that active cooling to subnormal temperatures (32–34°C) should be beneficial due to its well-known neuroprotective effect, as demonstrated in animal studies after brain ischaemia and also in humans after near-drowning and after active cooling following heart resuscitation, and the fact that hypothermia decreases an increased intracranial pressure (Polderman 2008; Grande et al. 2009). The mechanisms behind the hypothermia-induced neuroprotection are not clarified, but the reduced neuronal metabolism and the inflammatory response, and the reduction in toxic substances such as glutamate and a scavenging effect may be involved. It was therefore believed that active cooling should be beneficial in TBI patients, but we still lack studies giving support for active cooling in clinical practice. In this chapter, we give recommendations on how and when temperature should be reduced and the goal temperature in TBI patients, based on the results of the most recent studies and current knowledge in this field. It will be concluded that active cooling is associated with side effects and that we lack support for its use in TBI patients, and it can therefore not be recommended.

Head injuries can be categorized in several ways: by mechanism of injury (closed or penetrating injury), morphology (fractures, focal intracranial injury, diffuse intracranial injury), or severity of injury (mild to severe).

Near infrared spectroscopy (NIRS) measures the oxygenation of the haemoglobin in the cerebral tissue lying just underneath a probe. The probe is most often placed on the forehead since hair follicles affect the readings. Some doubts have been raised whether NIRS specifically measures the cerebral tissue or is contaminated by signals from extracerebral tissue it passes through. Furthermore, as haemoglobin absorbs infrared light, NIRS is affected by underlying blood of extravascular origin, such as in subdural haematomas, contusions, subarachnoid blood, as well as changes in cerebral blood volume (CBV). These factors are difficult to decipher, and at present the use of NIRS in TBI patients is controversial. However, by using more than one sensor and by focusing on trends, NIRS readings might be of value in this patient group.

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.

Two patients presented with benign cystic schwannomas, which originated from the brachial plexus and the sciatic nerve, respectively. The tumours were single, egg-shaped growths that were excised completely without damage to the nerve. Histopathological examination confirmed the diagnosis of encapsulated, cystic, benign schwannomas. Preoperative magnetic resonance imaging provided useful information and is recommended in the evaluation of peripheral nerve tumours.

Since the flow diverters (FDs) have been introduced it is possible to treat aneurysms that are considered difficult or impossible to treat with usual endovascular or surgical methods. It is still uncertain which aneurysms are suitable for this new treatment. We present the periprocedural complications, immediate result, late complications, imaging follow-up at 6 and 12 months and clinical follow-up at 2-23 months.Twenty-two patients with 26 wide-necked or blister-like aneurysms had 23 treatments with implantation of a Silk stent. Eleven patients had re-canalizations, and 11 patients were either untreated or had been treated for another aneurysm.Periprocedural complications were seen in four treatments (17%). However, none of these had clinical consequences. Mortality and morbidity rates were 1 of 22 (5%) and 1 of 22 (5%), respectively. Clinical outcome was unchanged in 16 patients (72%), 3 patients improved (14%) and 3 patients worsened (14%). The end-of-procedure angiography did not show complete occlusion of any of the aneurysms, but at 6 months follow-up angiography, 17 of 25 aneurysms (68%) were completely occluded, and at 12 months, 18 of 21 aneurysms (86%) were occluded.The effect of the Silk FD in terms of occlusion of the aneurysms seems to occur mainly during the first 6 months after placement but continues during the following time. Most delayed complications occur immediately after discontinuing the anticoagulation medication. Considering the complexity of the aneurysms treated, the rate of complications is acceptable.

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.

Intraventricular hemorrhage (IVH) subsequent to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity. The use of fibrinolytic agents to treat this condition has previously been reported in small clinical trials with limited numbers of patients. Variability regarding inclusion criteria, method of administration and outcome have made it difficult to draw firm conclusions regarding the efficacy of antifibrinolytic therapy. Nine patients with CT-diagnosed IVH were treated with Alteplase intrathecally for 3 to 5 days according to the CT-verified clearance of IVH. After the treatment period, a repeat CT scan was performed to evaluate treatment effect.

Background Endothelial dysfunction might be involved in the development of cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). Methods 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 ( V MCA ), 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. Results 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 ( P 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 ( P P P r =0.43, P V MCA , or S-100B. Conclusions 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.

