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  • 51.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Intracranial Pressure Changes During Fluid Percussion, Controlled Cortical Impact and Weight Drop Injury in RatsArtikkel i tidsskrift (Fagfellevurdert)
  • 52.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Cerebral glucose metabolism after traumatic brain injury in the rat studied by C-13-glucose and microdialysis2011Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 153, nr 3, s. 653-658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Following traumatic brain injury (TBI), a disturbed cerebral glucose metabolism contributes to secondary brain damage. To study local cerebral glucose metabolism after TBI, we delivered C-13-labeled glucose into brain tissue by microdialysis (MD). MD probes were inserted bilaterally into the parietal cortex of rat brain, one probe in the shear stress zone of the injury and the other at the corresponding contralateral coordinates. A moderately severe controlled cortical contusion was used to model TBI. Dialysate concentrations of glucose, pyruvate, lactate, and glycerol were measured, and following derivatization, C-13 enrichments of the compounds were determined by gas chromatography-mass spectrometry. We found that C-13-labeled glucose was rapidly converted into C-13-lactate and C-13-glycerol. In the hours following TBI, concentrations and C-13 enrichments of lactate and glycerol increased. The findings confirm the occurrence of anaerobic local glucose metabolism early after TBI. Only a small fraction of the glycerol was newly synthesized, suggesting that the hypothesis that most of the released glycerol after TBI comes from degradation of membrane phospholipids still holds. We conclude that the combination of microdialysis and stable isotope technique is a useful tool for investigating local glucose metabolism following brain injury.

  • 53.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hånell, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Björk, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mir, Anis K.
    Gram, Hermann
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Neutralization of interleukin-1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice2009Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 30, nr 3, s. 385-396Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.

  • 54.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hånell, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Israelsson, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Hedin, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ebendal, Ted
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Mir, Anis K.
    Gram, Hermann
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Neutralization of interleukin-1 beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice2011Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 34, nr 1, s. 110-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increasing evidence suggests that interleukin-1 beta (IL-1 beta) is a key mediator of the inflammatory response following traumatic brain injury (TBI). Recently, we showed that intracerebroventricular administration of an IL-1 beta-neutralizing antibody was neuroprotective following TBI in mice. In the present study, an anti-IL-1 beta antibody or control antibody was administered intraperitoneally following controlled cortical injury (CCI) TBI or sham injury in 105 mice and we extended our histological, immunological and behavioral analysis. First, we demonstrated that the treatment antibody reached target brain regions of brain-injured animals in high concentrations (> 11 nm) remaining up to 8 days post-TBI. At 48 h post-injury, the anti-IL-1b treatment attenuated the TBI-induced hemispheric edema (P < 0.05) but not the memory deficits evaluated using the Morris water maze (MWM). Neutralization of IL-1 beta did not influence the TBI-induced increases (P < 0.05) in the gene expression of the Ccl3 and Ccr2 chemokines, IL-6 or Gfap. Up to 20 days post-injury, neutralization of IL-1 beta was associated with improved visuospatial learning in the MWM, reduced loss of hemispheric tissue and attenuation of the microglial activation caused by TBI (P < 0.05). Motor function using the rotarod and cylinder tests was not affected by the anti-IL-1 beta treatment. Our results suggest an important negative role for IL-1 beta in TBI. The improved histological and behavioral outcome following anti-IL-1 beta treatment also implies that further exploration of IL-1 beta-neutralizing compounds as a treatment option for TBI patients is warranted.

  • 55.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Marklund, Niklas
    McArthur, David
    Olsson, Yngve
    Hillered, Lars
    Artikkel i tidsskrift (Fagfellevurdert)
  • 56.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lindh, Tone
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Shabnam, Salimi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Erlandsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Combination of growth factor treatment and scaffold deposition following traumatic brain injury has only a temporary effect on regeneration2014Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1588, s. 37-48Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The recovery after traumatic brain injury (TBI) is hampered by the poor regenerative capacity of the brain. Today there is no treatment available that effectively restores lost brain tissue, but much research is focused on the stimulation of endogenous neural stem cells to viably and functionally repopulate the injured parenchyma. It is crucial that the therapies have a proven long-term effect on both regeneration and functional recovery to be clinically interesting. Here we have studied the induction of stem cell activation in rats at three weeks and six weeks after inducing TBI using controlled cortical impact model at a severe setting. We combined intracerebroventricular growth factor and scaffold treatment in order to accomplish an optimal effect on the stem cell regeneration. Immediately after TBI epidermal growth factor infusion with osmotic minipumps was started and continued for seven days. The pumps were removed and an extracellular matrix scaffold containing vascular endothelial growth factor was deposited into the cortical cavity. Three weeks after injury there was a positive effect of the treatment with a significant increase in neuronal and astrocytic regeneration. However, after six weeks there was no difference in the number of newly generated neurons and astrocytes in treated or untreated rats. Evaluation of tissue loss and spatial learning in the Morris water maze corroborated that the treatment had no effect at the later time point. Our results highlight the importance of long-term studies to ensure that a promising effect on tissue regeneration and functional outcome is not only temporary.

  • 57.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundqvist, Hanna
    Ekmark, Sara
    Lewén, Anders
    Ebendal, Ted
    Hillered, Lars
    Oxygen Free Radical Dependent Activation of Extracellular Signal-regulated Kinase (ERK) Mediates Apoptosis-like Cell Death after Traumatic Brain InjuryArtikkel i tidsskrift (Fagfellevurdert)
  • 58.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Acute Inflammatory Biomarker Responses to Diffuse Traumatic Brain Injury in the Rat Monitored by a Novel Microdialysis Technique2019Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, nr 2, s. 201-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuroinflammation is a major contributor to the progressive brain injury process induced by traumatic brain injury (TBI), and may play an important role in the pathophysiology of axonal injury. The immediate neuroinflammatory cascade cannot be characterized in the human setting. Therefore, we used the midline fluid percussion injury model of diffuse TBI in rats and a novel microdialysis (MD) method providing stable diffusion-driven biomarker sampling. Immediately post-injury, bilateral amphiphilic tri-block polymer coated MD probes (100 kDa cut off membrane) were inserted and perfused with Dextran 500 kDa-supplemented artificial cerebrospinal fluid (CSF) to optimize protein capture. Six hourly samples were analyzed for 27 inflammatory biomarkers (9 chemokines, 13 cytokines, and 5 growth factors) using a commercial multiplex biomarker kit. TBI (n = 6) resulted in a significant increase compared with sham-injured controls (n = 6) for five chemokines (eotaxin/CCL11, fractalkine/CX3CL1, LIX/CXCL5, monocyte chemoattractant protein [MCP]1α/CCL2, macrophage inflammatory protein [MIP]1α /CCL3), 10 cytokines (interleukin [IL]-1α, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17α, IL-18, interferon [IFN]-γ, tumor necrosis factor [TNF]-α), and four growth factors (epidermal growth factor [EGF], granulocyte-macrophage colony-stimulating factor [GM-CSF], leptin, vascular endothelial growth factor [VEGF]). Therefore, diffuse TBI was associated with an increased level of 18 of the 27 inflammatory biomarkers at one through six time points, during the observation period whereas the remaining 9 biomarkers were unaltered. The study shows that diffuse TBI induces an acute increase in a number of inflammatory biomarkers. The novel MD technique provides stable MD sampling suitable for further studies on the early neuroinflammatory cascade in TBI.

