Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
Refine search result
123 1 - 50 of 143
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).

    Download full text (pdf)
    fulltext
  • 2.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: 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, Enblad: Neurosurgery.
    Intracranial pressure elevations in diffuse axonal injury: association with nonhemorrhagic MR lesions in central mesencephalic structures2019In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 131, no 2, p. 604-611Article in journal (Refereed)
    Abstract [en]

    Objective: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) 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 patients with DAI.

    Methods: Fifty-two patients with severe TBI (median age 24 years, range 9–61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.

    Results: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%–13%, p = 0.004) and young age (−0.2% of GMT with ICP > 20 mm Hg, 95% CI −0.07% to −0.3%, p = 0.002) were associated with increased ICP.

    Conclusions: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.

    Abbreviations: ADC = apparent diffusion coefficient; CPP = cerebral perfusion pressure; DAI = diffuse axonal injury; DWI = diffusion-weighted imaging; EVD = external ventricular drain; GCS = Glasgow Coma Scale; GMT = good monitoring time; GOSE = Glasgow Outcome Scale–Extended; ICC = intraclass correlation coefficient; ICP = intracranial pressure; MAP = mean arterial blood pressure; NICU = neurointensive care unit; SN-T = substantia nigra and mesencephalic tegmentum; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; T2*GRE = T2*-weighted gradient echo.

  • 3.
    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.

  • 4.
    Baldvinsdottir, Bryndis
    et al.
    Lund Univ, Dept Clin Sci, Neurosurg, Lund, Sweden..
    Klurfan, Paula
    Univ Gothenburg, Dept Clin Neurosci, Gothenburg, Sweden..
    Eneling, Johanna
    Linköping Univ, Dept Clin Sci, Linköping, Sweden..
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lindvall, Peter
    Umeå Univ, Dept Clin Sci, Umeå, Sweden..
    Aineskog, Helena
    Umeå Univ, Dept Clin Sci, Umeå, Sweden..
    Frioriksson, Steen
    Univ Gothenburg, Dept Clin Neurosci, Gothenburg, Sweden..
    Svensson, Mikael
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Alpkvist, Peter
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hillman, Jan
    Linköping Univ, Dept Clin Sci, Linköping, Sweden..
    Kronvall, Erik
    Lund Univ, Dept Clin Sci, Neurosurg, Lund, Sweden..
    Nilsson, Ola G.
    Lund Univ, Dept Clin Sci, Neurosurg, Lund, Sweden..
    Adverse events during endovascular treatment of ruptured aneurysms: A prospective nationwide study on subarachnoid hemorrhage in Sweden2023In: BRAIN AND SPINE, ISSN 2772-5294, Vol. 3, article id 102708Article in journal (Refereed)
    Abstract [en]

    Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.

    Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.

    Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.

    Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).

    Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.

    Download full text (pdf)
    fulltext
  • 5.
    Baldvinsdóttir, Bryndís
    et al.
    Lund Univ, Dept Clin Sci, Neurosurg, Lund, Sweden..
    Kronvall, Erik
    Lund Univ, Dept Clin Sci, Neurosurg, Lund, Sweden..
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lindvall, Peter
    Umeå Univ, Dept Clin Sci, Neurosurg, Umeå, Sweden..
    Aineskog, Helena
    Umeå Univ, Dept Clin Sci, Neurosurg, Umeå, Sweden..
    Fridriksson, Steen
    Univ Gothenburg, Dept Clin Neurosci, Neurosurg, Gothenburg, Sweden..
    Klurfan, Paula
    Univ Gothenburg, Dept Clin Neurosci, Neurosurg, Gothenburg, Sweden..
    Svensson, Mikael
    Karolinska Inst, Dept Clin Neurosci, Neurosurg, Stockholm, Sweden..
    Alpkvist, Peter
    Karolinska Inst, Dept Clin Neurosci, Neurosurg, Stockholm, Sweden..
    Hillman, Jan
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Eneling, Johanna
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Nilsson, Ola G.
    Lund Univ, Dept Clin Sci, Neurosurg, Lund, Sweden..
    Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden2023In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 94, no 7, p. 575-580Article in journal (Refereed)
    Abstract [en]

    Background Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome.

