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  • 301.
    Sköld, Mattias K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kanje, Martin
    Vascular Endothelial Growth Factor in Central Nervous System Injuries: A Vascular Growth Factor Getting Nervous?2008Inngår i: Current Neurovascular Research, ISSN 1567-2026, Vol. 5, nr 4, s. 246-259Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Vascular Endothelial Growth Factor ( VEGF) is recognized as a central factor in growth, survival and permeability of blood vessels in both physiological and pathological conditions. It is as such of importance for vascular responses in various central nervous system (CNS) disorders. Accumulating evidence suggest that VEGF may also act as a neuroprotective and neurotrophic factor supporting neuronal survival and neuronal regeneration. Findings of neuropilins as shared co-receptors between molecules with such seemingly different functions as the axon guidance molecules semaphorins and VEGF has further boosted the interest in the role of VEGF in neural tissue injury and repair mechanisms. Thus, VEGF most likely act in parallel or concurrent on cells in both the vascular and nervous system. The present review gives a summary of known or potential aspects of the VEGF system in the healthy and diseased nervous system. The potential benefits but also problems and pitfalls in intervening in the actions of such a multifunctional factor as VEGF in the disordered CNS are also covered.

  • 302.
    Smits, Anja
    et al.
    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.
    Lundin, Margareta
    Melin, Beatrice
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Grabowska, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Berntsson, Shala Ghaderi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Neurological Impairment Linked with Cortico-Subcortical Infiltration of Diffuse Low-Grade Gliomas at Initial Diagnosis Supports Early Brain Plasticity2015Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, artikkel-id 137Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.

  • 303.
    Sravani, Musunuri
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala University.
    Hamdeh, Sami Abu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mi, Jia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Shevchenko, Ganna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Differential proteomic analysis for the evaluation of protein expression in fresh human cortical brain biopsiesManuskript (preprint) (Annet vitenskapelig)
  • 304. Stell, A.
    et al.
    Sinnott, R.
    Donald, R.
    Chambers, I.
    Citerio, G.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gregson, B.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Kiening, K.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ragauskas, A.
    Sahuquillo, J.
    Piper, I.
    Supporting clinical trials to predict adverse events in the brain trauma domain2012Inngår i: IEEE Symposium on Computer-Based Medical Systems, 2012, s. 6266380-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    There are many serious and acute physiological conditions about which we have incomplete medical knowledge. To address this and develop effective treatments it is often the case that a wealth of clinical data is required for collection, analysis and feedback. Whilst such data often exists it is typically held in a variety of different formats and locations. This paper describes the EU FP7-funded Avert-IT project (www.avert-it.org), which has developed an integrated, real-time physiological data infrastructure (ICUnet) to address the specific issue of prediction of hypotensive events in the brain trauma domain. This system has been used to support a major multi-centre clinical trial. In this paper, the implementation and application of the ICUnet system is described, followed by the design and results of the clinical trial.

  • 305. Stell, Anthony
    et al.
    Sinnott, Richard
    Jiang, Jipu
    Donald, Rob
    Chambers, Iain
    Citerio, Giuseppe
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gregson, Barbara
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kiening, Karl
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ragauskas, Arminas
    Sahuquillo, Juan
    Piper, Ian
    Federating distributed clinical data for the prediction of adverse hypotensive events2009Inngår i: Philosophical Transactions. Series A: Mathematical, physical, and engineering science, ISSN 1364-503X, E-ISSN 1471-2962, Vol. 367, nr 1898, s. 2679-2690Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The ability to predict adverse hypotensive events, where a patient's arterial blood pressure drops to abnormally low (and dangerous) levels, would be of major benefit to the fields of primary and secondary health care, and especially to the traumatic brain injury domain. A wealth of data exist in health care systems providing information on the major health indicators of patients in hospitals (blood pressure, temperature, heart rate, etc.). It is believed that if enough of these data could be drawn together and analysed in a systematic way, then a system could be built that will trigger an alarm predicting the onset of a hypotensive event over a useful time scale, e.g. half an hour in advance. In such circumstances, avoidance measures can be taken to prevent such events arising. This is the basis for the Avert-IT project (http://www.avert-it.org), a collaborative EU-funded project involving the construction of a hypotension alarm system exploiting Bayesian neural networks using techniques of data federation to bring together the relevant information for study and system development.

  • 306.
    Sundblom, Jimmy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nowinski, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Casar Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Ryttlefors, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Removal of giant intraosseous meningioma followed by cranioplasty using a custom-made bioceramic implant: case report2019Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 131, nr 3, s. 735-739Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intraosseous meningioma of the chordoid type is a rare clinical entity. Radical surgical removal and subsequent cranioplasty is the treatment of choice. Here, the authors report a severe case involving more than 70% of the calvarial surface area, which was removed and repaired using a prefabricated custom-made, titanium-reinforced, bioceramic implant and bone-cutting guides. Tumor removal and good esthetic outcome were achieved, along with a 17.1% increase of intracranial volume. Bioceramic implants have shown promising initial results and may represent an important new tool in the surgeon's armamentarium.

  • 307.
    Sundström, Nina
    et al.
    Umea Univ, Dept Radiat Sci, Biomed Engn, Umea, Sweden..
    Malm, Jan
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Laurell, Katarina
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Lundin, Fredrik
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Kahlon, Babar
    Univ Hosp, Dept Neurosurg, Lund, Sweden..
    Cesarini, Kristina G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Leijon, Göran
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Wikkelso, Carsten
    Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Incidence and outcome of surgery for adult hydrocephalus patients in Sweden2017Inngår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 31, nr 1, s. 21-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Object: To present population-based and age related incidence of surgery and clinical outcome for adult patients operated for hydrocephalus, registered in the Swedish Hydrocephalus Quality Registry (SHQR). Methods: All patients registered in SHQR during 2004-2011 were included. Data on age, gender, type of hydrocephalus and type of surgery were extracted as well as three months outcome for patients with idiopathic normal pressure hydrocephalus (iNPH). Results: The material consisted of 2360 patients, 1229 men and 1131 women, age 63.8 +/- 14.4 years (mean standard deviation (SD)). The mean total incidence of surgery was 5.1 +/- 0.9 surgeries/100,000/year; 4.7 +/- 0.9 shunt surgeries and 0.4 +/- 0.1 endoscopic third ventriculostomies. For iNPH, secondary communicating hydrocephalus and obstructive hydrocephalus, the incidence of surgery was 2.2 +/- 0.8, 1.9 +/- 0.3 and 0.8 +/- 0.1/100,000/year, respectively. During 2004-2011, the incidence of surgery increased in total (p = .044), especially in age groups 70-79 years and > 80 years (p = .012 and p = .031). After surgery, 253 of 652 iNPH patients (38.8%) improved at least one step on the modified Rankin scale (mRS). Number needed to treat was 3.0 for improving one patient from unfavourable (mRS 3-5) to favourable (mRS 0-2). The mean score of a modified iNPH scale increased from 54 +/- 23 preoperatively to 63 +/- 25 postoperatively (p < .0001, n = 704), and 58% improved. No significant regional differences in incidence, surgical techniques or outcome were found. Conclusions: Incidence of hydrocephalus surgery increased significantly during 2004-2011, specifically in elderly patients. Surgical treatment of INPH markedly improved functional independence, but the improvement rate was low compared to recent single- and multicentre studies. Thus, the potential for surgical improvement is likely lower than generally reported when treating patients as part of everyday clinical care.

