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author:("romer, bertin")
1.  Therapeutic Hypothermia in Children and Adults with Severe Traumatic Brain Injury 
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.
PMCID: PMC3949439  PMID: 24660099
2.  Accuracy of physical examination for chronic lumbar radiculopathy 
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.
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.
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 <0.4. The overall clinical evaluation was slightly more accurate, with a positive LR of 6.28 (95% CI 1.06–37.21) for L4, 1.74 (95% CI 1.04–2.93) for L5, and 1.29 (95% CI 0.97–1.72) for S1 nerve root impingement. An overall clinical evaluation, concluding on the level and side of the radiculopathy was also performed, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) calculation for diagnostic accuracy of this evaluation was performed.
The accuracy of individual clinical index tests used to predict imaging findings of nerve root impingement in patients with chronic lumbar radiculopathy is low when applied in specialised care, but clinicians’ overall evaluation improves diagnostic accuracy slightly. The tests are not very helpful in clarifying the cause of radicular pain, and are therefore inaccurate for guidance in the diagnostic workup of the patients. The study population was highly selected and therefore the results from this study should not be generalised to unselected patient populations in primary care nor to even more selected surgical populations.
PMCID: PMC3716914  PMID: 23837886
Sensitivity; Accuracy; Likelihood ratio; Lumbar radiculopathy; Physical examination
3.  Can S100B Predict Cerebral Vasospasms in Patients Suffering from Subarachnoid Hemorrhage? 
Background: Protein S100B has proven to be a useful biomarker for cerebral damages. Increased levels of serum and cerebrospinal fluid (CSF) S100B have been shown in patients suffering subarachnoid hemorrhage (SAH), severe head injury and stroke. In patients with SAH, 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 SAH.
Materials and 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 3 days following ictus and the following four samples, once a day on days 5–8, 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 five patients had elevated and increasing serum S100B prior to vasospasm. Only one showed a peak level of S100B 1 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 SAH.
PMCID: PMC3674401  PMID: 23761779
protein S100B; subarachnoid hemorrhage; cerebral vasospasm; CT angiography; cerebrospinal fluid; serum
4.  Post-ischemic continuous infusion of erythropoeitin enhances recovery of lost memory function after global cerebral ischemia in the rat 
BMC Neuroscience  2013;14:27.
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.
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).
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.
PMCID: PMC3608158  PMID: 23497299
5.  Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update 
BMC Medicine  2013;11:50.
The management of minimal, mild and moderate head injuries is still controversial. In 2000, the Scandinavian Neurotrauma Committee (SNC) presented evidence-based guidelines for initial management of these injuries. Since then, considerable new evidence has emerged.
General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Systematic evidence-based review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, based upon relevant clinical questions with respect to patient-important outcomes, including Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and Centre of Evidence Based Medicine (CEBM) quality ratings. Based upon the results, GRADE recommendations, guidelines and discharge instructions were drafted. A modified Delphi approach was used for consensus and relevant clinical stakeholders were consulted.
We present the updated SNC guidelines for initial management of minimal, mild and moderate head injury in adults including criteria for computed tomography (CT) scan selection, admission and discharge with suggestions for monitoring routines and discharge advice for patients. The guidelines are designed to primarily detect neurosurgical intervention with traumatic CT findings as a secondary goal. For elements lacking good evidence, such as in-hospital monitoring, routines were largely based on consensus. We suggest external validation of the guidelines before widespread clinical use is recommended.
PMCID: PMC3621842  PMID: 23432764
computed tomography; GRADE; guidelines; head/brain injury/trauma; management; prediction rule; routines; S100/S100B/S100BB
6.  Initial experience with the Codman Certas adjustable valve in the management of patients with hydrocephalus 
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).
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.
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.
PMCID: PMC3490860  PMID: 22995221
Hydrocephalus; Shunt; Certas valve; Adjustable valve; Programmable valve
7.  The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomised controlled trial 
Trials  2012;13:102.
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.
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 NCT01447095.
PMCID: PMC3487886  PMID: 22747768
Subarachnoid haemorrhage; Prostacyclin; Epoprostenol; Vasospasm; Delayed ischaemic neurological deficit
8.  An observational study of compliance with the Scandinavian guidelines for management of minimal, mild and moderate head injury 
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.
