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  • 1.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

  • 2.
    Ahlström, Christer
    et al.
    Swedish National Rd and Transport Research Institute VTI, S-58195 Linkoping, Sweden.
    Jansson, Sabina
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Anund, Anna
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine. Swedish National Rd and Transport Research Institute VTI, S-58195 Linkoping, Sweden.
    Local changes in the wake electroencephalogram precedes lane departures2017In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 26, no 6, p. 816-819Article in journal (Refereed)
    Abstract [en]

    The objective of this exploratory study is to investigate if lane departures are associated with local sleep, measured via source-localized electroencephalography (EEG) theta power in the 5-9 Hz frequency range. Thirty participants drove in an advanced driving simulator, resulting in 135 lane departures at high levels of self-reported sleepiness. These lane departures were compared to matching non-departures at the same sleepiness level within the same individual. There was no correspondence between lane departures and global theta activity. However, at the local level an increased risk for lane departures was associated with increased theta content in brain regions related to motor function.

  • 3.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Rozental, Alexander
    Stockholm University, Sweden; UCL, England.
    Shafran, Roz
    UCL, England.
    Carlbring, Per
    Stockholm University, Sweden; UCL, England.
    Long-term effects of internet-supported cognitive behaviour therapy2018In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 18, no 1, p. 21-28Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Internet-supported and therapist-guided cognitive behaviour therapy (ICBT) is effective for a range of problems in the short run, but less is known about the long-term effects with follow-ups of two years or longer.Areas covered: This paper reviews studies in which the long-term effects of guided ICBT were investigated. Following literature searches in PubMed and other sources meta-analytic statistics were calculated for 14 studies involving a total of 902 participants, and an average follow-up period of three years. Studies were from Sweden (n=11) or the Netherlands (n=3). Long-term outcome studies were found for panic disorder, social anxiety disorder, generalized anxiety disorder, depression, mixed anxiety and depression, obsessive-compulsive disorder, pathological gambling, stress and chronic fatigue. The duration of the treatments was usually short (8-15weeks). The pre-to follow-up effect size was Hedges g=1.52, but with a significant heterogeneity. The average symptom improvement across studies was 50%. Treatment seeking in the follow-up period was not documented and few studies mentioned negative effects.Expert commentary: While effects may be overestimated, it is likely that therapist-supported ICBT can have enduring effects. Long-term follow-up data should be collected for more conditions and new technologies like smartphone-delivered treatments.

  • 4.
    Arfvidsson, John
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Wilhelminen Hospital, Austria.
    Ahlin, Fredrik
    Linköping University, Faculty of Medicine and Health Sciences. Wilhelminen Hospital, Austria.
    Vargas, Kris G.
    Wilhelminen Hospital, Austria.
    Thaler, Barbara
    Medical University of Vienna, Austria.
    Wojta, Johann
    Medical University of Vienna, Austria.
    Huber, Kurt
    Wilhelminen Hospital, Austria; Ludwig Boltzmann Cluster Cardiovasc Research, Austria; Sigmund Freud Private University, Austria.
    Monocyte subsets in myocardial infarction: A review2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 231, p. 47-53Article, review/survey (Refereed)
    Abstract [en]

    Background: Monocytes form an important part of the human innate immune system by taking part in inflammatory reactions. With time, monocytes have gained interest in the role they may play during the event of myocardial infarction (MI). The current paradigm suggests that monocytes consist of three subdivisions which differ in phenotypic and dynamic patterns after an MI. In the inflammation that ensues, the different subsets have been shown to have an impact on reparative processes and patient recovery. Methods results: We searched Medline and Embase until April 5, 2016, for observational studies or clinical trials regarding monocyte functions and dynamics in MI. Apart from studies in humans, extensive work has been done in mice in an effort to understand the complex nature of monocyte dynamics. Animal models might add useful information on mapping these processes. Conclusion: The question still remains whether animal data can, to a certain degree, be extrapolated to monocyte functions during human MI. This review aims to summarize current available evidence on both mice and men with particular focus on the understanding of monocyte subsets dynamics and effects in human MI. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 5.
    Augutis, M
    et al.
    FoU, Sundsvall Hospital, Sundsvall, Sweden.
    Malker, H
    Mid Sweden Research and Development Center, Vasternorrland County Council, Sundsvall, Sweden.
    Levi, Richard
    Karolinska Institute and Frosunda Center, Stockholm, Sweden.
    Pediatric spinal cord injury in Sweden; how to identify a cohort of rare events.2003In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 41, no 6, p. 337-346Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN:: Register study enhanced and verified by medical records and personal interviews and examinations. SETTINGS:: Sweden. OBJECTIVES:: To define a method of identifying a study population of rare events. To point out the relative importance of every step, an example is given of identifying persons who sustained traumatic spinal cord injury (SCI) in childhood. METHODS:: Cases were identified in seven steps that all needed to be fulfilled, from definition of selection criteria through combination of several data sources, to the use of several verification methods. RESULTS:: Initial screening by registers identified 384 possible cases, which however were found by subsequent analysis to include a large number of incorrect cases. At completion of all analytic steps, 35 living cases could be fully verified and 14 deceased cases could be partially verified. CONCLUSIONS:: Registers offer a practical initial source for study population identification. The screening of International Classification of Diseases codes defining SCI only included less than 30% of true SCIs. Subsequently, further refinement and quality control is necessary in order to ensure validity. Such further verification is time-consuming, but nevertheless necessary in order to verify a true cohort.Spinal Cord (2003) 41, 337-346. doi:andlt;highlightandgt;10.1038andlt;/highlightandgt;/andlt;highlightandgt;sj.scandlt;/highlightandgt;.andlt;highlightandgt;3101456andlt;/highlightandgt; [ABSTRACT FROM AUTHOR]

  • 6.
    Augutis, Marika
    et al.
    Landstinget Västernorrland, Sweden.
    Ertzgaard, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Levi, Richard
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Sverige bör centralisera den pediatriska ryggmärgsskadevården2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 35-36Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 7.
    Augutis, Marika
    et al.
    Karolinska Institute, Sweden.
    Levi, Richard
    Karolinska Institute, Sweden.
    Asplund, Kenneth
    Mid-Sweden University, Sundsvall, Sweden.
    Berg-Kelly, Kristina
    Karolinska Institute, Sweden.
    Psychosocial aspects of traumatic spinal cord injury with onset during adolescence: a qualitative study.2007In: Journal of Spinal Cord Medicine (JSCM), ISSN 1079-0268, E-ISSN 2045-7723, Vol. 30 Suppl 1, p. S55-S64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) occurring during adolescence poses additional challenges because of the concurrent age

  • 8.
    Awad, A
    et al.
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Levi, Richard
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Lindgren, L
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Hultling, C
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Westling, G
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Nyberg, L
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Eriksson, J
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Preserved somatosensory conduction in a patient with complete cervical spinal cord injury.2015In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, no 5, p. 426-431Article in journal (Refereed)
    Abstract [en]

    Objective: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel methodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury.andlt;br /andgt;Methods: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback.andlt;br /andgt;Results: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury.andlt;br /andgt;Conclusion: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

  • 9.
    Banefelt, J.
    et al.
    Quantify Research, Sweden.
    Hallberg, S.
    Quantify Research, Sweden.
    Fox, K. M.
    Strateg Healthcare Solut LLC, MD USA.
    Mesterton, J.
    Quantify Research, Sweden; Karolinska Institute, Sweden.
    Paoli, C. J.
    Amgen Inc, CA 91320 USA.
    Johansson, G.
    Uppsala University, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Sobocki, P.
    Karolinska Institute, Sweden; IMS Heatlh, Sweden.
    Gandra, S. R.
    Amgen Inc, CA 91320 USA.
    Work productivity loss and indirect costs associated with new cardiovascular events in high-risk patients with hyperlipidemia: estimates from population-based register data in Sweden2016In: European Journal of Health Economics, ISSN 1618-7598, E-ISSN 1618-7601, Vol. 17, no 9, p. 1117-1124Article in journal (Refereed)
    Abstract [en]

    Objectives To estimate productivity loss and associated indirect costs in high-risk patients treated for hyperlipidemia who experience cardiovascular (CV) events. Methods Retrospective population-based cohort study conducted using Swedish medical records linked to national registers. Patients were included based on prescriptions of lipid-lowering therapy between 1 January 2006 and 31 December 2011 and followed until 31 December 2012 for identification of CV events and estimation of work productivity loss (sick leave and disability pension) and indirect costs. Patients were stratified into two cohorts based on CV risk level: history of major cardiovascular disease (CVD) and coronary heart disease (CHD) risk equivalent. Propensity score matching was applied to compare patients with new events (cases) to patients without new events (controls). The incremental effect of CV events was estimated using a difference-in-differences design, comparing productivity loss among cases and controls during the year before and the year after the cases event. Results The incremental effect on indirect costs was largest in the CHD risk equivalent cohort (n = 2946) at (sic)3119 (P value amp;lt;0.01). The corresponding figure in the major CVD history cohort (n = 4508) was (sic)2210 (P value amp;lt;0.01). There was substantial variation in productivity loss depending on the type of event. Transient ischemic attack and revascularization had no significant effect on indirect costs. Myocardial infarction ((sic)), unstable angina ((sic)) and, most notably, ischemic stroke ((sic)) yielded substantial incremental cost estimates (P values amp;lt;0.01). Conclusions Indirect costs related to work productivity losses of CV events are substantial in Swedish high-risk patients treated for hyperlipidemia and vary considerably by type of event.

  • 10.
    Bellon-Harn, Monica L.
    et al.
    Lamar University, TX 77710 USA.
    Hartwell Azios, Jamie
    Lamar University, TX 77710 USA.
    Dockens, Ashley L.
    Lamar University, TX 77710 USA.
    Manchaiah, Vinaya
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Lamar University, TX 77710 USA; Audiol India, India.
    Speech-language pathologists preferences for patient-centeredness2017In: Journal of Communication Disorders, ISSN 0021-9924, E-ISSN 1873-7994, Vol. 68, p. 81-88Article in journal (Refereed)
    Abstract [en]

    Purpose: Preferences for patient-centeredness is an important indicator in healthcare service delivery. However, it remains largely unexplored in the field of communication science and disorders. This study investigated speech-language pathologists (SLPs) preferences for patient-centeredness Method: The study involved a cross-sectional survey design. SLPs (n = 102) fully completed the modified Patient-Practitioner Orientation Scale (PPOS; Krupat et al, 2000) and also provided demographic details. Data were analyzed using descriptive statistics, correlation, and linear regression methods. Results: Mean PPOS scores indicated that SLPs value patient-centeredness. There was a strong positive correlation among sharing and caring subscales with the full-scale. Results from the linear regression modeling suggested no relationship between demographic factors and preferences for patient-centeredness. Conclusions: SLPs value patient-centeredness, although there may be regional and cultural variations. Qualitative investigations may help uncover dimensions of patient-centeredness that were not captured in the PPOS scale. In addition, further research should explore congruence in preferences for patient-centeredness among SLPs and patients.

  • 11.
    Berntsson, S. G.
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, A.
    Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Feresiadou, A.
    Uppsala Univ, Sweden.
    Burman, J.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden Outlier or predecessor?2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 327-331Article in journal (Refereed)
    Abstract [en]

    ObjectivesOff-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis. Material and MethodsReview of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital. ResultsPresently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%. ConclusionsThe share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

  • 12.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Berling, P.
    UCB Pharma, Denmark.
    Morberg, S.
    UCB Pharma, Denmark.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Uppsala University, Sweden.
    Patterns of antiepileptic drug prescription in Sweden: A register-based approach2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 5, p. 521-527Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward. Material and methods: Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period. Results: For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013. Conclusions: A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.

  • 13.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Prevalence and cost of epilepsy in Sweden - a register-based approach2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 1, p. 37-44Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011. MethodsCost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications. ResultsThe prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from Euro2929 to Euro1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011. ConclusionsThe per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalenceless than1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005.

