uu.seUppsala University Publications
Change search
Refine search result
12 1 - 50 of 63
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Extended anatomical grading in diffuse axonal injury using MRI: Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome2017In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 5, no 34, p. 341-352Article in journal (Refereed)
    Abstract [en]

    Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p  = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).

  • 2.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Intracranial pressure elevations in diffuse axonal injury are associated with non-hemorrhagic MR lesions in central mesencephalic structuresIn: Article in journal (Other academic)
    Abstract [en]

    Objective: Increased intracranial pressure (ICP) in severe traumatic brain injury (TBI) patients with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in DAI patients.

    Methods: Fifty-two severe TBI patients (median 24, range 9-61 years), with ICP-monitoring and DAI on MRI, using T2*-weighted gradient echo, susceptibility-weighted and diffusion-weighted (DW) sequences, were enrolled. Proportion of good monitoring time (GMT) with ICP>20 mmHg during the first 120 hours post-injury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression. 

    Results: All patients had episodes of ICP>20 mmHg. The mean proportion of GMT with ICP>20 mmHg was 5% and 27% of the patients (14/52) had more than 5% of GMT with ICP>20 mmHg. Glasgow Coma Scale motor score at admission (P=0.04) and lesions on DW images in the substantia nigra and mesencephalic tegmentum (SN-T, P=0.001) were associated with the proportion of GMT with ICP>20 mmHg. In multivariate linear regression, lesions on DW images in SN-T (8% of GMT with ICP>20 mmHg, 95% CI 3–13%, P=0.004) and young age (-0.2% of GMT with ICP>20 mmHg, 95% CI -0.07–-0.3%, P=0.0008) were associated with increased ICP.   

    Conclusions: Increased ICP occurs in ~1/3 of severe TBI patients with DAI. Age and lesions on DW images in the central mesencephalon (SN-T) associate with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in DAI patients.

  • 3.
    Blomquist, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ronne Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Gál, Gyula
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Grusell, Erik
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs)2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 1, p. 105-112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the brain has been performed in Uppsala since 1991. An earlier study based on the first 26 patients concluded that proton beam can be used for treating large and medium sized AVMs that were considered difficult to treat with photons due to the risk of side effects. In the present study we analyzed the result from treating the subsequent 65 patients.

    MATERIAL AND METHODS: A retrospective review of the patients' medical records, treatment protocols and radiological results was done. Information about gender, age, presenting symptoms, clinical course, the size of AVM nidus and rate of occlusion was collected. Outcome parameters were the occlusion of the AVM, clinical outcome and side effects.

    RESULTS: The rate of total occlusion was overall 68%. For target volume 0-2cm(3) it was 77%, for 3-10 cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress of the AVM had significantly smaller target volumes (p < 0.009) higher fraction dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The target volume was an independent predictor of total occlusion (p = 0.03). There was no difference between those with and without total occlusion regarding mean age, gender distribution or symptoms at diagnosis. Forty-one patients developed a mild radiation-induced brain edema and this was more common in those that had total occlusion of the AVM. Two patients had brain hemorrhages after treatment. One of these had no effect and the other only partial occlusion from proton beams. Two thirds of those presenting with seizures reported an improved seizure situation after treatment.

    CONCLUSION: Our observations agree with earlier results and show that proton beam irradiation is a treatment alternative for brain AVMs since it has a high occlusion rate even in larger AVMs.

  • 4.
    Borota, Ljubisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Mahmoud, Ehab
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyberg, Christoffer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dual lumen balloon catheter - An effective substitute for two single lumen catheters in treatment of vascular targets with challenging anatomy2018In: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 51, p. 91-99, article id S0967-5868(17)31621-1Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to describe our experience in the treatment of various pathological conditions of the cranial and spinal blood vessels and hypervascularized lesions using dual lumen balloon catheters. Twenty-five patients were treated with endovascular techniques: two with vasospasm of cerebral blood vessels caused by subarachnoid hemorrhage, one with a hypervascularized metastasis in the vertebral body, two with spinal dural fistula, four with cerebral dural fistula, three with cerebral arteriovenous malformations, and 13 with aneurysms. The dual lumen balloon catheters were used for remodeling of the coil mesh, injection of various liquid embolic agents, particles and nimodipine, for the prevention of reflux and deployment of coils and stents. The diameter of catheterized blood vessels varied from 0.7 mm to 4 mm. Two complications occurred: perforation of an aneurysm in one case and gluing of the tip of balloon catheter by embolic material in another case. All other interventions were uneventful, and therapeutic goals were achieved in all cases except in the case with gluing of the tip of balloon catheter. The balloons effectively prevented reflux regardless of the type of the embolic material and diameter of blood vessel. The results of our study show that dual lumen balloon catheters allow complex interventions in the narrow cerebral and spinal blood vessels where the safe use of two single lumen catheters is either limited or impossible.

  • 5. Chambers, I.
    et al.
    Gregson, B.
    Citerio, G.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kiening, K.
    Mattern, J.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Piper, Ian
    Ragauskas, A.
    Sahuquillo, J.
    Yau, Y. H.
    BrainIT collaborative network: analyses from a high time-resolution dataset of head injured patients2009In: Intracranial Pressure and Brain Monitoring XIII: Mechanisms and Treatment / [ed] Manley, Geoffrey; Hemphill, Claude; Stiver, Shirley, Vienna: Springer , 2009, Vol. 102, p. 223-227Chapter in book (Other academic)
  • 6.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Interstitial F2-Isoprostane 8-Iso-PGF As a Biomarker of Oxidative Stress after Severe Human Traumatic Brain Injury2012In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, no 5, p. 766-775Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is a major contributor to the secondary injury process after experimental traumatic brain injury (TBI). The importance of oxidative stress in the pathobiology of human TBI is largely unknown. The F(2)-isoprostane 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), synthesized in vivo through non-enzymatic free radical catalyzed peroxidation of arachidonic acid, is a widely used biomarker of oxidative stress in multiple disease states, including TBI and cerebral ischemia/reperfusion. Our hypothesis is that harvesting of biomarkers directly in the injured brain by cerebral microdialysis (MD) is advantageous because of its high spatial and temporal resolution compared to blood or cerebrospinal fluid sampling. The aim of this study was to test the feasibility of measuring 8-iso-PGF(2α) in MD, ventricular cerebrospinal fluid (vCSF), and plasma samples collected from patients with severe TBI, and to compare the MD signals with MD-glycerol, implicated as a biomarker of oxidative stress, as well as MD-glutamate, a biomarker of excitotoxicity. Six patients (4 men, 2 women) were included in the study, three of whom had a focal/mixed TBI, and three a diffuse axonal injury (DAI). Following the bedside analysis of routine MD biomarkers (glucose, lactate:pyruvate ratio, glycerol, and glutamate), two 12-h MD samples per day were used to analyze 8-iso-PGF(2α) from 24 h up to 8 days post-injury. The interstitial levels of 8-iso-PGF(2α) were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF(2α) levels correlated strongly (p<0.05) with MD-glycerol and MD-glutamate, which are widely used biomarkers of membrane phospholipid degradation/oxidative stress and excitotoxicity, respectively. This study demonstrates the feasibility of analyzing 8-iso-PGF(2α) in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF(2α) in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.