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.
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.
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.
PMCID: PMC3352311  PMID: 22510221
Head injury; Guidelines; Implementation; Compliance
9.  Serial soluble neurofilament heavy chain in plasma as a marker of brain injury after cardiac arrest 
Critical Care  2012;16(2):R45.
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.
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.
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.
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.
PMCID: PMC3681370  PMID: 22410303
10.  Alcohol consumption, blood alcohol concentration level and guideline compliance in hospital referred patients with minimal, mild and moderate head injuries 
In 2000 the Scandinavian Neurotrauma Committee published guidelines for safe and cost-effective management of minimal, mild and moderate head injured patients.
The aims of this study were to investigate to what extent the head injury population is under the influence of alcohol, and to evaluate whether the physicians' compliance to the guidelines is affected when patients are influenced by alcohol.
This study included adult patients (≥15 years) referred to a Norwegian University Hospital with minimal, mild and moderate head injuries classified according to the Head Injury Severity Scale (HISS). Information on alcohol consumption was recorded, and in most of these patients blood alcohol concentration (BAC) was measured. Compliance with the abovementioned guidelines was registered.
The study includes 860 patients. 35.8% of the patients had consumed alcohol, and 92.1% of these patients had a BAC ≥ 1.00‰. Young age, male gender, trauma occurring during the weekends, mild and moderate head injuries were independent factors significantly associated with being under the influence of alcohol. Guideline compliance was 60.5%, and over-triage was the main violation. The guideline compliance showed no significant correlation to alcohol consumption or to BAC-level.
This study confirms that alcohol consumption is common among patients with head injuries. The physicians' guideline compliance was not affected by the patients' alcohol consumption, and alcohol influence could therefore not explain the low guideline compliance.
PMCID: PMC3101126  PMID: 21496318
11.  A severe case of tetracycline-induced intracranial hypertension 
Dermatology Reports  2011;3(1):e1.
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.
PMCID: PMC4211491  PMID: 25386253
tetracycline; intracranial hypertension.
12.  How does extracerebral trauma affect the clinical value of S100B measurements? 
Emergency Medicine Journal : EMJ  2010;28(11):941-944.
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.
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.
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<0.0001). The corresponding values at 6 h were 0.14, 0.31 and 0.15 μg/l, respectively (p<0.0001). S100B was significantly higher in patients with MTHI than in patients with IHI at both time points (p values 0.0005 and 0.01). There was no significant difference in S100B between patients having IHI and patients with NHI (p=0.81 and p=0.67).
High serum levels of S100B were found early after trauma. The highest concentrations of S100B were found in patients with multi trauma. This suggests that S100B serum concentrations are significantly affected by extracerebral injuries.
PMCID: PMC3198008  PMID: 20947920
S100B; traumatic brain damage; multi trauma; mental health; assessment; neurology; research; cost-effectiveness; trauma
13.  No impact of early intervention on late outcome after minimal, mild and moderate head injury 
To evaluate the effect of an educational intervention on outcome after minimal, mild and moderate head injury.
Three hundred and twenty six patients underwent stratified randomization to an intervention group (n = 163) or a control group (n = 163). Every second patient was allocated to the intervention group. Participants in this group were offered a cognitive oriented consultation two weeks after the injury, while subjects allocated to the control group were not. Both groups were invited to follow up 3 and 12 months after injury.
A total of 50 (15%) patients completed the study (intervention group n = 22 (13%), control group n = 28 (17%), not significant). There were no statistically significant differences between the intervention group and the control group.
There was no effect on outcomes from an early educational intervention two weeks after head injury.
PMCID: PMC2844351  PMID: 20181239
14.  Incidence of hospital referred head injuries in Norway: A population based survey from the Stavanger region 
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.
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).
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.
Comparison with previous Norwegian studies indicates decreasing annual incidence rates for hospital admitted head injury during the last 30 years.
PMCID: PMC2650679  PMID: 19232086
15.  Effect of caudal epidural steroid or saline injection in chronic lumbar radiculopathy: multicentre, blinded, randomised controlled trial 
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.
PMCID: PMC3172149  PMID: 21914755

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