  • 14.
    Boman, Andrea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lysosomal network proteins as biomarkers and therapeutic targets in neurodegenerative disease2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pre-symptomatic stage of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) occurs several decades before the clinical onset. Changes in the lysosomal network, i.e. the autophagosomal, endosomal and lysosomal vesicular system, are among the first alterations observed. There are currently no treatments to slow or cure neurodegenerative diseases, and there is a great need for discovery of treatment targets in cellular pathways where pathology pre-dates the neuronal death. It is also crucial to be able to diagnose neurodegenerative diseases earlier, both to enable early intervention treatment and aid in selecting clinical trial populations before the patient has widespread pathology.

    This thesis aims at investigating the potential of lysosomal network proteins as biomarkers and therapeutic targets in neurodegenerative disease.

    A targeted search for lysosomal network proteins was performed in cerebrospinal fluid (CSF) from AD patients, and seven proteins: early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), lysozyme, microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were elevated. The levels of EEA1, LAMP-1, LAMP-2, LC3, lysozyme and Rab3 were also measured in CSF from parkinsonian syndrome patients: PD, clinically diagnosed 4-repeat tauopathy, pathologically confirmed corticobasal degeneration (CBD) and pathologically confirmed progressive supranuclear palsy (PSP) patients. LAMP-1 and LAMP-2 were decreased in PD. LC3 and lysozyme levels were increased in 4-repeat tauopathy patients. EEA1 was decreased and lysozyme increased in PSP, and LAMP-1, LAMP-2, LC3 and lysozyme were increased in CBD. The lysosomal network proteins had different CSF protein profiles in all the parkinsonian syndromes, as well as in AD. It should be emphasized that only a select few of the lysosomal network proteins were observed to be changed, rather than a general change in lysosomal network proteins, which implicates the involvement of these seven proteins in specific pathological processes. The most interesting candidates, LAMP-2 and lysozyme, were selected for further study for their involvement in the pathology of AD.

    Lysozyme was found to co-localise with Aβ plaques in AD patients and overexpression prolonged survival and improved the activity in a Drosophila model of AD. Lysozyme was found to alter the aggregation pathway of Aβ1-42, to counteract the formation of toxic Aβ species and to protect from Aβ1-42 induced cell toxicity. Aβ1-42 in turn was found to increase the expression of lysozyme in both neuronal and glial cells. These data suggest that lysozyme levels rise in AD as a compensatory response which is protective against Aβ associated toxicity.

    LAMP-2 mRNA and protein were found increased in brain areas relevant for AD pathology and various cellular models showed complex involvement of LAMP-2 in Aβ related pathology, with extensive crosstalk between LAMP-2 and Aβ. Exposure to oligomeric Aβ1-42 caused an upregulation of LAMP-2 and in turn, overexpression of LAMP-2 caused a reduction in secreted levels of Aβ1-42, as well as changing the generation pattern of Aβ and affecting clearance and secretion of Aβ1-42. These data indicate that the increased levels of LAMP-2 in AD could be an attempt to regulate Aβ generation and secretion.

    In summary, this thesis reports that utilising lysosomal network proteins as biomarkers and novel therapeutic targets for neurodegenerative diseases holds great promise.

    List of papers
    1. Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease
    Open this publication in new window or tab >>Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease
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    2014 (English)In: Neuromolecular medicine, ISSN 1535-1084, E-ISSN 1559-1174, Vol. 16, no 1, p. 150-160Article in journal (Refereed) Published
    Abstract [en]

    The success of future intervention strategies for Alzheimers disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis.

    Place, publisher, year, edition, pages
    Humana Press, 2014
    Keywords
    PICALM; DRAM; TFEB; Cathepsins; Proteasome; hsc70
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-105235 (URN)10.1007/s12017-013-8269-3 (DOI)000331101900015 ()
    Available from: 2014-03-14 Created: 2014-03-14 Last updated: 2018-01-11
    2. Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease
    Open this publication in new window or tab >>Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease
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    2015 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 83, p. 122-133Article in journal (Refereed) Published
    Abstract [en]

    The hallmarks of Alzheimer disease are amyloid-β plaques and neurofibrillary tangles accompanied by signs of neuroinflammation. Lysozyme is a major player in the innate immune system and has recently been shown to prevent the aggregation of amyloid-β1-40 in vitro. In this study we found that patients with Alzheimer disease have increased lysozyme levels in the cerebrospinal fluid and lysozyme co-localized with amyloid-β in plaques. In Drosophila neuronal co-expression of lysozyme and amyloid-β1-42 reduced the formation of soluble and insoluble amyloid-β species, prolonged survival and improved the activity of amyloid-β1-42 transgenic flies. This suggests that lysozyme levels rise in Alzheimer disease as a compensatory response to amyloid-β increases and aggregation. In support of this, in vitro aggregation assays revealed that lysozyme associates with amyloid-β1-42 and alters its aggregation pathway to counteract the formation of toxic amyloid-β species. Overall, these studies establish a protective role for lysozyme against amyloid-β associated toxicities and identify increased lysozyme in patients with Alzheimer disease. Therefore, lysozyme has potential as a new biomarker as well as a therapeutic target for Alzheimer disease.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Lysozyme, Biomarker, Alzheimer disease, Drosophila, Aβ aggregation
    National Category
    Cell and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122341 (URN)10.1016/j.nbd.2015.08.024 (DOI)000366230000012 ()26334479 (PubMedID)
    Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2018-01-10Bibliographically approved
    3. Distinct lysosomal network protein profiles in parkinsonian syndrome cerebrospinal fluid
    Open this publication in new window or tab >>Distinct lysosomal network protein profiles in parkinsonian syndrome cerebrospinal fluid
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    2016 (English)In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 6, no 2, p. 307-315Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Clinical diagnosis of parkinsonian syndromes like Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy is hampered by overlapping symptomatology and lack of biomarkers for diagnosis, and definitive diagnosis is only possible post-mortem. Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that levels and profiles of lysosomal network proteins in cerebrospinal fluid could be changed in these parkinsonian syndromes.

    Methods: Cerebrospinal fluid samples were collected from Parkinson’s disease patients (n=18), clinically diagnosed 4-repeat tauopathy patients, corticobasal syndrome (n=6) and progressive supranuclear palsy (n=5), pathologically diagnosed progressive supranuclear palsy (n=8) and corticobasal degeneration patients (n=7). Each patient set was compared to its appropriate control group consisting of the same number of age and gender matched individuals. Lysosomal network protein levels were detected via Western blotting.

    Results: Lysosomal network proteins have markedly different cerebrospinal fluid protein levels and profiles in Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in Parkinson´s disease; early endosomal antigen 1 was decreased and lysozyme increased in progressive supranuclear palsy; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in corticobasal degeneration.

    Conclusions: Lysosomal network proteins hold promise of being interesting novel candidates for biomarker studies and for elucidating disease mechanisms of Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy, but further validation studies will be needed to assess the specificity and the predictive value of these proteins in CSF.

    Place, publisher, year, edition, pages
    IOS Press, 2016
    National Category
    Cell and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122342 (URN)10.3233/JPD-150759 (DOI)000378352200004 ()
    Note

    Funding agencies:This work was supported by the Swedish Alzheimer foundation, the Swedish Dementia foundation, Linkoping University Neurobiology Center, Karin & Sten CBD Solutions AB, AZ-KI TSC, ALF, US National Institutes of Health R01AG038791 and U54NS092089, the Tau Consortium, the Hellman Family Foundation.

    Vid tiden för disputationen förelåg publikationen endast som manuskript

    Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2018-01-10Bibliographically approved
    4. The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease
    Open this publication in new window or tab >>The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease
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    2015 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Dysfunction in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are implicated in the pathways in Alzheimer’s disease brain pathology. This dysfunction is mirrored in the cerebrospinal fluid where a specific subset of lysosomal network proteins are found at elevated levels, lysosomal associated membrane protein-2 (LAMP-2) being one of the identified lysosomal proteins. Here we report that hippocampus and frontal cortex in Alzheimer’s disease cases have increased mRNA and protein expression of LAMP-2, and thus these brain areas are likely involved in the increased LAMP-2 levels seen in cerebrospinal fluid from Alzheimer’s disease patients. The increased LAMP-2 levels correlated with increased levels of β-amyloid1-42 (Aβ1-42). Oligomeric Aβ1-42 caused an upregulation of intracellular LAMP-2 in neuroblastoma cells, but did not trigger the release of LAMP-2 to the extracellular milieu, indicating that other cell types or mechanisms are responsible for the LAMP-2 release seen in cerebrospinal fluid. Overexpression of LAMP-2 in neuroblastoma cells caused a trend of reduction of secreted Aβ1-42 and changed the processing pattern of the Aβ precursor protein. These results indicate that Aβ1-42 mediated increase of LAMP-2 expression can act as a regulator of Aβ generation and secretion. LAMP-2 overexpression did not change the cellular uptake of extracellularly added Aβ1-42, but caused a delayed clearance of Aβ1-42. Whether the prolonged intracellular localization of Aβ1-42 in LAMP-2 overexpressing cells can change the transmission or degradation of Aβ remains to be investigated.

    Keywords
    AβPP processing, Alzheimer’s disease, β-amyloid, autophagy, LAMP-2, lysosome
    National Category
    Cell and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122345 (URN)
    Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2018-01-10Bibliographically approved
  • 15.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Does the changing sex ratio of multiple sclerosis give opportunities for intervention?2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, p. 42-45Article, review/survey (Refereed)
    Abstract [en]

    In several international studies, an increasing women-to-men (w/m) ratio in patients with multiple sclerosis (MS) has been reported. Such sex ratios have been analysed by year of onset or by year of birth. In a Swedish study, data from the Swedish MS register (SMSreg) were used to analyse the w/m ratio in Sweden. The sex ratio was analysed both by year of birth (8834 patients) and by year of onset (9098 patients). No increased w/m ratio was seen in this study. The age-specific sex ratio did not demonstrate any significant changes. However, a new investigation of the sex ratio in Sweden, based on data from all available data sources (19,510 patients), showed a significantly increased w/m ratio of MS in Sweden from 1.70 to 2.67. Environmental factors such as cigarette smoking, hormonal factors and nutrition are of interest in this context, but the cause of the increasing w/m ratio in MS is yet not possible to explain.

  • 16.
    Broström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Gardner, Benjamin
    University College London, UK.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Fridlund, Bengt
    Jönköping University, Sweden.
    Arestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Linnaeus University & Palliative Research Centre, Ersta Sköndal University College and Ersta Hospital, Stockholm.
    Validation of the CPAP Habit Index-5: A Tool to Understand Adherence to CPAP Treatment in Patients with Obstructive Sleep Apnea.2014In: Sleep Disorders, ISSN 2090-3545, E-ISSN 2090-3553, Vol. 2014, p. 1-9, article id 929057Article in journal (Refereed)
    Abstract [en]

    Long-term adherence to continuous positive airway pressure (CPAP) is low among patients with obstructive sleep apnea (OSA). The potential role of "habit" in sustaining adherence to CPAP use has not been studied. This study aimed to establish the relevance of habit to CPAP adherence, via validation of an adaptation of the Self-Report Habit Index (the CPAP Habit Index-5; CHI-5). Analyses focused on the homogeneity, reliability, and factor structure of the CHI-5 and, in line with theoretical predictions, its utility as a predictor of long-term CPAP adherence in middle-aged patients with OSA. A prospective longitudinal design was used. 117 patients with objectively verified OSA intended for CPAP treatment were recruited. Data was collected via clinical examinations, respiratory recordings, questionnaires, and CPAP devices at baseline, 2 weeks, 6 months, and 12 months. The CHI-5 showed satisfactory homogeneity interitem correlations (0.42-0.93), item-total correlations (0.58-0.91), and reliability ( α = 0.92). CHI-5 data at 6 months showed a one-factor solution and predicted 63% of variance in total CPAP use hours after 12 months. Based on the satisfactory measurement properties and the high amount of CPAP use variance it explained, the CHI-5 can be seen as a useful tool in clinical practice.