  • 59.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Interstitial F2-Isoprostane 8-Iso-PGF As a Biomarker of Oxidative Stress after Severe Human Traumatic Brain Injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 5, s. 766-775Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 60.
    Clausen, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The nitrone free radical scavenger NXY-059 is neuroprotective when administered after traumatic brain injury in the rat2008Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 25, nr 12, s. 1449-1457Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI. NXY-059, a nitrone free radical trapping compound, has been shown to be neuroprotective in models of ischemic stroke but has not been evaluated in experimental TBI. In the present study, a continuous 24-h intravenous infusion of NXY-059 or vehicle was initiated 30min following a severe lateral fluid percussion brain injury (FPI) in adult rats (n=22), and histological and behavioral outcomes were evaluated. Sham-injured animals (n=22) receiving identical drug infusion were used as controls. Visuospatial learning was evaluated in the Morris water maze at post-injury days 11–14, followed by a probe trial (memory test) at day 18. The animals were sacrificed at day 18, and loss of hemispheric brain tissue was measured in microtubule-associated protein (MAP)–2stained sections. Brain-injured, NXY-059-treated animals showed a significant reduction of visuospatial learning deficits when compared to the brain-injured, vehicle-treated control animals (p<0.05). NXY-059-treated animals significantly reduced the loss of hemispheric tissue compared to brain-injured controls (43.0±11mm3 versus 74.4±19mm3, respectively; p<0.01). The results show that post-injury treatment with NXY-059 significantly attenuated the loss of injured brain tissue and improved cognitive outcome, suggesting a major role for ROS in the pathophysiology of TBI.

  • 61. Conte, Valeria
    et al.
    Raghupathi, Ramesh
    Watson, Deborah J
    Fujimoto, Scott
    Royo, Nicolas C
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Stocchetti, Nino
    McIntosh, Tracy K
    TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice2008Inngår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 26, nr 1, s. 45-56Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated.

    METHODS: Full-length trkB was overexpressed in the left hippocampus of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus.

    RESULTS: No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups.

    CONCLUSIONS: These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice.

  • 62.
    Covaciu, Lucian
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Allers, M.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lunderquist, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wieloch, T.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intranasal selective brain cooling in pigs2008Inngår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 78, nr 1, s. 83-88Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Special clinical situations where general hypothermia cannot be recommended but can be a useful treatment demand a new approach, selective brain cooling. The purpose of this study was to selectively cool the brain with cold saline circulating in balloon catheters introduced into the nasal cavity in pigs. MATERIAL AND METHODS: Twelve anaesthetised pigs were subjected to selective cerebral cooling for a period of 6 h. Cerebral temperature was lowered by means of bilaterally introduced nasal balloon catheters perfused with saline cooled by a heat exchanger to 8-10 degrees C. Brain temperature was measured in both cerebral hemispheres. Body temperature was measured in rectum, oesophagus and the right atrium. The pigs were normoventilated and haemodynamic variables were measured continuously. Acid-base and electrolyte status was measured hourly. RESULTS: Cerebral hypothermia was induced rapidly and within the first 20 min of cooling cerebral temperature was lowered from 38.1+/-0.6 degrees C by a mean of 2.8+/-0.6 to 35.3+/-0.6 degrees C. Cooling was maintained for 6 h and the final brain temperature was 34.7+/-0.9 degrees C. Concomitantly, the body temperature, as reflected by oesophageal temperature was decreased from 38.3+/-0.5 to 36.6+/-0.9 degrees C. No circulatory or metabolic disturbances were noted. CONCLUSIONS: Inducing selective brain hypothermia with cold saline via nasal balloon catheters can effectively be accomplished in pigs, with no major disturbances in systemic circulation or physiological variables. The temperature gradients between brain and body can be maintained for at least 6 h.

  • 63.
    Cubo, Rubén
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för systemteknik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Reglerteknik.
    Jiltsova, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Andersson, Helena
    Medvedev, Alexander
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för systemteknik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Reglerteknik.
    Optimization of deep brain stimulation by means of a patient-specific mathematical model2016Konferansepaper (Fagfellevurdert)
  • 64.
    Dahlin, Andreas P
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Hjort, Klas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sjödin, Marcus O D
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Quantification of Proteins Adsorbed to Surface Modified and Non-Modified Microdialysis Membranes using on-Surface Enzymatic Digestion (oSED) iTRAQ-MALDI-TOF/TOF MS2012Inngår i: 60th ASMS Conference on Mass Spectrometry and Allied Topics, May 20 - 24, Vancouver, Canada, 2012Konferansepaper (Fagfellevurdert)
  • 65.
    Dahlin, Andreas P
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Hjort, Klas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sjödin, Marcus O.D.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Multiplexed quantification of proteins adsorbed to surface-modified and non-modified microdialysis membranes2012Inngår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 402, nr 6, s. 2057-2067Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A simple and straightforward method for discovery and quantification of proteins adsorbed onto delicate and sensitive membrane surfaces is presented. The adsorbed proteins were enzymatically cleaved while still adsorbed onto the membranes using an on-surface enzymatic digestion (oSED). This was followed by isobaric tagging, nanoliquid chromatography, and tandem mass spectrometry. Protein adsorption on tri-block copolymer Poloxamer 407 surface-modified microdialysis (MD) membranes were compared with protein adsorption on unmodified MD membranes. Ventricular cerebrospinal fluid (vCSF) kept at 37 °C was used as sample matrix. In total, 19 proteins were quantified in two biological replicates. The surface-modified membranes adsorbed 33% less proteins than control membranes and the most abundant proteins were subunits of hemoglobin and clusterin. The adsorption of clusterin on the modified membranes was on average 36% compared to control membranes. The most common protein in vCSF, Albumin, was not identified adsorbed to the surface at all. It was also experimentally verified that oSED, in conjunction with tandem mass spectrometry can be used to quantify femtomole amounts of proteins adsorbed on limited and delicate surfaces, such as MD membranes. The method has great potential and can be used to study much more complex protein adsorption systems than previously reported.

  • 66.
    Dahlin, Andreas P
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Chu, Jiangtao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Sedigh, Amir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Lorant, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Refined microdialysis method for protein biomarker sampling in acute brain injury in the neurointensive care setting2014Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, nr 17, s. 8671-8679Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 67.
    Dahlin, Andreas P
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Improved Microdialysis Sampling of Proteins using Surface Modified Catheters: An in vivo Study in Standardized Pig Brain Death Model2013Konferansepaper (Fagfellevurdert)
  • 68.
    Dahlin, Andreas P.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi.
    Caldwell, Karin D.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hjort, Klas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Methodological aspects on microdialysis protein sampling and quantification in biological fluids: an in vitro study on human ventricular CSF.2010Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, nr 11, s. 4376-4385Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is growing interest in sampling of protein biomarkers from the interstitial compartment of the brain and other organs using high molecular cutoff membrane microdialysis (MD) catheters. However, recent data suggest that protein sampling across such MD membranes is a highly complex process that needs to be further studied. Here, we report three major improvements for microdialysis sampling of proteins in complex biological matrixes. The improvements in this in vitro study using human ventricular cerebrospinal fluid as the sample matrix include increased fluid recovery control, decreased protein adsorption on the microdialysis membrane and materials, and novel quantitative mass spectrometry analysis. Dextrans in different concentrations and sizes were added to the perfusion fluid. It was found that dextrans with molecular mass 250 and 500 kDa provided a fluid recovery close to 100%. An improved fluid recovery precision could be obtained by self-assembly triblock polymer surface modification of the MD catheters. The modified catheters also delivered a significantly increased extraction efficiency for some of the investigated proteins. The final improvement was to analyze the dialysates with isobaric tagged (iTRAQ) proteomics, followed by tandem mass spectrometric analysis. By using this technique, 48 proteins could be quantified and analyzed with respect to their extraction efficiencies. The novel aspects of microdialysis protein sampling, detection, and quantification in biological fluids presented in this study should be considered as a first step toward better understanding and handling of the challenges associated with microdialysis sampling of proteins. The next step is to optimize the developed methodology in vivo.