    Methods Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014–2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale.

    Results In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69).

    Conclusion Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.

  • 6.
    Björk, Sofie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Hånell, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Stenwall, Per-Anton
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Velle, Fartein
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Thiopental and decompressive craniectomy as last-tier ICP-treatments in aneurysmal subarachnoid hemorrhage: is functional recovery within reach?2023In: Neurosurgical review, ISSN 0344-5607, E-ISSN 1437-2320, Vol. 46, no 1, article id 231Article in journal (Refereed)
    Abstract [en]

    The study aimed to investigate the indication and functional outcome after barbiturates and decompressive craniectomy (DC) as last-tier treatments for elevated intracranial pressure (ICP) in aneurysmal subarachnoid hemorrhage ( aSAH). This observational study included 891 aSAH patients treated at a single center between 2008 and 2018. Data on demography, admission status, radiology, ICP, clinical course, and outcome 1-year post-ictus were collected. Patients treated with thiopental ( barbiturate) and DC were the main target group. Thirty-nine patients (4%) were treated with thiopental alone and 52 (6%) with DC. These patients were younger and had a worse neurological status than those who did not require these treatments. Before thiopental, the median midline shift was 0 mm, whereas basal cisterns were compressed/obliterated in 66%. The median percentage of monitoring time with ICP > 20 mmHg immediately before treatment was 38%, which did not improve after 6 h of infusion. Before DC, the median midline shift was 10 mm, and the median percentage of monitoring time with ICP > 20 mmHg before DC was 56%, which both significantly improved postoperatively. At follow-up, 52% of the patients not given thiopental or operated with DC reached favorable outcome, whereas this occurred in 10% of the thiopental and DC patients. In summary, 10% of the aSAH cohort required thiopental, DC, or both. Thiopental and DC are important integrated last-tier treatment options, but careful patient selection is needed due to the risk of saving many patients into a state of suffering.

    Download full text (pdf)
    FULLTEXT01
  • 7.
    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.

  • 8.
    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.

  • 9. 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)
  • 10.
    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.

  • 11.
    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.

  • 12.
    Decraene, Brecht
    et al.
    University Hospitals Leuven, Leuven, Belgium.
    Klein, Samuel P.
    University Hospitals Leuven, Leuven, Belgium.
    Piper, Ian
    Southern General Hospital, Glasgow, United Kingdom.
    Gregson, Barbara
    Newcastle University, Newcastle, United Kingdom.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ragauskas, Arminas
    Kaunas University of Technology, Kaunas, Lithuania.
    Citerio, Giuseppe
    University of Milano-Bicocca, Milano, Italy.
    Chambers, Iain
    James Cook University Hospital, Middlesbrough, United Kingdom.
    Neumann, Jan-Oliver
    Universitätsklinikum Heidelberg, Heidelberg, Germany.
    Sahuquillo, Juan
    University Hospital Vall d ́Hebron, Barcelona, Spain.
    Kiening, Karl
    Universitätsklinikum Heidelberg, Heidelberg, Germany.
    Moss, Laura
    Southern General Hospital, Glasgow, United Kingdom.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Donald, Rob
    Stats Research, Scotland, United Kingdom.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lo, Milly
    University of Edinburgh, Edinburgh, United Kingdom.
    Depreitere, Bart
    University Hospitals Leuven, Leuven, Belgium.
    Decompressive craniectomy as a second/third-tier intervention in traumatic brain injury: A multicenter observational study2023In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 54, no 9, article id 110911Article in journal (Refereed)
    Abstract [en]

    Objectives: RESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context.Methods: This is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008-2016) and one from the Brain-IT study, a European multicenter database (2003-2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thio-pental were analysed, as we l l as Extended Glasgow Outcome score (GOSE) at 6 months.Results: In the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recover y 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02).Conclusion: Outcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing se-vere TBI.