  • 308. Suominen, Tina
    et al.
    Uutela, Paivi
    Ketola, Raimo A.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Finel, Moshe
    Zhang, Hongbo
    Laakso, Aki
    Kostiainen, Risto
    Determination of Serotonin and Dopamine Metabolites in Human Brain Microdialysis and Cerebrospinal Fluid Samples by UPLC-MS/MS: Discovery of Intact Glucuronide and Sulfate Conjugates2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6, s. e68007-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An UPLC-MS/MS method was developed for the determination of serotonin (5-HT), dopamine (DA), their phase I metabolites 5-HIAA, DOPAC and HVA, and their sulfate and glucuronide conjugates in human brain microdialysis samples obtained from two patients with acute brain injuries, ventricular cerebrospinal fluid (CSF) samples obtained from four patients with obstructive hydrocephalus, and a lumbar CSF sample pooled mainly from patients undergoing spinal anesthesia in preparation for orthopedic surgery. The method was validated by determining the limits of detection and quantification, linearity, repeatability and specificity. The direct method enabled the analysis of the intact phase II metabolites of 5-HT and DA, without hydrolysis of the conjugates. The method also enabled the analysis of the regioisomers of the conjugates, and several intact glucuronide and sulfate conjugates were identified and quantified for the first time in the human brain microdialysis and CSF samples. We were able to show the presence of 5-HIAA sulfate, and that dopamine-3-O-sulfate predominates over dopamine-4-O-sulfate in the human brain. The quantitative results suggest that sulfonation is a more important phase II metabolism pathway than glucuronidation in the human brain.

  • 309.
    Svedung Wettervik, Teodor
    et al.
    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.
    Letter to the Editor: Decompressive craniectomy in traumatic brain injury—the discussion must continue2018Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 160, nr 6, s. 1303-1303Artikkel i tidsskrift (Fagfellevurdert)
  • 310.
    Svedung Wettervik, Teodor
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lenell, Samuel
    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.
    Howells, Tim
    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.
    Decompressive craniectomy in traumatic brain injury: usage and clinical outcome in a single centre2018Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 160, nr 2, s. 229-237Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Two randomised controlled trials (RCTs) of decompressive craniectomy (DC) in traumatic brain injury (TBI) have shown poor outcome, but there are considerations of how these protocols relate to real practice. The aims of this study were to evaluate usage and outcome of DC and thiopental in a single centre.

    Method: The study included all TBI patients treated at the neurointensive care unit, Akademiska sjukhuset, Uppsala, Sweden, between 2008 and 2014. Of 609 patients aged 16 years or older, 35 treated with DC and 23 treated with thiopental only were studied in particular. Background variables, intracranial pressure (ICP) measures and global outcome were analysed.

    Results: Of 35 DC patients, 9 were treated stepwise with thiopental before DC, 9 were treated stepwise with no thiopental before DC and 17 were treated primarily with DC. Six patients received thiopental after DC. For 23 patients, no DC was needed after thiopental. Eighty-eight percent of our DC patients would have qualified for the DECRA study and 38% for the Rescue-ICP trial. Favourable outcome was 44% in patients treated with thiopental before DC, 56% in patients treated with DC without prior thiopental, 29% in patients treated primarily with DC and 52% in patients treated with thiopental with no DC.

    Conclusions: The place for DC in TBI management must be evaluated better, and we believe it is important that future RCTs should have clearer and less permissive ICP criteria regarding when thiopental should be followed by DC and DC followed by thiopental.

  • 311.
    Svensson, Elisabeth
    et al.
    Örebro University, Dept Stat, Örebro, Sweden.
    Nyström, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Clin Spinal Surg, Strängnäs, Sweden.
    Goldie, Ian
    Karolinska Univ Hosp, Dept Orthopaed, Stockholm, Sweden.
    Landrø, Nils Inge
    Univ Oslo, Dept Psychol, Ctr Study Human Cognit, Oslo, Norway; Univ Oslo, Dept Psychol, Clin Neurosci Res Grp, Oslo, Norway.
    Sidén, Åke
    Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
    Staff, Peer
    Oslo Univ Hosp, Dept Phys Med & Rehabil, Oslo, Norway; Trakka 1, Oslo, Norway.
    Schillberg, Birgitta
    Clin Spinal Surg, Strängnäs, Sweden.
    Taube, Adam
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Superior outcomes following cervical fusion vs. multimodal rehabilitation in a subgroup of randomized Whiplash-Associated-Disorders (WAD) patients indicating somatic pain origin. Comparison of outcome assessments made by four examiners from different disciplines.2018Inngår i: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 18, nr 2, s. 175-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Whiplash-Associated Disorders (WAD) are characterized by great variability in long-term symptoms. Patients with central neck and movement-induced stabbing pain participated in a randomized study comparing cervical fusion and multimodal rehabilitation. As reported in our previous paper, more patients treated by cervical fusion than by rehabilitation experienced pain relief. Although patient reported outcome measures are a core component of outcome evaluation, independent examiner has been recommended. Because of the heterogeneity of WAD complaints the patients in our study were examined at baseline and follow-up by four experts representing neurology, orthopedics, psychology and physical medicine. The aim was to compare the professional assessments of change both regarding the possible impact of the different examiners’ perspectives on individual patient’s outcome, and also on the analysis of possible outcome differences between the treatment groups.

    Methods: WAD patients with long-term neck pain as the predominant symptom after a traffic accident were eligible. The neck pain origin should be in the midline and perceived as dull and aching, with sudden movement inducing midline stabbing pain. Of the 1,052 patients in contact with our team, 49 were eligible. The overall treatment effect was evaluated on a global outcome transitional scale. The criteria for the scale categories were defined by each expert’s professional perspective on change in the whiplash complaints. Statistical methods that take account of the non-metric properties of ordered categorical data were used. Observed inter-expert disagreement was evaluated by the Svensson method that identifies and measures systematic group-related disagreement separately from disagreement caused by individual variation. Possible differences in the distributions of assessments on the expert-specific outcome scales between the treatment groups were analyzed by the Kruskal-Wallis test.

    Results: The per-protocol evaluation showed that a majority of the 18 patients who underwent fusion surgery were assessed as somewhat or much better, ranging from 67% to 78% depending on the expert. Corresponding proportions of improvement in the 17 patients treated by multimodal rehabilitation ranged from 29% to 53%. The statistical analyses confirmed better outcomes in the patients treated by fusion surgery, with p-values ranging from 0.003 to 0.04. The experts’ assessments of intra-patient change disagreed more or less for all patients. The analyses of the paired comparisons confirmed that these disagreements could most probably be explained by the different profession-specific operational definitions of the outcome scales rather than by individual variations in data.

    Conclusions: The multi-dimensional complexity of WAD-related complaints was comprehensively demonstrated by the inter-disciplinary disagreements in assessing intra-patient outcomes. The superiority of positive treatment effects in patients who underwent cervical fusion compared with multimodal rehabilitation was evident to all experts.

    Implications: The results strengthen our previous opinion that neck pain in this subgroup of WAD patients has a somatic origin. More than one examiner is recommended for multi-dimensional outcome assessments.

  • 312.
    Thelin, Eric Peter
    et al.
    Univ Cambridge, Dept Clin Neurosci, Div Neurosurg, Cambridge Biomed Campus, Cambridge, England.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Helmy, Adel
    Univ Cambridge, Dept Clin Neurosci, Div Neurosurg, Cambridge Biomed Campus, Cambridge, England..
    Nelson, David W.
    Karolinska Inst, Sect Perioperat Med & Intens Care, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden..
    Editorial: Monitoring Pathophysiology in the injured Brain2018Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, artikkel-id 193Artikkel i tidsskrift (Annet vitenskapelig)
  • 313. Thompson, Hilaire J.
    et al.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    LeBold, David G.
    Morales, Diego M.
    Keck, Carrie A.
    Vinson, Mary
    Royo, Nicolas C.
    Grundy, Robert
    McIntosh, Tracy K.
    Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody2006Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 24, nr 11, s. 3063-3072Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n = 102) were subjected to either lateral fluid percussion brain injury (n = 59) or sham injury (n = 43). In surviving animals, beginning at 1 h post-injury, 8.64 mu g anti-MAG mAb (n = 33 injured, n = 21 sham) or control IgG (n = 26 injured, n = 22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n = 14 sham, n = 11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P < 0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P < 0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.