  • 17.
    Brundin, L.
    et al.
    Van Andel Research Institute, MI 49503 USA.
    Sellgren, C. M.
    Karolinska Institute, Sweden; Broad Institute MIT and Harvard, MA USA; Massachusetts Gen Hospital, MA USA.
    Lim, C. K.
    Macquarie University, Australia.
    Grit, J.
    Van Andel Research Institute, MI 49503 USA.
    Palsson, E.
    Gothenburg University, Sweden.
    Landen, M.
    Gothenburg University, Sweden.
    Samuelsson, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Karolinska Institute, Sweden.
    Lundgren, Kristoffer
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Brundin, P.
    Van Andel Research Institute, MI 49503 USA.
    Fuchs, D.
    Medical University of Innsbruck, Austria.
    Postolache, T. T.
    University of Maryland, MD 21201 USA; Rocky Mt MIRECC, CO USA.
    Traskman-Bendz, L.
    Lund University, Sweden.
    Guillemin, G. J.
    Macquarie University, Australia; NHMRC Centre Research Excellence Suicide Prevent CRESP, Australia.
    Erhardt, S.
    Karolinska Institute, Sweden.
    An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation2016In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 6, no e865Article in journal (Refereed)
    Abstract [en]

    Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (Pamp;lt;0.001) and blood (P=0.001 and Pamp;lt;0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.

  • 18.
    Bäcklund, Tomas
    et al.
    Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
    Frankel, Jennifer
    Department of Radiation Sciences, Radiation Physics, Umeå University, Umeå, Sweden.
    Israelsson, Hanna
    Region Östergötland. Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Malm, Jan
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Sundström, Nina
    Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
    Trunk sway in idiopathic normal pressure hydrocephalus-Quantitative assessment in clinical practice2017In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 54, p. 62-70Article in journal (Refereed)
    Abstract [en]

    In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body-worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)).

  • 19.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Edström, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An exploratory, discovery phase study2018In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, article id 116Article in journal (Refereed)
    Abstract [en]

    Background: Post-translational modifications (PTMs) generate a tremendous protein diversity from the similar to 20,000 protein-coding genes of the human genome. In chronic pain conditions, exposure to pathological processes in the central nervous system could lead to disease-specific PTMs detectable in the cerebrospinal fluid (CSF). In a previous hypothesis-generating study, we reported that seven out of 260 CSF proteins highly discriminated between neuropathic pain patients and healthy controls: one isoform of angiotensinogen (AG), two isoforms of alpha-1-antitrypsin (AT), three isoforms of haptoglobin (HG), and one isoform of pigment epithelium-derived factor (PEDF). The present study had three aims: (1) To examine the multivariate inter-correlations between all identified isoforms of these seven proteins; (2) Based on the results of the first aim, to characterize PTMs in a subset of interesting proteins; (3) To regress clinical pain data using the 260 proteins as predictors, thereby testing the hypothesis that the above-mentioned seven discriminating proteins and/or the characterized isoforms/fragments of aim (2) would be among the proteins having the highest predictive power for clinical pain data. Methods: CSF samples from 11 neuropathic pain patients and 11 healthy controls were used for biochemical analysis of protein isoforms. PTM characterization was performed using enzymatic reaction assay and mass spectrometry. Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was applied on the quantified protein isoforms. Results: We identified 5 isoforms of AG, 18 isoforms of AT, 5 isoforms of HG, and 5 isoforms of PEDF. Fragments and glycosylated isoforms of AT were studied in depth. When regressing the pain intensity data of patients, three isoforms of AT, two isoforms of PEDF, and one isoform of angiotensinogen "reappeared" as major results, i.e., they were major findings both when comparing patients with healthy controls and when regressing pain intensity in patients. Conclusions: Altered levels of fragments and/or glycosylated isoforms of alpha-1-antitrypsin might mirror pathophysiological processes in the spinal cord of neuropathic pain patients. In particular, we suggest that a putative disease-specific combination of the levels of two different N-truncated fragments of alpha-1-antitrypsin might be interesting for future CSF and/or plasma biomarker investigations in chronic neuropathic pain.

  • 20.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Lind, Anne-Li
    Uppsala University, Sweden.
    Thulin, Mans
    Uppsala University, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gordh, Torsten
    Uppsala University, Sweden.
    High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls2017In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 12, p. 2487-2495Article in journal (Refereed)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called "gliotransmitters," a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile of patients with neuropathic pain. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation. Samples of CSF were collected from 2 cohorts of patients with neuropathic pain (n = 11 and n = 16, respectively) and healthy control subjects (n 5 11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek Multiplex Inflammation I; Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares discriminant analysis, were used for statistical analyses. Levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23 in CSF, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared with healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in patients with fibromyalgia. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Because it has been suggested that prevalent comorbidities to chronic pain (eg, depression, anxiety, poor sleep, and tiredness) also are associated with neuroinflammation, it will be important to determine whether neuroinflammation is a common mediator.

  • 21.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Tanum, Lars
    Akershus University Hospital, Norway.
    Lind, Anne-Li
    Uppsala University, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Gordh, Torsten
    Uppsala University, Sweden.
    Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma2017In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 10Article in journal (Refereed)
    Abstract [en]

    In addition to central hyperexcitability and impaired top-down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n= 10) and plasma from blood donor controls (n= 46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.

  • 22.
    Caceres, R.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Richter, J.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Säfström, Kåge
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Editorial: Application of a vagal nerve stimulator in an epilepsy patient with cardiac pacemaker after post-ictal cardiac arrest2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 120, no 2, p. 139-142Article in journal (Other academic)
    Abstract [en]

    In this case report we present a patient with temporal lobe epilepsy (TLE) showing partial complex seizures and secondary generalization, and treated with several antiepileptic drugs. After two consecutive seizures she had an episode of cardiac arrest followed by AV-block III which led to the implantation of a cardiac pacemaker. She subsequently received a vagal nerve stimulator because of poor response to epilepsy treatment. Combined treatment with two different electromagnetic stimulators raises the question of safety during surgery which is discussed.

  • 23.
    Danielsson, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    The Clinical and Pathological Spectrum of Idiopathic Inflammatory Myopathies: Implications for pathogenesis, classification and diagnosis2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of diseases with severe consequences for the life of affected patients. Dermatomyositis, polymyositis and inclusion body myositis (IBM) are the classical representatives of this group. The treatments given today often have limited effects, and are taken at the cost of side effects. Major obstacles in the search for more effective treatments are; (1) an incomplete understanding of the disease mechanisms, (2) difficulties to delineate homogeneous disease groups for clinical studies and (3) the sometimes challenging task to diagnose these diseases.

    Aims: We addressed a number of “loose ends” in the areas of pathogenesis, classification and diagnosis; mechanisms of muscle fiber degeneration in IIM, with a focus of programmed cell death (apoptosis) and invasion of muscle  fibers by inflammatory cells (partial invasion); protecting and mediating factors present in muscle; the association of other diseases with IIM, in particular celiac disease ; the evaluation of two classification systems and laboratory methods for increased diagnostic performance.

    The studies: We included 106 patients, diagnosed at the Neuromuscular unit in Linköping, Sweden, with pathological muscle findings consistent with IIM. The incidence in the county of Östergötland (during 5 years) was 7.3 per million/year (3 patients each year). Of 88 patients with confirmed IIM 4 (4.5 %) had celiac disease, 33 (38%) had an associated systemic inflammatory disease and 5 (5.7 %) had a malignancy. Ninety-nine patients were included for a comparison of two classification systems using criteria of the European Neuromuscle Centre (Amato/ENMC), and the widely used Bohan and Peter classification, both with the addition of IBM according to Griggs et al. Using the Amato/ENMC criteria the most prevalent diagnostic group after IBM (30%) was nonspecific myositis (23%), followed by polymyositis (20%) and dermatomyositis 17%). A substantial number of patients meeting Bohan and Peter (or Griggs) criteria were excluded by Amato/ENMC criteria, most (21/23) due to lack of detectable muscle weakness. Extended muscle sectioning increased the sensitivity of a muscle biopsy by 15 % and the specificity by 22%, and showed an overlap between disease groups. Muscle biopsies from patients with IIM and controls were used to investigate pathological findings considered specific for disease groups, and for the presence of programmed cell death (apoptosis) and disease protecting and mediating factors in muscle. The presence of apoptotic muscle fiber nuclei was detected in muscle with partial invasion (however not in the invaded fibers) in the presence of granzyme B and CD8+ cytotoxic T cells. The major apoptosis inhibiting protein Bcl-2 was shown to be constitutionally expressed in healthy muscle but weakened in IIM.

    Conclusion: We present apoptosis as a possible disease mechanism in parallel with partial invasion of fibers. Furthermore, partial invasion may not be a suitable distinguishing feature in the pathogenesis, or for classification and diagnosis of IIM. We also introduce the anti-apoptotic Bcl-2 as a possible relevant muscle fiber protecting factor. A more extensive pathological work-up improves classification and diagnosis of IIM. The proposed Amato/ENMC creates a substantial portion of patients with non-specific or unclassified myositis. Associated diseases are common in IIM, and also include celiac disease.

    List of papers
    1. Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients
    Open this publication in new window or tab >>Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients
    2013 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, no 7, p. 1173-1182Article in journal (Refereed) Published
    Abstract [en]

    Objective. Insights into the pathogenesis of inflammatory myopathies have led to new diagnostic methods. The aims of our study were (1) to evaluate the consequences of using the classification of Amato/European Neuromuscular Centre Workshop (ENMC), compared to that of Bohan and Peter; and (2) to evaluate any diagnostic benefit in using an extended pathological investigation. less thanbrgreater than less thanbrgreater thanMethods. From a consecutive retrospective database, we evaluated 99 patients for classification. Patients with inclusion body myositis (IBM) were classified according to Griggs, et al. In addition to routine stainings and immunohistochemistry, a multilevel serial sectioning procedure was performed on paraffin-embedded material, to identify scarce pathological findings. less thanbrgreater than less thanbrgreater thanResults. Classification according to Bohan and Peter could be performed for 83 of the 99 patients, whereas only 60 patients met the Amato/ENMC criteria, the latter resulting in the following diagnostic groups: IBM (n = 18), nonspecific myositis (n = 14), polymyositis (n = 12), dermatomyositis (n = 10), dermatomyositis sine dermatitis (n = 5), and immune-mediated necrotizing myopathy (n = 1). Most of the Amato/ENMC diagnostic groups harbored patients from several of the Bohan and Peter groups, which included a substantial group lacking proximal muscle weakness. The serial sectioning procedure was essential for classification of 9 patients (15%), and led to a more specific diagnosis for 13 patients (22%) according to Amato/ENMC. less thanbrgreater than less thanbrgreater thanConclusion. The classification of Amato/ENMC was more restrictive, forming groups based on clinical criteria and specified myopathological findings, which clearly differed from the groups of the Bohan and Peter classification. An extended pathological investigation increased the diagnostic yield of a muscle biopsy and highlights the quantity and specificity of certain pathological findings.

    Place, publisher, year, edition, pages
    Journal of Rheumatology, 2013
    Keywords
    INFLAMMATORY MYOPATHIES, IDIOPATHIC INFLAMMATORY MYOPATHIES, POLYMYOSITIS, DERMATOMYOSITIS, INCLUSION BODY MYOSITIS
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-96992 (URN)10.3899/jrheum.120804 (DOI)000321993800023 ()
    Note

    Funding Agencies|University Hospital Linkoping||County Council of Ostergotland||

    Available from: 2013-09-02 Created: 2013-09-02 Last updated: 2017-12-06
    2. Expression of apoptosis related proteins in normal and diseased muscle: A possible role for Bcl-2 in protection of striated muscle
    Open this publication in new window or tab >>Expression of apoptosis related proteins in normal and diseased muscle: A possible role for Bcl-2 in protection of striated muscle
    2009 (English)In: NEUROMUSCULAR DISORDERS, ISSN 0960-8966, Vol. 19, no 6, p. 412-417Article in journal (Refereed) Published
    Abstract [en]

    The unique absence of major histocompatibility complex class I antigen (MHC-I) expression in normal muscle is one possible mechanism protecting striated muscle. In order to define their possible involvement in protection of normal muscle. we investigated the expression of molecules involved in muscle fibre death and survival mechanisms (Bcl-2, Fas, Fas-ligand and TRAIL), focusing on disorders with possible involvement of cytotoxic T cells. We studied muscle biopsies from 20 healthy volunteers, from 10 patients affected by polymyositis and 10 by Duchenne muscular dystrophy. By using immunohistochemistry, Western blot and real-time PCR we detected a constitutional expression of Bcl-2 in healthy muscle, whereas the expression was weaker in disease processes. Fas-L and TRAIL were not detected in muscle fibres, and Fas only in muscle affected by disease. Our findings indicate that the major apoptotic protein Bcl-2 might have a hitherto unrecognized role in the protection of normal muscle.