  • 13.
    Donald, Rob
    et al.
    Stats Res Ltd, Dingwall, Scotland.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Piper, Ian
    Queen Elizabeth Univ Hosp, Inst Neurol Sci, Clin Phys, Glasgow, Lanark, Scotland.
    Enblad, Per
    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.
    Chambers, I.
    James Cook Univ Hosp, Dept Med Phys, Middlesbrough, Cleveland, England.
    Gregson, B.
    Newcastle Univ, Neurosurg Trials Grp, Newcastle Upon Tyne, Tyne & Wear, England.
    Citerio, G.
    Hosp San Gerardo, Neurorianimaz, Monza, Italy.
    Kiening, K.
    Ruprecht Karls Univ Hosp, Dept Neurosurg, Heidelberg, Germany.
    Neumann, J.
    Ruprecht Karls Univ Hosp, Dept Neurosurg, Heidelberg, Germany.
    Ragauskas, A.
    Kaunas Univ Technol, Kaunas, Lithuania.
    Sahuquillo, J.
    Vall dHebron Univ Hosp, Dept Neurosurg, Barcelona, Spain.
    Sinnott, R.
    Univ Melbourne, Dept Informat Syst, Parkville, Vic, Australia.
    Stell, A.
    Univ Glasgow, Dept Clin Phys, Glasgow, Lanark, Scotland.
    Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care2019In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 33, no 1, p. 39-51Article in journal (Refereed)
    Abstract [en]

    Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.

  • 14.
    Dyhrfort, Philip
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Shen, Qiujin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala Univ, Dept Neurosci, Sect Neurosurg, Uppsala, Sweden.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics. Univ Edinburgh, Sch Math, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Maxwell Inst Math Sci, Edinburgh, Midlothian, Scotland.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care2019In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, no 20, p. 2872-2885Article in journal (Refereed)
    Abstract [en]

    Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One mu L MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48 h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96 h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96 h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.

    Download full text (pdf)
    FULLTEXT01
  • 15.
    Dyhrfort, Philip
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    A Dedicated 21-Plex Proximity Extension Assay Panel for High-Sensitivity Protein Biomarker Detection Using Microdialysis in Severe Traumatic Brain Injury: The Next Step in Precision Medicine?2023In: NEUROTRAUMA REPORTS, ISSN 2689-288X, Vol. 4, no 1, p. 25-40Article in journal (Refereed)
    Abstract [en]

    Cerebral protein profiling in traumatic brain injury (TBI) is needed to better comprehend secondary injury pathways. Cerebral microdialysis (CMD), in combination with the proximity extension assay (PEA) technique, has great potential in this field. By using PEA, we have previously screened >500 proteins from CMD samples collected from TBI patients. In this study, we customized a PEA panel prototype of 21 selected candidate protein biomarkers, involved in inflammation (13), neuroplasticity/-repair (six), and axonal injury (two). The aim was to study their temporal dynamics and relation to age, structural injury, and clinical outcome. Ten patients with severe TBI and CMD monitoring, who were treated in the Neurointensive Care Unit, Uppsala University Hospital, Sweden, were included. Hourly CMD samples were collected for up to 7 days after trauma and analyzed with the 21-plex PEA panel. Seventeen of the 21 proteins from the CMD sample analyses showed significantly different mean levels between days. Early peaks (within 48 h) were noted with interleukin (IL)-1 beta, IL-6, IL-8, granulocyte colony-stimulating factor, transforming growth factor alpha, brevican, junctional adhesion molecule B, and neurocan. C-X-C motif chemokine ligand 10 peaked after 3 days. Late peaks (>5 days) were noted with interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein (MCP)-2, MCP-3, urokinase-type plasminogen activator, Dickkopf-related protein 1, and DRAXIN. IL-8, neurofilament heavy chain, and TAU were biphasic. Age (above/below 22 years) interacted with the temporal dynamics of IL-6, IL-1ra, vascular endothelial growth factor, MCP-3, and TAU. There was no association between radiological injury (Marshall grade) or clinical outcome (Extended Glasgow Outcome Scale) with the protein expression pattern. The PEA method is a highly sensitive molecular tool for protein profiling from cerebral tissue in TBI. The novel TBI dedicated 21-plex panel showed marked regulation of proteins belonging to the inflammation, plasticity/repair, and axonal injury families. The method may enable important insights into complex injury processes on a molecular level that may be of value in future efforts to tailor pharmacological TBI trials to better address specific disease processes and optimize timing of treatments.