  • 314.
    Tsitsopoulos, Parmenion P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Aristotle Univ Thessaloniki, Hippokratio Gen Hosp, Thessaloniki, Greece..
    Abu Hamdeh, Sami
    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. Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden..
    Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain injury2017Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, artikkel-id 599Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short-and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI.

  • 315.
    Tsitsopoulos, Parmenion P.
    et al.
    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.
    Wanhainen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Tobieson, Lovisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hardemark, Hans-Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Improved outcome of patients with severe thalamic hemorrhage treated with cerebrospinal fluid drainage and neurocritical care during 1990-1994 and 2005-20092013Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, nr 11, s. 2105-2113Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with thalamic hemorrhage, depressed level of consciousness and/or signs of elevated intracranial pressure may be treated with neurocritical care (NCC) and external ventricular drainage (EVD) for release of cerebrospinal fluid. Forty-three patients with thalamic hemorrhage treated with NCC from 1990 to 1994 (n = 21) and from 2005-2009 (n = 22) were evaluated. Outcome was assessed using the Glasgow Coma Scale (GCS) score at discharge from our unit and the modified Rankin Scale (mRS) for long-term outcome. Patients' age was 59.5 +/- 7 years in 1990-1994, and 58.2 +/- 9 years in 2005-2009. The median (25th and 75th percentile) GCS score on admission for the two time periods was 9 (6-12) and 9 (4-14), respectively. Long-term follow-up was assessed at a mean of 37.1 (range 19-65) months after disease onset for the 1990-1994 cohort and at 37.4 (range 14-58) months for the 2005-2009 cohort. Compared to patients from 1990 to 1994, patients from 2005 to 2009 had a significantly better outcome (median mRS [25th and 75th percentile]: 5 [4-6] vs. 4 [2-4.5]; p < 0.01). Most patients (13/21, 62 %) treated from 1990 to 1994 had unchanged or lower GCS scores during their NCC stay in contrast to 7/22 (32 %) from 2005 to 2009. At the last follow-up, 13/21 (62 %) patients from 1990 to 1994 were dead in comparison to 4/21 (19 %) from 2005 to 2009 (p < 0.05). Negative prognostic factors were the 120 h post-admission GCS score in the 1990-1994 patient cohort (p = 0.07) and high age in the recent cohort (p = 0.04). Patients with thalamic hemorrhage and depressed level of consciousness on admission had a worse outcome in the early 1990s compared with the late 2000s, which may at least be partially attributed to refined neurocritical care.

  • 316.
    Tsitsopoulos, Parmenion P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Holtz, Anders
    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.
    Multiloculated extra-intradural spinal meningeal cyst associated with intradural tethering of the spinal cord2012Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, nr 7, s. 1247-1248Artikkel i tidsskrift (Fagfellevurdert)
  • 317.
    Tsitsopoulos, Parmenion P.
    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.
    A delayed spinocutaneous fistula after anterior cervical discectomy and fusion2015Inngår i: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 15, nr 4, s. 783-784Artikkel i tidsskrift (Annet vitenskapelig)
  • 318.
    Tsitsopoulos, Parmenion P
    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.
    Amyloid-β Peptides and Tau Protein as Biomarkers in Cerebrospinal and Interstitial Fluid Following Traumatic Brain Injury: A Review of Experimental and Clinical Studies2013Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 4, artikkel-id 79Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in many severe TBI patients, results in accumulation of amyloid precursor protein (APP). Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ) peptides, a hallmark finding in Alzheimer's disease (AD). At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF) using cerebral microdialysis and/or cerebrospinal fluid (CSF) following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques, and the complexity of TBI in the available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using methods such as rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long-term consequences of TBI.

  • 319.
    Tsitsopoulos, Parmenion P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tobieson, Lovisa
    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.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Prognostic factors and long-term outcome following surgical treatment of 76 patients with spontaneous cerebellar haematoma2012Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, nr 7, s. 1189-1195Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although large spontaneous cerebellar haematomas are associated with high mortality, surgical treatment may be life-saving. We evaluated the clinical outcome and identified prognostic factors in 76 patients with cerebellar haematoma, all treated with suboccipital decompression, haematoma evacuation and external ventricular drainage. Patients receiving surgical and neurocritical care treatment within a 10-year period were included. Level of consciousness during hospitalisation was evaluated using the Glasgow Coma Scale (GCS) score. Outcome was assessed with the modified Rankin Scale (mRS). Predictive prognostic factors were analysed using univariate and multivariate regression analysis. Prior to surgery, the median GCS score was 8.6 (range 3-13). At discharge it had improved to 12.1 (4-15) (p < 0.05). The median long-term follow-up period was 70.5 (22-124) months. At 6 months post-surgery, 19 patients were dead and 28 patients had a good outcome (mRS < 3). In the long term (70.5 months), 31 patients (41.9 %) were dead and the outcome was good in 27 patients (37.8 %). Although approximately 25 % of patients > 65 years old had a favourable outcome, age was the strongest negative predictor for a bad outcome at 6 months and long term (p = 0.02 and p = 0.01, respectively). The level of consciousness before surgery did not influence the 6-month or long-term outcome (p = 0.39 and p = 0.65, respectively). Although mortality was high, significant complications from the treatment were rare and most survivors had a good outcome, reaching functional independence. High age was the strongest prognostic factor for an unfavourable outcome.

  • 320.
    Tsitsopoulos, Parmenion P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tobieson, Lovisa
    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.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Surgical treatment of patients with unilateral cerebellar infarcts: clinical outcome and prognostic factors2011Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 153, nr 10, s. 2075-2083Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are limited data on the long-term outcome and on factors influencing the prognosis in patients with cerebellar infarcts treated with surgical decompression. Thirty-two patients (age 64.3 +/- 9.9 years) with expansive unilateral cerebellar infarcts were retrospectively evaluated. All patients were treated with ventriculostomy, suboccipital decompressive craniectomy and removal of the necrotic tissue. The Glasgow Coma Scale (GCS) and the Reaction Level Scale (RLS) scores evaluated the level of consciousness during hospitalization, while the modified Rankin Scale (mRS) was used for the 6-month and long-term outcome. Predicting factors were analyzed using a univariate logistic regression model. The median time from ictus to surgery was 48.4 h (range 8-120 h). Before surgery, the median GCS score was 9 (3-13). At discharge, the GCS score improved to 13.6 (7-15) (p < 0.05 compared to preoperative scores). At the long-term follow-up (median 67.5 months), ten patients were dead, and 77% of survivors had a good outcome (mRS score of a parts per thousand currency sign2). The number of days on a ventilator and the GCS score prior to surgery and at discharge were strong predictors of clinical outcome (p < 0.05), although one third of patients with a GCS a parts per thousand currency signaEuro parts per thousand 8 at the time of surgery had a good long-term outcome. In patients a parts per thousand yen70 years old, 50% had a good long-term outcome, and advanced age was not associated with a bad result (p > 0.05). Our results imply that surgical evacuation of significant cerebellar infarctions may be considered also in patients with advanced age and/or a decreased level of consciousness.