  • 7.
    Dahlin, Andreas P
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Purins, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Chu, Jiangtao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Refined microdialysis method for protein biomarker sampling in acute brain injury in the neurointensive care setting2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 17, p. 8671-8679Article in journal (Refereed)
    Abstract [en]

    There is growing interest in cerebral microdialysis (MD) for sampling of protein biomarkers in neurointensive care (NIC) patients. Published data point to inherent problems with this methodology including protein interaction and biofouling leading to unstable catheter performance. This study tested the in vivo performance of a refined MD method including catheter surface modification, for protein biomarker sampling in a clinically relevant porcine brain injury model. Seven pigs of both sexes (10-12 weeks old; 22.2-27.3 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure (ICP) and cerebral perfusion pressure was recorded during the stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 min) until brain death. One naïve MD catheter and one surface modified with Pluronic F-127 (10 mm membrane, 100 kDa molecular weight cutoff MD catheter) were inserted into the right frontal cortex and perfused with mock CSF with 3% Dextran 500 at a flow rate of 1.0 μL/min and 20 min sample collection. Naïve catheters showed unstable fluid recovery, sensitive to ICP changes, which was significantly stabilized by surface modification. Three of seven naïve catheters failed to deliver a stable fluid recovery. MD levels of glucose, lactate, pyruvate, glutamate, glycerol and urea measured enzymatically showed an expected gradual ischemic and cellular distress response to the intervention without differences between naïve and surface modified catheters. The 17 most common proteins quantified by iTRAQ and nanoflow LC-MS/MS were used as biomarker models. These proteins showed a significantly more homogeneous response to the ICP intervention in surface modified compared to naïve MD catheters with improved extraction efficiency for most of the proteins. The refined MD method appears to improve the accuracy and precision of protein biomarker sampling in the NIC setting.

  • 8.
    Edgren, E
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Enblad, P
    Department of Neuroscience.
    Grenvik, Å
    Lilja, A
    Valind, S
    Wiklund, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hedstrand, U
    Stiernstrom, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Persson, L
    Department of Neuroscience.
    Pontén, U
    Department of Neuroscience.
    Långström, B
    Cerebral blood flow and metabolism after cardiopulmonary resuscitation. A pathophysiologic and prognostic positron emission tomography pilot study.2003In: Resuscitation, Vol. 57, p. 161-Article in journal (Refereed)
  • 9.
    Elf, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care2002In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 30, no 9, p. 2129-2134Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate today's refined neurosurgical intensive care of patients with traumatic brain injury after implementation of an organized secondary insult program focused on the importance of avoiding secondary brain damage together with a standardized treatment protocol system.

    DESIGN: Clinical observational patient study.

    PATIENTS: A total of 154 patients 16-79 yrs of age with acute head trauma and pathologic computed tomographic findings treated between 1996 and 1997.

    SETTING: Neurointensive care unit.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Good recovery was obtained in 44% of the patients, moderate disability in 35%, severe disability in 16%, and no patient remained in a vegetative state. Six percent of the patients died, but only two of these patients (1.3%) died as direct result of their head injury. When the results for patients with Glasgow Coma Scale motor scores of >or=4 were compared with the periods 1980-1981 (preneurosurgical intensive care) and 1987-1988 (basic neurosurgical intensive care), mortality had decreased from 40% in the first period to 27% in the second period and to 2.8% in the present series. Favorable outcome in the same group of patients had increased steadily from 40% in the first period, to 68% in the second period, and finally, to 84% in the present series.

    CONCLUSIONS: The main observation in this hospital series of traumatic brain injury patients was a low rate of death directly caused by head injury and a high rate of favorable outcome. The comparison of patients with Glasgow Coma Scale motor scores of >or=4 with the previously reported results from the same unit indicate that substantial improvement in outcome has been achieved.

  • 10.
    Elf, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Prevention of secondary insults in neurointensive care of traumatic brain injury2003In: European Journal of Trauma, ISSN 1439-0590, E-ISSN 1615-3146, Vol. 29, no 2, p. 74-80Article in journal (Refereed)
    Abstract [en]

    Background: Secondary insults/complications have a major impact on the prognosis after traumatic brain injury (TBI). The aim was to study the occurrence and prognostic value of secondary insults occurring in TBI patients, during standardized neurointensive care (NIC) dedicated to avoiding secondary insults.

    Material and Methods: 154 patients, 17–79 years, with acute head trauma and pathologic CT, treated during a 2-year period at the NIC unit were studied. The occurrence of defined secondary insults (standard and severe) was recorded during the 1st week of NIC from bedside surveillance charts containing one value per hour and parameter (intracranial pressure, cerebral perfusion pressure, systolic blood pressure, PaO2, temperature, and blood glucose). The data set was analyzed using univariate and multivariate logistic regression with favorable outcome as the response variable. Both admission variables (Glasgow Coma Scale Motor Score [GCS M], CT class, Injury Severity Score [ISS], age, and gender) and secondary insult variables were included as explanatory variables.

    Results: In total, 1,570 insults were identified (320 severe). In the univariate analysis, the sum of all insults, blood glucose, GCS M, CT class, and ISS showed significant effects on outcome (p < 0.05). In the multiple regression analysis, GCS M was the only significant explanatory variable.

    Conclusions: The occurrence of secondary insults in the NIC unit was not negligible, despite the fact that major efforts were made to avoid them. The sum score of all insult categories and high blood glucose had a statistically significant effect on favorable outcome in the univariate analysis, but secondary insults did not add any prognostic information to the neurologic grade in the multivariate analysis. This finding indicates that the insults that occurred were related to the degree of primary injury/neurologic grade.

  • 11.
    Elf, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: A computerized secondary insult monitoring study2005In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 56, no 5, p. 962-971Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe the occurrence of secondary insults using a computerized monitoring data collecting system and to investigate their relationship to outcome when the neurointensive care was dedicated to avoiding secondary insults.

    METHODS: Patients 16 to 79 years old admitted to the neurointensive care unit between August 1998 and December 2002 with traumatic brain injury and 54 hours or more of valid monitoring within the first 120 hours after trauma (one value/min) were included. Monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), systolic blood pressure (BPs), and mean blood pressure (BPm) was required, and insult levels were defined (ICP >25/>35, BPs <100/<90/>160/>180, BPm <80/<70/>110/>120, and CPP <60/<50/>70/>80 mm Hg). Insults were quantified as proportion of valid monitoring time at the insult level. Logistic regression analyses were performed with admission and secondary insult variables as explanatory variables and favorable outcome as dependent variable.

    RESULTS: Eighty-one patients, 63 men and 18 women, with a mean age of 43.0 years, fulfilled the inclusion criteria. Seventy-two patients (89%) had Glasgow Coma Scale scores of 8 or less. Thirty-one patients (38%) had diffuse injury, and 50 (62%) had mass lesions. Mean Injury Severity Score was 26.6. After 6 months, 54% of the patients had achieved a favorable outcome. Most patients spent 5% or less of the monitoring time at the insult level except for CPP greater than 70 mm Hg. Low age, high Glasgow Coma Scale motor score, low Injury Severity Score, and CPP less than 60 mm Hg insults were significant predictors of favorable outcome in the final multiple logistic regression model.

    CONCLUSION: Overall, the secondary insults were rare, except for high CPP. The results suggest that patients with traumatic brain injury might benefit from a CPP slightly less than 60 mm Hg.