    Download full text (pdf)
    FULLTEXT01
  • 16.
    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)
  • 17.
    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.

  • 18.
    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.

  • 19.
    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.

  • 20.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Continuous monitoring of intracranial compliance in neurointensive care (Editorial by invitation)2018In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 160, no 12, p. 2289-2290Article in journal (Other academic)
  • 21.
    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)
  • 22.
    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)
  • 23.
    Engquist, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Hyperglycolysis as a common cause for elevated lactate in subarachnoid hemorrhage: Response2021In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, no 2, p. 682-682Article in journal (Other academic)
  • 24.
    Engquist, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: 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, Enblad: Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage2021In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, no 2, p. 555-564Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI.

    METHODS: CBF was assessed by bedside xenon-enhanced CT at days 0–3, 4–7, and 8–12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group.

    RESULTS: In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1–33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2–46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9–48.5) at baseline and 31.6 (IQR 22.4–35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients.

    CONCLUSIONS: Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

  • 25.
    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.

  • 26.
    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.
    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.
    Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT2019In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 30, no 2, p. 280-290Article in journal (Refereed)
    Abstract [en]

    Background: Compromised cerebral blood flow (CBF) is a crucial factor in delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Repeated measurement of CBF may improve our understanding of the temporal dynamics following SAH. The aim of this study was to assess CBF at different phases of the acute course in poor-grade SAH patients, hypothesizing more pronounced disturbances at day 4-7, and that the initial level of CBF determines the following course of CBF.

    Methods: Mechanically ventilated SAH patients were scheduled for bedside measurement of regional and global cortical CBF at day 0-3, 4-7, and 8-12, using xenon-enhanced computed tomography in a mobile setup. Patients were dichotomized depending on high or low initial global cortical CBF and cutoff level 30ml/100g/min.

    Results: Eighty-one patients were included, and 51 had measurements at day 0-3 and 4-7. In patients with high initial CBF, the level was unchanged at day 4-7; 37.7 (IQR 32.6-46.7) ml/100g/min versus 36.8 (IQR 29.5-44.8). The low-CBF group showed a slight increase from 23.6 (IQR 21.0-28.1) ml/100g/min to 28.4 (IQR 22.7-38.3) (P=0.025), still markedly lower than the high-CBF group (P=0.016). In the low-CBF group, CBF increased in patients who received hypertension, hypervolemia, and hemodilution (HHH therapy) but remained low in standard treated patients. For the subset of 27 patients examined also at day 8-12, the differences depending on initial CBF level were no longer statistically significant. Among patients with still low CBF at day 4-7, the proportion who had poor short-term outcome was 55% compared to 35% (n.s.) for patients with high CBF.

    Conclusions: CBF studied in poor-grade SAH patients at large did not show any statistically significant changes over time. Stratifying patients by high or low initial CBF and whether HHH therapy was given revealed an association between low initial CBF and persistent low CBF at day 4-7. These findings may be of clinical relevance in managing SAH patients with low early CBF.

    Download full text (pdf)
    fulltext
  • 27.
    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.

    Download full text (pdf)
    fulltext
  • 28.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Larsson, Elna-Marie
    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.
    High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease2020In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 41, no 3, p. 430-436Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling–derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease.

    MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient’s 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute–based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively.

    RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968–0.988) and 1.8 percentage points (95% CI, 0.3–3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively.

    CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.

  • 29.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.2023In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 14, article id 1137046Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD.

    METHODS: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography.

    RESULTS: Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol.

    CONCLUSION: Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

    Download full text (pdf)
    fulltext
  • 30.
    Fahlström, Markus
    et al.
    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.
    Borota, Ljubisa
    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, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Variable Temporal Cerebral Blood Flow Response to Acetazolamide in Moyamoya Patients Measured Using Arterial Spin Labeling2021In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 12, article id 615017Article in journal (Refereed)
    Abstract [en]

    Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.

    Download full text (pdf)
    FULLTEXT01
  • 31.
    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.

  • 32.
    Flechet, Marine
    et al.
    Univ Hosp Leuven, Dept Intens Care Med, Leuven, Belgium.;Univ Klinikum Tubingen, Klin Neurochirurg, Tubingen, Germany.;Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland.;NHS Greater Glasgow & Clyde, Dept Clin Phys & Bioengn, Glasgow, Lanark, Scotland.;Univ Hosp Leuven, Dept Neurosurg, Leuven, Lanark, Belgium..
    Meyfroidt, Geert
    Univ Hosp Leuven, Dept Intens Care Med, Leuven, Belgium.;Univ Klinikum Tubingen, Klin Neurochirurg, Tubingen, Germany.;Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland.;NHS Greater Glasgow & Clyde, Dept Clin Phys & Bioengn, Glasgow, Lanark, Scotland.;Univ Hosp Leuven, Dept Neurosurg, Leuven, Lanark, Belgium..
    Piper, Ian
    Southern Gen Hosp, Dept Clin Phys, Glasgow, Lanark, Scotland..
    Citerio, Giuseppe
    San Gerardo Hosp, Monza, Italy..
    Chambers, Iain
    James Cook Univ Hosp, Med Phys, Middlesbroughnza, England..
    Jones, Patricia A.
    Royal Hosp Sick Children, Dept Paediat Neurol, Edinburgh, Midlothian, Scotland..
    Lo, Tsz-Yan Milly
    Royal Hosp Sick Children, Dept Paediat Intens Care, Edinburgh, Midlothian, Scotland..
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Feyen, Bart
    Antwerp Univ Hosp, Dept Neurosurg, Edegem, Belgium..
    Jorens, Philippe
    Antwerp Univ Hosp, Dept Intens Care Med, Edegem, Belgium..
    Maas, Andrew
    Antwerp Univ Hosp, Dept Neurosurg, Edegem, Belgium..
    Schuhmann, Martin U.
    Univ Klinikum Tubingen, Klin Neurochirurg, Tubingen, Germany..
    Donald, Rob
    Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland..
    Moss, Laura
    NHS Greater Glasgow & Clyde, Dept Clin Phys & Bioengn, Glasgow, Lanark, Scotland..
    Van den Berghe, Greet
    Univ Hosp Leuven, Dept Intens Care Med, Leuven, Belgium.;Univ Klinikum Tubingen, Klin Neurochirurg, Tubingen, Germany.;Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland.;NHS Greater Glasgow & Clyde, Dept Clin Phys & Bioengn, Glasgow, Lanark, Scotland.;Univ Hosp Leuven, Dept Neurosurg, Leuven, Lanark, Belgium..
    Depreitere, Bart
    Univ Hosp Leuven, Dept Neurosurg, Leuven, Lanark, Belgium..
    Guiza, Fabian
    Univ Hosp Leuven, Dept Intens Care Med, Leuven, Belgium.;Univ Klinikum Tubingen, Klin Neurochirurg, Tubingen, Germany.;Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland.;NHS Greater Glasgow & Clyde, Dept Clin Phys & Bioengn, Glasgow, Lanark, Scotland.;Univ Hosp Leuven, Dept Neurosurg, Leuven, Lanark, Belgium..
    Visualizing Cerebrovascular Autoregulation Insults and Their Association with Outcome in Adult and Paediatric Traumatic Brain Injury2018In: Intracranial pressure & neuromonitoring XVI / [ed] Heldt, T, Springer Nature , 2018, p. 291-295Conference paper (Refereed)
    Abstract [en]

    Objective: The aim of this study is to assess visually the impact of duration and intensity of cerebrovascular autoregulation insults on 6-month neurological outcome in severe traumatic brain injury.