  • 321.
    Tsitsopoulos, Parmenion
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tobieson, L.
    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.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clinical outcome following surgical treatment for bilateral cerebellar infarction2011Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, nr 5, s. 345-351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives - To analyze the initial clinical and radiological findings, the surgical treatment, and the clinical outcome following surgical decompression in patients with space-occupying bilateral cerebellar infarction. Materials and Methods - Ten patients with expansive bilateral cerebellar infarction and decreased level of consciousness were operated with suboccipital craniectomy, removal of the infarcted tissue, and placement of external ventricular drainage. Long-term outcome was assessed using the modified Rankin scale (mRS). Results - Mean Glasgow coma scale (GCS) score before surgery was 8.9 +/- 3.3 and improved to 12.6 +/- 3.6 at discharge. At the long-term follow-up (median 57.6 months), six patients had a favorable outcome (mRS 1.3 +/- 0.8). Four patients, all with an associated brain stem infarct, had a poor outcome. Conclusions - In the absence of brain stem infarcts, surgical treatment resulted in a favorable clinical outcome and should be considered a treatment option for patients with expansive bilateral cerebellar infarction.

  • 322. Tängdén, Thomas
    et al.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ullberg, Måns
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Neurosurgical gram-negative bacillary ventriculitis and meningitis: a retrospective study evaluating the efficacy of intraventricular gentamicin therapy in 31 consecutive cases.2011Inngår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, nr 52, s. 10-16Artikkel i tidsskrift (Fagfellevurdert)
  • 323.
    Tängdén, Thomas
    et al.
    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.
    Ullberg, Måns
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Neurosurgical Gram-Negative Bacillary Ventriculitis and Meningitis: A Retrospective Study Evaluating the Efficacy of Intraventricular Gentamicin Therapy in 31 Consecutive Cases2011Inngår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 52, nr 11, s. 1310-1316Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Gram-negative bacillary (GNB) ventriculitis and meningitis are rare but serious complications after neurosurgery. Prospective studies on antibiotic treatment for these infections are lacking, and retrospective reports are sparse. At our hospital in Uppsala, Sweden, meropenem has been recommended as empirical therapy since 1996, with the addition of intraventricular gentamicin in cases that do not respond satisfactorily to treatment. In this study, we retrospectively compare the efficacy of combination treatment with intraventricular gentamicin to that of systemic antibiotics alone. In addition, we report our experience of meropenem for the treatment of GNB ventriculomeningitis. Methods. Adult consecutive patients with gram-negative bacteria isolated from cerebrospinal fluid during a 10-year period and with postneurosurgical GNB ventriculitis or meningitis were included retrospectively. Data were abstracted from the medical records. Results. Thirty-one patients with neurosurgical GNB ventriculitis or meningitis and follow-up for 3 months were identified. The main intravenous therapies were meropenem (n = 24), cefotaxime (n = 3), ceftazidime (n = 2), imipenem (n = 1), and trimethoprim-sulfamethoxazole (n = 1). Thirteen patients were given combination treatment with appropriate intraventricular gentamicin. These patients had a higher cure rate and a lower relapse rate than did those treated with intravenous antibiotics alone (P = .03). Relapse occurred in 0 of 13 patients treated intraventricularly and in 6 of 18 patients treated with systemic antibiotics alone. The mortality rate was 19%; 3 patients in each group died, but in no case was death considered to be attributable to meningitis. Conclusions. Our results support combination treatment with intraventricular gentamicin for postneurosurgical GNB ventriculomeningitis. Meropenem seems to be an effective and safe alternative for the systemic antibiotic treatment of these neurointensive care infections.

  • 324.
    Vedung, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. Uppsala Univ, PET Ctr, Uppsala, Sweden..
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ, PET Ctr, Uppsala, Sweden..
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Persistent Decrease Of Cerebral Blood Flow In Traumatic Brain Injury And Sports-Related Concussion2017Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, nr 13, s. A8-A9Artikkel i tidsskrift (Annet vitenskapelig)
  • 325.
    Vedung, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hanni, Sofie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Tegner, Yelverton
    Lulea Univ Technol, Hlth Sci, Lulea, Sweden.
    Johansson, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    CONCUSSION INCIDENCE IN SWEDISH ELITE SOCCER2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A270-A270Artikkel i tidsskrift (Annet vitenskapelig)
  • 326.
    Vedung, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lanni, Francesco
    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.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Localized Injury Along White Matter Tracts In Patients With Traumatic Brain Injury Affects Memory Functions In Chronic State2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A140-A141Artikkel i tidsskrift (Annet vitenskapelig)
  • 327.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Cesarini, Kristina G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Laurell, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    The CSF tap test in normal pressure hydrocephalus: evaluation time, reliability and the influence of pain2012Inngår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, nr 2, s. 271-276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:  The cerebrospinal fluid tap test (TT) is a diagnostic tool used to select patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. The procedure and the evaluation of the TT vary between centres. We aimed to describe the evaluation time after the TT, to assess the variability between repeated measurements, the interrater agreement of the gait tests chosen and finally to investigate whether pain affects the gait performance post-TT.

    Methods:  Forty patients (21 men and 19 women) under evaluation for iNPH underwent a TT. Standardized gait analyses were performed before and 2, 4, 6, 8 and 24 h after the TT and repeated twice on every occasion. Independent of each other, two investigators evaluated the quality of gait. At each assessment time, the patients graded headache and back pain on a visual analogue scale.

    Results:  Twenty-seven patients (15 men and 12 women) responded to TT. Improvements in gait speed and number of steps were significant at every assessment time post-TT. The variability between two measurements was low (Intra class correlation coefficient = 0.97), and the inter-rater agreement was good with a κ = 0.74. Pain correlated negatively with improvement in gait speed (r = -0.40, P < 0.05).

    Conclusions:  We suggest that the TT can be evaluated at any time within the first 24 h and should be repeated if the patient does not initially improve. Gait analysis appears reliable between two evaluators. Further, it is indicated that post-lumbar puncture pain negatively affects the gait and should be minimized.

  • 328.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Department of Pharmacology and Clinical Neuroscience, Östersund, Umeå University.
    Ahlgren, André
    Department of Medical Radiation Physics, Lund University.
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal2014Inngår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 34, nr 11, s. 1771-1778Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pseudo-continuous arterial, spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.

  • 329.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Umeå University, Umeå, Sweden.
    Cesarini, Kristina G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Increase in callosal angle and decrease in ventricular volume after shunt surgery in patients with idiopathic normal pressure hydrocephalus2019Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 130, nr 1, s. 130-135Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE Postoperative decrease in ventricle size is usually not detectable either by visual assessment or by measuring the Evans index in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of the present study was to investigate whether the angle between the lateral ventricles (the callosal angle [CA]) increases and ventricular volume decreases after shunt surgery in patients with iNPH. METHODS Magnetic resonance imaging of the brain was performed before and 3 months after shunt surgery in 18 patients with iNPH. The CA and Evans index were measured on T1-weighted 3D MR images, and ventricular volume contralateral to the shunt valve was measured with quantitative MRI. RESULTS The CA was larger postoperatively (mean 78°, 95% CI 69°-87°) than preoperatively (mean 67°, 95% CI 60°-73°; p < 0.001). The volume of the lateral ventricle contralateral to the shunt valve decreased from 73 ml (95% CI 66-80 ml) preoperatively to 63 ml (95% CI 54-72 ml) postoperatively (p < 0.001). The Evans index was 0.365 (95% CI 0.35-0.38) preoperatively and 0.358 (95% CI 0.34-0.38) postoperatively (p < 0.05). Postoperative change of CA showed a negative correlation with change of ventricular volume (r = -0.76, p < 0.01). CONCLUSIONS In this sample of patients with iNPH, the CA increased and ventricular volume decreased after shunt surgery. The relative difference was most pronounced for the CA, indicating that this accessible, noninvasive radiological marker should be evaluated further as an indirect method to determine shunt function in patients with iNPH.