  • 12.
    Enblad, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Hesselager, Göran
    Department of Genetics and Pathology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Bongcam-Rudloff, Erik
    Department of Genetics and Pathology.
    Hallin, Inga
    Department of Genetics and Pathology.
    Westermark, Bengt
    Department of Genetics and Pathology.
    Nistér, Monica
    Department of Genetics and Pathology.
    Modulation of phenotype and induction of irregular vessels accompany high tumorigenic potential of clonal human glioma cells xenografted to nude-rat brain2000In: Int J Cancer, Vol. 85, p. 819-828Article in journal (Refereed)
  • 13.
    Engquist, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Response to "Letter to the Editor" by R. Dhar: Re: Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage2018In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 28, no 2, p. 259-259Article in journal (Other academic)
  • 14.
    Engquist, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Johnson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hemodynamic Disturbances in the Early Phase After Subarachnoid Hemorrhage: Regional Cerebral Blood Flow Studied by Bedside Xenon-enhanced CT.2018In: Journal of Neurosurgical Anesthesiology, ISSN 0898-4921, E-ISSN 1537-1921, Vol. 30, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The mechanisms leading to neurological deterioration and the devastating course of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) are still not well understood. Bedside xenon-enhanced computerized tomography (XeCT) enables measurements of regional cerebral blood flow (rCBF) during neurosurgical intensive care. In the present study, CBF characteristics in the early phase after severe SAH were explored and related to clinical characteristics and early clinical course outcome.

    MATERIALS AND METHODS: Patients diagnosed with SAH and requiring mechanical ventilation were prospectively enrolled in the study. Bedside XeCT was performed within day 0 to 3.

    RESULTS: Data from 64 patients were obtained. Median global CBF was 34.9 mL/100 g/min (interquartile range [IQR], 26.7 to 41.6). There was a difference in CBF related to age with higher global CBF in the younger patients (30 to 49 y). CBF was also related to the severity of SAH with lower CBF in Fisher grade 4 compared with grade 3. rCBF disturbances and hypoperfusion were common; in 43 of the 64 patients rCBF<20 mL/100 g/min was detected in more than 10% of the region-of-interest (ROI) area and in 17 patients such low-flow area exceeded 30%. rCBF was not related to the localization of the aneurysm; there was no difference in rCBF of ipsilateral compared with contralateral vascular territories. In patients who initially were in Hunt & Hess grade I to III, median global CBF day 0 to 3 was significantly lower for patients who were in poor neurological state at discharge compared with patients in good neurological state, 25.5 mL/100 g/min (IQR, 21.3 to 28.3) versus 37.8 mL/100 g/min (IQR, 30.5 to 47.6).

    CONCLUSIONS: CBF disturbances are common in the early phase after SAH. In many patients, CBF was heterogenic and substantial areas with low rCBF were detected. Age and CT Fisher grade were factors influencing global cortical CBF. Bedside XeCT may be a tool to identify patients at risk of deteriorating so they can receive intensified management, but this needs further exploration.

  • 15.
    Engquist, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT2018In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 28, no 2, p. 143-151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions.

    METHODS:

    Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0-3, 4-7, and 8-12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0-48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients.

    RESULTS:

    Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6-33.9) to 38.4 (IQR 27.0-41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time.

    CONCLUSIONS:

    HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.

  • 16.
    Fischerström, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Acute neurosurgery for traumatic brain injury by general surgeons in Swedish county hospitals: A regional study2014In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 156, no 1, p. 177-185Article in journal (Refereed)
    Abstract [en]

    Traditionally acute life-saving evacuations of extracerebral haematomas are performed by general surgeons on vital indication in county hospitals in the Uppsala-A-rebro health care region in Sweden, a region characterized by long distances and a sparsely distributed population. Recently, it was stated in the guidelines for prehospital care of traumatic brain injury from the Scandinavian Neurosurgical Society that acute neurosurgery should not be performed in smaller hospitals without neurosurgical expertise. The aim of this study was to investigate: how often does acute decompressive neurosurgery occur in county hospitals in the Uppsala-A-rebro region today, what is the indication for surgery, and what is the clinical outcome? Finally, the goal was to evaluate whether the current practice in the Uppsala-A-rebro region should be revised. Patients referred to the neurointensive care unit at the Department of Neurosurgery in Uppsala after acute evacuation of intracranial haematomas in the county hospitals 2005-2010 were included in the study. Data was collected retrospectively from the medical records following a predefined protocol. The presence of vital indication, radiological and clinical results, and long-term outcome were evaluated. A total of 49 patients (17 epidural haematomas and 32 acute subdural haematomas) were included in the study. The operation was judged to have been performed on vital indication in all cases. The postoperative CT scan was improved in 92 % of the patients. The reaction level and pupillary reactions were significantly improved after surgery. Long-term outcomes showed 51 % favourable outcome, 33 % unfavourable outcome, and in 16 % the outcome was unknown. Looking at the indication for acute neurosurgery, the postoperative clinical and radiological results, and the long-term outcome, it appears that our regional policy regarding life-saving decompressive neurosurgery in county hospitals by general surgeons should not be changed. We suggest a curriculum aimed at educating general surgeons in acute neurosurgery.

  • 17.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahlin, Andreas P
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Chu, Jiangtao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebral microdialysis for protein biomarker monitoring in the neurointensive care setting - a technical approach2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, p. 245-Article in journal (Refereed)
    Abstract [en]

    Cerebral microdialysis (MD) was introduced as a neurochemical monitoring method in the early 1990s and is currently widely used for the sampling of low molecular weight molecules, signaling energy crisis, and cellular distress in the neurointensive care (NIC) setting. There is a growing interest in MD for harvesting of intracerebral protein biomarkers of secondary injury mechanisms in acute traumatic and neurovascular brain injury in the NIC community. The initial enthusiasm over the opportunity to sample protein biomarkers with high molecular weight cut-off MD catheters has dampened somewhat with the emerging realization of inherent methodological problems including protein-protein interaction, protein adhesion, and biofouling, causing an unstable in vivo performance (i.e., fluid recovery and extraction efficiency) of the MD catheter. This review will focus on the results of a multidisciplinary collaborative effort, within the Uppsala Berzelii Centre for Neurodiagnostics during the past several years, to study the features of the complex process of high molecular weight cut-off MD for protein biomarkers. This research has led to new methodology showing robust in vivo performance with optimized fluid recovery and improved extraction efficiency, allowing for more accurate biomarker monitoring. In combination with evolving analytical methodology allowing for multiplex biomarker analysis in ultra-small MD samples, a new opportunity opens up for high-resolution temporal mapping of secondary injury cascades, such as neuroinflammation and other cell injury reactions directly in the injured human brain. Such data may provide an important basis for improved characterization of complex injuries, e.g., traumatic and neurovascular brain injury, and help in defining targets and treatment windows for neuroprotective drug development.

  • 18.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahlin, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Purins, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hjort, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    New Microdialysis Method for Protein Biomarker Sampling in the Neurointensive Care Setting2014In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, no 5, p. A22-A22Article in journal (Refereed)
  • 19.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nonischemic energy metabolic crisis in acute brain injury2008In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 36, no 10, p. 2952-2953Article in journal (Refereed)
  • 20.
    Howells, Tim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Elf, Kristin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Jones, Patricia
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Piper, Ian
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Andrews, Peter
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma2005In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 102, no 2, p. 311-317Article in journal (Refereed)
    Abstract [en]

    OBJECT: The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP).

    METHODS: A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently. The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean arterial blood pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow Outcome Scale (GOS). The prognostic value of secondary insults and pressure reactivity was determined using linear methods and a neural network. In patients treated according to the CPP-oriented protocol, even short durations of CPP insults were strong predictors of death. In patients treated according to the ICP-oriented protocol, even long durations of CPP insult-mostly in the range of 50 to 60 mm Hg--were significant predictors of favorable outcome (GOS Score 4 or 5). Among those who had undergone ICP-oriented treatment, pressure-passive patients (MABP/ICP slope > or = 0.13) had a better outcome. Among those who had undergone CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients had a better outcome.