    Material and methods: Retrospective analysis of prospectively collected minute-by-minute intracranial pressure (ICP) and mean arterial blood pressure data of 259 adult and 99 paediatric traumatic brain injury (TBI) patients from multiple European centres. The relationship of the 6-month Glasgow Outcome Scale with cerebrovascular autoregulation insults (defined as the low-frequency autoregulation index above a certain threshold during a certain time) was visualized in a colour-coded plot. The analysis was performed separately for autoregulation insults occurring with cerebral perfusion pressure (CPP) below 50 mmHg, with ICP above 25 mmHg and for the subset of adult patients that did not undergo decompressive craniectomy.

    Results: The colour-coded plots showed a time-intensity-dependent association with outcome for cerebrovascular autoregulation insults in adult and paediatric TBI patients. Insults with a low-frequency autoregulation index above 0.2 were associated with worse outcomes and below -0.6 with better outcomes, with and approximately exponentially decreasing transition curve between the two intensity thresholds. All insults were associated with worse outcomes when CPP was below 50 mmHg or ICP was above 25 mmHg.

    Conclusions: The colour-coded plots indicate that cerebrovascular autoregulation is disturbed in a dynamic manner, such that duration and intensity play a role in the determination of a zone associated with better neurological outcome.

  • 33.
    Galos, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery. Dept Surg Sci Anesthes & Intens Care, Uppsala, Sweden..
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Capturing of intracranial pressure treatment during neurointensive care in patients with acute brain injury using a novel tablet-based method2022In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 36, no 6, p. 1731-1738Article in journal (Refereed)
    Abstract [en]

    Critical care is complex and stressful. It is difficult to register in real time data not recorded by automatic systems. Time-specific knowledge of manual measures is important for understanding pathophysiology and for analyzing treatment and quality of care. Therefore, a novel iPad-based method for registration of manual measures was developed, which many can build themselves. Using a configuration for intracranial pressure (ICP) management, the methodology was validated, ICP treatment captured, and the quality of ICP management evaluated. Twenty-two patients with acute brain injuries were studied. The iPad-system was totally used for 2538 h. Thirteen-hundred-five manual measures were entered. Thirty-nine episodes of predefined ICP insults were identified. During 16/39 episodes, ICP treatments were registered. For 4/39 episodes treatments were registered within 90 s before or after the episode. For 3/39 episodes it was registered that treatment was intentionally refrained. In 15/16 episodes without registered treatment, the insult was mild or reasonable explanations were found when medical records and the Patient data management system were reviewed. In one situation without particular circumstances, morphine and clonidine were given to decrease ICP but not registered. No episodes of downtime or loss of data occurred. The developed methodology appears to be stable and robust as well as feasible and user-friendly. It was possible to capture the treatment of ICP insults with high temporal resolution, and to evaluate the quality of ICP management. An own developed novel tablet-based system like our system may be a promising potential tool useful in various future intensive care applications.

    Download full text (pdf)
    FULLTEXT01
  • 34.
    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, 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.

    Download full text (pdf)
    fulltext
  • 35.
    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)
  • 36.
    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)
  • 37.
    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.

  • 38.
    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 %.

  • 39.
    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.

  • 40.
    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.

  • 41.
    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.

  • 42.
    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)
  • 43.
    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)
  • 44.
    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.

    Download full text (pdf)
    fulltext
  • 45.
    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.