  • 330.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Cesarini, Kristina G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Preoperative Prognostic Value of MRI Findings in 108 Patients with Idiopathic Normal Pressure Hydrocephalus2014Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 35, nr 12, s. 2311-2318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    MR imaging is used in the diagnostic evaluation of patients with idiopathic normal pressure hydrocephalus. The aim of this study was to describe the prevalence of several imaging features and their prognostic use in the selection of shunt candidates with idiopathic normal pressure hydrocephalus.

    MATERIALS AND METHODS:

    Preoperative MR imaging scans of the brain were retrospectively evaluated in 108 patients with idiopathic normal pressure hydrocephalus who had undergone a standardized, clinical evaluation before and 12 months after shunt surgery. The MR imaging features investigated were the Evans index, callosal angle, narrow sulci at the high convexity, dilation of the Sylvian fissure, diameters of the third ventricle and temporal horns, disproportionately enlarged subarachnoid space hydrocephalus, flow void through the aqueduct, focal bulging of the roof of the lateral ventricles, deep white matter hyperintensities, periventricular hyperintensities, and focal widening of sulci and aqueductal stenosis.

    RESULTS:

    In logistic regression models, with shunt outcome as a dependent variable, the ORs for the independent variables, callosal angle, disproportionately enlarged subarachnoid space hydrocephalus, and temporal horns, were significant (P < .05), both in univariate analyses and when adjusted for age, sex, and previous stroke.

    CONCLUSIONS:

    A small callosal angle, wide temporal horns, and occurrence of disproportionately enlarged subarachnoid space hydrocephalus are common in patients with idiopathic normal pressure hydrocephalus and were significant predictors of a positive shunt outcome. These noninvasive and easily assessed radiologic markers could aid in the selection of candidates for shunt surgery.

  • 331.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Department of Pharmacology and Clinical Neuroscience, Östersund, Umeå University.
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Preoperative Prognostic Value of MRI Findings in 109 Patients with Idiopathic Normal Pressure HydrocephalusManuskript (preprint) (Annet vitenskapelig)
  • 332.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus2014Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, nr 1, s. 178-184Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Object

    Different neuroimaging biomarkers have been studied to find a tool for prediction of response to CSF shunting in idiopathic normal-pressure hydrocephalus (iNPH). The callosal angle (CA) has been described as useful in discriminating iNPH from ventricular dilation secondary to atrophy. However, the usefulness of the CA as a prognostic tool for the selection of shunt candidates among patients with iNPH is unclear. The aim of this study was to compare the CA in shunt responders with that in nonresponders and clarify whether the CA can serve as a predictor of the outcome.

    Methods

    Preoperative MRI brain scans were evaluated in 109 patients who had undergone shunt surgery for iNPH during 2006-2010. Multiplanar reconstruction was performed interactively to obtain a coronal image through the posterior commissure, perpendicular to the anterior-posterior commissure plane. The CA was measured as the angle between the lateral ventricles on the coronal image. The patients were examined clinically before surgery and at 12 months postoperatively.

    Results

    Shunt responders had a significantly smaller mean preoperative CA compared with nonresponders: 59° (95% CI 56°-63°) versus 68° (95% CI 61°-75°) (p < 0.05). A CA cutoff value of 63° showed the best prognostic accuracy.

    Conclusions

    The preoperative CA is smaller in patients whose condition improves after shunt surgery and may be a useful tool in the selection of shunt candidates among patients with iNPH.

  • 333.
    Vlachogiannis, Pavlos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gudjonsson, Olafur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Montelius, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Grusell, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Isacsson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Nilsson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas2017Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, nr 12, s. 2391-2400Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for complications.

  • 334.
    Vlachogiannis, Pavlos
    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.
    Khalil, F.
    Karolinska Inst, Neurosci..
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Interleukin-6 levels in cerebrospinal fluid and plasma in patients with severe spontaneous subarachnoid hemorrhage2017Inngår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 496-496Artikkel i tidsskrift (Annet vitenskapelig)
  • 335.
    Vlachogiannis, Pavlos
    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.
    Khalil, Fattema
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Enblad, Per
    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.
    Interleukin-6 Levels in Cerebrospinal Fluid and Plasma in Patients with Severe Spontaneous Subarachnoid Hemorrhage2019Inngår i: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 122, s. E612-E618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Inflammatory processes play a key role in the pathophysiology of subarachnoid hemorrhage (SAH). This study evaluated whether different temporal patterns of intrathecal and systemic inflammation could be identified in the acute phase after SAH. The intensity of the inflammation was also assessed in clinical subgroups. METHODS: Cerebrospinal fluid (CSF) and blood samples were collected at days 1, 4, and 10 after ictus in 44 patients with severe SAH. Interleukin-6 (IL-6) was analyzed by a routine monoclonal antibody-based method. Median IL-6 values for each day were calculated. Day 4 IL-6 values were compared in dichotomized groups (age, sex, World Federation of Neurosurgical Societies [WFNS] grade, Fisher scale grade, outcome, vasospasm, central nervous system infection and systemic infections). RESULTS: CSF IL-6 levels were significantly elevated from day 1 to days 4 and 10, whereas plasma IL-6 showed a different trend at lower levels. Median CSF IL-6 concentrations for days 1, 4, and 10 were 876.5, 3361, and 1567 ng/L, whereas plasma was 26, 27.5, and 15.9 ng/L, respectively. No significant differences in CSF concentrations were observed between the subgroups, with the most prominent one being in day 4 IL-6 in the WFNS subgroups (grades 1-3 vs. 4-5, 1158.5 vs. 5538 ng/L; P = 0.056). Patients with systemic infection had significantly higher plasma IL-6 concentrations than patients without infection (31 vs. 16.05 ng/L, respectively; P = 0.028). CONCLUSIONS: Distinctly different inflammatory patterns could be seen intrathecally compared with the systemic circulation. In plasma, a significant difference in the intensity of the inflammation was seen in cases with systemic infection. No other subgroup showed statistically significant differences.

  • 336.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Otterberck, Alexander
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Miklós, Lipscey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mitochondrial stress in early experimental sepsis revealed by electron transport chain inhibitionManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Increased plasma lactate in sepsis may not be due to insufficient oxygen

    delivery, but accelerated glycolysis and mitochondrial dysfunction may also contribute. To

    assess critical pathophysiological steps in non-ischemic lactate increase we studied the muscle metabolism with microdialysis in a sepsis model in pigs submitted to continuous E. coli infusion (sepsis group, n=12) for 3 hours (h). A control group (sham group, n=4) underwent the same procedures but did not receive E. coli. Protocolized interventions were applied to normalize oxygen delivery (DO2) and blood pressure. Metabolism was intervened locally via microdialysis catheters with the electron-transport chain inhibitor sodium cyanide and the inhibitor of the major energy consuming enzyme Na+/K+-ATPase ouabain.

    Results: All pigs in the sepsis group had positive blood cultures at 1 h. Median (range) Sequential Organ Failure Assessment (SOFA) score at 0 h was 0 (0-1) in both groups. At 3 h, SOFA increased to 6 (3-6) in the sepsis group but remained virtually unchanged in the sham group. Plasma lactate increased in the sepsis group despite that protocolized interventions maintained DO2.

    Sepsis accelerated glycolysis with a decrease in glucose, maintained or increased in lactate and pyruvate with a virtually normal lactate-to-pyruvate ratio (LPR) in microdialysate from catheters without intervention. The local cyanide intervention produced a severe energy crisis as evidenced by a dramatically elevated LPR, a lowered pyruvate and an increased lactate in both the sepsis and sham group. During sepsis, when the cyanide effect gradually diminished, this energy crisis normalized in the sham group but partly persisted in the sepsis group.

    Conclusions: Our findings suggest a reduction in mitochondrial oxidative capacity induced by sepsis, as revealed by cyanide inhibition. Decreasing energy consumption with a local ouabain intervention did not impact glucose and fat metabolism in sepsis or sham animals.

