Non-surgical patient characteristics best predict outcome after 6 months in patients surgically treated for chronic subdural haematoma.

BACKGROUND: Chronic subdural haematoma (CSDH) is one of the most common conditions encountered in neurosurgical practice. After surgery, the patients often improve dramatically; but their long-term outcome is more uncertain. The purpose of this study was to investigate predictors of outcome 6 months after surgery. METHODS: Retrospective data were collected on patients in Orebro County, Sweden, who had undergone surgery for CSDH at the Orebro University Hospital between 2013 and 2019. The outcomes were defined as favourable or unfavourable in terms of the modified Rankin Scale (mRS). A favourable outcome was defined as either mRS 0-2 or an unchanged mRS score in patients scoring 3-5 before surgery. From the variables in the data collected, a multiple logistic regression model was constructed. RESULTS: The study comprised 180 patients, of whom 134 (74.4%) were male. Median age was 79.2 years (IQR 71.7-85.5), and 129 (71.7%) patients had a favourable outcome at 6 months. In the group with an unfavourable outcome, 18 (10%) had died and 33 (18.3%) had either lost their independence in daily living or become somewhat less independent. The final multiple logistic regression model consisted of pre-surgery variables only: age (OR 0.92, 95% CI 0.87-0.97), CRP (OR 0.96, 95% CI 0.94-0.99), GCS > 13 (OR 3.66, 95% CI 1.09-12.3), Hb (OR 1.03, 95% CI 1.00-1.05), and ASA score < 3 (OR 2.58, 95% CI 0.98-6.79). The whole model had an AUC of 0.88. CONCLUSION: CSDH requiring surgery is associated with high morbidity and mortality at 6 months after surgery. Age, CRP, GCS, Hb and ASA score on admission for surgery are the variables that best predicts outcome. This knowledge can help to identify the patients at greatest risk for an unfavourable outcome, who may need additional support from the health care system. UNSTRUCTURED ABSTRACT: Chronic subdural haematoma (CSDH) is one of the most common conditions encountered in neurosurgical practice. After surgery, the patients often improve dramatically; but their long-term outcome is more uncertain. The purpose of this study was to investigate predictors of outcome, in terms of the modified Rankin Scale (mRS), 6 months after surgery. The study comprised 180 patients, of whom 134 (74.4%) were male. Median age was 79.2 years (IQR 71.7-85.5), and 129 (71.7%) patients had a favourable outcome at 6 months. In the group with an unfavourable outcome, 18 (10%) had died and 33 (18.3%) had either lost their independence in daily living or become somewhat less independent. The final multiple logistic regression model consisted of pre-surgery variables only: age (OR 0.92, 95% CI 0.87-0.97), CRP (OR 0.96, 95% CI 0.94-0.99), GCS > 13 (OR 3.66, 95% CI 1.09-12.3), Hb (OR 1.03, 95% CI 1.00-1.05), and ASA score < 3 (OR 2.58, 95% CI 0.98-6.79). The whole model had an AUC of 0.88. In conclusion, CSDH requiring surgery is associated with high morbidity and mortality at 6 months after surgery. Age, CRP, GCS, Hb and ASA score on admission for surgery are the variables that best predicts outcome. This knowledge can help to identify the patients at greatest risk for an unfavourable outcome, who may need additional support from the health care system.

[Treatment of traumatic brain injury in the acute setting - An overview]. / Modern handläggning minimerar följder av traumatisk hjärnskada.

Traumatic brain injury (TBI) is the leading cause of death among the young, and has an increasing incidence among the elderly. In Sweden there are 20 000 new TBI cases each year, of which most are mild. The primary impact can lead to different types of brain hemorrhages, fractures and diffuse axonal injuries. The level of consciousness is used to define injury severity. Of all TBIs,  4-5 percent require surgical intervention. The primary impact initiates injury processes exacerbating the initial brain injury, and the goal of the acute management and neurointensive care treatment is to prevent these secondary insults. Among unconscious TBI patients, monitoring of intracranial pressure and cerebral perfusion pressure (CPP, defined as the difference between the mean arterial pressure and intracranial pressure) is routine. In this article we present an overview on different types of TBI, and describe the treatment of patients in the acute setting.

Risk for morbidity and mortality after neurosurgery in older patients with high grade gliomas - a retrospective population based study.

BACKGROUND: Although high grade gliomas largely affect older patients, current evidence on neurosurgical complications is mostly based on studies including younger study populations. We aimed to investigate the risk for postoperative complications after neurosurgery in a population-based cohort of older patients with high grade gliomas, and explore changes over time. METHODS: In this retrospective study we have used data from the Swedish Brain Tumour Registry and included patients in Sweden age 65 years or older, with surgery 1999-2017 for high grade gliomas. We analysed number of surgical procedures per year and which factors contribute to postoperative morbidity and mortality. RESULTS: The study included 1998 surgical interventions from an area representing 60% of the Swedish population. Over time, there was an increase in surgical interventions in relation to the age specific population (p < 0.001). Postoperative morbidity for 2006-2017 was 24%. Resection and not having a multifocal tumour were associated with higher risk for postoperative morbidity. Postoperative mortality for the same period was 5%. Increased age, biopsy, and poor performance status was associated with higher risk for postoperative mortality. CONCLUSIONS: This study shows an increase in surgical interventions over time, probably representing a more active treatment approach. The relatively low postoperative morbidity- and mortality-rates suggests that surgery in older patients with suspected high grade gliomas can be a feasible option. However, caution is advised in patients with poor performance status where the possible surgical intervention would be a biopsy only. Further, this study underlines the need for more standardised methods of reporting neurosurgical complications.

Older meningioma patients: a retrospective population-based study of risk factors for morbidity and mortality after neurosurgery.

BACKGROUND: Meningioma is the most common primary CNS tumour. Most meningiomas are benign, and most patients are 65 years or older. Surgery is usually the primary treatment option. Most prior studies on early surgical outcomes in older patients with meningioma are small, and there is a lack of larger population-based studies to guide clinical decision-making. We aimed to explore the risks for perioperative mortality and morbidity in older patients with meningioma and to investigate changes in surgical incidence over time. METHODS: In this retrospective population-based study on patients in Sweden, 65 years or older with surgery 1999-2017 for meningioma, we used data from the Swedish Brain Tumour Registry. We analysed factors contributing to perioperative mortality and morbidity and used official demographic data to calculate yearly incidence of surgical procedures for meningioma. RESULTS: The final study cohort included 1676 patients with a 3.1% perioperative mortality and a 37.6% perioperative morbidity. In multivariate analysis, higher age showed a statistically significant association with higher perioperative mortality, whereas larger tumour size and having preoperative symptoms were associated with higher perioperative morbidity. A numerical increased rate of surgical interventions after 2012 was observed, without evidence of worsening short-term surgical outcomes. CONCLUSIONS: Higher mortality with increased age and higher morbidity risk in larger and/or symptomatic tumours imply a possible benefit from considering surgery in selected older patients with a growing meningioma before the development of tumour-related symptoms. This study further underlines the need for a standardized method of reporting and classifying complications from neurosurgery.

A Validation Study of Kwon's Prognostic Scoring System for Chronic Subdural Hematoma.

OBJECTIVE: Surgery for chronic subdural hematoma is one of the most frequent operations in neurosurgical practice. Chronic subdural hematoma mostly afflicts the elderly population. In 2018, Kwon and co-workers, published the Kwon scoring system (KSS), whereby 6 clinical and radiological factors are used to facilitate, and promote quality in, surgical decision-making and counseling of relatives. The aim of this study is to validate the KSS. METHODS: Patients operated on for unilateral chronic subdural hematoma at Örebro University Hospital, Sweden, between 2013 and 2019 constituted the study population. General data and the 6 outcome predictors according to the KSS were extracted from the electronic patient records. The preoperative modified Rankin Scale score and the postoperative 6-month modified Rankin Scale score were assessed. RESULTS: We identified 133 patients (69.2% male) with a median age of 80.2 years (interquartile range 72.6-85.9). The median Glasgow Coma Scale score at admission was 15; 57.1% had motor deficits and 36.81% were disoriented. For 39.1% of the patients, the prognosis was a favorable outcome (modified Rankin Scale 0-1) at 6 months. The median KSS score was 9; 63.9% of the patients scored ≥9, and 36 (42.4%) of these patients actually achieved a favorable outcome. This corresponds to a prediction model sensitivity of 0.667 and specificity of 0.424. A receiver operator characteristic curve analysis of the model yielded an area under the receiver operator characteristic curve of 0.62441. CONCLUSIONS: In our material, the KSS did not predict outcome precisely enough to base treatment decisions or counseling of relatives on the scores obtained.

The significance of direct transportation to a trauma center on survival for severe traumatic brain injury.

INTRODUCTION: While timely specialized care can contribute to improved outcomes following traumatic brain injury (TBI), this condition remains the most common cause of post-injury death worldwide. The purpose of this study was to investigate the difference in mortality between regional trauma centers in Sweden (which provide neurosurgical services round the clock) and non-trauma centers, hypothesizing that 1-day and 30-day mortality will be lower at regional trauma centers. PATIENTS AND METHODS: This retrospective cohort study used data extracted from the Swedish national trauma registry and included adults admitted with severe TBI between January 2014 and December 2018. The cohort was divided into two subgroups based on whether they were treated at a trauma center or non-trauma center. Severe TBI was defined as a head injury with an AIS score of 3 or higher. Poisson regression analyses with both univariate and multivariate models were performed to determine the difference in mortality risk [Incidence Rate Ratio (IRR)] between the subgroups. As a sensitivity analysis, the inverse probability of treatment weighting (IPTW) method was used to adjust for the effects of confounding. RESULTS: A total of 3039 patients were included. Patients admitted to a trauma center had a lower crude 30-day mortality rate (21.7 vs. 26.4% days, p = 0.006). After adjusting for confounding variables, patients treated at regional trauma center had a 28% [adj. IRR (95% CI): 0.72 (0.55-0.94), p = 0.015] decreased risk of 1-day mortality and an 18% [adj. IRR (95% CI): 0.82 (0.69-0.98)] reduction in 30-day mortality, compared to patients treated at a non-trauma center. After adjusting for covariates in the Poisson regression analysis performed after IPTW, admission and treatment at a trauma center were associated with a 27% and 17% reduction in 1-day and 30-day mortality, respectively. CONCLUSION: For patients suffering a severe TBI, treatment at a regional trauma center confers a statistically significant 1-day and 30-day survival advantage over treatment at a non-trauma center.

Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage.

BACKGROUND: This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored. METHODS: Patients with sTBI aged 15-70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE. RESULTS: In 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score. CONCLUSIONS: We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood-brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.

Validation of the scandinavian guidelines for initial management of minor and moderate head trauma in children.

BACKGROUND: Head trauma in children is common, with a low rate of clinically important traumatic brain injury. CT scan is the reference standard for diagnosis of traumatic brain injury, of which the increasing use is alarming because of the risk of induction of lethal malignancies. Recently, the Scandinavian Neurotrauma Committee derived new guidelines for the initial management of minor and moderate head trauma. Our aim was to validate these guidelines. METHODS: We applied the guidelines to a population consisting of children with mild and moderate head trauma, enrolled in the study: "Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study" by Kuppermann et al. (Lancet 374(9696):1160-1170, https://doi.org/10.1016/S0140-6736(09)61558-0 , 2009). We calculated the negative predictive values of the guidelines to assess their ability to distinguish children without clinically-important traumatic brain injuries and traumatic brain injuries on CT scans, for whom CT could be omitted. RESULTS: We analysed a population of 43,025 children. For clinically-important brain injuries among children with minimal head injuries, the negative predictive value was 99.8% and the rate was 0.15%. For traumatic findings on CT, the negative predictive value was 96.9%. Traumatic finding on CT was detected in 3.1% of children with minimal head injuries who underwent a CT examination, which accounts for 0.45% of all children in this group. CONCLUSION: Children with minimal head injuries can be safely discharged with oral and written instructions. Use of the SNC-G will potentially reduce the use of CT.

Prostacyclin Affects the Relation Between Brain Interstitial Glycerol and Cerebrovascular Pressure Reactivity in Severe Traumatic Brain Injury.

BACKGROUND: Cerebral injury may alter the autoregulation of cerebral blood flow. One index for describing cerebrovascular state is the pressure reactivity (PR). Little is known of whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. The aim of this investigation was to explore whether increased interstitial levels of glycerol, a marker of cell membrane damage, are associated with PR, and if prostacyclin, a membrane stabilizer and regulator of the microcirculation, may affect this association in a beneficial way. MATERIALS AND METHODS: Patients suffering severe traumatic brain injury (sTBI) were treated according to an intracranial pressure (ICP)-targeted therapy based on the Lund concept and randomized to an add-on treatment with prostacyclin or placebo. Inclusion criteria were verified blunt head trauma, Glasgow Coma Score ≤ 8, age 15-70 years, and a first measured cerebral perfusion pressure of ≥ 10 mmHg. Multimodal monitoring was applied. A brain microdialysis catheter was placed on the worst affected side, close to the penumbra zone. Mean (glycerolmean) and maximal glycerol (glycerolmax) during the 96-h sampling period were calculated. The mean PR was calculated as the ICP/mean arterial pressure (MAP) regression coefficient based on hourly mean ICP and MAP during the first 96 h. RESULTS: Of the 48 included patients, 45 had valid glycerol and PR measurements available. PR was higher in the placebo group as compared to the prostacyclin group (p = 0.0164). There was a positive correlation between PR and the glycerolmean (ρ = 0.503, p = 0.01) and glycerolmax (ρ = 0.490, p = 0.015) levels in the placebo group only. CONCLUSIONS: PR is correlated to the glycerol level in patients suffering from sTBI, a relationship that is not seen in the group treated with prostacyclin. Glycerol has been associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular PR.

A study of the opinions of Swedish healthcare personnel regarding acceptable outcome following decompressive hemicraniectomy for ischaemic stroke.

BACKGROUND: Decompressive hemicraniectomy (DC) is an established lifesaving treatment for malignant infarction of the middle cerebral artery (mMCAI). However, surgical decompression will not reverse the effects of the stroke and many survivors will be left severely disabled. The objective of this study was to assess what neurological outcome would be considered acceptable in these circumstances amongst Swedish healthcare workers. METHOD: Healthcare workers were invited to participate in a presentation that outlined the pathophysiology of mMCAI, the rationale behind DC and outcome data from randomised controlled trials that have investigated efficacy of the procedure. They were then asked which neurological outcome would they feel to be acceptable based on the modified Rankin Score (mRS) and the Aphasia Handicap Scale (AHS). Information regarding sex, age, marital status, relatives, religion, earlier experience of stroke and occupation was also collected. RESULTS: Six hundred and nine persons participated. The median accepted mRS was 3. An mRS of 4 or 5 was perceived to be acceptable by only 30.5% of participants. Therefore the most likely outcome, based on the results of the randomised controlled trials, would be unacceptable to most of the participants [OR 0.39 (CI, 0.22-0.69)]. The median accepted AHS was 3. A worst language outcome of restricted autonomy of verbal communication (AHS 3) or better would be accepted by 44.6%. CONCLUSIONS: This study has highlighted the ethical problems when obtaining consent for DC following mMCAI, because for many of the participants the most likely neurological outcome would be deemed unacceptable. These issues need to be considered prior to surgical intervention and the time may have come for a broader societal discussion regarding the value of a procedure that converts death into survival with severe disability given the attendant financial and healthcare resource implications.

Aspects on the Physiological and Biochemical Foundations of Neurocritical Care.

Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood-brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

Comment on: Early CSF and serum S 100B concentrations for outcome prediction in traumatic brain injury and subarachoid haemorrhage.

BACKGROUND AND METHODS: In the letter the authors discuss the findings in Kellerman and co-worker's paper: Early CSF and Serum S 100B Concentrations for Outcome Prediction in Traumatic Brain Injury and Subarachoid Haemorrhage published in this journal. Among the findings reported in this paper is that an initial S 100B value of more than 0.7µg/l would strongly indicate a very poor prognosis. This finding is discussed. CONCLUSION: That a use of S 100B as a prognostic tool for clinical decision making is very doubtful and should most probably be refrained from.

Prostacyclin influences the pressure reactivity in patients with severe traumatic brain injury treated with an ICP-targeted therapy.

BACKGROUND: This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. METHODS: Blunt head trauma patients, Glasgow coma scale ≤8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR ≤0. RESULTS: Mean PR over 96 h (PRtot) was 0.077 ± 0.168, in the prostacyclin group 0.030 ± 0.153 and in the placebo group 0.120 ± 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 ± 0.182 in the unfavorable (GOSE 1-4) and 0.029 ± 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. CONCLUSIONS: Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.

Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury-a randomised clinical study.

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

Increased paired box transcription factor 8 has a survival function in glioma.

BACKGROUND: The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis. METHODS: PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression. RESULTS: Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death. CONCLUSIONS: PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.

The complications and the position of the Codman MicroSensor™ ICP device: an analysis of 549 patients and 650 Sensors.

BACKGROUND: Complications of and insertion depth of the Codman MicroSensor ICP monitoring device (CMS) is not well studied. OBJECTIVE: To study complications and the insertion depth of the CMS in a clinical setting. METHODS: We identified all patients who had their intracranial pressure (ICP) monitored using a CMS device between 2002 and 2010. The medical records and post implantation computed tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and insertion depth. RESULTS: In all, 549 patients were monitored using 650 CMS. Mean monitoring time was 7.0 ± 4.9 days. The mean implantation depth was 21.3 ± 11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these were less than 1 ml, and one was 8 ml. No clinically significant bleeding was found. There was no statistically significant increase in the number of hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and the calculated infection rate per 1,000 catheter days was 0.8. CONCLUSION: The risk for hemorrhagic and infectious complications when using the CMS for ICP monitoring is low. The depth of insertion varies considerably and should be taken into account if patients are treated with head elevation, since the pressure is measured at the tip of the sensor. To meet the need for ICP monitoring, an intraparenchymal ICP monitoring device should be preferred to the use of an external ventricular drainage (EVD).

Complications of vagal nerve stimulation for drug-resistant epilepsy: a single center longitudinal study of 143 patients.

PURPOSE: To longitudinally study surgical and hardware complications to vagal nerve stimulation (VNS) treatment in patients with drug-resistant epilepsy. METHODS: In a longitudinal retrospective study, we analyzed surgical and hardware complications in 143 patients (81 men and 62 women) who between 1994 and 2010 underwent implantation of a VNS-device for drug-resistant epilepsy. The mean follow-up time was 62 ± 46 months and the total number of patient years 738. RESULTS: 251 procedures were performed on 143 patients. 16.8% of the patients were afflicted by complications related to surgery and 16.8% suffered from hardware malfunctions. Surgical complications were: superficial infection in 3.5%, deep infection needing explantation in 3.5%, vocal cord palsy in 5.6%, which persisted in at least 0.7% for over one year, and other complications in 5.6%. Hardware-related complications were: lead fracture in 11.9% of patients, disconnection in 2.8%, spontaneous turn-off in 1.4% and stimulator malfunction in 1.4%. We noted a tendency to different survival times between the two most commonly used lead models as well as a tendency to increased infection rate with increasing number of stimulator replacements. CONCLUSION: In this series we report on surgical and hardware complications from our 16 years of experience with VNS treatment. Infection following insertion of the VNS device and vocal cord palsy due to damage to the vagus nerve are the most serious complications related to the surgery. Avoiding unnecessary reoperations in order to reduce the appearances of these complications are of great importance. It is therefore essential to minimize technical malfunctions that will lead to additional surgery. Further studies are needed to evaluate the possible superiority of the modified leads.

Use of the CRASH study prognosis calculator in patients with severe traumatic brain injury treated with an intracranial pressure-targeted therapy.

Based on the Corticosteroid Randomisation after Significant Head Injury (CRASH) trial database, a prognosis calculator has been developed for the prediction of outcome in an individual patient with a head injury. In 47 patients with severe traumatic brain injury (sTBI) prospectively treated using an intracranial pressure (ICP) targeted therapy, the individual prognosis for mortality at 14 days and unfavourable outcome at 6 months was calculated and compared with the actual outcome. An overestimation of the risk of mortality and unfavourable outcome was found. The mean risk for mortality and unfavourable outcome were estimated to be 44.6±32.5% (95% confidence interval [CI], 35.1-54.2%) and 69.3±23.7% (95% CI, 62.3-76.2%). The actual outcome was 4.3% and 42.6% respectively. The absolute risk reduction (ARR) for mortality was 33.1% and for unfavourable outcome 29.8%. A logistic fit for outcome at 6 months shows a statistically significant difference (p<0.01). A receiver operating characteristic (ROC) curve analysis shows an area under the curve (AUC) of 0.691. The CRASH prognosis calculator overestimates the risk of mortality and unfavourable outcome in patients with sTBI treated with an ICP-targeted therapy based on the Lund concept. We do not advocate the use of the calculator for treatment decisions in individual patients. We further conclude that patients with blunt sTBI admitted within 8 hours of trauma should be treated regardless of their clinical status as long as the initial cerebral perfusion pressure is >10 mmHg.

Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine.

OBJECTIVE: Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endothelial dysfunction. The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls. METHODS: A prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained 3 months later. A single blood sample for ADMA was collected from age- and sex-matched healthy controls (n = 40, two for each case). RESULTS: CRP increased significantly from day 2; 16 (Confidence interval (CI) 10-23) mg/L to day 4; 84 (CI 47-120) mg/L, (p < 0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17-0.27) µmol/L, to day 7; 0.37 (CI 0.21-0.54) µmol/L, p < 0.01. ADMA remained elevated at a 3-month follow-up: 0.36 (CI 0.31-0.42) µmol/L. ADMA in the first sample from the patients (day 1-3); 0.25 (CI 0.19-0.30) µmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20-0.31), p > 0.05. CONCLUSION: After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated 3 months later.

Frequency of non-convulsive seizures and non-convulsive status epilepticus in subarachnoid hemorrhage patients in need of controlled ventilation and sedation.

BACKGROUND: Non-convulsive seizures (NCSZ) can be more prevalent than previously recognized among comatose neuro-intensive care patients. The aim of this study was to evaluate the frequency of NCSZ and non-convulsive status epilepticus (NCSE) in sedated and ventilated subarachnoid hemorrhage (SAH) patients. METHODS: Retrospective study at a university hospital neuro-intensive care unit, from January 2008 until June 2010. Patients were treated according to a local protocol, and were initially sedated with midazolam or propofol or combinations of these sedative agents. Thiopental was added for treatment of intracranial hypertension. No wake-up tests were performed. Using NicoletOne(®) equipment (VIASYS Healthcare Inc., USA), continuous EEG recordings based on four electrodes and a reference electrode was inspected at full length both in a two electrode bipolar and a four-channel referential montage. RESULTS: Approximately 5,500 h of continuous EEG were registered in 28 SAH patients (33 % of the patients eligible for inclusion). The median Glasgow Coma scale was 8 (range 3-14) and the median Hunt and Hess score was 4 (range 1-4). During EEG registration, no clinical seizures were observed. In none of the patients inter ictal epileptiform activity was seen. EEG seizures were recorded only in 2/28 (7 %) patients. One of the patients experienced 4 min of an NCSZ and one had a 5 h episode of an NCSE. CONCLUSION: Continuous EEG monitoring is important in detecting NCSZ in sedated patients. Continuous sedation, without wake-up tests, was associated with a low frequency of subclinical seizures in SAH patients in need of controlled ventilation.