    CONCLUSION: Based on data from this study, the authors concluded that ICP-oriented therapy should be used in patients whose slope of the MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients. If the slope is less than 0.13, then hypertensive CPP therapy is likely to produce a better outcome.

  • 21.
    Howells, Tim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Johnson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    McKelvey, Tomas
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    An optimal frequency range for assessing the pressure reactivity index in patients with traumatic brain injury2015In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 29, no 1, p. 97-105Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to identify the optimal frequency range for computing the pressure reactivity index (PRx). PRx is a clinical method for assessing cerebral pressure autoregulation based on the correlation of spontaneous variations of arterial blood pressure (ABP) and intracranial pressure (ICP). Our hypothesis was that optimizing the methodology for computing PRx in this way could produce a more stable, reliable and clinically useful index of autoregulation status. The patients studied were a series of 131 traumatic brain injury patients. Pressure reactivity indices were computed in various frequency bands during the first 4 days following injury using bandpass filtering of the input ABP and ICP signals. Patient outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The optimization criterion was the strength of the correlation with GOSe of the mean index value over the first 4 days following injury. Stability of the indices was measured as the mean absolute deviation of the minute by minute index value from 30-min moving averages. The optimal index frequency range for prediction of outcome was identified as 0.018-0.067 Hz (oscillations with periods from 55 to 15 s). The index based on this frequency range correlated with GOSe with rho = -0.46 compared to -0.41 for standard PRx, and reduced the 30-min variation by 23 %.

  • 22.
    Howells, Tim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Johnson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    McKelvey, Tomas
    Chalmers, Dept Signals & Syst, Gothenburg, Sweden..
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The effects of ventricular drainage on the intracranial pressure signal and the pressure reactivity index2017In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, no 2, p. 469-478Article in journal (Refereed)
    Abstract [en]

    In subarachnoid hemorrhage (SAH) patients intracranial pressure (ICP) is usually monitored via an extraventricular drain (EVD), which can produce false readings when the drain is open. It is established that both the ICP cardiac pulse frequency and long term trends over several hours are often seriously corrupted. The aim of this study was to establish whether or not the intermediate frequency bands [respiratory, Mayer wave and very low frequency (VLF)] were also corrupted. The VLF range is of special interest because it is important in cerebral autoregulation studies. Using a pattern recognition algorithm we retrospectively identified 718 cases of EVD opening in 80 SAH patients. An analysis of differences between closed and open-drain periods showed that ICP amplitude decreased significantly in all of the three lower frequency bands when the EVD was open. A similar analysis of systemic arterial pressure signal revealed similar changes in the same frequency bands that were positively correlated with the ICP changes. Therefore we concluded that the changes in the ICP signal represented real, physiological changes and not artifact. Pressure reactivity index (PRx) values were also computed during closed and open-drain periods. We found a small but statistically significant decrease during open-drain periods. Based on analysis of the change in the PRx distribution during open drainage we concluded that this decrease also represented physiological changes rather than artifact. In summary the ICP respiratory, Mayer wave, and VLF frequency bands are not corrupted when the EVD is open, and it safe to use these for autoregulation studies.

  • 23.
    Howells, Tim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    An evaluation of three measures of intracranial compliance in traumatic brain injury patients2012In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, no 6, p. 1061-1068Article in journal (Refereed)
    Abstract [en]

    To compare intracranial pressure (ICP) amplitude, ICP slope, and the correlation of ICP amplitude and ICP mean (RAP index) as measures of compliance in a cohort of traumatic brain injury (TBI) patients. Mean values of the three measures were calculated in the 2-h periods before and after surgery (craniectomies and evacuations), and in the 12-h periods preceding and following thiopental treatment, and during periods of thiopental coma. The changes in the metrics were evaluated using the Wilcoxon test. The correlations of 10-day mean values for the three metrics with age, admission Glasgow Motor Score (GMS), and Extended Glasgow Outcome Score (GOSe) were evaluated. Patients under and over 60 years old were also compared using the Student test. The correlation of ICP amplitude with systemic pulse amplitude was analyzed. ICP amplitude was significantly correlated with GMS, and also with age for patients 35 years old and older. The correlations of ICP slope and the RAP index with GMS and with age were not significant. All three metrics indicated significant improvements in compliance following surgery and during thiopental coma. None of the metrics were significantly correlated with outcome, possibly due to confounding effects of treatment factors. The correlation of systemic pulse amplitude with ICP amplitude was low ( = 0.18), only explaining 3 % of the variance. This study provides further validation for all three of these features of the ICP waveform as measures of compliance. ICP amplitude had the best performance in these tests.

  • 24.
    Howells, Tim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Smielewski, Peter
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Donnelly, Joseph
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Czosnyka, Marek
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England.;Warsaw Univ Technol, Inst Elect Syst, Warsaw, Poland..
    Hutchinson, Peter J. A.
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Menon, David K.
    Univ Cambridge, Addenbrookes Hosp, Div Anaesthesia, Cambridge, England..
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Aries, Marcel J. H.
    Maastricht Univ, Med Ctr, Dept Crit Care, Maastricht, Netherlands..
    Optimal Cerebral Perfusion Pressure in Centers With Different Treatment Protocols2018In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, no 3, p. e235-e241Article in journal (Refereed)
    Abstract [en]

    Objectives: The three centers in this study have different policies regarding cerebral perfusion pressure targets and use of vasopressors in traumatic brain injury patients. The aim was to determine if the different policies affected the estimation of cerebral perfusion pressure which optimizes the strength of cerebral autoregulation, termed "optimal cerebral perfusion pressure." Design: Retrospective analysis of prospectively collected data. Setting: Three neurocritical care units at university hospitals in Cambridge, United Kingdom, Groningen, the Netherlands, and Uppsala, Sweden. Patients: A total of 104 traumatic brain injury patients were included: 35 each from Cambridge and Groningen, and 34 from Uppsala. Interventions: None. Measurements and Main Results: In Groningen, the cerebral perfusion pressure target was greater than or equal to 50 and less than 70mm Hg, in Uppsala greater than or equal to 60, and in Cambridge greater than or equal to 60 or preferably greater than or equal to 70. Despite protocol differences, median cerebral perfusion pressure for each center was above 70mm Hg. Optimal cerebral perfusion pressure was calculated as previously published and implemented in the Intensive Care Monitoring+ software by the Cambridge group, now replicated in the Odin software in Uppsala. Periods with cerebral perfusion pressure above and below optimal cerebral perfusion pressure were analyzed, as were absolute difference between cerebral perfusion pressure and optimal cerebral perfusion pressure and percentage of monitoring time with a valid optimal cerebral perfusion pressure. Uppsala had the highest cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Uppsala patients were older than the other centers, and age is positively correlated with cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Optimal cerebral perfusion pressure was significantly lower in Groningen than in Cambridge. There were no significant differences in percentage of monitoring time with valid optimal cerebral perfusion pressure. Summary optimal cerebral perfusion pressure curves were generated for the combined patient data for each center. These summary curves could be generated for Groningen and Cambridge, but not Uppsala. The older age of the Uppsala patient cohort may explain the absence of a summary curve. Conclusions: Differences in optimal cerebral perfusion pressure calculation were found between centers due to demographics (age) and treatment (cerebral perfusion pressure targets). These factors should be considered in the design of trials to determine the efficacy of autoregulation-guided treatment.