    Keywords
    Inflammatory myopathy, Apoptosis, Bcl-2, TRAIL, Fas and Fas-L
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-19795 (URN)10.1016/j.nmd.2009.03.008 (DOI)
    Available from: 2009-08-10 Created: 2009-08-10 Last updated: 2016-11-23
  • 24.
    Danielsson, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindvall, Björn
    University Hospital Örebro, Sweden.
    Hallert, Claes
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Increased prevalence of celiac disease in idiopathic inflammatory myopathies2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 10, article id e00803Article in journal (Refereed)
    Abstract [en]

    ObjectivesIdiopathic inflammatory myopathies (IIM) are often associated with other immune-mediated diseases or malignancy. Some studies have reported a high frequency of celiac disease in IIM. The aim of this study was to investigate the prevalence of celiac disease, systemic inflammatory diseases, and malignancy in a cohort of IIM patients, and estimate the incidence of IIM in the county of ostergotland, Sweden. Material and MethodsWe reviewed medical records and analyzed sera from 106 patients, fulfilling pathological criteria of inflammatory myopathy, for the presence of IgA antibodies against endomysium and gliadin. Antibody-positive patients were offered further investigation with small bowel biopsy or investigation for the presence of antibodies against antitissue transglutaminase (t-TG). The patients were classified according to Bohan and Peter or Griggs criteria. The presence of celiac disease, systemic inflammatory, and malignant diseases was documented. ResultsFour of 88 patients classified as IIM (4.5%) had biopsy-confirmed celiac disease, which is higher than the prevalence in the general population, detected with a similar screening procedure (0.53%). Thirty-three patients (38%) had a systemic inflammatory disease and five (5.7%) a malignancy. The incidence of confirmed IIM in the county of ostergotland was 7.3 per million/year. ConclusionsThe results highlight the high frequency of associated inflammatory and malignant diseases and confirm an increased prevalence of celiac disease in IIM.

  • 25.
    Davidovic, Monika
    et al.
    University of Gothenburg, Sweden.
    Jonsson, Emma H.
    University of Gothenburg, Sweden.
    Olausson, Håkan
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Björnsdotter Åberg, Malin
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Posterior Superior Temporal Sulcus Responses Predict Perceived Pleasantness of Skin Stroking2016In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 10, no 432Article in journal (Refereed)
    Abstract [en]

    Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress-like skin stroking. We collected functional magnetic resonance imaging data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS) responses predicted healthy participants perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment.

  • 26.
    Dawson, Andreas
    et al.
    Region Östergötland, Public Dental Health Care. Malmö University, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Stensson, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    List, Thomas
    Malmö University, Sweden; Skåne University Hospital, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Svensson, Peter
    Aarhus University, Denmark; Aarhus University Hospital, Denmark; Karolinska Institute, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Ernberg, Malin
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Dopamine in plasma - a biomarker for myofascial TMD pain?2016In: Journal of Headache and Pain, ISSN 1129-2369, E-ISSN 1129-2377, Vol. 17, no 65Article in journal (Refereed)
    Abstract [en]

    Background: Dopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects. Methods: Fifteen patients with M-TMD and 15 age-and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0-100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken. Results: Dopamine in plasma differed significantly between patients with M-TMD (4.98 +/- 2.55 nM) and healthy controls (2.73 +/- 1.24 nM; P amp;lt; 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P amp;lt; 0.001) and had lower PPTs (P amp;lt; 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P amp;lt; 0.05) and perceived mental stress (r = 0.34, n = 28, P amp;lt; 0.05). Conclusions: The results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain.

  • 27.
    Dietrich, Franciele
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. CAPES Fdn, Brazil; Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Hammerman, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tätting, Love
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Faccin Bampi, Vinicius
    Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Braga Silva, Jefferson
    Pontificia University of Catolica Rio Grande do Sul PUCRS, Brazil.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Effect of platelet-rich plasma on rat Achilles tendon healing is related to microbiota2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, p. 416-421Article in journal (Refereed)
    Abstract [en]

    Background and purpose - In 3 papers in Acta Orthopaedica 10 years ago, we described that platelet-rich plasma (PRP) improves tendon healing in a rat Achilles transection model. Later, we found that microtrauma has similar effects, probably acting via inflammation. This raised the suspicion that the effect ascribed to growth factors within PRP could instead be due to unspecific influences on inflammation. While testing this hypothesis, we noted that the effect seemed to be related to the microbiota. Material and methods - We tried to reproduce our old findings with local injection of PRP 6h after tendon transection, followed by mechanical testing after 11 days. This failed. After fruitless variations in PRP production protocols, leukocyte concentration, and physical activity, we finally tried rats carrying potentially pathogenic bacteria. In all, 242 rats were used. Results - In 4 consecutive experiments on pathogen-free rats, no effect of PRP on healing was found. In contrast, apparently healthy rats carrying Staphylococcus aureus showed increased strength of the healing tendon after PRP treatment. These rats had higher levels of cytotoxic T-cells in their spleens. Interpretation - The failure to reproduce older experiments in clean rats was striking, and the difference in response between these and Staphylococcus-carrying rats suggests that the PRP effect is dependent on the immune status. PRP functions may be more complex than just the release of growth factors. Extrapolation from our previous findings with PRP to the situation in humans therefore becomes even more uncertain.1

  • 28.
    Divanoglou, A
    et al.
    Division of Neuro-rehabilitation, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Westgren, N
    Division of Neuro-rehabilitation, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Bjelak, S
    Rehab Station Stockholm, Stockholm, Sweden.
    Levi, Richard
    Division of Neuro-rehabilitation, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Medical conditions and outcomes at 1 year after acute traumatic spinal cord injury in a Greek and a Swedish region: a prospective, population-based study2010In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 48, no 6, p. 470-476Article in journal (Refereed)
    Abstract [en]

    Study design: Prospective, population-based study. This paper is part of the Stockholm Thessaloniki Acute Traumatic Spinal Cord Injury Study (STATSCIS).andlt;br /andgt;Objectives: To evaluate and compare outcomes, length of stay (LOS), associated conditions and medical complications at 1-year post-trauma.andlt;br /andgt;Settings: The Greater Thessaloniki region, Greece, and the Greater Stockholm region, Sweden. While Stockholm follows a SCI system of care, Thessaloniki follows a fragmented non-system approach.andlt;br /andgt;Subjects: Out of the 87 cases in Thessaloniki and the 49 cases in Stockholm who comprised the study population of STATSCIS, 75 and 42 cases respectively were successfully followed-up during the first year post-trauma.andlt;br /andgt;Results: Significantly superior outcomes (that is, survival with neurological recovery, functional ability and discharge to home) and shorter LOS for initially motor complete cases occurred in Stockholm. Management routines known to increase long-term morbidity, for example, long-term tracheostomy and indwelling urethral catheters were significantly more common in Thessaloniki. Major medical complications, that is, multiple pressure ulcers, heterotopic ossification and bacteremia/sepsis were more frequent in Thessaloniki.andlt;br /andgt;Conclusions: Our findings show how two rather similar cohorts of TSCI manifest large discrepancies in terms of 1-year outcomes and complications, depending on the type of management they receive. As the major difference between regions was the presence or absence of a SCI system of care, rather than differences in availability of modern medicine, the mere presence of the latter does not seem to be sufficient to guarantee adequate outcomes. This study provides strong evidence as to the urgent need of implementing a SCI system of care in Greece. Spinal Cord (2010) 48, 470-476; doi: andlt;highlightandgt;10.1038andlt;/highlightandgt;/andlt;highlightandgt;scandlt;/highlightandgt;.andlt;highlightandgt;2009.147andlt;/highlightandgt;; published online 22 December 2009

  • 29.
    Divanoglou, Anestis
    et al.
    Division of Neurorehabilitation, Karolinska Institutet, Stockholm, Sweden.
    Westgren, Ninni
    Division of Neurorehabilitation, Karolinska Institutet, Stockholm, Sweden.
    Seiger, Ake
    Division of Neurorehabilitation, Karolinska Institutet, Stockholm, Sweden.
    Hulting, Claes
    Division of Neurorehabilitation, Karolinska Institutet, Stockholm, Sweden.
    Levi, Richard
    Division of Neurorehabilitation, Karolinska Institutet, Stockholm, Sweden.
    Late mortality during the first year after acute traumatic spinal cord injury: a prospective, population-based study.2010In: Journal of Spinal Cord Medicine (JSCM), ISSN 1079-0268, E-ISSN 2045-7723, Vol. 33, no 2, p. 117-127Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the possible impact of the system of care on mortality during the first year after acute traumatic spinal cord injury (TSCI).

    OBJECTIVE: To evaluate late mortality (i.e., >7 days after trauma) during the first year after acute TSCI in 2 European Union (EU) regions, Thessaloniki in Greece and Stockholm in Sweden.

    METHODS: This paper is part of the Stockholm Thessaloniki Acute Traumatic Spinal Cord Injury Study (STATSCIS), which is a prospective, population-based study. Incidence cohorts of TSCI cases were identified and followed up in both study regions through STATSCIS. Data from Thessaloniki region were collected through physical examination, medical records review, and interviews with TSCI individuals and the medical teams. Data from Stockholm were retrieved mainly from the Nordic Spinal Cord Injury Registry, as well as from direct contact with all intensive care facilities of the region.

    RESULTS: The annual case mortality rate after acute TSCI was nearly 20% in Thessaloniki and 0% in Stockholm. The mean time of survival after trauma for the 12 mortality cases of Thessaloniki was 47 days (median = 24, SD +/- 67, range = 8-228). Factors associated with mortality were higher age and presence of comorbid spinal disorders but also the inefficient transfer logistics, initially missed spinal instability, and unsuccessfully treated complications.

    CONCLUSIONS: The annual case mortality rate in Thessaloniki was dramatically higher than in Stockholm. The different approaches to care, one systematic and the other not, is postulated to be an important factor leading to such major discrepancies between the outcomes of these 2 EU regions.

  • 30.
    Dragioti, Elena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. University of Ioannina, Greece.
    Karathanos, V.
    University of Ioannina, Greece.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Evangelou, E.
    University of Ioannina, Greece; Imperial Coll London, England.
    Does psychotherapy work? An umbrella review of meta-analyses of randomized controlled trials2017In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 136, no 3, p. 236-246Article, review/survey (Refereed)
    Abstract [en]

    Objective: To map and evaluate the evidence across meta-analyses of randomized controlled trials (RCTs) of psychotherapies for various outcomes. Methods: We identified 173 eligible studies, including 247 meta-analyses that synthesized data from 5157 RCTs via a systematic search from inception to December 2016 in the PubMed, PsycINFO and Cochrane Database of Systematic Reviews. We calculated summary effects using random-effects models, and we assessed between-study heterogeneity. We estimated whether large studies had significantly more conservative results compared to smaller studies (small-study effects) and whether the observed positive studies were more than expected by chance. Finally, we assessed the credibility of the evidence using several criteria. Results: One hundred and ninety-nine meta-analyses were significant at P-value amp;lt;= 0.05, and almost all (n = 196) favoured psychotherapy. Large and very large heterogeneity was observed in 130 meta-analyses. Evidence for small-study effects was found in 72 meta-analyses, while 95 had evidence of excess of significant findings. Only 16 (7%) provided convincing evidence that psychotherapy is effective. These pertained to cognitive behavioural therapy (n = 6), meditation therapy (n = 1), cognitive remediation (n = 1), counselling (n = 1) and mixed types of psychotherapies (n = 7). Conclusions: Although almost 80% meta-analyses reported a nominally statistically significant finding favouring psychotherapy, only a few meta-analyses provided convincing evidence without biases.

  • 31.
    Dunn, James S.
    et al.
    University of Western Sydney, Australia.
    Mahns, David A.
    University of Western Sydney, Australia.
    Nagi, Saad S.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Western Sydney, Australia.
    Why does a cooled object feel heavier? Psychophysical investigations into the Webers Phenomenon2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, article id 4Article in journal (Refereed)
    Abstract [en]

    Background: It has long been known that a concomitantly cooled stimulus is perceived as heavier than the same object at a neutral temperature-termed Webers Phenomenon (WP). In the current study, we re-examined this phenomenon using well-controlled force and temperature stimuli to explore the complex interplay between thermal and tactile systems, and the peripheral substrates contributing to these interactions. A feedback-controlled apparatus was constructed using a mechanical stimulator attached to a 5- x 5-mm thermode. Force combinations of 0.5 and 1 N (superimposed on 1-N step) were applied to the ulnar territory of dorsal hand. One of the forces had a thermal component, being cooled from 32 to 28 degrees C at a rate of 2 degrees C/s with a 3-s static phase. The other stimulus was thermally neutral (32 degrees C). Participants were asked to report whether the first or the second stimulus was perceived heavier. These observations were obtained in the all-fibre-intact condition and following the preferential block of myelinated fibres by compression of ulnar nerve. Results: In normal condition, when the same forces were applied, all subjects displayed a clear preference for the cooled tactile stimulus as being heavier than the tactile-only stimulus. The frequency of this effect was augmented by an additional similar to 17% when cooling was applied concurrently with the second stimulus. Following compression block, the mean incidence of WP was significantly reduced regardless of whether cooling was applied concurrently with the first or the second stimulus. However, while the effect was abolished in case of former (elicited in amp;lt; 50% of trials), the compression block had little effect in four out of nine participants in case of latter who reported WP in at least 80% of trials (despite abolition of vibration and cold sensations). Conclusions: WP was found to be a robust tactile-thermal interaction in the all-fibre-intact condition. The emergence of inter-individual differences during myelinated block suggests that subjects may adopt strategies, unbeknownst to them, that focus on the dominant input (myelinated fibres, hence WP abolished by block) or the sum of convergent inputs (myelinated and C fibres, hence WP preserved during block) in order to determine differences in perceived heaviness.

  • 32.
    Eckerström, C.
    et al.
    Institute of Neuroscience and Physiology, Göteborg University, Sweden.
    Olsson, E.
    Department of Philosophy, Göteborg University, Sweden, Institute of Biomedicine, Göteborg University, Sweden.
    Borga, Magnus
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ekholm, S.
    Department of Radiology, University of Rochester Medical Center, United States.
    Ribbelin, S.
    Department of Radiology, Göteborg University, Sweden.
    Rolstad, S.
    Institute of Neuroscience and Physiology, Göteborg University, Sweden.
    Starck, G.
    Department of Radiology, Göteborg University, Sweden, Department of Radiation Physics, Göteborg University, Sweden.
    Edman, A.
    Edman, Å., Institute of Neuroscience and Physiology, Göteborg University, Sweden.
    Wallin, A.
    Institute of Neuroscience and Physiology, Göteborg University, Sweden.
    Malmgren, H.
    Department of Philosophy, Göteborg University, Sweden.
    Small baseline volume of left hippocampus is associated with subsequent conversion of MCI into dementia: The Göteborg MCI study2008In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 272, no 1-2, p. 48-59Article in journal (Refereed)
    Abstract [en]

    Background: Earlier studies have reported that hippocampal atrophy can to some extent predict which patients with mild cognitive impairment (MCI) will subsequently convert to dementia, and that converters have an enhanced rate of hippocampal volume loss. Objective: To further validate the hypothesis that hippocampal atrophy predicts conversion from MCI to dementia, to relate baseline hippocampal volume to different forms of dementia, and to investigate the role of hippocampal side differences and rate of volume loss over time. Patients: The subjects (N = 68) include patients with MCI at baseline and progression to dementia at the two-year follow-up (N = 21), stable MCI patients (N = 21), and controls (N = 26). Among the progressing patients, 13 were diagnosed as having AD. Methods: The Göteborg MCI study is a clinically based longitudinal study with biannual clinical assessments. Hippocampal volumetry was performed manually on the MRI investigations at baseline and at the two-year follow-up. Results: Hippocampal volumetry could predict conversion to dementia in both the AD and the non-AD subgroup of converters. Left hippocampal volume in particular discriminated between converting and stable MCI. Cut off points for individual discrimination were shown to be potentially useful. The converting MCI group had a significantly higher rate of hippocampal volume loss as compared to the stable MCI group. Conclusions: In MCI patients, hippocampal volumetry at baseline gives prognostic information about possible development of AD and non-AD dementia. Contrary to earlier studies, we found that left hippocampal volume has the best predictive power. Reliable predictions appear to be possible in many individual cases. © 2008 Elsevier B.V. All rights reserved.

  • 33.
    Edell-Gustafsson, Ulla
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Svanborg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences.
    Sleep-activity profile and quality of life in patients with stable coronary disease2003In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 26, no Abstract supplement, p. A357-A357Article in journal (Other academic)
    Abstract [en]

    Introduction: Previous studies have examined the relationship between initiation sleep difficulties and quality of life. However, when reviewing the literature in this area we found no reports of a relationship between evening physical activity and health related quality of life in patients with coronary disease. This study was designed to investigate assumed sleep, circadian rhythm, evening physical activity and health related quality of life.

    Methods: Twenty-six men and 21 women, mean age 64.0 (SD 8.9) years and 63 (SD 9.3) years, respectively, with stable angina pectoris were included. For assessment of health related quality of life the patients completed the SF36 questionnaire. The data were compared with those for men and women in the general Swedish population. Physical activity was continuously recorded at home, using actigraphy with an integral light recorder (Model AW-L, Cambridge Neurotechnology Ltd, UK) in 1-minute epochs during one week. The data were downloaded by Actiwatch Reader and imported to the Actiwatch software for Windows 98.

    Results: Average time of going to bed was 22.37, sleep latency 27 minutes, assumed sleep duration 7.59 hr, time in bed 8.56 hr and sleep efficiency 79.2%. No differences were found during the seven nights. Nonparametric analysis of the circadian rhythm showed that 39 of 47 patients had the lowest 5-hour count activity onset at 00.00 p.m. and 41of 47 patients had the maximal 10 hr count onset 08.00 a.m. or later. Sleep analysis indicated reduced activity in the evening (p.m. 06.00-09.00). Some actigraphic parameters of the evening activity associated significantly with circadian rhythm parameters. Compared to the general Swedish population, the patients ́ health related quality of life waspoor. Linear stepwise regression analysis showed that reduced activity 3 evenings/week significantly explained health related quality of life in32.3% of role function outcome, due to physical causes (p=0.0001) and in 24.7% (p<0.01) of social function, whereas reduced activity 2 evenings/week explained 20% (p<0.01) of body pain.

    Conclusions: These data indicate that sleep-activity profile is associated with health related quality of life in patients with stable angina pectoris.

  • 34.
    Edström, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Regulation of immunity in Multiple Sclerosis: CD4+ T cells and the influence of natalizumab2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) and the most common neurological cause of disability in young adults. In most cases, the disease course is characterised by the cycling of relapses and remissions, so called relapsing-remitting MS (RR-MS). Although extensively studied, the underlying mechanisms are not fully elucidated, yet CD4+ T cells have been shown to be of importance in disease pathology. A range of treatments are available; the most effective to date being natalizumab, a monoclonal antibody directed against the adhesion molecule VLA-4 on the lymphocyte surface, thereby preventing entry into the CNS.

    The aim of this thesis was to assess the nature of lymphocyte populations in MS. This was achieved by studying CD4+ T helper cells (TH) and regulatory T cells (TREG) in peripheral blood. In addition, the influence of natalizumab was also investigated, both regarding the effect of the drug on the composition of the peripheral lymphocyte compartment as well as its effects on CD4+ T cells in vitro.

    We showed an imbalance in the mRNA expression of CD4+ T helper cell lineage specific transcription factors in peripheral blood. While TH1 and TH17 associated TBX21 and RORC expression was comparable in MS and healthy individuals, the TH2 and TREG associated GATA3 and FOXP3 expression was decreased in RR-MS. Given the reciprocally inhibitory nature of TH subsets, this might imply not only diminished function of TH2 and TREG cells but also a permissive state of harmful TH1 and TH17 cells. The size of the peripheral TREG population was unaltered in RR-MS. When analysed in detail, activated and resting TREG were distinguished, showing clear differences in FOXP3 and CD39 expression. Furthermore, when investigating these subpopulations functionally, the ability of activated TREG to suppress proliferation of responder T cells was found to be decreased in RR-MS patients compared to controls. To further investigate this defect, the global gene expression of TREG was compared between patients and controls. Gene set enrichment analysis revealed an enrichment (over-expression) of chemokine receptor signalling genes in RR-MS TREG, possibly suggesting a role for  chemokines in TREG function.

    A sizable effect of natalizumab treatment was seen in the composition of peripheral lymphocyte populations after one year of treatment. While the number of lymphocytes increased over all, the largest increase was seen in the NK and B cell compartments. Furthermore, T cells from patients with MS displayed decreased responsiveness towards antigens and mitogens in vitro. Natalizumab treatment was able to normalise the responsiveness in blood, an effect not solely dependent on the increased number of cells.

    The importance of CD4+ T cells in human disease, including MS, was shown by a systems biology approach; using GWAS data, genes associated with CD4+ T cell differentiation were enriched for many, not only immunerelated, diseases. Furthermore, global CD4+ T cell gene expression (by microarray) could discriminate between patients and controls. Lastly, using in vitro treated CD4+ T cells, we could show that natalizumab perturbated gene expression differently in patients responding to the drug compared to those not responding.

    In conclusion, our results demonstrate an imbalance of peripheral CD4+ T cells in MS, along with a functional deficiency in the case of TREG. Taken together, these aberrations might result in differentiation and activation of harmful TH1 and TH17 cells, resulting in CNS tissue damage. The importance of CD4+ T cells was further demonstrated by the finding that genes associated with CD4+ T cell differentiation constitute a pleiotropic module common to a number of diseases. Investigation of natalizumab revealed drastic changes in the peripheral lymphocyte compartment caused by treatment. It also appears as treatment might influence the responsiveness of peripheral T cells to antigens. In addition, by using CD4+ T cell transcriptomics after in vitro drug exposure, prediction of treatment outcome may be possible.

    List of papers
    1. Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood
    Open this publication in new window or tab >>Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood
    Show others...
    2011 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, no 1, p. 57-66Article in journal (Refereed) Published
    Abstract [en]

    Background:Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors.

    Objective:The aim of this study was to assess the balance of CD4+T cell populations in relapsing-remitting MS.

    Methods:Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers.

    Results:In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4+CD25hiTreg. Immunoregulatory EBI3 and Th2-associated GATA3 ([a-z]+) was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005).

    Conclusion:Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4+phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.

    Place, publisher, year, edition, pages
    Sage Publications, 2011
    Keywords
    EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-64758 (URN)10.1177/1352458510381256 (DOI)000285867200006 ()20847001 (PubMedID)
    Available from: 2011-02-04 Created: 2011-02-04 Last updated: 2017-12-11
    2. Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines
    Open this publication in new window or tab >>Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines
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    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND Regulatory T cells (Treg) are critical for immune regulation and homeostasis. In multiple sclerosis (MS), the function of these cells has been shown to be impaired, although the underlying mechanism has yet to be shown. In the current study, we aimed to characterize and assess the phenotypical, functional and transcriptional characteristics of memory and naïve Treg in MS patients and controls.

    MATERIAL AND METHODS 27 patients with relapsing-remitting disease were included, along with 29 healthy controls. Flow cytometry was used for detailed phenotyping of Treg subpopulations CD4+CD45RA+/- and CD4dimCD25++ and their expression of FOXP3, CD39 and HELIOS. CFSE (proliferation marker) and CD69 (activation marker) were used to investigate the functional capacity of Treg. A microarray was employed for genome-wide transcriptional characterization of isolated Treg.

    RESULTS CD4+CD45RA–CD25++ activated Treg displayed a higher expression of FOXP3 and CD39 than resting CD4+CD45RA+CD25+ Treg, while no significant phenotypical differences were observed in Treg subpopulations between patients and controls. However, a lower anti-proliferative capacity was observed in activated Treg of MS patients compared with those of controls (p<0.05), while suppression of activation was similar to controls. Gene set enrichment analysis (GSEA) of microarray data revealed enrichment for the GO gene set ‘chemokine receptor binding’ in MS Treg.

    CONCLUSION Although numerical phenotypical assessment of resting and activated Tregs did not reveal any significant difference between patients and controls, functional co-culturing experiments showed an impaired function in activated Treg of MS patients. Furthermore, GSEA revealed immune-related gene sets overexpressed in Treg of MS patients, possibly containing clues to the functional impairment. In particular over-activity in chemokine signalling in Treg would be of interest for further investigation.

    Keywords
    EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
    National Category
    Clinical Medicine Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-108908 (URN)
    Available from: 2014-07-11 Created: 2014-07-11 Last updated: 2018-01-11Bibliographically approved
    3. An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients
    Open this publication in new window or tab >>An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients
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    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81685Article in journal (Refereed) Published
    Abstract [en]

    Background

    Changes in the peripheral blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.

    Objectives

    To assess changes in circulating lymphocyte subpopulation compositions and T-cell responses during natalizumab treatment.

    Material and methods

    A broad panel of markers for blood lymphocyte populations, including states of activation and co-stimulation as well as T-cell responses to recall antigens and mitogens, was assessed by flow cytometry in 40 patients with relapsing multiple sclerosis before and after one-year natalizumab treatment.

    Results

    Absolute numbers of all major populations of lymphocytes increased after treatment, most markedly for NK- and B-cells. The fraction of both memory and presumed regulatory B-cell subsets increased, as did CD3-CD56dim cytotoxic NK-cells, whereas CD3-CD56bright regulatory NK-cells decreased. Treatment was also associated with a restored T-cell responsiveness to recall antigens and mitogens.

    Conclusions

    Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK- and B-cells. This supports reduction of lymphocyte extravasation as a main mode of action, although the differential composition of lymphocyte subpopulations suggests cell-signalling effects may also be operative. The systemic increase in T-cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses become correspondingly decreased.

    Place, publisher, year, edition, pages
    San Francisco, USA: Public Library of Science, 2013
    Keywords
    Multiple sclerosis, natalizumab, flow cytometry, T-cells, NK-cells, B-cells, lymphocyte proliferation
    National Category
    Neurology Immunology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-84268 (URN)10.1371/journal.pone.0081685 (DOI)000327944500088 ()24312575 (PubMedID)2-s2.0-84891420120 (Scopus ID)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2018-01-12Bibliographically approved
    4. Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment
    Open this publication in new window or tab >>Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment
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    2014 (English)In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 17Article in journal (Refereed) Published
    Abstract [en]

    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

    Place, publisher, year, edition, pages
    BioMed Central, 2014
    National Category
    Clinical Medicine Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-106873 (URN)10.1186/gm534 (DOI)000334631300002 ()
    Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2018-04-10
  • 35.
    Ekerstad, Niklas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. NU NAL Uddevalla Hosp Grp, Sweden.
    Karlsson, Thomas
    Univ Gothenburg, Sweden.
    Soderqvist, Sara
    NU NAL Uddevalla Hosp Grp, Sweden.
    Karlson, Bjorn W.
    NU NAL Uddevalla Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Hospitalized frail elderly patients - atrial fibrillation, anticoagulation and 12 months outcomes2018In: Clinical Interventions in Aging, ISSN 1176-9092, E-ISSN 1178-1998, Vol. 13, p. 749-756Article in journal (Refereed)
    Abstract [en]

    Background and objective: Multiple chronic conditions and recurring acute illness are frequent among elderly people. One such condition is atrial fibrillation (AF), which increases the risk of stroke up to fivefold. The aim of this study was to investigate the prevalence of AF among hospitalized frail elderly patients, their use of anticoagulation and their 12-month outcomes. Patients and methods: This was a clinical observational study of acutely hospitalized frail patients over the age of 75 years. The CHA2DS2-VASc Score was used to evaluate ischemic stroke risk in patients with AF. Clinically relevant outcomes were the composite of ischemic stroke and/or bleeding within 12 months, which was considered as primary in the analysis, ischemic stroke/transient ischemic attack (TIA), mortality, bleeding and hospital care consumption. Students (test, Fishers exact test, Mann Whitney U test and a Cox proportional hazards model were used for the analyses. Results: The prevalence of AF was 47%, and 63% of them were prescribed an anticoagulant. AF patients without anticoagulation were older, more often females, more often in residential care, and they had worse Mini Nutritional Assessment and activities of daily living scores. Of the patients without anticoagulation, 56% had a documented contraindication. In univariate analysis, there were significantly more events among AF patients without anticoagulation regarding the composite outcome of ischemic stroke and/or bleeding (hazard ratio [1112] 3.65, 95% CI = 1.70-7.86; p amp;lt; 0.001). When adjusting for potential confounders in Cox regression analysis, the difference remained significant (HR 4.54, 95% CI = 1.83-11.25; p = 0.001). Conclusion: The prevalence of AF in a hospitalized frail elderly population was 47%. Of these, 63% were prescribed anticoagulation therapy. Almost half of the patients without stroke pro-phylaxis had no documented contraindication. At 1 year, there were significantly more events in terms of ischemic stroke and/or bleeding among AF patients without anticoagulation therapy than among those with.

  • 36.
    Eleftheriou, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Circadian rhythm in idiopathic normal pressure hydrocephalus2018In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 164, p. 72-74Article in journal (Refereed)
    Abstract [en]

    Objectives: The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) takes place in structures close to the cerebral ventricular system. Suprachiasmatic nucleus (SCN), situated close to the third ventricle, is involved in circadian rhythm. Diurnal disturbances are well-known in demented patients. The cognitive decline in iNPH is potentially reversible after a shunt operation. Diurnal rhythm has never been studied in iNPH. We hypothesize that there is a disturbance of circadian rhythm in iNPH-patients and the aim was to study any changes of the diurnal rhythm (mesor and circadian period) as well as any changes of the diurnal amplitude and acrophase of the activity in iNPH-patients before and after a shunt operation. Patients and methods: Twenty consecutive iNPH-patients fulfilling the criteria of the American iNPH-guidelines, 9 males and 11 females, mean age 73 (49-81) years were included. The patients underwent a pre-operative clinical work-up including 10 m walk time (w10mt) steps (w10 ms), TUG-time (TUGt) and steps (TUGs) and for cognitive function an MMSE score was measured. In order to receive circadian rhythm data actigraphic recordings were performed using the SenseWear 2 (BodyMedia Inc Pittsburgh, PA, USA) actigraph. Cosinor analyses of accelerometry data were performed in "R" using non-linear regression with Levenburg-Marquardt estimation. Pre- and post-operative data regarding mesor, amplitude and circadian period were compared using Wilcoxon-Mann-Whitney test for paired data. Results: Twenty patients were evaluated before and three month post-operatively. Motor function (w10mt, w10 ms, TUGt, TUGs) was significantly improved while MMSE was not significantly changed. Actigraphic measurements (mesor, amplitude and circadian period) showed no significant changes after shunt operation. Conclusion: This is the first systematic study of circadian rhythm in iNPH-patients. We found no significant changes in circadian rhythm after shunt surgery. The conceptual idea of diurnal rhythm changes in hydrocephalus is still interesting from a theoretical standpoint and warrants further studies that could include a combination of better designed actigraphic studies in combination with neuroendocrine markers and imaging methods

  • 37.
    Engstrand, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hand function in patients with Dupuytren’s disease: Assessment, results & patients’ perspectives2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Dupuytren’s Disease (DD) is a soft tissue disorder that leads to finger joint contractures affecting hand function. DD can be treated with surgery or injection and hand therapy to improve finger joint extension and thereby improve hand function. However, this does not cure the disease and recurrence is common. Previous research on DD has shown improvement in finger joint extension and in self-reported disability of the upper extremity after surgery and hand therapy for DD. However, this provides only a limited perspective on hand function, and multiple dimensions of changes in hand function (i.e. physical, psychosocial aspects and including the patients’ views of results) have not been reported as a whole.

    Aim: The overall aim of the thesis was to explore hand function before and after surgery and hand therapy in patients with DD, including assessment, results and patients’ perspectives.

    Methods: The thesis comprises three studies: Study A was a methodological study of interrater reliability in goniometry of the finger joints. Study B was a prospective cohort study with a repeated measures design. Study C was a qualitative interview study, using the model of Patient Evaluation Process and content analysis.

    Results: Interrater reliability was high or very high for goniometer measurement of finger joint range of motion (ROM) in patients with DD when experienced raters follow our standardized guidelines developed for the study. Changes in hand function consisted of improvement of finger joint extension while active finger flexion was significantly impaired during the first year after surgery and hand therapy. No patient reached a normal ROM, but the majority reached a functional ROM. Sensibility remained unaffected. Patients with surgery on multiple fingers had worse scar pliability than patients with surgery on a single finger. Most patients had their expectations met and were pleased or delighted with their hand function at 12 months after surgery and hand therapy. Safety issues of hand function were of greater concern than social issues. Patients reported less disability and improved health-related quality of life after surgery and hand therapy. The three variables “need to take special precautions”, “avoid using the hand in social context”, and health-related quality of life had significant importance for patients’ rating of functional recovery. Together, these variables explained 62% of the variance in functional recovery. Patients’ perspectives of undergoing a surgical intervention process were described through five categories. Previous experiences of care influenced participants’ expectations of results and the care they were about to receive. Previous experiences and expectations were used as references for appraisal of results, which concerned perceived changes in hand function, the care process, competency, and organization. Appraisal of results could also vary in relation to  patient character. Appraisal of results of the intervention process influenced participants’ expectations of future hand function, health and care.

    Conclusions: Surgery and hand therapy for DD improve hand function and patients regain a functional ROM needed for performance of common daily activities. Despite the negative effect on finger flexion present during the first year after surgery, patients’ regards their hand function as recovered six to eight months after surgery and hand therapy. Measuring digital ROM in the finger joints with a goniometer is a reliable assessment method. However, from the patient’s perspective, it is not enough to evaluate results only in terms of digital extension or ROM. From their view, results of treatment concern consequences on daily use of the hand, what happens during the care process in terms of interaction between patient and health care provider, as well as their view of the competence and logistics of the organization providing the care.

    List of papers
    1. Interrater Reliability in Finger Joint Goniometer Measurement in Dupuytrens Disease
    Open this publication in new window or tab >>Interrater Reliability in Finger Joint Goniometer Measurement in Dupuytrens Disease
    2012 (English)In: American Journal of Occupational Therapy, ISSN 0272-9490, E-ISSN 1943-7676, Vol. 66, no 1, p. 98-103Article in journal (Refereed) Published
    Abstract [en]

    We investigated interrater reliability of range of motion (ROM) measurement in the finger joints of people with Dupuytrens disease. Eight raters measured flexion and extension of the three finger joints in one affected finger of each of 13 people with different levels of severity of Dupuytrens disease, giving 104 measures of joints and motions. Reliability measures, represented by intraclass correlation coefficient (ICC), standard error of the mean (SEM), and differences between raters with the highest and lowest mean scores, were calculated. ICCs ranged from .832 to .973 depending on joint and motion. The SEM was andlt;= 3 degrees for all joints and motions. Differences in mean between highest and lowest raters were larger for flexion than for extension; the largest difference was in the distal interphalangeal joint. The results indicate that following these standardized guidelines, the interrater reliability of goniometer measurements is high for digital ROM in people with Dupuytrens disease.

    Place, publisher, year, edition, pages
    American Occupational Therapy Association, 2012
    Keywords
    arthrometry, articular, Dupuytren contracture, finger joint, range of motion, articular, reproducibility of results
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-75284 (URN)10.5014/ajot.2012.001925 (DOI)000299362000012 ()
    Available from: 2012-02-27 Created: 2012-02-24 Last updated: 2017-12-07
    2. Hand function and quality of life before and after fasciectomy for Dupuytren contracture
    Open this publication in new window or tab >>Hand function and quality of life before and after fasciectomy for Dupuytren contracture
    2014 (English)In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 39, no 7, p. 1333-1343Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE:

    To describe changes in joint motion, sensibility, and scar pliability and to investigate the patients' expectations, self-reported recovery, and satisfaction with hand function, disability, and quality of life after surgery and hand therapy for Dupuytren disease.

    METHODS:

    This prospective cohort study collected measurements before surgery and 3, 6, and 12 months after surgery and hand therapy. Ninety patients with total active extension deficits of 60° or more from Dupuytren contracture were included. Outcomes measures were range of motion; sensibility; scar pliability; self-reported outcomes on expectations, recovery, and satisfaction with hand function; Disabilities of the Arm, Shoulder, and Hand scores; safety and social issues of hand function; physical activity habits; and quality of life with the Euroqol.

    RESULTS:

    The extension deficit decreased, and there was a transient decrease in active finger flexion during the first year after surgery. Sensibility remained unaffected. Generally, patients with surgery on multiple fingers had worse scar pliability. The majority of the patients had their expectations met, and at 6 months, 32% considered hand function as fully recovered, and 73% were satisfied with their hand function. Fear of hurting the hand and worry about not trusting the hand function were of greatest concern among safety and social issues. The Disability of the Arm, Shoulder, and Hand score and the Euroqol improved over time.

    CONCLUSIONS:

    After surgery and hand therapy, disability decreased independent of single or multiple operated fingers. The total active finger extension improved enough for the patients to reach a functional range of motion despite an impairment of active finger flexion still present 12 months after treatment.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Dupuytren contracture; surgical treatment; range of motion; satisfaction; occupational therapy
    National Category
    Clinical Medicine Physiotherapy
    Identifiers
    urn:nbn:se:liu:diva-109387 (URN)10.1016/j.jhsa.2014.04.029 (DOI)000338905000014 ()24969497 (PubMedID)
    Available from: 2014-08-15 Created: 2014-08-15 Last updated: 2017-12-05Bibliographically approved
    3. Factors affecting functional recovery after surgery and hand therapy in patients with Dupuytren's disease
    Open this publication in new window or tab >>Factors affecting functional recovery after surgery and hand therapy in patients with Dupuytren's disease
    2015 (English)In: Journal of Hand Therapy, ISSN 0894-1130, E-ISSN 1545-004X, Vol. 28, no 3, p. 255-260Article in journal (Refereed) Published
    Abstract [en]

    Study design: Prospective cohort study. Introduction: The evidence of the relationship between functional recovery and impairment after surgery and hand therapy are inconsistent. Purpose of the study: To explore factors that were most related to functional recovery as measured by DASH in patients with Dupuytrens disease. Methods: Eighty-one patients undergoing surgery and hand therapy were consecutively recruited. Functional recovery was measured by the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Explanatory variables: range of motion of the finger joints, five questions regarding safety and social issues of hand function, and health-related quality of life (Euroqol). Results: The three variables "need to take special precautions", "avoid using the hand in social context", and health-related quality of life (EQ-5D index) explained 62.1% of the variance in DASH, where the first variable had the greatest relative effect. Discussion: Safety and social issues of hand function and quality of life had an evident association with functional recovery. Level of evidence: IV.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Dupuytrens contracture; Emotional function; Range of motion; Recovery of function; Quality of life
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-121325 (URN)10.1016/j.jht.2014.11.006 (DOI)000359329100005 ()25998546 (PubMedID)
    Note

    Funding Agencies|Medical Research Council of southeast Sweden [FORSS-72231]; County Council of Ostergotland, Sweden [LIO-77311]

    Available from: 2015-09-14 Created: 2015-09-14 Last updated: 2017-12-04
    4. Patients'€™ perspective on surgical intervention for Dupuytren'€™s disease€: experiences, expectations and appraisal of results
    Open this publication in new window or tab >>Patients'€™ perspective on surgical intervention for Dupuytren'€™s disease€: experiences, expectations and appraisal of results
    2016 (English)In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 38, no 24-26, p. 2538-2549Article in journal (Refereed) Published
    Abstract [en]

    Purpose To explore patients’ perspectives on surgical intervention for Dupuytren’s disease (DD), focusing on patients’ appraisal of results, involving previous experiences, expectations and patient characters.

    Method The participants were 21 men, mean age 66 years, scheduled for DD surgery. Qualitative interviews were conducted 2–4 weeks before surgery and 6–8 months after surgery. The model of the Patient Evaluation Process was used as theoretical framework. Data were analyzed using problem-driven content analysis.

    Results Five categories are described: previous experiences, expectations before surgery, appraisal of results, expectations of the future and patient character. Previous experiences influenced participants’ expectations, and these were used along with other aspects as references for appraisal of results. Participants’ appraisal of results concerned perceived changes in hand function, care process, competency and organization, and could vary in relation to patient character. The appraisal of results influenced participants’ expectations of future hand function, health and care.

    Conclusions Patients’ appraisal of results involved multidimensional reasoning reflecting on hand function, interaction with staff and organizational matters. Thus, it is not enough to evaluate results after DD surgery only by health outcomes as this provides only a limited perspective. Rather, evaluation of results should also cover process and structure aspects of care.

    Implications for Rehabilitation

    • To improve health care services, it is important to be aware of the role played by patient’s previous experiences, expectations as well as staff and organizational aspects of care.
    • Knowledge about patients’ experience and view of the results from surgery and rehabilitation should be established by assessment of care effects on health as well as structure and process aspects of care.
    • Evaluation of structure and process aspects of care can be done by using questions about if the patient felt listened to, received clear information and explanations, was included in decision-making, and their view of waiting time or continuity of care.
    • Improving health care services means not only providing the best treatment method available but also developing individualized care by ensuring good interaction with the patient, providing accurate information, and working to improve the structure of the care process.
    • Before treatment, health care providers should have a dialogue with the patient and consider previous experiences and expectations in order to ensure the patient has balanced expectations of the outcome.
    Keywords
    Care process; hand function; hand surgery; interviews; outcome
    National Category
    Health Care Service and Management, Health Policy and Services and Health Economy Nursing Physiotherapy
    Identifiers
    urn:nbn:se:liu:diva-125964 (URN)10.3109/09638288.2015.1137981 (DOI)000385478900020 ()26878688 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland, Sweden

    Available from: 2016-03-10 Created: 2016-03-10 Last updated: 2017-11-30Bibliographically approved
  • 38.
    Engstrand, Christina
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    The Role of Hand Therapy in Dupuytren Disease2018In: Hand Clinics, ISSN 0749-0712, E-ISSN 1558-1969, Vol. 34, no 3, p. 395-401Article in journal (Refereed)
    Abstract [en]

    The role of hand therapy in the treatment of Dupuytren disease varies depending on the patient and the procedure. There is limited evidence for hand therapy as a preventive treatment of Dupuytren disease. Before corrective treatment, the hand therapist can contribute with assessments to promote evaluation of outcome. After corrective treatment, hand therapy is tailored to each patients needs and consists of orthoses, exercise, edema control, and pain or scar management. Orthoses are usually part of the hand therapy protocol after corrective procedures despite lack of strong supporting evidence and should be provided based on individual patient needs.

  • 39.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Flensner, Gullvi
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. University West, Trollhättan, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Thalamo-striato-cortical determinants to fatigue in multiple sclerosis2013In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 3, no 6, p. 715-728Article in journal (Refereed)
    Abstract [en]

    Background

    The aim was to explore the thalamo-striato-cortical theory of central fatigue in multiple sclerosis (MS) patients with self-reported fatigue. If the theory correctly predicted fatigue based on disruptions of the thalamo-striato-cortical network, we expected altered brain activation in this network in MS participants while performing a complex cognitive task that challenged fatigue.

    Methods

    MS participants with self-reported fatigue were examined by functional magnetic resonance imaging (fMRI) during the performance of a complex working memory task. In this task, cognitive effort was challenged by a parametric design, which modeled the cerebral responses at increasing cognitive demands. In order to explore the theory of central fatigue in MS we also analyzed the cerebral responses by adding perceived fatigue scores as covariates in the analysis and by calculating the functional connectivity between regions in the thalamo-striatocortical network. The main findings were that MS participants elicited altered brain responses in the thalamo-striato-cortical network, and that brain activation in the left posterior parietal cortex and the right substantia nigra was positively correlated to perceived fatigue ratings. MS participants had stronger cortical-to-cortical and subcortical-to-subcortical connections, whereas they had weaker cortical-to-subcortical connections.

    Conclusions

    The findings of the present study indicate that the thalamo-striato-cortical network is involved in the pathophysiology of fatigue in MS, and provide support for the theory of central fatigue. However, due to the limited number of participants and the somewhat heterogeneous sample of MS participants, these results have to be regarded as tentative, though they might serve as a basis for future studies.

  • 40.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    New hypothesis on pontine-frontal eye field connectivity in Kleine-Levin syndrome2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, no 6, p. 716-719Article in journal (Refereed)
    Abstract [en]

    Previous studies have indicated involvement of the thalamus and the pons in Kleine-Levin syndrome. In the present study, functional connectivity of the thalamus and the pons was investigated in asymptomatic patients with Kleine-Levin syndrome and healthy controls. Twelve patients and 14 healthy controls were investigated by functional magnetic resonance imaging during rest. Resting state images were analysed using seed regions of interest in the thalamus and the pons. The results showed significantly lower functional connectivity between the pons and the frontal eye field in persons with Kleine-Levin syndrome compared with healthy controls. There were no connectivity differences involving the thalamus. Based on these findings, a relation is proposed between the sleep disorder Kleine-Levin syndrome and cerebral control of eye movements, which in turn is related to visual attention and working memory. This hypothesis has to be tested in future studies of oculomotor control in Kleine-Levin syndrome.

  • 41.
    Ertzgaard, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Anhammer, M.
    Ipsen, Sweden.
    Forsmark, A.
    Nordic Health Econ AB, Sweden.
    Regional disparities in botulinum toxin A (BoNT-A) therapy for spasticity in Sweden: budgetary consequences of closing the estimated treatment gap2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, no 3, p. 366-372Article in journal (Refereed)
    Abstract [en]

    Objectives: As no national treatment guidelines for spasticity have been issued in Sweden, different regional treatment practices may potentially occur. This study examines botulinum toxin A (BoNT-A) treatment for spasticity on a regional level in Sweden and presents budgetary consequences of closing the estimated treatment gap. Materials and Methods: Prevalence of spasticity in Sweden was estimated from published data. Regional sales data for BoNT-A were acquired from IMS Health. A set proportion of hospital BoNT-A use was assumed to represent treatment of spasticity. Total intervention cost of BoNT-A treatment was gathered from healthcare regional tariffs, while costs associated with spasticity were derived from publications on multiple sclerosis and stroke. Results: Results show that the regional variation in treatment of spasticity with BoNT-A is large, with approximately every fourth patient being treated in Southern healthcare region compared to every tenth in the Stockholm-Gotland or Western healthcare regions. The incremental cost of filling the reported treatment gap was also assessed and was estimated at around 9.4 million EUR. However, for the incremental cost to be offset by savings in spasticity-related costs, only a small proportion of treatment responders (defined as patients transitioning to a lower severity grade of spasticity) was required (12%). Conclusions: The study revealed apparent regional disparities of BoNT-A treatment for spasticity in Sweden. The results further suggest that the incremental cost of eliminating the treatment gap has a high probability of being offset by savings in direct costs, even at a low proportion of the patients reaching clinical improvement.

  • 42.
    Ertzgaard, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Campo, Claudia
    Medtron EMEA Regional Clin Centre, Italy.
    Calabrese, Alessandra
    Medtron Int Trading Sarl, Switzerland.
    EFFICACY AND SAFETY OF ORAL BACLOFEN IN THE MANAGEMENT OF SPASTICITY: A RATIONALE FOR INTRATHECAL BACLOFEN2017In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 49, no 3, p. 193-203Article, review/survey (Refereed)
    Abstract [en]

    Oral baclofen has long been a mainstay in the management of spasticity. This review looks at the clinical evidence for the efficacy and safety of oral baclofen in patients with spasticity of any origin or severity, to determine whether there is a rationale for the use of intrathecal baclofen. Results suggest that oral baclofen may be effective in many patients with spasticity, regardless of the underlying disease or severity, and that it is at least comparable with other antispasmodic agents. However, adverse effects, such as muscle weakness, nausea, somnolence and paraesthesia, are common with oral baclofen, affecting between 25% and 75% of patients, and limiting its usefulness. Intrathecal baclofen may be an effective alternative as the drug is delivered directly into the cerebrospinal fluid, thus bypassing the blood-brain barrier and thereby optimizing the efficacy of baclofen while minimizing drug-related side-effects. Intrathecal baclofen is a viable option in patients who experience intolerable side-effects or who fail to respond to the maximum recommended dose of oral baclofen.