  • 46.
    Kevci, Rozerin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Velle, Fartein
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lumbar puncture-verified subarachnoid hemorrhage: bleeding sources, need of radiological examination, and functional recovery2023In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 165, no 7, p. 1847-1854Article in journal (Refereed)
    Abstract [en]

    Background The primary aim was to determine the diagnostic yield of vascular work-up, the clinical course during neurointensive care (NIC), and rate of functional recovery for patients with computed tomography (CT)-negative, lumbar puncture (LP)-verified SAH.

    Methods In this retrospective study, 1280 patients with spontaneous SAH, treated at our NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2018, were included. Demography, admission status, radiological examinations (CT angiography (CTA) and digital subtraction angiography (DSA)), treatments, and functional outcome (GOS-E) at 12 months were evaluated.

    Results Eighty (6%) out of 1280 SAH patients were computed tomography (CT)-negative, LP-verified cases. Time between ictus and diagnosis was longer for the LP-verified SAH cohort in comparison to the CT-positive patients (median 3 vs 0 days, p < 0.001). One fifth of the LP-verified SAH patients exhibited an underlying vascular pathology (aneurysm/AVM), which was significantly less common than for the CT-verified SAH cohort (19% vs. 76%, p < 0.001). The CTA- and DSA-findings were consistent in all of the LP-verified cases. The LP-verified SAH patients exhibited a lower rate of delayed ischemic neurological deficits, but no difference in rebleeding rate, compared to the CT-verified cohort. At 1-year post-ictus, 89% of the LP-verified SAH patients had recovered favorably, but 45% of the cases did not reach good recovery. Having an underlying vascular pathology and an external ventricular drainage were associated with worse functional recovery (p = 0.02) in this cohort.

    Conclusions LP-verified SAH constituted a small proportion of the entire SAH population. Having an underlying vascular pathology was less frequent in this cohort, but still occurred in one out of five patients. Despite the small initial bleeding in the LP-verified cohort, many of these patients did not reach good recovery at 1 year, this calls for more attentive follow-up and rehabilitation in this cohort.

    Download full text (pdf)
    FULLTEXT01
  • 47.
    Kultanen, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Svedung Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Antithrombotic agent usage before ictus in aneurysmal subarachnoid hemorrhage: relation to hemorrhage severity, clinical course, and outcome2023In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 165, no 5, p. 1241-1250Article in journal (Refereed)
    Abstract [en]

    Background

    The number of patients with aneurysmal subarachnoid hemorrhage (aSAH) who are on antithrombotic agents before ictus is rising. However, their effect on early brain injury and disease development remains unclear. The primary aim of this study was to determine if antithrombotic agents (antiplatelets and anticoagulants) were associated with a worse initial hemorrhage severity, rebleeding rate, clinical course, and functional recovery after aSAH.

    Methods

    In this observational study, those 888 patients with aSAH, treated at the neurosurgical department, Uppsala University Hospital, between 2008 and 2018 were included. Demographic, clinical, radiological (Fisher and Hijdra score), and outcome (Extended Glasgow Outcome Scale one year post-ictus) variables were assessed.

    Results

    Out of 888 aSAH patients, 14% were treated with antithrombotic agents before ictus. Seventy-five percent of these were on single therapy of antiplatelets, 23% on single therapy of anticoagulants, and 3% on a combination of antithrombotic agents. Those with antithrombotic agents pre-ictus were significantly older and exhibited more co-morbidities and a worse coagulation status according to lab tests. Antithrombotic agents, both as one group and as subtypes (antiplatelets and anticoagulants), were not associated with hemorrhage severity (Hijdra score/Fisher) nor rebleeding rate. The clinical course did not differ in terms of delayed ischemic neurological deficits or last-tier treatment with thiopental and decompressive craniectomy. These patients experienced a higher mortality and lower rate of favorable outcome in univariate analyses, but this did not hold true in multiple logistic regression analyses after adjustment for age and co-morbidities.

    Conclusions

    After adjustment for age and co-morbidities, antithrombotic agents before aSAH ictus were not associated with worse hemorrhage severity, rebleeding rate, clinical course, or long-term functional recovery.