Rebleeding from subarachnoid haemorrhage (SAH) usually occurs within the first six hours after the initial bleeding. Rebleeding can be prevented effectively with tranexamic acid (TXA). Although a broad consensus has evolved that SAH should be treated as an emergency, it is likely that delays do exist in the diagnosis and treatment of SAH patients. The aim of this study was to prospectively assess the interval between symptom onset, emergency room (ER) admission, initial diagnosis and treatment, and final closure of the aneurysm.We prospectively studied the time course from the initial bleeding to ER admission, computed tomography (CT), TXA treatment, referral to the neurosurgical department, and to the final closure of the aneurysm.A total of 133 patients with SAH due to ruptured intracranial aneurysms were admitted to two neurosurgical units in Copenhagen, Denmark, during a one-year period. The median time to admission was 60 min. The median delay from admission to CT scan was 55 min. Long pre-hospital delay (p = 0.03) and high Glasgow Coma Scale score on arrival (p = 0.0006) were associated with a longer time to CT scan. The median time from CT scan to initiation of TXA treatment was 50 min. The median time from initial insult to final closure of the aneurysm was 30 hours.The present study demonstrates that considerable diagnostic delays exist in connection with CT and TXA treatment after patients' arrival to the ER.

We present a Danish algorithm for the neurointensive care of patients with severe traumatic brain injury. The primary goal is to avoid cerebral ischaemia and hypoxia and secondarily brain injury. Patient evaluation by a neurosurgeon is mandatory, and decision-making concerning extended cerebral monitoring should take place immediately. Treatment aiming at diminishing increased intracranial pressure should be initiated early. Early critical care management of patients with severe traumatic brain injury should be performed in a teamwork comprising various specialties.

A Cochrane metaanalysis and a study performed on children have recently confirmed that therapeutic hypothermia does not improve outcome after severe traumatic brain injury (TBI). TBI is not comparable to a short episode of global ischemia, where therapeutic hypothermia has been shown to improve outcome. The difference may be explained by the fact that hypothermia-induced stress after a traumatic brain injury reduces cerebral perfusion in the penumbra zone, where local circulation is already reduced. Thus, to date there is no indication for therapeutic hypothermia in TBI patients.

Subarachnoid hemorrhage (SAH) is a serious condition, occurring more frequently in females than in males. SAH is mainly caused by rupture of an intracranial aneurysm, which is formed by localized dilation of the intracranial arterial vessel wall, usually at the apex of the arterial bifurcation. The female preponderance is usually explained by systemic factors (hormonal influences and intrinsic wall weakness); however, the uneven sex distribution of intracranial aneurysms suggests a possible physiologic factor-a local sex difference in the intracranial arteries.The aim of this study was to explore sex variation in the bifurcation anatomy of the middle cerebral artery (MCA) and internal carotid artery (ICA), and the subsequent hemodynamic impact.Vessel radii and bifurcation angles were measured in patients with MCA and ICA bifurcations. Data from a previously published study of 55 patients undergoing diagnostic cerebral digital subtraction angiography at Dalcross Private Hospital in Sydney, Australia, between 2002 and 2003, were available for analysis. The measurements were used to create idealized, averaged bifurcations of the MCA and ICA for females and males. Computational fluid dynamics simulations were performed to calculate hemodynamic forces in the models.The vessel radii and bifurcation angles of 47 MCA and 52 ICA bifurcations in 49 patients (32 females, 17 males; mean age, 53 years; age range, 14-86 years) were measured. Statistically significant sex differences were found in vessel diameter (males larger than females; P0.05), but not in bifurcation angle. Computational fluid dynamics simulations revealed higher wall shear stress in the female MCA (19%) and ICA (50%) bifurcations compared with the male bifurcations.This study of MCA and ICA bifurcations in female and male patients suggests that sex differences in vessel size and blood flow velocity result in higher hemodynamic forces acting on the vessel wall in females. This new hypothesis may partly explain why intracranial aneurysms and SAH are more likely to occur in females than in males.

Background: Studies indicate a relationship between hospital caseload and health outcomes after both surgical and endovascular repair of intracranial aneurysms. Purpose: To evaluate outcomes after introduction of endovascular embolization for intracranial aneurysms in a low-volume regional university hospital. Material and Methods: Retrospective study of 243 consecutive patients treated for 284 intracranial aneurysms with endovascular embolization or surgical clipping from 2000 to 2006 at the University Hospital of North Norway. Postoperative complications were registered. The Glasgow Outcome Scale (GOS) was used for assessment of outcome. Results: The mean annual number of procedures was 39 (microsurgery 23, embolization 16). Seventy-four percent of patients with ruptured aneurysms and all patients with unruptured aneurysms had a favorable outcome (GOS 4 or 5) at 1 year follow-up. Patients with subarachnoid hemorrhage were more likely to experience postoperative complications than patients treated for unruptured aneurysms (42% versus 8% of the patients, P Conclusion: The present study indicates that acceptable outcome from aneurysm treatment, both endovascular and microsurgical, is possible in a low-volume institution.

The risk of acute intracranial complications after minor head injury (MHI) is low. Despite this, computed tomography (CT) is generally recommended with clinical observation as a secondary option. Both options have disadvantages. Clinical studies have shown the potential advantages of using the biomarker S100B. The specificity of S100B is low, but a high sensitivity for brain damage results in a clinically useful, high negative predictive value (NPV). Integration of S100B into existing management routines can reduce the need for CT scans or admission by over 30%.