  • 69.
    Danfors, Torsten
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Samuelsson, Carolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Mats, Bergström
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsyManuskript (preprint) (Annet vitenskapelig)
  • 70.
    Donald, Rob
    et al.
    Stats Res Ltd, Dingwall, Scotland.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Piper, Ian
    Queen Elizabeth Univ Hosp, Inst Neurol Sci, Clin Phys, Glasgow, Lanark, Scotland.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    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 care2019Inngår i: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 33, nr 1, s. 39-51Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 71.
    Duffau, Hugues
    et al.
    Montpellier Med Univ Ctr, Hop Guide Chauliac, Dept Neurosurg, Montpellier, France.;Inst Neurosci, INSERM U1051, Montpellier, France.;Univ Montpellier, Montpellier, France..
    Mandonnet, Emmanuel
    Lariboisiere Hosp, AP HP, Dept Neurosurg, Paris, France.;Univ Paris 07, Paris, France.;IMNC, UMR 8165, Orsay, France..
    Pallud, Johan
    St Anna Hosp, Dept Neurosurg, Paris, France.;Paris Descartes Univ, Sorbonne Paris Cite, Paris, France.;INSERM, U894, Ctr Psychiat & Neurosci, Paris, France..
    Krieg, Sandro
    Tech Univ Munich, Klinikum Rechts Isar, Dept Neurosurg, Munich, Germany..
    Gil Robles, Santiago
    Hosp Univ Quiron, Madrid, Spain.;Bio Cruces Res, Bilbao, Spain..
    Hamer, Philip de Witt
    Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, Amsterdam, Netherlands..
    Schucht, Philippe
    Univ Hosp Bern, Dept Neurosurg, Bern, Switzerland..
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Santarius, Thomas
    Univ Cambridge, Addenbrookes Hosp, Dept Neurosurg, Cambridge, England..
    Colle, Henry
    AZ St Luca, Funct Neurosurg, Ghent, Belgium..
    Ryan, Mathew
    Leeds Gen Infirm, Dept Neurosurg, Leeds, W Yorkshire, England..
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Inst Neurosci & Physiol, Gothenburg, Sweden..
    von Campe, Gord
    Med Univ Graz, Dept Neurosurg, Graz, Austria..
    Bello, Lorenzo
    Univ Milan, Dept Oncol & Hematooncol, Neurosurg Oncol Unit, Milan, Italy.;IRCCS, Humanitas Res Hosp, Milan, Italy..
    Forster, Marie-Therese
    Goethe Univ, Dept Neurosurg, Frankfurt, Germany..
    Sarubbo, Silvio
    Santa Chiara Hosp, Struct & Funct Connectiv Lab, Trento, Italy..
    Spena, Giannantonio
    Spedali Civil Brescia, Clin Neurochirurg, Brescia, Italy..
    Baron, Marie-Helene
    CHRU Jean Minjoz, Dept Oncol Radiotherapie, Besancon, France..
    Yordanova, Yordanka
    Percy Army Training Hosp, Neurosurg Dept, Clamart, France..
    Darlix, Amelie
    Inst Regional Canc Montpellier ICM, Dept Med Oncol, Montpellier, France..
    Viegas, Catarina
    Hosp Garcia Orta, Dept Neurosurg, Almada, Portugal..
    Almairac, Fabien
    Univ Hosp Nice, Dept Neurosurg, Nice, France..
    Martino, Juan
    Hosp Univ Marques Valdecilla, Fdn Inst Invest Marques Valdecilla IDIVAL, Dept Neurol Surg, Avda Valdecilla S-N, Santander, Spain.;Inst Salud Carlos III, Avda Valdecilla S-N, Santander, Spain..
    Goodden, John
    Dept Neurosurg, Leeds, W Yorkshire, England..
    Chumas, Paul
    Dept Neurosurg, Leeds, W Yorkshire, England..
    Freyschlag, Christian
    Med Univ Innsbruck, Dept Neurosurg, Innsbruck, Austria..
    Robe, Pierre
    Univ Med Ctr Utrecht, Dept Neurosurg, Utrecht, Netherlands..
    Wager, Michel
    Univ Poitiers Hosp, INSERM U1084, Neurosurg Dept, Poitiers, France..
    Polivka, Marc
    Lariboisiere Hosp, AP HP, Dept Neuropathol, Paris, France..
    Giakoumettis, Dimitris
    Neurosurg Evangelismos Hosp, Athens, Greece..
    Robert, Erik
    AZ SintLucas & AZ Maria Middelares, Dept of Aphasiol, Ghent, Belgium..
    Guillevin, Remy
    Univ Poitiers Hosp, Neuroradiol Dept, Poitiers, France..
    Grivas, Athanasios
    Univ Glasgow, Queen Elizabeth Univ Hosp, Inst Neurol Sci, Dept Neurosurg, Glasgow, Lanark, Scotland..
    Fontaine, Denys
    Univ Hosp Nice, Dept Neurosurg, Nice, France..
    van Geemen, Kim
    Brain Res Ctr Amsterdam, Amsterdam, Netherlands..
    Lubrano, Vincent
    Univ Toulouse, CHU Toulouse, Toulouse NeuroImaging Ctr, INSERM UMR 1214,ToNIC, Toulouse, France..
    Rutten, Geert-Jan
    St Elisabeth Tweesteden Hosp, Dept Neurosurg, Tilburg, Netherlands..
    Barone, Fabio
    Cannizzaro Gen Hosp, Dept Neurosurg & Gamma Knife, Catania, Italy..
    Rofes, Adria
    Trinity Coll Dublin, Global Brain Hlth Inst, Dublin, Ireland..
    Rech, Fabien
    CHRU Nancy, Serv Neurochirurg, Nancy, France..
    Rigau, Valerie
    Gui Chauliac Hosp, Dept Pathol, Montpellier, France..
    Wagemakers, Michiel
    Univ Med Ctr, Neurosurg Dept, Groningen, Belgium..
    Papagno, Costanza
    Univ Trento, CeRiN & CIMeC, Rovereto, Italy..
    Aerts, Annelies
    AZ Sint Lucas, Ghent, Belgium.;Artevelde Univ Coll, Ghent, Belgium..
    Visch-Brink, Evy
    Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurosurg, Rotterdam, Netherlands..
    Tate, Matthew
    Northwester Med Group, Dept Neurosurg, Chicago, IL USA..
    Garg, Neha
    Univ Delhi, Delhi, India..
    Klein, Martin
    Vrije Univ Amsterdam Med Ctr, Clin Neuropsychol Dept, Amsterdam, Netherlands..
    Satoer, Djaina
    Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurosurg, Rotterdam, Netherlands..
    de Witte, Elke
    Vrije Univ Brussel, Neurolinguist Dept, Brussels, Belgium..
    Van Brussel, Lore
    Onze Lieve Vrouw Hosp, Neurosurg Dept, Moorselbaan, Aalst, Belgium..
    Reyes, Andres
    Univ Groningen, Dept Clin Linguist, Groningen, Netherlands.;EMCL Univ Potsdam, Potsdam, Germany.;El Bosque Univ, Expt Psychol Lab, Fac Psychol, Bogota, Colombia.;Inst Neurosci, Bogota, Colombia..
    van Ierschot, Fleur
    Univ Trent, Ctr Mind Brain Sci, Trento, Italy.;Univ Groningen, Fac Arts, Groningen, Belgium.;Macquarie Univ, Dept Cognit Sci, Sydney, NSW, Australia..
    Veenstra, Wencke
    Univ Groningen, Dept Linguist, Groninge, Belgium..
    Snijders, Tom
    Univ Med Ctr Utrecht, Dept Neurol & Neurosurg Hosp, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Taillandier, Luc
    CHU Nancy, Neurol Dept, Nancy, France..
    Blonski, Marie
    CHU Nancy, Neurol Dept, Nancy, France..
    Evidenced-based medicine in glioma: molecular biology is only part of the story2017Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, nr 8, s. E429-E429Artikkel i tidsskrift (Fagfellevurdert)
  • 72.
    Edberg, M
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Neurointensive care of patients with severe community-acquired meningitis2011Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, nr 6, s. 732-739Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Reports about neurointensive care of severe community-acquired meningitis are few. The aims of this retrospective study were to review the acute clinical course, management and outcome in a series of bacterial meningitis patients receiving neurointensive care.