    Download full text (pdf)
    fulltext
  • 48.
    Lenell, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Neurointensive care of traumatic brain injury in the elderly: age-specific secondary insult levels and optimal physiological levels to target need to be defined2022In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 164, no 1, p. 117-128Article in journal (Refereed)
    Abstract [en]

    Background

    Elderly patients with traumatic brain injury increase. Current targets and secondary insult definitions during neurointensive care (NIC) are mostly based on younger patients. The aim was therefore to study the occurrence of predefined secondary insults and the impact on outcome in different ages with particular focus on elderly.

    Methods

    Patients admitted to Uppsala 2008–2014 were included. Patient characteristics, NIC management, monitoring data, and outcome were analyzed. The percentage of monitoring time for ICP, CPP, MAP, and SBP above-/below-predefined thresholds was calculated.

    Results

    Five hundred seventy patients were included, 151 elderly ≥ 65 years and 419 younger 16–64 years. Age ≥ 65 had significantly higher percentage of CPP > 100, MAP > 120, and SBP > 180 and age 16–64 had higher percentage of ICP ≥ 20, CPP ≤ 60, and MAP ≤ 80. Age ≥ 65 contributed independently to the different secondary insult patterens. When patients in all ages were analyzed, low percentage of CPP > 100 and SBP > 180, respectively, was significant predictors of favorable outcome and high percentage of ICP ≥ 20, CPP > 100, SBP ≤ 100, and SBP > 180, respectively, was predictors of death. Analysis of age interaction showed that patients ≥ 65 differed and had a higher odds for favorable outcome with large proportion of good monitoring time with SBP > 180.

    Conclusions

    Elderly ≥ 65 have different patterns of secondary insults/physiological variables, which is independently associated to age. The finding that SBP > 180 increased the odds of favorable outcome in the elderly but decreased the odds in younger patients may indicate that blood pressure should be treated differently depending on age.

    Download full text (pdf)
    fulltext
  • 49.
    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.

  • 50.
    Lenell, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Clinical outcome and prognostic factors in elderly traumatic brain injury patients receiving neurointensive care2019In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, no 6, p. 1243-1254Article in journal (Refereed)
    Abstract [en]

    Background: The probability of favorable outcome after traumatic brain injury (TBI) decreases with age. Elderly,≥60 years, are an increasing part of our population. Recent studies have shown an increase of favorable outcome in elderly over time. However,the optimal patient selection and neurointensive care (NIC) treatments may differ in the elderly and the young. The aims of this study were to examine outcome in a larger group of elderly TBI patients receiving NIC and to identify demographic and treatmentrelated prognostic factors.

    Methods: Patients with TBI≥60 years receiving NIC at our department between 2008 and 2014 were included. Demographics, co-morbidity, admission characteristics, and type of treatments were collected. Clinical outcome at around 6 months was assessed. Potential prognostic factors were included in univariate and multivariate regression analysis with favorable outcomeas dependent variable.

    Results: Two hundred twenty patients with mean age 70 years (median 69; range 60–87) were studied. Overall, favorable outcome was 46% (Extended Glasgow Outcome Scale (GOSE) 5–8), unfavorable outcome 27% (GOSE 2–4), and mortality 27% (GOSE 1). Significant independent negative prognostic variables were high age (p< 0.05), multiple injuries (p<0.05),GCSM≤3 on admission (p< 0.05), and mechanical ventilation (p<0.001).

    Conclusions: Overall, the elderly TBI patients> 60 years receiving modern NIC in this study had a fair chance of favorable outcome without large risks for severe deficits and vegetative state, also in patients over 75 years of age. High age, multiple injuries, GCS M≤3 on admission, and mechanical ventilation proved to be independent negative prognostic factors. The results underline that a selected group of elderly with TBI should have access to NIC

    Download full text (pdf)
    fulltext
123 1 - 50 of 143
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