  • 337.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Engström, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Maripuu, Enn
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Widström, Charles
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig2017Inngår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, nr 4, s. 514-519Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

  • 338.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial2015Inngår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, nr 6, s. 604-611Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.

    METHODS: Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg or placebo and subjected to 6 h endotoxin infusion at 0.5 μg x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.

    RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively) (P=0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group, but not in the tigecycline group at 4-6 h (P=0.009 and p=0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism and acid-base parameters were unaffected by tigecycline.

    CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

  • 339.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skorup, Paul
    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 medicinska vetenskaper, Infektionssjukdomar.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Miklós, Lipscey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The role of oxygen delivery and inflammatory response on plasma lactate and organ dysfunction in experimental septic shockManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Elevated plasma lactate and organ dysfunction in septic shock may be due to insufficient oxygen delivery (DO2). However, other mechanisms, as mitochondrial dysfunction or adrenergic glycolysis may contribute to elevated lactate. We conducted a retrospective cohort analysis of 104 pigs in bacteremic and endotoxemic shock to investigate the impact of DO2, oxygen consumption (VO2), hemodynamics and inflammatory response on elevation in plasma lactate, tissue metabolism and organ dysfunction in experimental bacteremic and endotoxemic shock.

    Experimental septic shock was induced by continuous infusion of live bacteria and endotoxin for 6 hours (h). Hemodynamic parameters and DO2 were measured with pulmonary artery catheters and oximetry. Lactate, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were analyzed in plasma. Muscle metabolism was investigated with microdialysis. At 3 h, DO2 was 289±68 mL x min-1 x m-2 (mean±SD) and plasma lactate levels were 2.9±1.2 mmol x L-1. Elevated plasma lactate was dependent on DO2, but only at DO2 levels <250 mL x min-1 x m-2. Despite increased plasma lactate and decreased DO2, no decrease in VO2 was seen. Muscle pyruvate levels increased and lactate-to-pyruvate ratio decreased. Urinary output, but not static lung compliance, was DO2-dependent. In a multiple regression model DO2, mean arterial pressure and IL-6 were the strongest predictors of increased plasma lactate. Urinary output, but not static lung compliance, was DO2-dependent.

    In muscle accelerated glycolysis contributes to increased lactate. In addition, inflammatory response, manifested as plasma IL-6 but not as TNF-a, was associated with an elevation in plasma lactate levels. 

  • 340.
    Wall, Jacob
    et al.
    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.
    Neurointensive care of patients with cerebral venous sinus thrombosis and intracerebral haemorrhage2018Inngår i: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 58, s. 83-88Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim was to review the neurointensive care (NIC) of cerebral venous sinus thrombosis patients with haemorrhage during a 15-year period. This is a severe condition with substantial mortality caused by increased intracranial pressure (ICP) and studies are lacking describing the complex picture of the NIC, which offers a large treatment arsenal for intracranial hypertension. Patients treated 2000-2015 were investigated. Data regarding patient characteristics, symptoms, imaging, ICP-treatment, NIC-treatment intensity, and outcome were collected and analysed. Twenty-four patients (13 women) were studied, mean age 46 (range 16-75). Twenty patients were in Glasgow coma scale motor score 6 (obeys), 2 in score 5 (localizes) and 2 in score 2 (extension) on admission. Mean haemorrhage volume was 17 ml (range 1-70). Twenty patients (83%) received unfractionated heparin and 3 (13%) low molecular weight heparin. Haemorrhagic progression occurred in 10 patients (42%). In 9 patients (38%), 4-6 of the treatment options mechanical ventilation, hyperventilation, ICP-monitoring, cerebrospinal fluid-drainage, osmotherapy, barbiturates or surgery were used. In 3 patients mechanical ventilation only was used (hyperventilation in 1). Twelve patients were not managed with any of those treatment options. At follow up, 15/24 patients (62%) had favourable outcome (4 missing). The study shows that many patients needed multiple actions to treat intracranial preassure but more than 60% achieved favourable clinical outcome. Preferably, patients with cerebral venous sinus thrombosis and haemorrhage who are awake should have fast access to NIC because it appears difficult to predict who will deteriorate and promptly need NIC treatment.

  • 341.
    Wallenquist, Ulrika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Brännvall, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Clausen, Fredrik
    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.
    Forsberg-Nilsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Grafted neural progenitors migrate and form neurons after experimental traumatic brain injury2009Inngår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 27, nr 4, s. 323-334Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE

    Neural stem and progenitor cells (NSPC) generate neurons and glia, a feature that makes them attractive for cell replacement therapies. However, efforts to transplant neural progenitors in animal models of brain injury typically result in high cell mortality and poor neuronal differentiation.

    METHODS

    In an attempt to improve the outcome for grafted NSPC after controlled cortical impact we transplanted Enhanced Green Fluorescent Protein (EGFP)-positive NSPC into the contra lateral ventricle of mice one week after injury.

    RESULTS

    Grafted EGFP-NSPC readily migrated to the injured hemisphere where we analyzed the proportion of progenitors and differentiated progeny at different time points. Transplantation directly into the injured parenchyma, resulted in few brains with detectable EGFP-NSPC. On the contrary, in more than 90% of the mice that received a transplant into the lateral ventricle detectable EGFP-positive cells were found. The cells were integrated into the lateral ventricle wall of the un-injured hemisphere, throughout the corpus callosum, and in the cortical perilesional area. At one-week post transplantation, grafted cells that had migrated to the perilesion area mainly expressed markers of neural progenitors and neurons, while in the corpus callosum and the ventricular lining, grafted cells with a glial fate were more abundant. After 3 months, grafted cells in the perilesion area were less abundant whereas cells that had migrated to the walls of the third- and lateral- ventricle of the injured hemisphere were still detectable, suggesting that the injury site remained a hostile environment.

    CONCLUSION

    Transplantation to the lateral ventricle, presumably for being a neurogenic region, provides a favorable environment improving the outcome for grafted NSPC both in term of their appearance at the cortical site of injury, and their acquisition of neural markers.

  • 342.
    Wallenquist, Ulrika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Holmqvist, Karin
    Hånell, Anders
    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.
    Forsberg-Nilsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    Ibuprofen attenuates the inflammatory response and allows formation of migratory neuroblasts from grafted stem cells after traumatic brain injury2012Inngår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 30, nr 1, s. 9-19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: There is hope for neural stem and progenitor cells (NSPC) to enhance regeneration when transplanted to the injured brain after traumatic brain injury (TBI). So far, the therapeutic effects of NSPC transplantation have been hampered mainly by the notable death of the transplanted cells. Neuroinflammation may lead to additional cell death after TBI and we hypothesized that survival of grafted NSPC could be enhanced by anti-inflammatory treatment.

    Methods: Mice that were subjected to controlled cortical impact TBI and grafted with NSPC, were treated with the non-steroidal anti-inflammatory drug ibuprofen.

    Results: Ibuprofen was found to down-regulate the TBI-induced inflammatory response. In addition, migrating neuroblasts from transplanted cells were observed near the contusion and in the ipsilateral hippocampus in ibuprofen-treated animals only, suggesting that the anti-inflammatory treatment had beneficial effects on graft survival and/or differentiation. However, Morris Water Maze performance or TBI-induced tissue loss was not influenced by ibuprofen treatment.

    Conclusions: Our data suggests that anti-inflammatory strategies may be a complement to enhance the outcome for the cell transplants following TBI.

  • 343.
    Wallmark, Svante
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Contact with medical and social services after the acute phase of subarachnoid hemorrhageManuskript (preprint) (Annet vitenskapelig)
  • 344.
    Wallmark, Svante
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Life after Subarachnoid Hemorrhage2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease with mean age of 59 years. SAH accounts for 5% of all stroke and more than one quarter of potential life years lost through stroke. With the advanced neurosurgical methods of today two thirds of the patients survive. We know, however, that various cognitive, psychiatric and physical impairments are common that affect quality of life, social life, and the ability to work in the aftermath of SAH. The overall aim constituting this PhD dissertation is to better understand some of the challenges often faced by those surviving SAH.