  • 43.
    Evangelista, Lorraine S.
    et al.
    Univ Calif Irvine, CA 92717 USA.
    Cacciata, Marysol
    Univ Calif Irvine, CA 92717 USA.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dracup, Kathleen
    Univ Calif San Francisco, CA 94143 USA.
    Dose-Response Relationship Between Exercise Intensity, Mood States, and Quality of Life in Patients With Heart Failure2017In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 32, no 6, p. 530-537Article in journal (Refereed)
    Abstract [en]

    Background: We conducted a secondary analysis to (1) compare changes in mood disorders and quality of life (QOL) among 4 groups of patients with heart failure in a home-based exercise program who had varying degrees of change in their exercise capacity and (2) determine whether there was an association between exercise capacity, mood disorders, and QOL. Methods: Seventy-one patients were divided into 4 groups based on changes in exercise capacity from baseline to 6 months: group 1showed improvements of greater than 10% (n = 19), group 2 showed improvements of 10% or less (n = 16), group 3 showed reductions of 10% or less (n = 9), and group 4 showed reductions of greater than 10% (n = 27). Results: Over time, patients in all 4 groups demonstrated significantly lower levels of depression and hostility (P amp;lt; .001) and higher levels of physical and overall quality of life (P = .046). Group differences over time were noted in anxiety (P = .009), depression (P = .015), physical quality of life (P amp;lt; .001), and overall quality of life (P = .002). Greater improvement in exercise capacity was strongly associated with lower depression scores (r = -0.49, P = .01). Conclusions: An improvement in exercise capacity with exercise training was associated with a decrease in depression and anxiety and an increase in QOL in patients with heart failure.

  • 44.
    Falkmer, Torbjörn
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Transport mobility for children and adolescents with cerebral palsy (CP)2001Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Background: The transport mobility of children and adolescents with cerebral palsy (CP) is of vital interest for the individual, as well as for society. Enhanced transport mobility can be related to improved functional health status and a higher degree of autonomy, which in turn may reduce the demand for societal support. UN Resolution 48/96, together with Swedish legislation and "Vision Zero" have in different ways established that the transport system must be designed to meet also the needs of children and adolescents with disabilities. Hence, it is necessary to identify and eliminate obstacles hindering children and adolescents with CP from using public transport and other means of transport, such as their own cars, at the same level as other members of society. However, in the case of children and adolescents with CP, the transport situation and the learner driver's educational situation have so far been largely unknown.

    Aim: The general aim of the thesis was to describe and analyse, from a legislative and a public health perspective, the transport mobility situation for children and adolescents with CP. Furthermore, the general aim was to identify obstacles for the target group to use public transport and other means of transportation, at the same level as other members of the society, and to suggest improvements that will remove the identified obstacles.

    Material and methods: Several different data collection methods were used. Data, concerning travel habits and parents' perceived risks regarding transportation, were taken from a postal questionnaire addressed to parents of children and adolescents with CP. In order to estimate the numbers of potential learner drivers with CP in each age group in Sweden, a literature review was conducted, based on Swedish material. Furthermore, logbooks for learner drivers with CP were analysed retrospectively, in order to identify procedures, problems and key tasks in their driver education. Visual search strategies for learner drivers with CP were analysed, utilizing an eye tracker, and an attempt was made to introduce a screening tool for predicting the outcome of driver education.

    Results: Children and adolescents with CP were found to be transported under unsafe conditions, causing worry among their parents. When transporting children in the family vehicle, the parents were exposed to a very heavy burden, which increased their worry. The prevalence of potential learner drivers with CP who were in need of highly specialised driver education, including individually adapted driver training vehicles, was estimated to be 0.15 per 1,000 of a population-based age group of learner drivers in Sweden. Complex procedures, structural problems and financial obstacles made it difficult for adolescents with CP to obtain a driving licence and an adapted vehicle. The total duration of the driving tuition given by a driving instructor was found to be almost nine times higher for learner drivers with CP than for non-disabled learner drivers. Visual search strategies among learner drivers with CP were found to be less flexible than among other learner drivers. This fact indicated a need for better methods of teaching such strategies to this group as an integral component of their driver education. The validity of the motor-free visual perceptual test, TVPS-UL, for predicting the outcome of driver education for learner drivers, was found to be low. In order to find a reliable and valid screening tool for this purpose, future studies should focus on cross-validation of visual perceptual and dual task performance tests for different types of independent variables, such as obtaining a driving licence or not, accident involvement and driving ability.

    Conclusion: The transport system was found, from a legislative and public health perspective, to be unsuitable to meet the needs of children and adolescents with CP. Suggestions for improving transport mobility for children and adolescents with CP are provided. Several of these suggestions are practical, concrete and contextual for Swedish conditions, and some of them necessitate future research. However, a number of these suggestions are also applicable in an international context.

  • 45.
    Fornander, Lotta
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nyman, Torbjörn
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Hansson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Brismar, Tom
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Inter-hemispheric plasticity in patients with median nerve injury2016In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 628, p. 59-66Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured amp;gt;2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.21 +/- 0.15) compared to healthy controls (0.60 +/- 0.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with changes in the afferent signal inflow to the contralateral primary somatosensory cortex.

  • 46.
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The Non-Invasive Liver Biopsy: Determining Hepatic Function in Diffuse and Focal LiverDisease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.

    Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.

    Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.

    The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).

    The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.

    Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).

    In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

    List of papers
    1. Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Open this publication in new window or tab >>Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Show others...
    2013 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 1, p. 174-181Article in journal (Refereed) Published
    Abstract [en]

    Objectives

    To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.

    Methods

    A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.

    Results

    Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.

    Conclusions

    Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

    Place, publisher, year, edition, pages
    Springer, 2013
    Keywords
    Quantification, Gd-EOB-DTPA, Dynamic contrast-enhanced MRI, Pharmacokinetics, Liver
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-87242 (URN)10.1007/s00330-012-2583-2 (DOI)000312324500022 ()
    Projects
    NILB
    Note

    Funding Agencies|Swedish Research Council|VR/M 2007-2884|Medical Research Council of South-east Sweden|FORSS 12621|Linkoping University, Linkoping University Hospital Research Foundations||County Council of Ostergotland||

    Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2017-12-06
    2. Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Open this publication in new window or tab >>Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Show others...
    2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. 0095700-Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. Methods: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. Results: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. Conclusions: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.

    Place, publisher, year, edition, pages
    Public Library of Science, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106962 (URN)10.1371/journal.pone.0095700 (DOI)000335226500139 ()
    Available from: 2014-06-04 Created: 2014-06-02 Last updated: 2017-12-05
    3. Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
    Open this publication in new window or tab >>Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
    Show others...
    2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 1, p. 53-+Article in journal (Refereed) Published
    Abstract [en]

    It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-136544 (URN)10.1053/j.gastro.2017.03.005 (DOI)000403918300022 ()
    Note

    Funding agencies: Swedish Research Council/Medicine and Health [VR/M 2007-2884, VR/M 2012-3199]; Swedish Research Council/Natural and Engineering Sciences [VR/NT 2014-6157]; Swedish Innovation Agency VINNOVA [2013-01314]; Region Ostergotland (ALF)

    Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2018-04-18Bibliographically approved
  • 47.
    Gauffin, Helena
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    van Ettinger-Veenstra, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ulrici, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    McAllister, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Speech and Language Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Karlsson, Thomas
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Impaired language function in generalized epilepsy: Inadequate suppression of the default mode network2013In: Epilepsy & Behavior, ISSN 1525-5050, E-ISSN 1525-5069, Vol. 28, no 1, p. 26-35Article in journal (Refereed)
    Abstract [en]

    We aimed to study the effect of a potential default mode network (DMN) dysfunction on language performance in epilepsy. Language dysfunction in focal epilepsy has previously been connected to brain damage in language-associated cortical areas. In this work, we studied generalized epilepsy (GE) without focal brain damage to see if the language function was impaired. We used functional magnetic resonance imaging (fMRI) to investigate if the DMN was involved. Eleven persons with GE and 28 healthy controls were examined with fMRI during a sentence-reading task. We demonstrated impaired language function, reduced suppression of DMN, and, specifically, an inadequate suppression of activation in the left anterior temporal lobe and the posterior cingulate cortex, as well as an aberrant activation in the right hippocampal formation. Our results highlight the presence of language decline in people with epilepsy of not only focal but also generalized origin.

  • 48.
    Gentile, Giovanni
    et al.
    Karolinska Institute, Sweden.
    Åberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Petkova, Valeria I.
    Karolinska Institute, Sweden.
    Abdulkarim, Zakaryah
    Karolinska Institute, Sweden.
    Henrik Ehrsson, H.
    Karolinska Institute, Sweden.
    Patterns of neural activity in the human ventral premotor cortex reflect a whole-body multisensory percept2015In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 109, p. 328-340Article in journal (Refereed)
    Abstract [en]

    Previous research has shown that the integration of multisensory signals from the body in fronto-parietal association areas underlies the perception of a body part as belonging to ones physical self. What are the neural mechanisms that enable the perception of ones entire body as a unified entity? In one behavioral and one fMRI multivoxel pattern analysis experiment, we used a full-body illusion to investigate how congruent visuo-tactile signals from a single body part facilitate the emergence of the sense of ownership of the entire body. To elicit this illusion, participants viewed the body of a mannequin from the first-person perspective via head-mounted displays while synchronous touches were applied to the hand, abdomen, or leg of the bodies of the participant and the mannequin; asynchronous visuo-tactile stimuli served as controls. The psychometric data indicated that the participants perceived ownership of the entire artificial body regardless of the body segment that received the synchronous visuo-tactile stimuli. Based on multivoxel pattern analysis, we found that the neural responses in the left ventral premotor cortex displayed illusion-specific activity patterns that generalized across all tested pairs of body parts. Crucially, a tripartite generalization analysis revealed the whole-body specificity of these premotor activity patterns. Finally, we also identified multivoxel patterns in the premotor, intraparietal, and lateral occipital cortices and in the putamen that reflected multisensory responses specific to individual body parts. Based on these results, we propose that the dynamic formation of a whole-body percept may be mediated by neuronal populations in the ventral premotor cortex that contain visuo-tactile receptive fields encompassing multiple body segments.

  • 49.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Centre Diagnost Radiol Carouge SA, Switzerland; Uppsala University, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

    Background: Olfactory impairment is an early manifestation of Parkinsons disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

  • 50.
    Gren, Magnus
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Shahim, Pashtun
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Lautner, Ronald
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Wilson, David H.
    Quanterix, Lexington, MA, USA,.
    Andreasson, Ulf
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Norgren, Niklas
    UmanDiagnostics, Umeå, Sweden.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK.
    Blood biomarkers indicate mild neuroaxonal injury and increased amyloid β production after transient hypoxia during breath-hold diving2016In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 30, no 10, p. 1226-1230Article in journal (Refereed)
    Abstract [en]

    Objective: To determine whether transient hypoxia during breath-hold diving causes neuronal damage or dysfunction or alters amyloid metabolism as measured by certain blood biomarkers.

    Design: Sixteen divers competing in the national Swedish championship in breath-hold diving and five age-matched healthy control subjects were included. Blood samples were collected at baseline and over a course of 3 days where the divers competed in static apnea (STA), dynamic apnea without fins (DYN1) and dynamic apnea with fins (DYN2).

    Main outcomes: Biomarkers reflecting brain injury and amyloid metabolism were analysed in serum (S-100β, NFL) and plasma (T-tau, Aβ42) using immunochemical methods.

    Results: Compared to divers’ baseline, Aβ42 increased after the first event of static apnea (p = 0.0006). T-tau increased (p = 0.001) in STA vs baseline and decreased after one of the dynamic events, DYN2 (p = 0.03). Further, T-tau correlated with the length of the apneic time during STA (ρ = 0.7226, p = 0.004) and during DYN1 (ρ = 0.66, p = 0.01).

    Conclusion: The findings suggest that transient hypoxia may acutely increase the levels of Aβ42 and T-tau in plasma of healthy adults, further supporting that general hypoxia may cause mild neuronal dysfunction or damage and stimulate Aβ production.

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