    METHODS:

    Thirty patients (median age 51, range 1-81) admitted from a population of 2 million people during 7 years were studied. The neurointensive care protocol included escalated stepwise treatment with mild hyperventilation, cerebrospinal fluid (CSF) drainage, continuous thiopentotal infusion and decompressive craniectomy. Clinical outcome was assessed using the Glasgow outcome scale.

    RESULTS:

    Twenty-eight patients did not respond to commands on arrival, five were non-reacting and five had dilated pupils. Twenty-two patients had positive CSF cultures: Streptococcus pneumoniae (n=18), Neisseria meningitidis (n=2), β-streptococcus group A (n=1) and Staphylococcus aureus (n=1). Thirty-five patients were mechanically ventilated. Intracranial pressure (ICP) was monitored in 28 patients (intraventricular catheter=26, intracerebral transducers=2). CSF was drained in 15 patients. Three patients received thiopentothal. Increased ICP (>20 mmHg) was observed in 7/26 patients with available ICP data. Six patients died during neurointensive care: total brain infarction (n=4), cardiac arrest (n=1) and treatment withdrawal (n=1). Seven patients died after discharge, three due to meningitis complications. At follow-up, 14 patients showed good recovery, six moderate disability, two severe disability and 13 were dead.

    CONCLUSION:

    Patients judged to have severe meningitis should be admitted to neurointensive care units without delay for ICP monitoring and management according to modern neurointensive care principles.

  • 73.
    Ekmark Lewén, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cellular Reactions and Behavioral Changes in Focal and Diffuse Traumatic Brain Injury: A Study in the Rat and Mouse2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Traumatic brain injury (TBI) is a severe condition and a major cause of death and disability. There is no pharmacological treatment available in clinical practice today and knowledge of brain injury mechanisms is of importance for development of neuroprotective drugs. The aims of the thesis were to get a better understanding of astrocyte reactions and immune responses, as well as behavioral changes after focal unilateral cortical contusion injury and diffuse bilateral central fluid percussion injury in rats and mice.

    In the focal injury models, the astrocyte reactions were generally restricted to the ipsilateral hemisphere. After diffuse TBI, vimentin and glial fibrillary acidic protein (GFAP) positive reactive astrocytes were bilaterally expressed in brain regions even distant from the injury site, including regions where axonal injury was seen. Early after diffuse TBI, there was a robust immune response, including activation of macrophages/microglia (Mac-2+) and infiltration of neutrophils (GR-1+) and T-cells (CD3+).

    In order to measure functional outcome, the recently established Multivariate Concentric Square Field™ (MCSF) test for complex behaviors, including risk taking and explorative strategies was used. The Morris water maze (MWM) was applied for testing learning and memory. The MCSF test revealed alterations in risk taking, risk assessment and exploratory behavior, in the mice subjected to focal injury whereas mice subjected to the diffuse injury showed a deviant stereotyped behavior. After focal injury mice showed a decreased ability to adapt to the arena in the second trial, when tested repeatedly in the MCSF test. Mice subjected to diffuse injury had an impaired memory but not learning, in the MWM test. Post-injury treatment with the anti-inflammatory anti-interleukin-1β (IgG2 a/k) antibody showed a positive effect on functional outcome in the diffuse injury model. Altogether, the results demonstrate that focal and diffuse TBI models produce differences in cellular reactions and behavioral outcome and that the immune response plays a key role in the pathology after brain injury. 

    Delarbeid
    1. Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain
    Åpne denne publikasjonen i ny fane eller vindu >>Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain
    Vise andre…
    2010 (engelsk)Inngår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 28, nr 3, s. 311-321Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Purpose: Astroglial responses after traumatic brain injury are difficult to detect with routine morphological methods. The aims for this study were to compare the temporal and spatial expression pattern of vimentin-and glial fibrillary acidic protein (GFAP) in a weight drop model of mild cerebral contusion injury in the rat. We also wanted to study the vimentin response with immunohistochemistry and vimentin mRNA RT-PCR analysis in severe cortical contusion injury produced by the controlled cortical impact in the mouse. Methods: Vimentin and GFAP immunohistochemistry (1day, 3 days and 7 days) combined with vimentin mRNA RT-PCR analysis (1 h, 4 h, 22 h, 3 days and 7 days) were used after experimental traumatic brain injury in the rat and mouse. Results: Increases in post-traumatic vimentin mRNA levels in the cortex and in the hippocampus appeared together with vimentin immunoreactivity in astrocytes in the perimeter of the cortical lesion, in the subcortical white matter and in the hippocampus starting at one day after severe trauma. GFAP immunostaining revealed hypertrophic astrocytes peaking at day 3 in the perifocal cortical region. There was no significant increase in GFAP immunoreactivity in the white matter in the rat. However, in the mouse there was a slight increase in the number of GFAP positive cells in this region, 3 days after trauma. Overall the pattern of vimentin immunoreactivity was very similar in the rat and mouse. Conclusions: Vimentin immunoreactivity was more sensitive than the GFAP staining method to demonstrate the distribution and time course of astrocyte reactions after a contusion injury, especially in the white matter distant from the cortical lesion.

    Emneord
    Traumatic brain injury, rat, mouse, astrocytes, gliosis
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-136066 (URN)10.3233/RNN-2010-0529 (DOI)000278442500002 ()
    Tilgjengelig fra: 2010-12-10 Laget: 2010-12-09 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. The Multivariate Concentric Square Field Test Reveals Behavioral Profiles of Risk Taking, Exploration, and Cognitive Impairment in Mice Subjected to Traumatic Brain Injury
    Åpne denne publikasjonen i ny fane eller vindu >>The Multivariate Concentric Square Field Test Reveals Behavioral Profiles of Risk Taking, Exploration, and Cognitive Impairment in Mice Subjected to Traumatic Brain Injury
    2010 (engelsk)Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 27, nr 9, s. 1643-1655Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    There is a need for more efficient tests to evaluate functional outcome following experimental traumatic brain injury (TBI), reflecting deficits in cognitive, sensory, and motor functions that are seen in TBI patients. The Multivariate Concentric Square Field (TM) (MCSF) test is a relatively new behavioral model that measures exploration, risk taking, risk assessment, and shelter seeking, all of which are evolutionarily-conserved strategies for survival. The multivariate design enables scoring of different functional domains in a single test situation, with a free choice of optional environmental settings. Furthermore, repeated trials permits cognitive effects to be measured. In the present study, 11 anesthetized C57BL6 mice received controlled cortical injury (CCI) (0.5mm and 3.3 m/sec) over the right parietal cerebral cortex or sham surgery (n - 12). Naive mice (n 12) not subjected to any surgical procedure were also included. The animals were evaluated in the MCSF test at 2 and 7 days post-surgery, and behavioral profiles were analyzed. The results revealed differences in risk taking and explorative behavior between the sham animals and the animals subjected to trauma. Animals subjected to trauma were characterized by taking more risks and had a higher level of exploration activity, but they sought less shelter. Repeated exposure to the MCSF caused a general decrease in activity in the naive and sham group, while a more specific behavioral impairment was seen in injured mice, suggesting cognitive dysfunction. We submit that the MCSF test is a useful complementary tool for functional outcome evaluation in experimental TBI.

    Emneord
    cognition, functional outcome, mouse, Multivariate Concentric Square Field Test, traumatic brain injury
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-134829 (URN)10.1089/neu.2009.0953 (DOI)000281796500011 ()
    Tilgjengelig fra: 2010-12-02 Laget: 2010-12-01 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes
    Åpne denne publikasjonen i ny fane eller vindu >>Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes
    Vise andre…
    2013 (engelsk)Inngår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 10, nr 1, s. 44-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the murine central fluid percussion injury (cFPI) TAI model, the neuroinflammatory and astroglial response and behavioral changes are unknown.

    Methods

    Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data).

    Results

    At all post-injury time points, beta-amyloid precursor protein (beta-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood--brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P<0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls.