  • 25.
    Jansson, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Efficacy and safety of cefotaxime in combination with metronidazole for empirical treatment of brain abscess in clinical practice: a retrospective study of 66 consecutive cases2004In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 23, no 1, p. 7-14Article in journal (Refereed)
  • 26.
    Johansson, Mats
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Norbäck, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Gal, G
    Department of Oncology, Radiology and Clinical Immunology. Neuroröntgen.
    Cesarini, Kristina G.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Tovi, Metin
    Department of Oncology, Radiology and Clinical Immunology.
    Solander, Sten
    Department of Oncology, Radiology and Clinical Immunology.
    Contant, Charlie
    Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Enblad, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Clinical outcome after endovascular coil embolization in elderly patients with subarachnoid hemorrhage2004In: Neuroradiology: Interventional Neuroradiology, Vol. 46, p. 385-391Article in journal (Refereed)
  • 27.
    Johnson, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP2017In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, no 6, p. 1065-1071Article in journal (Refereed)
    Abstract [en]

    Background Cerebral pressure autoregulation can be quantified with the pressure reactivity index (PRx), based on the correlation between blood pressure and intracranial pressure. Using PRx optimal cerebral perfusion pressure (CPPopt) can be calculated, i.e., the level of CPP where autoregulation functions best. The relation between cerebral blood flow (CBF) and CPPopt has not been examined. The objective was to assess to which extent CPPopt can be calculated in SAH patients and to investigate CPPopt in relation to CBF.

    Methods Retrospective study of prospectively collected data. CBF was measured bedside with Xenon-enhanced CT (Xe-CT). The difference between actual CPP and CPPopt was calculated (CPPa dagger). Correlations between CPPa dagger and CBF parameters were calculated with Spearman's rank order correlation coefficient (rho). Separate calculations were done using all patients (day 0-14 after onset) as well as in two subgroups (day 0-3 and day 4-14).

    Results Eighty-two patients with 145 Xe-CT scans were studied. Automated calculation of CPPopt was possible in adjunct to 60% of the Xe-CT scans. Actual CPP < CPPopt was associated with higher numbers of low-flow regions (CBF < 10 ml/100 g/min) in both the early phase (day 0-3, n = 39, Spearman's rho = -0.38, p = 0.02) and late acute phase of the disease (day 4-14, n = 35, Spearman's rho = -0.39, p = 0.02). CPP level per se was not associated with CBF.

    Conclusions Calculation of CPPopt is possible in a majority of patients with severe SAH. Actual CPP below CPPopt is associated with low CBF.

  • 28.
    Johnson, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?2014In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, no 2, p. 259-265Article in journal (Refereed)
    Abstract [en]

    The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes. 107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to "diffuse" (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or "focal" (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 x 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP. Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx > 0.1), CPP > 70 mmHg was associated with better outcome (p = 0.03). TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.

  • 29.
    Lenell, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Updated periodic evaluation of standardized neurointensive care shows that it is possible to maintain a high level of favorable outcome even with increasing mean age2015In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 157, no 3, p. 417-425Article in journal (Refereed)
    Abstract [en]

    Periodic evaluation of neurointensive care (NIC) is important. There is a risk that quality of daily care declines and there may also be unrecognized changes in patient characteristics and management. The aim of this work was to investigate the characteristics and outcome for traumatic brain injury (TBI) patients in the period 2008-2009 in comparison with 1996-1997 and to some extent also with earlier periods. TBI patients 16-79 years old admitted from 2008 to 2009 were selected for the study. Glasgow Coma Scale Motor score at admission (GCS M), radiology, surgery, and outcome (Glasgow Outcome Extended Scale) were collected from Uppsala Traumatic Brain Injury Register. The study included 148 patients (mean age, 45 years). Patients > 60 years old increased from 16 % 1996-1997 to 30 % 2008-2009 (p < 0.01). The proportion of GCS M 4-6 were similar, 92 vs. 93 % (NS). In 1996-1997 patients, 73 % had diffuse injury (Marshall classification) compared to 77 % for the 2008-2009 period (NS). More patients underwent surgery during 2008-2009 (43 %) compared to 1996-1997 (32 %, p < 0.05). Good recovery increased and mortality decreased substantially from 1980-1981 to 1987-1988 and to 1996-1997, but then the results were unchanged in the 2008-2009 period, with 73 % favorable outcome and 11 % mortality. Mortality increased in GCS M 6-4, from 2.8 % in 1996-1997 to 10 % in 2008-2009 (p < 0.05); most of the patients that died had aggravating factors, e.g., high age, malignancy. A large-proportion favorable outcome was maintained despite that patients > 60 years with poorer prognosis doubled, indicating that the quality of NIC has increased or at least is unchanged. More surgery may have contributed to maintaining the large proportion of favorable outcome. For future improvements, more knowledge about TBI management in the elderly is required.

  • 30.
    Ljunghill Hedberg, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Söderberg, Jessika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Johansson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Kayhty, Helena
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Pneumococcal polysaccharide vaccination administered early after neurotrauma or neurosurgery2017In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, no 6, p. 909-915Article in journal (Refereed)
    Abstract [en]

    Objectives: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). Methods: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10 days after neurotrauma or neurosurgery. Twenty-nine neurosurgical patients vaccinated >= 3 weeks after neurotrauma or neurosurgery served as controls. Serotype-specific anti-polysaccharide binding IgG antibody levels to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme immunoassay. Results: The vaccination was safe and a highly significant antibody response was found against all serotypes in all groups (p < 0.001 for each of the serotypes). There were no differences between groups or in the group by time interaction in any of the serotypes. After early and late vaccination, protective levels were found in >80% for serotypes 9V, 14, 18C, 19F and 23F and in 70% and 50% for serotypes 6B and 4, respectively. Conclusion: Patients vaccinated with PPSV within 10 days after neurotrauma or neurosurgery respond similarly to those vaccinated after >= 3 weeks, indicating that PPSV can be administered early after neurotrauma or neurosurgery.

  • 31.
    Magnéli, Sara
    et al.
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Howells, Timothy
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Saiepour, Daniel
    Univ Uppsala Hosp, Dept Plast Surg, S-75185 Uppsala, Sweden.
    Nowinski, Daniel
    Univ Uppsala Hosp, Dept Plast Surg, S-75185 Uppsala, Sweden.
    Enblad, Per
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Nilsson, Pelle
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Telemetric intracranial pressure monitoring: a noninvasive method to follow up children with complex craniosynostoses. A case report2016In: Child's nervous system (Print), ISSN 0256-7040, E-ISSN 1433-0350, Vol. 32, no 7, p. 1311-1315Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There are no reliable noninvasive methods of monitoring ICP. Most assessments are made by indirect measures and are difficult to follow over time. Invasive studies can be used but up until now have required in-hospital transcutaneous measurements. Accurate ICP recordings over longer periods of time can be very valuable in timing different surgical procedures in syndromal cases. This case shows that telemetric ICP monitoring can be used for long-term follow-up in patients that may need repeated surgeries related to their craniosynostosis condition.

    CASE REPORT: In this report, the telemetric ICP probe (Raumedic Neurovent-P-tel) was implanted before surgery and was used for repeated "noninvasive" ICP recordings pre- and postoperatively in a patient with craniosynostosis. The patient was an eight-year-old girl with pansynostosis with only the right lambdoid suture open. A telemetric ICP probe was implanted the day before cranial vault remodeling and the ICP was monitored pre- and postoperatively. The ICP was above 15 mmHg 72.2 % of the monitoring time before surgery, and the amplitude of the curve was greater than normal suggesting impaired compliance. Direct postoperative ICP was normal, and the amplitude was lower. The ICP was then monitored both in out-patient clinic and in four longer hospital stays. Both the values and the curves were analyzed, and the time with ICP above 15 mmHg decreased over time, and the waveform amplitude of the curves improved.