    Two SAH patient cohorts have been studied. The first followed 96 consecutively included patients during the first year after ictus. Spasticity and cognitive impairment was assessed after 6 months and the Swedish stroke register follow-up form was used to investigate family support and the use of medical and social services. Return to work was assessed at 12 months. The second cohort assessed attention deficits using the test of variables of attention (T.O.V.A.) at 7 months after ictus in 19 patients with moderate to good recovery.

    Spasticity was just as common in our SAH patients as after other stroke, though it was rarely treated pharmacologically. By assessing cognitive impairment at 6 months after ictus using the Montreal cognitive assessment, 68% of the patients could be correctly predicted as having returned/not returned to work at 12 months. Seventeen percent of the patients had not had a follow-up appointment 6 months after ictus. These patients were older, more often living alone, had a lower quality of life, more depressive symptoms and more cognitive impairment compared to those having had a follow-up appointment. Twenty percent had had a follow-up in primary care. Seventy-eight percent of those with moderate to severe disability were living in their own accommodations. Fifty-eight percent of the patients had attention deficits. Challenges after SAH were common and often dealt with in the home environment of the patients.

    The results of this thesis highlight the importance of assisting the patients and their relatives in their struggle back to life after SAH.

    Delarbeid
    1. Prevalence of spasticity after aneurysmal subarachnoid haemorrhage
    Åpne denne publikasjonen i ny fane eller vindu >>Prevalence of spasticity after aneurysmal subarachnoid haemorrhage
    2014 (engelsk)Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 46, nr 1, s. 23-27Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: The prevalence of spasticity after stroke is approximately 20%. There is, so far, little information in the literature on the development of spasticity after aneurysmal subarachnoid haemorrhage. The objectives of this study were to estimate the prevalence of spasticity after aneurysmal subarachnoid haemorrhage and to identify possible risk factors in the acute phase. Methods: A total of 87 patients were assessed for spasticity with the Modified Ashworth Scale after 6 months. A multivariate logistic regression model was used to evaluate risk factors. Results: Spasticity was present after 6 months in 19 (22%) of the patients, but was treated pharmacologically in only 1 case. Worse clinical status at admission carried a high risk for spasticity (odds ratio (OR) 10.2; 95% confidence interval (CI) 2.4-43.2), followed by the presence of infection (OR 7.4; 95% CI 1.6-33.8) and vasospasm (OR 4.8; 95% CI 1.2-19.0) during the intensive care phase. Conclusion: Spasticity after aneurysmal subarachnoid haemorrhage occurred with the same prevalence as after other stroke. Risk factors for spasticity were worse clinical condition at admission and the occurrence of infection and vasospasm during the intensive care period. Pharmacological treatment was not commonly used.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-218699 (URN)10.2340/16501977-1229 (DOI)000330421800004 ()24201997 (PubMedID)
    Tilgjengelig fra: 2014-02-14 Laget: 2014-02-14 Sist oppdatert: 2018-06-28
    2. Predicting return to work after subarachnoid hemorrhage using the Montreal Cognitive Assessment (MoCA)
    Åpne denne publikasjonen i ny fane eller vindu >>Predicting return to work after subarachnoid hemorrhage using the Montreal Cognitive Assessment (MoCA)
    2016 (engelsk)Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 158, nr 2, s. 233-239Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Returning to work is a major issue for patients having had an aneurysmal subarachnoid hemorrhage (SAH). It is important, at an early stage, to identify the patients that are unlikely to return to work. The objective of this study was to assess the predictive value of the Montreal Cognitive Assessment (MoCA) at 6 months after ictus on return to work at 12 months. In this prospective study were 96 patients with SAH included in the acute phase. Cognitive functions were assessed at 6 months using the MoCA and return to work at 12 months. The predictive value of MoCA on return to work was analyzed using the area under the receiver operating characteristic curve as well as logistic regression. Of those that had work before the SAH, 52 % were working at 12 months after the ictus. These patients had scored significantly better on MoCA at 6 months (p = 0.01). The area under the receiver operating characteristic curve was 0.75. By using a cut-off on MoCA of < 27, 68 % of the patients could be correctly classified as returned/not returned to work. Adding data from the acute phase to the MoCA in a logistic regression model increased the percentage of patients correctly classified as returned/not returned to work by 2 %. Returning to work is a major issue for SAH patients. It is important to identify factors that may interfere with a patient's ability to return to work, and address these issues appropriately. In our study, estimating cognitive functions at 6 months after SAH using the MoCA alone allowed us to predict return to work correctly in 68 % of the cases. We feel that this provides useful information in planning rehabilitation, but that other post-SAH symptoms have to be considered as well.

    Emneord
    Subarachnoid hemorrhage, Aneurysmal, Cognitive symptoms, Cognitive impairment, Work capacity, Return to work
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-277979 (URN)10.1007/s00701-015-2665-4 (DOI)000368603400004 ()26676517 (PubMedID)
    Tilgjengelig fra: 2016-03-02 Laget: 2016-02-23 Sist oppdatert: 2018-06-28
    3. Contact with medical and social services after the acute phase of subarachnoid hemorrhage
    Åpne denne publikasjonen i ny fane eller vindu >>Contact with medical and social services after the acute phase of subarachnoid hemorrhage
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-307376 (URN)
    Tilgjengelig fra: 2016-11-14 Laget: 2016-11-14 Sist oppdatert: 2016-11-24
    4. Attention Deficits After Aneurysmal Subarachnoid Hemorrhage Measured Using the Test of Variables of Attention
    Åpne denne publikasjonen i ny fane eller vindu >>Attention Deficits After Aneurysmal Subarachnoid Hemorrhage Measured Using the Test of Variables of Attention
    2015 (engelsk)Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, nr 5, s. 1374-1376Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND AND PURPOSE:

    The aim of this pilot study was to assess attention deficits in patients with aneurysmal subarachnoid hemorrhage using the test of variables of attention (TOVA). This is a computer-based continuous performance test providing objective measures of attention. We also compared the TOVA results with the attention and concentration domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment, 2 examiner-administrated neuropsychological instruments.

    METHODS:

    Nineteen patients with moderate to good recovery (Glasgow outcome scale, 4-5) were assessed using the TOVA, Montgomery Åsberg Depression Rating Scale, and Montreal cognitive assessment. The measurements were done when the patients visited the hospital for a routine magnetic resonance imaging control of the aneurysm.

    RESULTS:

    TOVA performance was pathological in 58%. The dominating pattern was a worsening of performance in the second half of the test, commonly a failing to react to correct stimuli. We found no correlation between TOVA and the performance in concentration and attention domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment.

    CONCLUSIONS:

    Attention deficits, measured by the TOVA, were common after subarachnoid hemorrhage. This should be further studied to improve outcome.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-248055 (URN)10.1161/STROKEAHA.115.009092 (DOI)000353559800054 ()25791712 (PubMedID)
    Tilgjengelig fra: 2015-03-26 Laget: 2015-03-26 Sist oppdatert: 2018-06-28
  • 345.
    Wallmark, Svante
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundström, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Attention Deficits After Aneurysmal Subarachnoid Hemorrhage Measured Using the Test of Variables of Attention2015Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, nr 5, s. 1374-1376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    The aim of this pilot study was to assess attention deficits in patients with aneurysmal subarachnoid hemorrhage using the test of variables of attention (TOVA). This is a computer-based continuous performance test providing objective measures of attention. We also compared the TOVA results with the attention and concentration domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment, 2 examiner-administrated neuropsychological instruments.