    Conclusions

    Traumatic axonal injury in mice resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting traumatic axonal injury.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-198322 (URN)10.1186/1742-2094-10-44 (DOI)000318852600001 ()
    Tilgjengelig fra: 2013-04-11 Laget: 2013-04-11 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. Functional outcome after diffuse traumatic axonal injury in mice is improved by post-injury neutralization of interleukin-1ß
    Åpne denne publikasjonen i ny fane eller vindu >>Functional outcome after diffuse traumatic axonal injury in mice is improved by post-injury neutralization of interleukin-1ß
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-198738 (URN)
    Tilgjengelig fra: 2013-04-23 Laget: 2013-04-23 Sist oppdatert: 2018-01-11
  • 74.
    Ekmark-Lewén, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Flygt, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Fridgeirsdottir Andrea, Gudrun
    Kiwanuka, Olivia
    Hånell, Anders
    Meyerson J, Bengt
    Mir K, Anis
    Gram, Hermann
    Lewén, Anders
    Marklund, Niklas
    Hillered, Lars
    Functional outcome after diffuse traumatic axonal injury in mice is improved by post-injury neutralization of interleukin-1ßManuskript (preprint) (Annet vitenskapelig)
  • 75.
    Ekmark-Lewén, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Flygt, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Fridgeirsdottir, Gudrun A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kiwanuka, Olivia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Hanell, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Meyerson, Bengt J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Mir, Anis K.
    Novartis Inst Biomed Res, Basel, Switzerland..
    Gram, Hermann
    Novartis Inst Biomed Res, Basel, Switzerland..
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β2016Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 43, nr 8, s. 1016-1033Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1 has not been established in TAI. An IL-1-neutralizing or a control antibody was administered intraperitoneally at 30min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n=41) were compared with sham-injured controls (n=20) and untreated, naive mice (n=9). The anti-IL-1 antibody reached the target brain regions in adequate therapeutic concentrations (up to similar to 30g/brain tissue) at 24h post-injury in both cFPI (n=5) and sham-injured (n=3) mice, with lower concentrations at 72h post-injury (up to similar to 18g/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9days post-injury, and the Morris water maze (MWM) at 14-21days post-injury. Following TAI, the IL-1-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1 is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI.

  • 76.
    Ekmark-Lewén, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Flygt, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kiwanuka, Olivia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Meyerson, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes2013Inngår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 10, nr 1, s. 44-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the murine central fluid percussion injury (cFPI) TAI model, the neuroinflammatory and astroglial response and behavioral changes are unknown.

    Methods

    Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data).

    Results

    At all post-injury time points, beta-amyloid precursor protein (beta-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood--brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P<0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls.

    Conclusions

    Traumatic axonal injury in mice resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting traumatic axonal injury.

  • 77.
    Elf, Kristin
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Secondary Insults in Neurointensive Care of Patients with Traumatic Brain Injury2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Traumatic brain injury (TBI) is a major cause of death and disability. Intracranial secondary insults (e.g. intracranial haematoma, brain oedema) and systemic secondary insults (e.g. hypotension, hypoxaemia, hyperthermia) lead to secondary brain injury and affect outcome adversely. In order to minimise secondary insults and to improve outcome in TBI-patients, a secondary insult program and standardised neurointensive care (NIC) was implemented. The aim of this thesis was to describe patient outcome and to explore the occurrence and prognostic value of secondary insults after the implementation.

    Favourable outcome was achieved in 79% and 6% died of the 154 adult TBI patients treated in the NIC unit 1996-97. In an earlier patient series from the department, 48% made a favourable outcome and 31% died. Hence, the outcome seems to have improved when NIC was standardised and dedicated to avoiding secondary insults.

    Secondary insults counted manually from hourly recordings on surveillance charts did not hold any independent prognostic information. When utilising a computerised system, which enables minute-by-minute data collection, the proportion of monitoring time with systolic blood pressure > 160 mm Hg decreased the odds of favourable outcome independent of admission variables (odds ratio 0.66). Hyperthermia was related to unfavourable outcome. Hypertension was correlated to hyperthermia and may be a part of a hyperdynamic state aggravating brain oedema.

    Increased proportion of monitoring time with cerebral perfusion pressure (CPP) < 60 mm Hg increased the odds of favourable outcome (odds ratio 1.59) in patients treated according to an intracranial pressure (ICP)-oriented protocol (Uppsala). In patients given a CPP-oriented treatment (Edinburgh), CPP <60 mm Hg was coupled to an unfavourable outcome. It was shown that pressure passive patients seem to benefit from an ICP-oriented protocol and pressure active patients from a CPP-oriented protocol. The overall outcome would improve if patients were given a treatment fit for their condition.

    Delarbeid
    1. Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care
    Åpne denne publikasjonen i ny fane eller vindu >>Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care
    2002 (engelsk)Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 30, nr 9, s. 2129-2134Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92748 (URN)12352052 (PubMedID)
    Tilgjengelig fra: 2005-03-30 Laget: 2005-03-30 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Prevention of secondary insults in neurointensive care of traumatic brain injury
    Åpne denne publikasjonen i ny fane eller vindu >>Prevention of secondary insults in neurointensive care of traumatic brain injury
    2003 (engelsk)Inngår i: European Journal of Trauma, ISSN 1439-0590, E-ISSN 1615-3146, Vol. 29, nr 2, s. 74-80Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92749 (URN)10.1007/s00068-003-1273-9 (DOI)
    Tilgjengelig fra: 2005-03-30 Laget: 2005-03-30 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: A computerized secondary insult monitoring study
    Åpne denne publikasjonen i ny fane eller vindu >>Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: A computerized secondary insult monitoring study
    Vise andre…
    2005 (engelsk)Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 56, nr 5, s. 962-971Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92750 (URN)10.1227/01.NEU.0000158317.00603.40 (DOI)15854244 (PubMedID)
    Tilgjengelig fra: 2005-03-30 Laget: 2005-03-30 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma
    Åpne denne publikasjonen i ny fane eller vindu >>Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma
    Vise andre…
    2005 (engelsk)Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 102, nr 2, s. 311-317Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    Emneord
    traumatic brain injury, intracranial pressure, cerebral perfusion pressure, pressure reactivity, outcome
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92751 (URN)15739560 (PubMedID)
    Tilgjengelig fra: 2005-03-30 Laget: 2005-03-30 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    5. Temperature disturbances in traumatic brain injury: relationship to secondary insults, barbiturate treatment and outcome
    Åpne denne publikasjonen i ny fane eller vindu >>Temperature disturbances in traumatic brain injury: relationship to secondary insults, barbiturate treatment and outcome
    Vise andre…
    2008 (engelsk)Inngår i: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 30, nr 10, s. 1097-1105Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objectives: To describe the occurrence of spontaneous hyper- and hypothermia in patients with traumatic brain injury using a computerized data collecting system, to show how temperature correlates with other secondary insults, to describe how temperature affects outcome and to show how barbiturate treatment influences those analyses.

    Methods: Patients with >= 54 hours of valid monitoring within the first 120 hours after trauma (one value/min) for temperature, intracranial pressure, cerebral perfusion pressure, systolic blood pressure, mean blood pressure and heart rate were included. Correlation analyses were performed between temperature and other secondary insult variables. The non-linear relationship between temperature and outcome (measured by Glasgow outcome scale 6 months post-trauma) was illustrated using a neural network.

    Results: Of the 53 patients, 44 experienced hyperthermia (>38 degrees C) and 29 experienced hypothermia (<36 degrees C). Hyperthermia correlated with occurrence of high blood pressure and high CPP. In individuals, hyperthermia also correlated with ICP and tachycardia. There was a trend towards better outcome for patients with normal temperature than those with hyper- or hypothermia (favorable outcome 64% versus 29 and 33% respectively). When patients treated with barbiturates were excluded, 60% showed favorable outcome in the hypothermia group as well. Barbiturate treatment also confounded analyses regarding temperature and other secondary insults.