    CONCLUSION: This "noninvasive" way of recording ICP is a feasible and helpful tool in decision-making and intervening in patients with craniosynostosis.

  • 32.
    Marklund, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Farrokhnia, Nina
    Hanell, Anders
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterberg, Henrik
    Blennow, Kaj
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Monitoring of amyloid-beta dynamics after human traumatic brain injury2012In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, no 10, p. A185-A185Article in journal (Other academic)
  • 33.
    Marklund, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Farrokhnia, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hånell, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Vanmechelen, Eugeen
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterberg, Henrik
    Blennow, Kaj
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Monitoring of beta-Amyloid Dynamics after Human Traumatic Brain Injury2014In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, no 1, p. 42-55Article in journal (Refereed)
    Abstract [en]

    Epidemiological evidence links severe or repeated traumatic brain injury (TBI) to the development of Alzheimer's disease (AD). Accumulation of amyloid precursor protein (APP) occurs with high frequency after TBI, particularly in injured axons, and APP may be cleaved to amyloid- (A) peptides playing key pathophysiological roles in AD. We used cerebral microdialysis (MD) to test the hypothesis that interstitial A levels are altered following TBI and are related to the injury type, cerebral energy metabolism, age of the patient, and level of consciousness. In the present report, we evaluated 10 mechanically ventilated patients (7 male, 3 female, ages 18-76 years) with a severe TBI, who had intracranial pressure and MD monitoring. Each MD sample was analyzed for hourly routine energy metabolic biomarkers (MD-lactate, MD-pyruvate, MD-glucose, and MD-lactate/pyruvate ratio), cellular distress biomarkers (MD-glutamate, MD-glycerol), and MD-urea. The remaining MD samples were analyzed for A1-40 (A40; n=765 samples) and A1-42 (A42; n=765 samples) in pooled 2h fractions up to 14 days post-injury, using the Luminex xMAP technique, allowing detection with high temporal resolution of the key A peptides A40 and A42. Data are presented using medians and 25th and 75th percentiles. Both A40 and A42 were consistently higher in patients with predominately diffuse axonal injury compared with patients with focal TBI at days 1-6 post- injury, A42 being significantly increased at 113-116h post-injury (p<0.05). The A levels did not correlate with the interstitial energy metabolic situation, age of the patient, or the level of consciousness. These results support that interstitial generation of potentially toxic A species may occur following human TBI, particularly related to axonal injury.

  • 34.
    Merzo, Abraham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lenell, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Promising clinical outcome of elderly with TBI after modern neurointensive care2016In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 158, no 1, p. 125-133Article in journal (Refereed)
    Abstract [en]

    The increasing number of elderly patients with traumatic brain injury (TBI) leads to specific neurointensive care (NIC) challenges. Therefore, elderly subjects with TBI need to be further studied. In this study we evaluated the demographics, management and outcome of elderly TBI patients receiving modern NIC. Patients referred to our NIC unit between 2008 and 2010 were included. Patients were divided in two age groups, elderly (E) a parts per thousand yen65 years and younger (Y) 64-15 years. Parameters studied were the dominant finding on CT scans, neurological motor skills and consciousness, type of monitoring, neurosurgical procedures/treatments and Glasgow Outcome Scale Extended score at 6 months after injury. Sixty-two E (22 %) and 222 Y (78 %) patients were included. Falls were more common in E (81 %) and vehicle accidents were more common in Y patients (37 %). Acute subdural hematoma was significantly more common in E (50 % of cases) compared to Y patients (18 %). Intracranial pressure was monitored in 44 % of E and 57 % of Y patients. Evacuation of significant mass lesions was performed more common in the E group. The NIC mortality was similar in both groups (4-6 %). Favorable outcome was observed in 72 % of Y and 51 % of E patients. At the time of follow-up 25 % of E and 7 % of Y patients had died. The outcome of elderly patients with TBI was significantly worse than in younger patients, as expected. However, as much as 51 % of the elderly patients showed a favorable outcome after NIC. We believe that these results encourage modern NIC in elderly patients with TBI. We need to study how secondary brain injury mechanisms differ in the older patients and to identify specific outcome predictors for elderly patients with TBI.

  • 35.
    Mogensen, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lubenow, Norbert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Knutson, Folke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nowinski, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery2017In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 27, no 7, p. 711-717Article in journal (Refereed)
    Abstract [en]

    Background: Surgical correction for craniosynostosis is often associated with significant perioperative hemorrhage. We implemented a transfusion strategy with a strict protocol including transfusion triggers, frequent assessment of coagulation tests, and the use of a novel transfusion unit, the mixed pediatric unit. Aim: The aim of the study was to evaluate if the applied transfusion strategy could reduce total blood loss and number of blood donors. Methods: Children <1 year old admitted for craniosynostosis surgery were included for the study. On the day before surgery, an adult red blood cell unit was mixed with plasma and split into two mixed pediatric units-one intended for intraoperative use and the other saved for the postoperative period. A series of blood samples were obtained for standard coagulation parameters as well as thromboelastography to evaluate potential coagulopathy. Estimated blood loss, the number of additional standard packed red cell units opened in the first 24 h after surgery, the volume of fluid administered, and the total transfusion volumes were compared to a historical control group with similar age and characteristics. Results: Nineteen infants were included in the study group, and were compared to 21 historical controls. There was a significant reduction of intraoperative transfusion volume. Twelve patients were transfused postoperatively, but in 8 of these additional exposure to packed red cell donor blood was avoided by using the saved mixed pediatric unit. In the historical controls, a total of 10 packed red cell units were used in nine patients postoperatively. No additional transfusions of plasma, platelets, fibrinogen, or tranexamic acid were needed in either group, and the coagulation parameters including thromboelastography remained within their respective normal ranges in the study group. Conclusion: For craniofacial surgery in infants, moderate perioperative blood loss and avoidance of coagulopathy is possible when a multifactorial approach is implemented. In this setting, intraoperative, but not total perioperative blood loss was reduced with the studied protocol. The study indicates that there may be a role for mixed pediatric units to reduce exposure to multiple donors although the reduction in total donor exposure was not significant.

  • 36.
    Nowinski, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Saiepour, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Leikola, Junnu
    Messo, Elias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Posterior cranial vault expansion performed with rapid distraction and time-reduced consolidation in infants with syndromic craniosynostosis2011In: Child's nervous system (Print), ISSN 0256-7040, E-ISSN 1433-0350, Vol. 27, no 11, p. 1999-2003Article in journal (Refereed)
  • 37.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Predictive Factors That May Contribute to Secondary Insults With Nursing Interventions in Adults With Traumatic Brain Injury2017In: Journal of Neuroscience Nursing, ISSN 0888-0395, E-ISSN 1945-2810, Vol. 49, no 1, p. 49-55Article in journal (Refereed)
    Abstract [en]

    Background: Nursing interventions pose risks and benefits to patients with traumatic brain injury at a neurointensive care unit. Objectives: The aim of this study was to investigate the risk of inducing high intracranial pressure (ICP) related to interventions and whether intracranial compliance, baseline ICP, or autoregulation could be used as predictors. Methods: The study had a quantitative, prospective, observational design. Twenty-eight patients with TBI were included, and 67 interventions were observed. The definition of a secondary ICP insult was ICP of 20 mm Hg or greater for 5 minutes or more within a continuous 10-minute period. Results: Secondary ICP insults related to nursing interventions occurred in 6 patients (21%) and 8 occasions (12%). Patients with baseline ICP of 15 mm Hg or greater had 4.7 times higher risk of developing an insult. The predictor with the best combination of sensitivity and specificity was baseline ICP. Conclusions: Baseline ICP of 15 mm Hg or greater was the most important factor to determine the risk of secondary ICP insult related to nursing intervention.