    METHODS:

    Nineteen patients with moderate to good recovery (Glasgow outcome scale, 4-5) were assessed using the TOVA, Montgomery Åsberg Depression Rating Scale, and Montreal cognitive assessment. The measurements were done when the patients visited the hospital for a routine magnetic resonance imaging control of the aneurysm.

    RESULTS:

    TOVA performance was pathological in 58%. The dominating pattern was a worsening of performance in the second half of the test, commonly a failing to react to correct stimuli. We found no correlation between TOVA and the performance in concentration and attention domains of Montgomery Åsberg Depression Rating Scale and Montreal cognitive assessment.

    CONCLUSIONS:

    Attention deficits, measured by the TOVA, were common after subarachnoid hemorrhage. This should be further studied to improve outcome.

  • 346.
    Wallmark, Svante
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundström, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Predicting return to work after subarachnoid hemorrhage using the Montreal Cognitive Assessment (MoCA)2016Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 158, nr 2, s. 233-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Returning to work is a major issue for patients having had an aneurysmal subarachnoid hemorrhage (SAH). It is important, at an early stage, to identify the patients that are unlikely to return to work. The objective of this study was to assess the predictive value of the Montreal Cognitive Assessment (MoCA) at 6 months after ictus on return to work at 12 months. In this prospective study were 96 patients with SAH included in the acute phase. Cognitive functions were assessed at 6 months using the MoCA and return to work at 12 months. The predictive value of MoCA on return to work was analyzed using the area under the receiver operating characteristic curve as well as logistic regression. Of those that had work before the SAH, 52 % were working at 12 months after the ictus. These patients had scored significantly better on MoCA at 6 months (p = 0.01). The area under the receiver operating characteristic curve was 0.75. By using a cut-off on MoCA of < 27, 68 % of the patients could be correctly classified as returned/not returned to work. Adding data from the acute phase to the MoCA in a logistic regression model increased the percentage of patients correctly classified as returned/not returned to work by 2 %. Returning to work is a major issue for SAH patients. It is important to identify factors that may interfere with a patient's ability to return to work, and address these issues appropriately. In our study, estimating cognitive functions at 6 months after SAH using the MoCA alone allowed us to predict return to work correctly in 68 % of the cases. We feel that this provides useful information in planning rehabilitation, but that other post-SAH symptoms have to be considered as well.

  • 347.
    Wallmark, Svante
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundström, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Prevalence of spasticity after aneurysmal subarachnoid haemorrhage2014Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 46, nr 1, s. 23-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The prevalence of spasticity after stroke is approximately 20%. There is, so far, little information in the literature on the development of spasticity after aneurysmal subarachnoid haemorrhage. The objectives of this study were to estimate the prevalence of spasticity after aneurysmal subarachnoid haemorrhage and to identify possible risk factors in the acute phase. Methods: A total of 87 patients were assessed for spasticity with the Modified Ashworth Scale after 6 months. A multivariate logistic regression model was used to evaluate risk factors. Results: Spasticity was present after 6 months in 19 (22%) of the patients, but was treated pharmacologically in only 1 case. Worse clinical status at admission carried a high risk for spasticity (odds ratio (OR) 10.2; 95% confidence interval (CI) 2.4-43.2), followed by the presence of infection (OR 7.4; 95% CI 1.6-33.8) and vasospasm (OR 4.8; 95% CI 1.2-19.0) during the intensive care phase. Conclusion: Spasticity after aneurysmal subarachnoid haemorrhage occurred with the same prevalence as after other stroke. Risk factors for spasticity were worse clinical condition at admission and the occurrence of infection and vasospasm during the intensive care period. Pharmacological treatment was not commonly used.

  • 348.
    Wang, Chao
    et al.
    Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
    Iashchishyn, Igor A.
    Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
    Kara, John
    Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
    Fodera, Vito
    Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark.
    Vetri, Valeria
    Univ Palermo, Dipartimento Fis & Chim, I-90128 Palermo, Italy;Univ Palermo, Aten Ctr, I-90128 Palermo, Italy.
    Sancataldo, Giuseppe
    Univ Palermo, Dipartimento Fis & Chim, I-90128 Palermo, Italy;Univ Palermo, Aten Ctr, I-90128 Palermo, Italy.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Morozova-Roche, Ludmilla A.
    Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
    Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model2019Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 699, s. 199-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer's and Parkinson's. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer's as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post- TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain tissues during post-TBI recovery. By using sequential immunohistochemistry we have shown that S100A9 was produced by both neuronal and microglial cells. However, A beta peptide deposits characteristic for Alzheimer's disease were not detected in any post-TBI animals. On the first and third post-TBI days S100A9 was found to aggregate intracellularly into amyloid oligomers, similar to what was previously observed in human TBI tissues. Complementary, by using Rayleigh scatting, intrinsic fluorescence and atomic force microscopy we demonstrated that in vitro S100A9 self- assembles into amyloid oligomers within minutes. Its amyloid aggregation is highly dependent on changes of environmental conditions such as variation of calcium levels, pH, temperature and reduction/oxidation, which might be relevant to perturbation of cellular and tissues homeostasis under TBI. Present results demonstrate that S100A9 induction mechanisms in TBI are similar in mice and humans, emphasizing that S100A9 is an important marker of brain injury and therefore can be a potential therapeutic target.

  • 349.
    Watanabe, Hiroyuki
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Zhang, Mengliang
    Lund Univ, Dept Expt Med Sci, Neuronano Res Ctr, Lund, Sweden.
    Sarkisyan, Daniil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kononenko, Olga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Iakovleva, Tatiana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Asymmetric Hindlimb Motor Response To Focal Traumatic Brain Injury Is Controlled By Side-Specific Opioid Mechanism2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A79-A79Artikkel i tidsskrift (Annet vitenskapelig)
  • 350.
    Wetterhall, Magnus
    et al.
    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.
    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.
    Dahlin, Andreas P
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Identification of human cerebrospinal fluid proteins and their distribution in an in vitro microdialysis sampling system2014Inngår i: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 57, nr SI, s. 34-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A qualitative study is presented on how proteins from a complex biological sample are distributed in a microdialysis sample system. A comparison between proteins identified in the human ventricular cerebrospinal fluid (CSF) sample, the collected dialysate and the proteins adsorbed onto the membrane was conducted. The microdialysis experiment was performed in vitro at 37 °C for the duration of 24h. Thereafter, the membranes were removed from the catheter and the adsorbed proteins were tryptically digested using the on-surface enzymatic digestion (oSED) protocol. The CSF samples and the dialysates were digested using a standard in-solution trypsin digestion protocol.  In the final phase, the samples were analysed using nano-liquid chromatography in combination with tandem mass spectrometry. In the four sample compartments analysed (CSF start, Membrane, Dialysate, CSF end) a total of 134 different proteins were found. However, most of the identified proteins(n=87) were uniquely found in one sample compartment only. Common CSF proteins such as albumin, apolipoproteins and cystatin C together with plasma proteins such as hemoglobin and fibrinogen were among the 11 proteins that were found in all samples. These proteins are present in high concentrations in CSF, which means that they effectively block out the detection signal of less abundant proteins.  Therefore, only 25 % of the proteins adsorbed onto the membrane were detected in the CSF compared with the dialysate that shared 44% of its proteins with the CSF. The proteins adsorbed onto the membrane were significantly more hydrophobic, had a lower instability index and more thermostable compared to the proteins in the CSF and the dialysate. The results suggest that proteins adsorbed onto the microdialysis membranes may escape detection because they are prevented from passing the membrane into the dialysate. Thus, the membrane needs to be examined after sample collection in order to better verify the protein content in the original sample. This is particularly important when searching for new protein biomarkers for neurodegenerative diseases.

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