    Discussion: Patients with hyperthermia, hypertension, high CPP and tachycardia may suffer from a hyperdynamic state. This may worsen outcome and hence clinical awareness is important. Barbiturate treatment confounds several analyses which have not been shown before. We recommend those patients to be analysed separately in future studies.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92752 (URN)10.1179/174313208X319125 (DOI)000263024900015 ()
    Tilgjengelig fra: 2005-03-30 Laget: 2005-03-30 Sist oppdatert: 2017-12-14bibliografisk kontrollert
  • 78.
    Elf, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Carlsson, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Santeliz Rivas, Liliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Widnersson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nyholm, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Electroencephalographic Patterns During Common Nursing Interventions in Neurointensive Care: A Descriptive Pilot Study2019Inngår i: Journal of Neuroscience Nursing, ISSN 0888-0395, E-ISSN 1945-2810, Vol. 51, nr 1, s. 10-15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Many patients with neurological insults requiring neurointensive care have an increased risk of acute symptomatic seizures. Various nursing interventions performed when caring for these patients may elicitpathological cerebral electrical activity including seizures and stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs). The aim was to explore changes in electroencephalogram (EEG) due to neurointensive care nursing interventions.

    Methods: A convenience sample was recruited between November 2015 and April 2016, consisting of 12 adult patients with impaired consciousness due to a neurosurgical condition. Continuous EEG and simultaneous video recordings of nursing interventions were collected 48 continuous hours for each patient. Two analysts categorized the video recordings for common nursing interventions, and a neurophysiologist analyzed the EEGs.

    Results: In total, 976 nursing interventions were observed. Epileptiform activity was observed in 4 patients (33%), during 1 nursing intervention episode each (0.4%). The 4 observed episodes of epileptiform activity occurred during multiple simultaneous nursing interventions (n = 3) and hygienic interventions (n = 1). Stimulus-induced rhythmic, periodic, or ictal discharges were observed in 1patient (8%), in 1 single nursing intervention (0.1%). The observed SIRPID soccurred during repositioning of thepatient. All patients had muscle artifacts, during 353 nursing interventions (36.3%). The duration of nursing interventions was longer for those with simultaneous muscle artifacts (median, 116 seconds) than those without muscle artifacts, epileptiform activity, or SIRPIDs (median, 89.0 seconds). With regard to epileptiform activityand SIRPIDs, the median durations of the nursing interventions were 1158 and 289 seconds, respectively.

    Conclusion: The results of this pilot study indicate that muscle artifacts seem prevalent during nursing interventions and may be a sign of stress. Nurses should be aware of the risk of inducing stress by performing regular nursing interventions in daily practice, consider shorter or fewer interventions at a time in sensitive patients, and administer sedation accordingly. Considering that this was a pilot study, more research that investigates correlations between EEG patterns and nursing interventions in larger samples is needed.

  • 79.
    Elf, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care2002Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 30, nr 9, s. 2129-2134Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 80.
    Elf, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Prevention of secondary insults in neurointensive care of traumatic brain injury2003Inngår i: European Journal of Trauma, ISSN 1439-0590, E-ISSN 1615-3146, Vol. 29, nr 2, s. 74-80Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 81.
    Elf, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: A computerized secondary insult monitoring study2005Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 56, nr 5, s. 962-971Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 82.
    Elf, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Temperature disturbances in traumatic brain injury: relationship to secondary insults, barbiturate treatment and outcome2008Inngår i: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 30, nr 10, s. 1097-1105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To describe the occurrence of spontaneous hyper- and hypothermia in patients with traumatic brain injury using a computerized data collecting system, to show how temperature correlates with other secondary insults, to describe how temperature affects outcome and to show how barbiturate treatment influences those analyses.

    Methods: Patients with >= 54 hours of valid monitoring within the first 120 hours after trauma (one value/min) for temperature, intracranial pressure, cerebral perfusion pressure, systolic blood pressure, mean blood pressure and heart rate were included. Correlation analyses were performed between temperature and other secondary insult variables. The non-linear relationship between temperature and outcome (measured by Glasgow outcome scale 6 months post-trauma) was illustrated using a neural network.

    Results: Of the 53 patients, 44 experienced hyperthermia (>38 degrees C) and 29 experienced hypothermia (<36 degrees C). Hyperthermia correlated with occurrence of high blood pressure and high CPP. In individuals, hyperthermia also correlated with ICP and tachycardia. There was a trend towards better outcome for patients with normal temperature than those with hyper- or hypothermia (favorable outcome 64% versus 29 and 33% respectively). When patients treated with barbiturates were excluded, 60% showed favorable outcome in the hypothermia group as well. Barbiturate treatment also confounded analyses regarding temperature and other secondary insults.

    Discussion: Patients with hyperthermia, hypertension, high CPP and tachycardia may suffer from a hyperdynamic state. This may worsen outcome and hence clinical awareness is important. Barbiturate treatment confounds several analyses which have not been shown before. We recommend those patients to be analysed separately in future studies.

  • 83.
    Elobeid, Adila
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Laurell, Katarina
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Correlations Between Mini-Mental State Examination Score, Cerebrospinal Fluid Biomarkers, and Pathology Observed in Brain Biopsies of Patients With Normal-Pressure Hydrocephalus2015Inngår i: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 74, nr 5, s. 470-479Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-beta-amyloid (A beta) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant A beta and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between A beta-immunostained area fraction in tissue and A beta 42 (42-amino-acid form of A beta) in cerebrospinal fluid (CSF). Levels of A beta 42 were significantly lower in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of A beta (A beta 42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.

  • 84.
    Enblad, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Martinsson, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Population-based experience on primary central nervous system lymphoma 2000-2012: the incidence is increasing2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 4, s. 599-607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare lymphomas with a poor prognosis. Recently, an increased incidence has been reported. The present study is a population-based study of all patients with PCNSL in the Uppsala/Örebro region of middle Sweden.

    PATIENTS AND METHODS: All patients diagnosed with a PCNSL at Uppsala University Hospital 2000-2012 were identified. Altogether, 96 patients (50 women and 46 men) were included. The median age at diagnosis was 66 years (17-95).

    RESULTS: There was a statistically significant increase in age-standardized incidence during the study period, 30 patients were diagnosed in the first half and 66 in the second half of the period. No patient had an HIV-infection. Two patients had undergone kidney transplantation and were treated with immunosuppressive drugs. A high proportion of the patients, 29%, had a history of an autoimmune or inflammatory disease. The prognosis was poor with a median survival of only four months. In the 70 (73%) patients treated with curative intention the median survival was 12 months. Patients treated with high-dose methotrexate, radiotherapy and/or temozolomide appeared to have a better survival. There was no improvement in survival during the study period or after the introduction of rituximab. There also was no difference in any of the analyzed variables that could explain the increased incidence.

    CONCLUSION: In this population-based study we could confirm the previously described increased incidence of PCNSL. The prognosis remains poor despite the inclusion of treatment with rituximab during the study period. A high proportion of the patients had a history of an autoimmune or inflammatory disease not previously described but there was no increase during the study period.

  • 85.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Continuous monitoring of intracranial compliance in neurointensive care (Editorial by invitation)2018Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 160, nr 12, s. 2289-2290Artikkel i tidsskrift (Annet vitenskapelig)
  • 86.
    Engquist, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Response to "Letter to the Editor" by R. Dhar: Re: Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage2018Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 28, nr 2, s. 259-259Artikkel i tidsskrift (Annet vitenskapelig)
  • 87.
    Engquist, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Johnson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Rostami, Elham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hemodynamic Disturbances in the Early Phase After Subarachnoid Hemorrhage: Regional Cerebral Blood Flow Studied by Bedside Xenon-enhanced CT.2018Inngår i: Journal of Neurosurgical Anesthesiology, ISSN 0898-4921, E-ISSN 1537-1921, Vol. 30, nr 1, s. 49-58Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 88.
    Engquist, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Rostami, Elham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT2019Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 30, nr 2, s. 280-290Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 89.
    Engquist, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Rostami, Elham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT2018Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 28, nr 2, s. 143-151Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 90.
    Engquist, Markus
    et al.
    Ryhov Hosp, Dept Orthopaed, S-55185 Jonkoping, Sweden.
    Lofgren, Hakan
    Ryhov Hosp, Neuroorthoped Ctr, Jonkoping, Sweden.
    Oberg, Birgitta
    Linkoping Univ, Fac Hlth Sci, Div Physiotherapy, Dept Med & Hlth Sci, Linkoping, Sweden.
    Holtz, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Peolsson, Anneli
    Linkoping Univ, Fac Hlth Sci, Div Physiotherapy, Dept Med & Hlth Sci, Linkoping, Sweden.
    Soderlund, Anne
    Malardalen Univ, Sch Hlth Care & Social Welf, Dept Physiotherapy, Vasteras, Sweden.
    Vavruch, Ludek
    Ryhov Hosp, Neuroorthoped Ctr, Jonkoping, Sweden.
    Lind, Bengt
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden;Spine Ctr Goteborg, Gothenburg, Sweden.
    A 5-to 8-year randomized study on the treatment of cervical radiculopathy: anterior cervical decompression and fusion plus physiotherapy versus physiotherapy alone2017Inngår i: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 26, nr 1, s. 19-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE The aim of this study was to evaluate the 5- to 8-year outcome of anterior cervical decompression and fusion (ACDF) combined with a structured physiotherapy program as compared with that following the same physiotherapy program alone in patients with cervical radiculopathy. No previous prospective randomized studies with a follow-up of more than 2 years have compared outcomes of surgical versus nonsurgical intervention for cervical radiculopathy. METHODS Fifty-nine patients were randomized to ACDF surgery with postoperative physiotherapy (30 patients) or to structured physiotherapy alone (29 patients). The physiotherapy program included general and specific exercises as well as pain coping strategies. Outcome measures included neck disability (Neck Disability Index [NDI]), neck and arm pain intensity (visual analog scale [VAS]), health state (EQ-5D questionnaire), and a patient global assessment. Patients were followed up for 5-8 years. RESULTS After 5-8 years, the NDI was reduced by a mean score% of 21 (95% CI 14-28) in the surgical group and 11% (95% CI 4%-18%) in the nonsurgical group (p = 0.03). Neck pain was reduced by a mean score of 39 mm (95% CI 26-53 mm) compared with 19 mm (95% CI 7-30 mm; p = 0.01), and arm pain was reduced by a mean score of 33 mm (95% CI 18-49 mm) compared with 19 mm (95% CI 7-32 mm; p = 0.1), respectively. The EQ-5D had a mean respective increase of 0.29 (95% CI 0.13-0.45) compared with 0.14 (95% CI 0.01-0.27; p = 0.12). Ninety-three percent of patients in the surgical group rated their symptoms as "better" or "much better" compared with 62% in the nonsurgical group (p = 0.005). Both treatment groups experienced significant improvement over baseline for all outcome measures. CONCLUSIONS In this prospective randomized study of 5- to 8-year outcomes of surgical versus nonsurgical treatment in patients with cervical radiculopathy, ACDF combined with physiotherapy reduced neck disability and neck pain more effectively than physiotherapy alone. Self-rating by patients as regards treatment outcome was also superior in the surgery group. No significant differences were seen between the 2 patient groups as regards arm pain and health outcome.

  • 91. Engquist, Markus
    et al.
    Lofgren, Hakan
    Oberg, Birgitta
    Holtz, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Peolsson, Anneli
    Soderlund, Anne
    Vavruch, Ludek
    Lind, Bengt
    Surgery Versus Nonsurgical Treatment of Cervical Radiculopathy A Prospective, Randomized Study Comparing Surgery Plus Physiotherapy With Physiotherapy Alone With a 2-Year Follow-up2013Inngår i: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 38, nr 20, s. 1715-1722Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study Design. Prospective randomized controlled trial. Objective. To study the outcome of anterior cervical decompression and fusion combined with a structured physiotherapy program compared with the same physiotherapy program alone for patients with cervical radiculopathy. Summary of Background Data. Knowledge concerning the effects of interventions for patients with cervical radiculopathy is scarce due to a lack of randomized studies. Methods. Sixty-three patients were randomized to surgery with postoperative physiotherapy (n = 31) or physiotherapy alone (n = 32). The surgical group was treated with anterior cervical decompression and fusion. The physiotherapy program included general/specific exercises and pain-coping strategies. The outcome measures were disability (Neck Disability Index), neck and arm pain intensity (visual analogue scale), and the patient's global assessment. Patients were followed for 24 months. Results. The result from the repeated-measures analysis of variance showed no significant between-group difference for Neck Disability Index (P = 0.23). For neck pain intensity, the repeated-measures analysis of variance showed a significant between-group difference during the study period in favor of the surgical group (P = 0.039). For arm pain intensity, no significant between-group differences were found according to the repeated-measures analysis of variance (P = 0.580). Eighty-seven percent of the patients in the surgical group rated their symptoms as "better/much better" at the 12-month follow-up compared with 62% in the nonsurgical group (P < 0.05). At 24 months, the corresponding figures were 81% and 69% (P = 0.28). The difference was significant only at the 12-month follow-up in favor of the surgical group. Significant reduction in Neck Disability Index, neck pain, and arm pain compared with baseline was seen in both groups (P < 0.001). Conclusion. In this prospective, randomized study of patients with cervical radiculopathy, it was shown that surgery with physiotherapy resulted in a more rapid improvement during the first postoperative year, with significantly greater improvement in neck pain and the patient's global assessment than physiotherapy alone, but the differences between the groups decreased after 2 years. Structured physiotherapy should be tried before surgery is chosen.

  • 92.
    Engquist, Markus
    et al.
    Ryhov Hosp, Dept Orthopaed, S-55185 Jonkoping, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden..
    Löfgren, Håkan
    Ryhov Hosp, Neuroorthoped Ctr, S-55185 Jonkoping, Sweden..
    Öberg, Birgitta
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden..
    Holtz, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Pålsson, Anneli
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden..
    Söderlund, Anne
    Malardalen Univ, Sch Hlth Care & Social Welf, Dept Physiotherapy, Vasteras, Sweden..
    Vavruch, Ludek
    Ryhov Hosp, Neuroorthoped Ctr, S-55185 Jonkoping, Sweden..
    Lind, Bengt
    Univ Gothenburg, Sahlgrenska Acad, Dept Orthopaed, Inst Clin Sci, Gothenburg, Sweden.;Spine Ctr Goteborg, Gothenburg, Sweden..
    Factors Affecting the Outcome of Surgical Versus Nonsurgical Treatment of Cervical Radiculopathy2015Inngår i: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 40, nr 20, s. 1553-1563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study Design. Prospective randomized controlled trial. Objective. To analyze factors that may influence the outcome of anterior cervical decompression and fusion (ACDF) followed by physiotherapy versus physiotherapy alone for treatment of patients with cervical radiculopathy. Summary of Background Data. An understanding of patient-related factors affecting the outcome of ACDF is important for preoperative patient selection. No previous prospective, randomized study of treatment effect modifiers relating to outcome of ACDF compared with physiotherapy has been carried out. Methods. 60 patients with cervical radiculopathy were randomized to ACDF followed by physiotherapy or physiotherapy alone. Data for possible modifiers of treatment outcome at 1 year, such as sex, age, duration of pain, pain intensity, disability (Neck Disability Index, NDI), patient expectations of treatment, anxiety due to neck/arm pain, distress (Distress and Risk Assessment Method), self-efficacy (Self-Efficacy Scale) health status (EQ-5D), and magnetic resonance imaging findings were collected. A multivariate analysis was performed to find treatment effect modifiers affecting the outcome regarding arm/neck pain intensity and NDI. Results. Factors that significantly altered the treatment effect between treatment groups in favor of surgery were: duration of neck pain less than 12 months (P = 0.007), duration of arm pain less than 12 months (P = 0.01) and female sex (P = 0.007) (outcome: arm pain), low EQ-5D index (outcome: neck pain, P = 0.02), high levels of anxiety due to neck/arm pain (outcome: neck pain, P = 0.02 and NDI, P = 0.02), low Self-Efficacy Scale score (P = 0.05), and high Distress and Risk Assessment Method score (P = 0.04) (outcome: NDI). No factors were found to be associated with better outcome with physiotherapy alone. Conclusion. In this prospective, randomized study of patients with cervical radiculopathy, short duration of pain, female sex, low health quality, high levels of anxiety due to neck/arm pain, low self-efficacy, and a high level of distress before treatment were associated with better outcome from surgery. No factors were found to be associated with better outcome from physiotherapy alone.

  • 93.
    Engström, Maria
    et al.
    Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; CMIV, Linköpings universitet, Linköping, Sweden.
    Latini, Francesco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Neuroimaging in the Kleine-Levin Syndrome2018Inngår i: Current Neurology and Neuroscience Reports, ISSN 1528-4042, E-ISSN 1534-6293, Vol. 18, nr 9, artikkel-id 58Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    PURPOSE OF REVIEW: The purpose was to review the most recent literature on neuroimaging in the Kleine-Levin syndrome (KLS). We aimed to investigate if frontotemporal and thalamic dysfunction are key KLS signatures, and if recent research indicates other brain networks of interest that elucidate KLS symptomatology and aetiology.

    RECENT FINDINGS: In a comprehensive literature search, we found 12 original articles published 2013-2018. Most studies report deviations related to cerebral perfusion, glucose metabolism, or blood-oxygen-level-dependent responses in frontotemporal areas and/or the thalamus. Studies also report dysfunction in the temporoparietal junction and the oculomotor network that also were related to clinical parameters. We discuss these findings based on recent research on thalamocortical networks and brain stem white matter tracts. The hypothesis of frontotemporal and thalamic involvement in KLS was confirmed, and additional findings in the temporoparietal junction and the oculomotor system suggest a broader network involvement, which can be investigated by future high-resolution and multimodal imaging.

  • 94.
    Erlandsson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lin, Chia-Hsun Anthony
    Yu, Fenggang
    Morshead, Cindi M.
    Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury2011Inngår i: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 230, nr 1, s. 48-57Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent work has demonstrated that self-repair in the adult brain can be augmented by the infusion of growth factors to activate endogenous neural precursor cells that contribute to new tissue formation and functional recovery in a model of stroke. Using both a genetic model and drug treatment, we demonstrate that immunosuppression mimics the effects of growth factor activation, including tissue regeneration, neural precursor cell migration and functional recovery following ischemic injury. In the absence of growth factor treatment, mice with a functional immune system develop a prominent cavity in the cortex underlying the ischemic injury. In untreated immunodeficient NOD/SCID mice, however, the cortical cavity forms but is then filled with regenerated cortical tissue containing glial cells and subependyma derived neural stem and progenitor cells that migrate from their niche lining the lateral ventricles. The daily administration of Cyclosporine A also results in endogenous neural precursor cell migration and regenerated cortical tissue at the site of the cortical injury. Different from growth factor-treated animals is the finding that the regenerated cortical tissue in immunosuppressed animals is devoid of new neurons. Interestingly, both the growth factor and immunosuppressed (NOD/SCID and Cyclosporine A) treated animals displayed functional behavioural recovery despite the lack of neurogenesis within the regenerated cortical tissue. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."

  • 95.
    Fahlström, Andreas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tobieson, Lovisa
    Linkoping Univ, Dept Neurosurg, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Redebrandt, Henrietta Nittby
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Zeberg, Hugo
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Bartek, Jiri, Jr.
    Karolinska Inst, Dept Med & Clin Neurosci, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden;Rigshosp, Copenhagen Univ Hosp, Dept Neurosurg, Copenhagen, Denmark.
    Bartley, Andreas
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Clin Neurosci,Neurosurg, Gothenburg, Sweden.
    Erkki, Maria
    Umea Univ, Umea Univ Hosp, Dept Clin Neurosci, Neurosurg, Umea, Sweden.
    Hessington, Amel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Troberg, Ebba
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Mirza, Sadia
    Karolinska Inst, Dept Med & Clin Neurosci, Stockholm, Sweden.
    Tsitsopoulos, Parmenion P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Linkoping Univ, Dept Neurosurg, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden;Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients2019Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, nr 5, s. 955-965Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Supratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden.

    Objective

    In this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated.

    Methods

    Patient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015.

    Results

    In total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p<.05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p<.05). The 30-day mortality ranged between 10 and 28%.

    Conclusions

    Although indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.

  • 96.
    Falk Delgado, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Markus, Nilsson
    Bioimaging center, Lunds Universitet.
    Ghaderi Berntsson, Shala
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    van Westen, Danielle
    Clinical Sciences, Lunds Universitet.
    Lätt, Jimmy
    MR Department, Center for medical imaging and physiology, Lund University Hospital.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Preoperative diffusion kurtosis imaging in suspected low-grade gliomas: A prospective study of diffusional properties in tumour and perilesional regions with histopathological correlationsManuskript (preprint) (Annet vitenskapelig)
  • 97.
    Falk Delgado, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Nilsson, Markus
    Lund Univ, Bioimaging Ctr, Lund, Sweden..
    Berntsson, Shala G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Libard, Sylwia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    van Westen, Danielle
    Lund Univ, Clin Sci Lund, Diagnost Radiol, Lund, Sweden..
    Lätt, Jimmy
    Skane Univ Healthcare, Dept Imaging & Funct, Lund, Sweden..
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation2017Inngår i: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 51, nr 2, s. 121-129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).

    Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.

    Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.

    Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

  • 98.
    Falk Delgado, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Markus, Nilsson
    Bioimaging center, Lunds Universitet.
    Latini, Francesco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mårtensson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ghaderi Berntsson, Shala
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lätt, Jimmy
    MR Department, Center for medical imaging and physiology, Lund University Hospital.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Preoperative quantitative MR tractography analysis compared with visual tract evaluation in patients with suspected low-grade gliomas.Manuskript (preprint) (Annet vitenskapelig)
  • 99.
    Falk Delgado, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Nilsson, Markus
    Latini, Francesco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mårtensson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Berntsson, Shala G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lätt, Jimmy
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study2016Inngår i: Radiology Research and Practice, ISSN 2090-1941, E-ISSN 2090-195X, artikkel-id 7671854Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

  • 100.
    Finnsson, Johannes
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sundblom, Jimmy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Dahl, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Melberg, Atle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Raininko, Raili
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course2015Inngår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 78, nr 3, s. 412-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Duplication of the LMNB1 gene encoding lamin B1 causes adult-onset autosomal-dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia. Magnetic resonance imaging (MRI) of the brain reveals characteristic findings. This is the first longitudinal study on this disease. Our objective is to describe the natural clinical and radiological course of LMNB1-related ADLD.

    METHODS: Twenty-three subjects in two families with LMNB1 duplications were studied over two decades with clinical assessment and MRI of the brain and spinal cord. They were 29 to 70 years old at their first MRI. Repeated MRIs were performed in 14 subjects over a time period of up to 17 years.

    RESULTS: Pathological MRI findings were found in the brain and spinal cord in all examinations (i.e., even preceding clinical symptoms). MRI changes and clinical symptoms progressed in a definite order. Autonomic dysfunction appeared in the fifth to sixth decade, preceding or together with gait and coordination difficulties. Motor signs developed ascending from spastic paraplegia to tetraplegia and pseudobulbar palsy in the seventh decade. There were clinical, radiological, and neurophysiological signs of myelopathy. Survival lasted more than two decades after clinical onset.

    INTERPRETATION: LMNB1-related ADLD is a slowly progressive neurological disease. MRI abnormalities of the brain and spinal cord can precede clinical symptoms by more than a decade and are extensive in all symptomatic patients. Spinal cord involvement is a likely contributing factor to early autonomic symptoms and spastic paraplegia. Ann Neurol 2015;78:412-425.

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