  • 38.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Introduction of the Uppsala Traumatic Brain Injury register for regular surveillance of patient characteristics and neurointensive care management including secondary insult quantification and clinical outcome2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 3, p. 169-180Article in journal (Refereed)
    Abstract [en]

    Background. To improve neurointensive care (NIC) and outcome for traumatic brain injury (TBI) patients it is crucial to define and monitor indexes of the quality of patient care. With this purpose we established the web-based Uppsala TBI register in 2008. In this study we will describe and analyze the data collected during the first three years of this project. Methods. Data from the medical charts were organized in three columns containing: 1) Admission data; 2) Data from the NIC period including neurosurgery, type of monitoring, treatment, complications, neurological condition at discharge, and the amount of secondary insults; 3) Outcome six months after injury. Indexes of the quality of care implemented include: 1) Index of improvement; 2) Index of change; 3) The percentages of 'Talk and die' and `Talk and deteriorate' patients. Results. Altogether 314 patients were included 2008-2010: 66 women and 248 men aged 0-86 years. Automatic reports showed that the proportion of patients improving during NIC varied between 80% and 60%. The percentage of deteriorated patients was less than 10%. The percentage of Talk and die/Talk and deteriorate cases was <1%. The mean Glasgow Coma Score (Motor) improved from 5.04 to 5.68 during the NIC unit stay. The occurrences of secondary insults were less than 5% of good monitoring time for intracranial pressure (ICP) >25 mmHg, cerebral perfusion pressure (CPP) <50 mmHg, and systolic blood pressure <100 mmHg. Favorable outcome was achieved by 64% of adults. Conclusion. The Uppsala TBI register enables the routine monitoring of NIC quality indexes.

  • 39.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 3, p. 177-184Article in journal (Refereed)
    Abstract [en]

    Background: Hyperthermia is a common secondary insult in traumatic brain injury (TBI). The aim was to evaluate the relationship between hyperthermia and intracranial pressure (ICP), and if intracranial compliance and cerebral blood flow (CBF) pressure autoregulation affected that relationship. The relationships between hyperthermia and cerebral oximetry (B(ti)pO(2)) and cerebral metabolism were also studied. Methods: A computerized multimodality monitoring system was used for data collection at the neurointensive care unit. Demographic and monitoring data (temperature, ICP, blood pressure, microdialysis, B(ti)pO(2)) were analyzed from 87 consecutive TBI patients. ICP amplitude was used as measure of compliance, and CBF pressure autoregulation status was calculated using collected blood pressure and ICP values. Mixed models and comparison between groups were used. Results: The influence of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and B(ti)pO(2)) was small, but individual differences were seen. Linear mixed models showed that hyperthermia raises ICP slightly more when temperature increases in the groups with low compliance and impaired CBF pressure autoregulation. There was also a tendency (not statistically significant) for increased B(ti)pO(2), and for increased pyruvate and lactate, with higher temperature, while the lactate/pyruvate ratio and glucose were stable. Conclusions: The major finding was that the effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and B(ti)pO(2)) were not extensive in general, but there were exceptional cases. Hyperthermia treatment has many side effects, so it is desirable to identify cases in which hyperthermia is dangerous. Information from multimodality monitoring may be used to guide treatment in individual patients.

  • 40.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Fröjd, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The use of nurse checklists in a bedside computer-based information system to focus on avoiding secondary insults in neurointensive care2012In: ISRN Neurology, ISSN 2090-5505, E-ISSN 2090-5513, Vol. 2012, p. 903954-Article in journal (Refereed)
    Abstract [en]

    The feasibility and accuracy of using checklists after every working shift in a bedside computer-based information system for documentation of secondary insults in the neurointensive care unit were evaluated. The ultimate goal was to get maximal attention to avoid secondary insults. Feasibility was investigated by assessing if the checklists were filled in as prescribed. Accuracy was evaluated by comparing the checklists with recorded minute-by-minute monitoring data for intracranial pressure-ICP, cerebral perfusion pressure CPP, systolic blood pressure SBP, and temperature. The total number of checklist assessments was 2,184. In 85% of the shifts, the checklists were filled in. There was significantly longer duration of monitoring time at insult level when Yes was filled in regarding ICP (mean 134 versus 30 min), CPP (mean 125 versus 26 min) and temperature (mean 315 versus 120 min). When a secondary insult was defined as >5% of monitoring time spent at insult level, the sensitivity/specificity for the checklist assessments was 31%/100% for ICP, 38%/99% for CPP, and 66%/88% for temperature. Checklists were feasible and appeared relatively accurate. Checklists may elevate the alertness for avoiding secondary insults and help in the evaluation of the patients. This concept may be the next step towards tomorrow critical care.

  • 41.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Steffansson, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Fröjd, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Secondary insults related to nursing interventions in neurointensive care: a descriptive pilot study2014In: Journal of Neuroscience Nursing, ISSN 0888-0395, E-ISSN 1945-2810, Vol. 46, no 5, p. 285-291Article in journal (Refereed)
    Abstract [en]

    The patients at a neurointensive care unit are frequently cared for in many ways, day and night. The aim of this study was to investigate the amount of secondary insults related to oral care, repositioning, endotracheal suctioning, hygienic measures, and simultaneous interventions at a neurointensive care unit with standardized care and maximum attention on avoiding secondary insults. The definition of a secondary insult was intracranial pressure > 20 mm Hg, cerebral perfusion pressure < 60 mm Hg and systolic blood pressure < 100 mm Hg for 5 minutes or more in a 10-minute period starting from when the nursing intervention began. The insult minutes did not have to be consecutive. The study included 18 patients, seven women and 11 men, aged 36-76 years with different neurosurgical diagnoses. The total number of nursing interventions analyzed was 1,717. The most common kind of secondary insults after a nursing measure was high intracranial pressure (n = 93) followed by low cerebral perfusion pressure (n = 43) and low systolic blood pressure (n = 14). Repositioning (n = 39) and simultaneous interventions (n = 32) were the nursing interventions causing most secondary insults. There were substantial variations between the patients; only one patient had no secondary insult. There were, overall, a limited number of secondary insults related to nursing interventions when a standardized management protocol system was applied to reduce the occurrence of secondary insults. Patients with an increased risk of secondary insults should be recognized, and their care and treatment should be carefully planned and performed to avoid secondary insults.

  • 42.
    Purins, Karlis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model2012In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 16, no 3, p. 462-469Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B(ti)pO(2)) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30).

    METHODS:

    B(ti)pO(2), L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved.

    RESULTS:

    Baseline level of B(ti)pO(2) was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B(ti)pO(2) and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B(ti)pO(2) to <10 mmHg.

    CONCLUSIONS:

    A severe increase of ICP leading to CPP below 30 mmHg and B(ti)pO(2) below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.

  • 43.
    Purins, Karlis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 64Article in journal (Refereed)
    Abstract [en]

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

    Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

    Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

    Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

  • 44.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kothimbakam, Raj
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Outcome from spontaneous subarachnoid haemorrhage: results from 2007-2011 and comparison with our previous series2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 1, p. 38-43Article in journal (Refereed)
    Abstract [en]

    Objectives

    The management of patients with spontaneous subarachnoid haemorrhage (SAH) has changed, in part due to interventions now being extended to patients who are older and in a worse clinical condition. This study evaluates the effects of these changes on a complete 5-year patient material.

    Methods

    Demographic data and results from 615 patients with SAH admitted from 2007 to 2011 were put together. Aneurysms were found in 448 patients (72.8%). They were compared with the aneurysm group (n = 676) from a previously published series from our centre (2001-2006). Linear regression was used to determine variables predicting functional outcome in the whole aneurysm group (2001-2011).

    Results

    Patients in the more recent aneurysm group were older, and they were in a worse clinical condition on admission. Regarding younger patients admitted in World Federation of Neurosurgical Societies SAH grading (WFNS) 3, there were fewer with a good outcome. In the whole aneurysm group 2001-2011, outcome was best predicted by age, clinical condition at admission, and the size of the bleeding, and not by treatment mode or localization of aneurysm.

    Conclusion

    It seems important for the outcome that aneurysms are treated early. The clinical course after that depends largely on the condition of the patient on admission rather than on aneurysm treatment method. This, together with the fact that older patients and those in worse condition are now being admitted, increases demands on neurointensive care. Further improvement in patient outcome depends on better understanding of acute brain injury mechanisms and improved neurointensive care as well as rehabilitation measures.

  • 45.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Outcome After Spontaneous Subarachnoid Hemorrhage Measured With the EQ-5D2011In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 42, no 11, p. 3284-3286Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The EQ-5D measures quality of life based on self-reported health status in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In this study, the EQ-5D was evaluated as an outcome measure for patients with subarachnoid hemorrhage.

    METHODS: The EQ-5D was completed in 710 patients 9 months after subarachnoid hemorrhage. Relevant demographic and clinical factors were evaluated as predictors of the 5 outcome dimensions in a series of linear regression models.

    RESULTS: Worse health status in mobility, self-care, and usual activities was predicted by increasing age and by a more severe disease as indicated by the presence of an aneurysm, worse clinical condition at admission, or more blood on the CT scan. Younger age and female gender predicted worse health status regarding anxiety/depression. '

    CONCLUSIONS: The evaluation of the EQ-5D reveals age-related differences in the nature of the challenges faced by these patients.

  • 46.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Health-related quality of life at median 12 months after aneurysmal subarachnoid hemorrhage, measured with EuroQoL-5D2013In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, no 4, p. 587-593Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    A measurement of quality of life (QoL) should cover the important aspects of daily life and be easy to perform. Ease of performance is especially important for patients with spontaneous subarachnoid haemorrhage (SAH), since fatigue and cognitive disabilities are known sequeles. EuroQoL (EQ-5D) is a preference-based instrument measuring QoL, based on self-reported health status in five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort and Anxiety/Depression. In the present study EuroQoL was used in patients with aneurysmal SAH (aSAH) in comparison with a Swedish reference population. We also determined the extent to which demographic characteristics and clinical parameters predicted outcome.

    METHODS:

    Seven hundred fifty-five patients with aSAH were studied after a median 12 months. The proportion of patients in the best QoL category for each dimension was compared with the corresponding proportion in an age matched reference population. Disease severity was measured using the World Federation of Neurosurgical Societies' SAH grading system and the Fisher scale. The extent to which demographic and clinical factors predicted outcome was evaluated using linear regression.

    RESULTS:

    Aneurysmal SAH patients generally had a worse QoL compared with the reference population, in all five dimensions of EQ-5D. In the patient population, disease severity predicted worse outcome in all five dimensions. Female gender and surgery as treatment method (in the case of anterior aneurysms) predicted worse outcome in Usual Activities and Anxiety/Depression.

    CONCLUSION:

    The nature of the sequeles after SAH depends on severity of disease, gender and treatment method. These factors should be more emphasised in planning rehabilitation.

  • 47.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Imaging of cerebral blood flow in patients with severe traumatic brain injury in the neurointensive care2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 114Article in journal (Refereed)
    Abstract [en]

    Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI.

  • 48.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The Correlation between Cerebral Blood Flow Measured by Bedside Xenon-CT and Brain Chemistry Monitored by Microdialysis in the Acute Phase following Subarachnoid Hemorrhage2017In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 369Article in journal (Refereed)
    Abstract [en]

    Cerebral microdialysis (MD) may be used in patients suffering from subarachnoid hemorrhage (SAH) to detect focal cerebral ischemia. The cerebral MD catheter is usually placed in the right frontal lobe and monitors the area surrounding the catheter. This generates the concern that a fall in cerebral blood flow (CBF) and ischemic events distant to the catheter may not be detected. We aimed to investigate if there is a difference in the association between the MD parameters and CBF measured around the MD catheter compared to global cortical CBF and to CBF in the vascular territories following SAH in the early acute phase. MD catheter was placed in the right frontal lobe of 30 SAH patients, and interstitial glucose, lactate, pyruvate, glycerol, and lactate/pyruvate ratio were measured hourly. CBF measurements were performed during day 0-3 after SAH. Global cortical CBF correlated strongly with CBF around the microdialysis catheter (CBF-MD) (r = 0.911, p ≤ 0.001). This was also the case for the anterior, middle, and posterior vascular territories in the right hemisphere. A significant negative correlation was seen between lactate and CBF-MD (r = -0.468, p = 0.009). The same relationship was observed between lactate and CBF in anterior vascular territory but not in the middle and posterior vascular territories. In conclusion, global CBF 0-3 days after severe SAH correlated strongly with CBF-MD. High lactate level was associated with low global CBF and low regional CBF in the right anterior vascular territory, when the MD catheter was placed in the right frontal lobe.

  • 49.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Engquist, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Johnson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Monitoring of Cerebral Blood Flow and Metabolism Bedside in Patients with Subarachnoid Hemorrhage - A Xenon-CT and Microdialysis Study2014In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 89Article in journal (Refereed)
    Abstract [en]

    Cerebral ischemia is the leading cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Although 70% of the patients show angiographic vasospasm only 30% develop symptomatic vasospasm defined as delayed cerebral ischemia (DCI). Early detection and management of reversible ischemia is of critical importance in patients with SAH. Using a bedside Xenon enhanced computerized tomography (Xenon-CT) scanner makes it possible to measure quantitative regional Cerebral blood flow (CBF) bedside in the neurointensive care setting and intracerebral microdialysis (MD) is a method that offers the possibility to monitor the metabolic state of the brain continuously. Here, we present results from nine SAH patients with both MD monitoring and bedside Xenon-CT measurements. CBF measurements were performed within the first 72 h following bleeding. Six out of nine patients developed DCI at a later stage. Five out of six patients who developed DCI had initial global CBF below 26 ml/100 g/min whereas one had 53 ml/100 g/min. The three patients who did not develop clinical vasospasm all had initial global CBF above 27 ml/100 g/min. High lactate/pyruvate (L/P) ratio was associated with lower CBF values in the area surrounding the catheter. Five out of nine patients had L/P ratio ≥25 and four of these patients had CBF ≤ 22 ml/100 g/min. These preliminary results suggest that patients with initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially low global CBF was accompanied with metabolic disturbances determined by the MD. Most importantly, pathological findings on the Xenon-CT and MD could be observed before any clinical signs of DCI. Combining bedside Xenon-CT and MD was found to be useful and feasible. Further studies are needed to evaluate if DCI can be detected before any other signs of DCI to prevent progress to infarction.

  • 50.
    Samuelsson, Carolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Salci, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients2007In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 27, no 7, p. 1309-1317Article in journal (Refereed)
    Abstract [en]

    Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt–Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt–Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not stronger than the correlation between L/P and Glt (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r=0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt–Gln cycling in the brain.

12 1 - 50 of 63
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf