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  • 51.
    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.

  • 52.
    Epstein, David H.
    et al.
    NIDA, MD 21224 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Shaham, Yavin
    NIDA, MD 21224 USA.
    Science-Based Actions Can Help Address the Opioid Crisis2018In: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 39, no 11, p. 911-916Article in journal (Other academic)
    Abstract [en]

    The epidemic of addiction and over-dose is real. Addiction among pain patients accounts for only a small proportion but a large number. Scientific opinion leaders can be most effective on two fronts, each relatively low-tech: dissemination and oversight of empirically established treatments, and promulgation of social-science-based strategies for population-level prevention.

  • 53.
    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.

  • 54.
    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.

  • 55.
    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.

  • 56.
    Fahlström, Andreas
    et al.
    Department of Neuroscience, Neurosurgery, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
    Redebrandt, Henrietta Nittby
    Department of Clinical Sciences Lund, Neurosurgery, Lund University, Skane University Hospital, Lund, Sweden.
    Zeberg, Hugo
    Department of Neuroscience, Karolinska Institutet, Sweden.
    Bartek, Jiri
    Karolinska University Hospital, Stockholm, Sweden; Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
    Bartley, Andreas
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tobieson, Lovisa
    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 Neurosurgery.
    Erkki, Maria
    Umeå University Hospital, Umeå, Sweden.
    Hessington, Amel
    Uppsala University Hospital, Uppsala, Sweden.
    Troberg, Ebba
    Skane University Hospital, Lund, Sweden.
    Mirza, Sadia
    Karolinska University Hospital, Stockholm, Sweden.
    Tsitsopoulos, Parmenion P.
    Uppsala University Hospital, Uppsala, Sweden.
    Marklund, Niklas
    Uppsala University Hospital, Uppsala, Sweden; Skane University Hospital, Lund, Sweden.
    A grading scale for surgically treated patients with spontaneous supratentorial intracerebral hemorrhage: the Surgical Swedish ICH Score2019In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Journal of Neurosurgery JNSArticle in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    The authors aimed to develop the first clinical grading scale for patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH).

    METHODS

    A nationwide multicenter study including 401 ICH patients surgically treated by craniotomy and evacuation of a spontaneous supratentorial ICH was conducted between January 1, 2011, and December 31, 2015. All neurosurgical centers in Sweden were included. All medical records and neuroimaging studies were retrospectively reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the Surgical Swedish ICH [SwICH] Score) was developed using weighting of independent predictors based on strength of association.

    RESULTS

    Factors independently associated with 30-day mortality were Glasgow Coma Scale (GCS) score (p = 0.00015), ICH volume ≥ 50 mL (p = 0.031), patient age ≥ 75 years (p = 0.0056), prior myocardial infarction (MI) (p = 0.00081), and type 2 diabetes (p = 0.0093). The Surgical SwICH Score was the sum of individual points assigned as follows: GCS score 15–13 (0 points), 12–5 (1 point), 4–3 (2 points); age ≥ 75 years (1 point); ICH volume ≥ 50 mL (1 point); type 2 diabetes (1 point); prior MI (1 point). Each increase in the Surgical SwICH Score was associated with a progressively increased 30-day mortality (p = 0.0002). No patient with a Surgical SwICH Score of 0 died, whereas the 30-day mortality rates for patients with Surgical SwICH Scores of 1, 2, 3, and 4 were 5%, 12%, 31%, and 58%, respectively.

    CONCLUSIONS

    The Surgical SwICH Score is a predictor of 30-day mortality in patients treated surgically for spontaneous supratentorial ICH. External validation is needed to assess the predictive value as well as the generalizability of the Surgical SwICH Score.

  • 57.
    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.

  • 58.
    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.

  • 59.
    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: 2019-06-14
    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: 2019-06-14
    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: 2019-06-14Bibliographically approved
  • 60.
    Forslin, Y.
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Martola, J.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bergendal, A.
    Karolinska Inst, Sweden.
    Fredrikson, S.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Kristoffersen Wiberg, Maria
    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. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Granberg, T.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Gadolinium Retention in the Brain: An MRI Relaxometry Study of Linear and Macrocyclic Gadolinium-Based Contrast Agents in Multiple Sclerosis2019In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 40, no 8, p. 1265-1273Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain gadolinium retention is consistently reported for linear gadolinium-based contrast agents, while the results for macrocyclics are contradictory and potential clinical manifestations remain controversial. Furthermore, most previous studies are based on conventional T1-weighted MR imaging. We therefore aimed to quantitatively investigate longitudinal and transversal relaxation in the brain in relation to previous gadolinium-based contrast agent administration and explore associations with disability in multiple sclerosis. MATERIALS AND METHODS: Eighty-five patients with MS and 21 healthy controls underwent longitudinal and transverse relaxation rate (R-1 and R-2) relaxometry. Patients were divided into linear, mixed, and macrocyclic groups based on previous gadolinium-based contrast agent administration. Neuropsychological testing was performed in 53 patients. The dentate nucleus, globus pallidus, caudate nucleus, and thalamus were manually segmented. Repeatability measures were also performed. RESULTS: The relaxometry was robust (2.0% scan-rescan difference) and detected higher R-1 (dentate nucleus, globus pallidus, caudate nucleus, thalamus) and R-2 (globus pallidus, caudate nucleus) in patients receiving linear gadolinium-based contrast agents compared with controls. The number of linear gadolinium-based contrast agent administrations was associated with higher R-1 and R-2 in all regions (except R-2 in the thalamus). No similar differences and associations were found for the macrocyclic group. Higher relaxation was associated with lower information-processing speed (dentate nucleus, thalamus) and verbal fluency (caudate nucleus, thalamus). No associations were found with physical disability or fatigue. CONCLUSIONS: Previous linear, but not macrocyclic, gadolinium-based contrast agent administration is associated with higher relaxation rates in a dose-dependent manner. Higher relaxation in some regions is associated with cognitive impairment but not physical disability or fatigue in MS. The findings should be interpreted with care but encourage studies into gadolinium retention and cognition.

  • 61.
    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.

  • 62.
    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.

  • 63.
    Georgiopoulos, Charalampos
    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.
    Imaging Studies of Olfaction in Health and Parkinsonism2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Olfactory loss is a common non-motor symptom of Parkinson’s disease (PD), often preceding the cardinal motor symptoms of the disease. The aim of this thesis was to: (a) evaluate whether olfactory examination can increase diagnostic accuracy, and (b) study the structural and functional neural basis of olfactory dysfunction in PD with different applications of Magnetic Resonance Imaging (MRI).

    Paper I was a comparison of the diagnostic accuracy between a simple smell identification test and DaTSCAN Single Photon Emission Computerized Tomography (SPECT), a nuclear medicine tomographic imaging technique that is commonly used in patients with suspected parkinsonism. The results indicate that smell test is inferior to DaTSCAN SPECT, but the combination of these two methods can lead to improved diagnostic accuracy.

    Paper II showed that diffusion MRI could detect discrete microstructural changes in the white matter of brain areas that participate in higher order olfactory neurotransmission, whereas MRI with Magnetization Transfer contrast could not.

    Paper III was a methodological study on how two different acquisition parameters can affect the activation pattern of olfactory brain areas, as observed with functional MRI (fMRI). The results indicate that brief olfactory stimulation and fast sampling rate should be preferred on olfactory fMRI studies.

    Paper IV used olfactory fMRI and resting-state fMRI in order to elucidate potentially altered activation patterns and functional connectivity within olfactory brain areas, between PD patients and healthy controls. Olfactory fMRI showed that olfactory impairment in PD is associated with significantly lower recruitment of the olfactory network. Resting-state fMRI did not detect any significant changes in the functional connectivity within the olfactory network of PD patients.

    In conclusion, the included studies provide evidence of: (a) disease-related structural and functional changes in olfactory brain areas, and (b) beneficial addition of olfactory tests in the clinical work-up of patients with parkinsonism.

    List of papers
    1. The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes
    Open this publication in new window or tab >>The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes
    Show others...
    2015 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed) Published
    Abstract [en]

    The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinsons disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand I-123-FP-CIT (DaTSCAN (R)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

    Place, publisher, year, edition, pages
    Springer Berlin/Heidelberg, 2015
    Keywords
    Parkinsons disease; Atypical parkinsonism; Parkinsonian syndromes; Olfaction; I-123-FP-CIT SPECT
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-122669 (URN)10.1007/s00415-015-7830-4 (DOI)000363035400018 ()26122543 (PubMedID)
    Note

    Funding Agencies|Ostergotland County Council (ALF); Swedish Parkinsons Foundation

    Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2019-03-05Bibliographically approved
    2. Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging
    Open this publication in new window or tab >>Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging
    Show others...
    2017 (English)In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    IOS PRESS, 2017
    Keywords
    Parkinson disease; smell; diffusion tensor imaging; magnetization transfer contrast imaging
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-138300 (URN)10.3233/JPD-161060 (DOI)000401801600010 ()28482644 (PubMedID)
    Note

    Funding Agencies|Swedish Parkinson Foundation; Linkoping University Hospital Research Fund; ALF Grants from Region Ostergotland

    Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2019-03-05
    3. Olfactory fMRI: Implications of Stimulation Length and Repetition Time
    Open this publication in new window or tab >>Olfactory fMRI: Implications of Stimulation Length and Repetition Time
    Show others...
    2018 (English)In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed) Published
    Abstract [en]

    Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

    Place, publisher, year, edition, pages
    OXFORD UNIV PRESS, 2018
    Keywords
    fMRI; olfaction; smell; repetition time
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-149862 (URN)10.1093/chemse/bjy025 (DOI)000438293600001 ()29726890 (PubMedID)
    Note

    Funding Agencies|Swedish Parkinson Foundation, Linkoping University Hospital Research Fund; ALF Grants from Region Ostergotland

    Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2019-04-17
  • 64.
    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.

  • 65.
    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.

  • 66.
    Gustafsson, Greta
    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, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Broström, Anders
    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. Department of Nursing Science, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    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.
    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.
    Svanborg, Eva
    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.
    Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation2015In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 126, no 8, p. 1493-1497Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To determine if melatonin is equally efficient as partial sleep deprivation in inducing sleep without interfering with epileptiform discharges in EEG recordings in children 1-16years old.

    METHODS:

    We retrospectively analysed 129 EEGs recorded after melatonin intake and 113 EEGs recorded after partial sleep deprivation. Comparisons were made concerning occurrence of epileptiform discharges, the number of children who fell asleep and the technical quality of EEG recordings. Comparison between different age groups was also made.

    RESULTS:

    No significant differences were found regarding occurrence of epileptiform discharges (33% after melatonin intake, 36% after sleep deprivation), or proportion of unsuccessful EEGs (8% and 10%, respectively). Melatonin and sleep deprivation were equally efficient in inducing sleep (70% in both groups). Significantly more children aged 1-4years obtained sleep after melatonin intake in comparison to sleep deprivation (82% vs. 58%, p⩽0.01), and in comparison to older children with melatonin induced sleep (58-67%, p⩽0.05). Sleep deprived children 9-12years old had higher percentage of epileptiform discharges (62%, p⩽0.05) compared to younger sleep deprived children.

    CONCLUSION:

    Melatonin is equally efficient as partial sleep deprivation to induce sleep and does not affect the occurrence of epileptiform discharges in the EEG recording. Sleep deprivation could still be preferable in older children as melatonin probably has less sleep inducing effect.

    SIGNIFICANCE:

    Melatonin induced sleep have advantages, especially in younger children as they fall asleep easier than after sleep deprivation. The procedure is easier for the parents than keeping a young child awake for half the night.

  • 67.
    Guterstam, Arvid
    et al.
    Karolinska Institute, Sweden.
    Björnsdotter 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.
    Gentile, Giovanni
    Karolinska Institute, Sweden.
    Ehrsson, H. Henrik
    Karolinska Institute, Sweden.
    Posterior Cingulate Cortex Integrates the Senses of Self-Location and Body Ownership2015In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 25, no 11, p. 1416-1425Article in journal (Refereed)
    Abstract [en]

    The senses of owning a body and being localized somewhere in space are two key components of human self-consciousness. Despite a wealth of neurophysiological and neuroimaging research on the representations of the spatial environment in the parietal and medial temporal cortices, the relationship between body ownership and self-location remains unexplored. To investigate this relationship, we used a multisensory out-of-body illusion to manipulate healthy participants perceived self-location, head direction, and sense of body ownership during high-resolution fMRI. Activity patterns in the hippocampus and the posterior cingulate, retrosplenial, and intraparietal cortices reflected the sense of self-location, whereas the sense of body ownership was associated with premotor-intraparietal activity. The functional interplay between these two sets of areas was mediated by the posterior cingulate cortex. These results extend our understanding of the role of the posterior parietal and medial temporal cortices in spatial cognition by demonstrating that these areas not only are important for ecological behaviors, such as navigation and perspective taking, but also support the perceptual representation of the bodily self in space. Our results further suggest that the posterior cingulate cortex has a key role in integrating the neural representations of self-location and body ownership.

  • 68.
    Hagg, Mary
    et al.
    Hudiksvall Hospital, Sweden; Uppsala University, Sweden.
    Tibbling, Lita
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Clinical and Experimental Medicine.
    Effect of IQoro (R) training on impaired postural control and oropharyngeal motor function in patients with dysphagia after stroke2016In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, no 7, p. 742-748Article in journal (Refereed)
    Abstract [en]

    Conclusion All patients with dysphagia after stroke have impaired postural control. IQoro (R) screen (IQS) training gives a significant and lasting improvement of postural control running parallel with significant improvement of oropharyngeal motor dysfunction (OPMD). Objectives The present investigation aimed at studying the frequency of impaired postural control in patients with stroke-related dysphagia and if IQS training has any effect on impaired postural control in parallel with effect on OPMD. Method A prospective clinical study was carried out with 26 adult patients with stroke-related dysphagia. The training effect was compared between patients consecutively investigated at two different time periods, the first period with 15 patients included in the study more than half a year after stroke, the second period with 11 patients included within 1 month after stroke. Postural control tests and different oropharyngeal motor tests were performed before and after 3 months of oropharyngeal sensorimotor training with an IQS, and at a late follow-up (median 59 weeks after end of training). Result All patients had impaired postural control at baseline. Significant improvement in postural control and OPMD was observed after the completion of IQS training in both intervention groups. The improvements were still present at the late follow-up.

  • 69.
    Hauff, K.
    et al.
    Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Canada.
    Zamzow, C.
    Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
    Law, W. J.
    Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Canada.
    De Melo, J.
    Department of Anatomy, University of Manitoba, Winnipeg, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Canada.
    Kennedy, K.
    Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Canada.
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system2005In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 53, no 4, p. 308-320Article in journal (Refereed)
    Abstract [en]

    In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood-brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase-1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.

  • 70.
    Huang-Link, YuMin
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Eleftheriou, Andreas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Yang, G.
    Southern Med Univ, Peoples R China.
    Johansson, J. M.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Apostolou, Alexandros
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Link, H.
    Karolinska Inst, Sweden.
    Jin, Y-P
    Univ Toronto, Canada.
    Optical coherence tomography represents a sensitive and reliable tool for routine monitoring of idiopathic intracranial hypertension with and without papilledema2019In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no 5, p. 808-+Article in journal (Refereed)
    Abstract [en]

    Background and purpose We previously reported that certain optical coherence tomography (OCT) measures were sensitive and reliable in identifying idiopathic intracranial hypertension (IIH). This prospective study aimed to define OCT measures that allow differentiation of IIH with and without papilledema, thereby helping clinical decision-making. Methods Eight patients with IIH with papilledema, nine without papilledema and 19 with other neurological diseases were included. OCT measures were obtained before lumbar puncture and within 2 h, 1, 3 and 6 months after lumbar puncture with cerebrospinal fluid (CSF) removal. Results All patients with papilledema had increased retinal nerve fiber layer (RNFL) thickness and elevated CSF pressure. All patients without papilledema had normal RNFL but elevated CSF pressure. After CSF removal, reduced RNFL thickness was registered in all eight patients with IIH with papilledema. No significant change in RNFL thickness after CSF removal was observed in IIH without papilledema or in patients with other neurological diseases, although reduced CSF pressure was documented. RNFL thickness tended to be normal in patients with IIH with papilledema at 3-6 months after CSF removal. All patients with IIH showed increased rim area and rim thickness, but reduced optic cup volume regardless of RNFL thickness or papilledema. Conclusions Retinal nerve fiber layer thickness is sensitive for monitoring acute IIH and evaluating treatment effect. Increased rim area and rim thickness and decreased optic cup volume are reliable parameters that indicate persistently increased CSF pressure and risk of relapse. OCT measures are sensitive and reliable for diagnosing subtle IIH even in the absence of papilledema.

  • 71.
    Huang-Link, Yu-Min
    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.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Link, Hans
    Karolinska Institute, Sweden.
    Benign Multiple Sclerosis is Associated with Reduced Thinning of the Retinal Nerve Fiber and Ganglion Cell Layers in Non-Optic-Neuritis Eyes2015In: JOURNAL OF CLINICAL NEUROLOGY, ISSN 1738-6586, Vol. 11, no 3, p. 241-247Article in journal (Refereed)
    Abstract [en]

    Background and Purpose It is exceedingly difficult to differentiate benign multiple sclerosis (BMS) from relapsing-remitting multiple sclerosis (RRMS) based on clinical characteristics, neuroimaging, and cerebrospinal fluid tests. Optical coherence tomography (OCT) allows quantification of retinal structures, such as the retinal nerve fiber layer (RNFL) thickness, at the optic disc and the ganglion cell layer (GCL) at the macula, on a micrometer scale. It can also be used to trace minor alterations and the progression of neurodegeneration, help predict BMS, and influence the choice of therapy. To utilize OCT to detect the extent of changes of the optic disk and macular microstructure in patients with BMS and RRMS compared to healthy controls (HCs), with special focus on changes related to the presence/absence of optic neuritis (ON). Methods Spectral-domain OCT was applied to examine eyes from 36 patients with multiple sclerosis (MS), comprising 11 with BMS and 25 with RRMS, and 34 HCs. Results The RNFL and GCL were significantly thinner in eyes previously affected by ON, irrespective of the type of MS (i.e., BMS or RRMS), than in HCs. Significant thinning of the GCL was also observed in non-ON RRMS (and not non-ON BMS) compared to HCs. Correspondingly, a significant association between disease duration and thinning rates of the RNFL and GCL was observed only in non-ON RRMS (-0.54 +/- 0.24 and -0.43 +/- 0.21 mu m/year, mean SE; pless than0.05 for both), and not in non-ON BMS (-0.11 +/- 0.27 and -0.24 +/- 0.24 mu m/year). Conclusions The RNFL and GCL were thinner in both ON- and non-ON MS, but the change was more pronounced in ON MS, irrespective of the MS subtype studied herein. GCL thinning and the thinning rate of both the GCL and RNFL were less pronounced in non-ON BMS than in non-ON RRMS. These findings may help to predict the course of BMS.

  • 72.
    Hultling, C
    et al.
    Spinalis SCI Research Unit, Karolinska Hospital, Stockholm.
    Levi, Richard
    Spinalis SCI Research Unit, Karolinska Hospital, Stockholm.
    Amark, S P
    Neuropediatric Section, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm.
    Sjöblom, P
    Department of Obstetrics and Gynaecology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Semen retrieval and analysis in men with myelomeningocele.2000In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 42, no 10, p. 681-684Article in journal (Refereed)
    Abstract [en]

    The introduction of advanced assisted reproduction technologies (ART) has created opportunities for the treatment of infertility among patients with myelomeningocele (MMC). The aim of this study was to assess the possibility of semen retrieval and to analyse the semen quality in men with MMC. Nine men, aged 22 to 39 with MMC participated in the study. Two participants were able to achieve unassisted ejaculation. Vibratory stimulation was unsuccessfully attempted in the remaining seven participants who then underwent electroejaculation under general anaesthesia. In total, enough spermatozoa for intracytoplasmic spermatozoa injection were retrieved from five participants. In four cases, no spermatozoa were observed in the ejaculates. Testicular biopsies, however, revealed spermatogenesis, and thus a reproductive potential, in one of these men. Therefore, in six of the nine men with MMC, fatherhood seemed possible with modern ART, despite the semen quality generally being very poor.

  • 73.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    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.
    Askmark, Håkan
    University of Uppsala Hospital, Sweden.
    Pirskanen, Ritva
    Karolinska Institute, Sweden.
    Carlson, Kristina
    University Hospital, Sweden.
    Piehl, Fredrik
    Karolinska Institute, Sweden.
    Hägglund, Hans
    University Hospital, Sweden.
    Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 1, p. 90-93Article in journal (Refereed)
    Abstract [en]

    Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG. (c) 2016 Elsevier B.V. All rights reserved.

  • 74.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    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).
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Blennow, K.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Zetterberg, H.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; UCL Institute Neurol, England.
    Lundberg, Peter
    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). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    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. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    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.
    Ernerudh, Jan
    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.
    Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 5, p. 703-712Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Methods: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. Results: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. Conclusions: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.

  • 75.
    Håkansson, Irene
    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.
    Tisell, Anders
    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). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Cassel, Petra
    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.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England; UCL, England.
    Lundberg, Peter
    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). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    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.
    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.
    Ernerudh, Jan
    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.
    Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis2018In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 15, article id 209Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. Methods: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. "No evidence of disease activity-3" (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI (R)) were recorded during 4 years of follow-up. Results: NFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p amp;lt; 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions. Conclusions: Serum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively.

  • 76.
    Ingberg, Edvin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Dock, Hua
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    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 Neurosurgery.
    Ström, Jakob O.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Effect of laser Doppler flowmetry and occlusion time on outcome variability and mortality in rat middle cerebral artery occlusion: inconclusive results2018In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 19, article id 24Article in journal (Refereed)
    Abstract [en]

    Background: Stroke is among the leading causes of death and disability. Although intense research efforts have provided promising treatment options in animals, most clinical trials in humans have failed and the therapeutic options are few. Several factors have been suggested to explain this translational difficulty, particularly concerning methodology and study design. Consistent infarcts and low mortality might be desirable in some, but not all, studies. Here, we aimed to investigate whether the use of laser Doppler flowmetry (LDF) and the occlusion time (60 vs. 45 min) affected outcome variability and mortality in a rat stroke model. Eighty ovariectomized female Wistar rats were subjected to ischemic stroke using intraluminal filament middle cerebral artery occlusion with or without LDF and with occlusion times of 45 or 60 min. Outcome was evaluated by triphenyl tetrazolium chloride staining of brain slices to measure infarct size and a modified sticky tape test. Results: Neither LDF nor occlusion times of 45 versus 60 min significantly affected mortality, outcome variability or outcome severity. Conclusions: Due to the unexpectedly high mortality and variability the statistical power was very low and thus the results were inconclusive.

  • 77.
    Jasim, Hajer
    et al.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Folktandvarden Stockholm AB, Sweden.
    Carlsson, Anders
    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.
    Hedenberg-Magnusson, Britt
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Folktandvarden Stockholm AB, Sweden.
    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.
    Ernberg, Malin
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Saliva as a medium to detect and measure biomarkers related to pain2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3220Article in journal (Refereed)
    Abstract [en]

    Saliva is often neglected as a body fluid of diagnostic or prognostic value, even though generally well accepted by the patients. This is due to lack of a standardized collection procedure. The aim of this study was to identify the ideal saliva collection technique and develop new sensitive methods to detect and analyse markers related to pain in healthy pain-free subjects. Plasma and five different saliva collection approached was evaluated during strictly controlled conditions. Levels of nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and brain derived neurotropic factor (BDNF) were determined using novel western blotting based technology. Glutamate and substance P (SP) was determined using commercial available methods. Several new isoforms were found for NGF, CGRP and BDNF in saliva. The isoform pattern showed significant variation in both expression and chemiluminescence levels between different collection methods. New sensitive methods to study pain related markers in saliva were developed in this study. Furthermore, we are first to demonstrate a correlation between the Glutamate concentration in stimulated whole saliva and blood. However, the fundamental conclusion drawn is the importance of consistency in the collection method.

  • 78.
    Johansson, Peter
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Broström, Anders
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Jonköping University, Sweden.
    Sanderman, Robbert
    Health Psychology Section, Department of Health Sciences, University of Groningen, University Medical Centre Groningen, the Netherlands.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences.
    The Course of Sleep Problems in Patients With Heart Failure and Associations to Rehospitalizations.2015In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 30, no 5, p. 403-410Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Sleep problems are common in patients with heart failure (HF) and might be associated with patient outcomes.

    AIMS: The aim of this study was to describe the course of sleep problems in HF patients over 1 year and the association between sleep problems and rehospitalization.

    METHODS: Data from 499 HF patients (mean age, 70 years) were used in this analysis. Sleep problems were assessed with the item "Was your sleep restless" from the Center for Epidemiological Studies Depression Scale during hospitalization for HF (baseline) and after 1 year.

    RESULTS: A total of 43% of patients (n = 215) reported sleep problems at baseline, and 21% of patients (n = 105), after 1 year. Among the 215 patients with problems with sleep at baseline, 30% (n = 65) continued to have sleep problems over time. Among the 284 patients without sleep problems at baseline, 14% (n = 40) reported sleep problems after 1 year. After adjustments for potential cofounders, patients with continued sleep problems had an almost 2-fold increased risk for all-cause hospitalizations (hazard ratio, 2.1; P = .002) and cardiovascular hospitalizations (hazard ratio, 2.2; P = .004).

    CONCLUSION: One-third of HF patients with sleep problems at discharge experienced persistent sleep problems at follow-up. Continued sleep problems were associated with all-cause and cardiovascular rehospitalizations.

  • 79.
    Järemo, Petter
    et al.
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Eriksson-Franzen, Marie
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Oweling, Magnus
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Milovanovic, Micha
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Platelets and inflammatory parameters do not affect long-term survival after acute stroke. Journal of Stroke and Cerebrovascular Diseases,2016In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 25, no 8, p. 1936-1938Article in journal (Refereed)
    Abstract [en]

    Rationale

    According to literature, the inflammatory response and platelets are associated with coronary heart disease mortality. In this study, we examine if similar relationships exist after acute cerebral infarctions.

    Design

    Between 2005 and 2007, individuals (n = 61) hospitalized with acute stroke were investigated 2.1 ± .3 (SD) days after hospital admission. After 9.3 ± .7 (SD) years, 29 patients (age 79 ± 8 [SD]; 12 women) had died. They were compared with survivors (age 69 ± 9 [SD]; 9 women) with respect to inflammatory parameters and platelet features such as activity and reactivity.

    Results and conclusion

    Inflammation and platelets at the acute event do not forecast long-term survival of stroke sufferers

  • 80.
    Jönsson, Anna K
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet and Forens Chem, Linkoping, Sweden.
    Schill, Johan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Jönköping, Sweden.
    Olsson, Hans
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Region Jönköping, Sweden.
    Spigset, Olav
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Venous Thromboembolism During Treatment with Antipsychotics: A Review of Current Evidence2018In: CNS Drugs, ISSN 1172-7047, E-ISSN 1179-1934, Vol. 32, no 1, p. 47-64Article, review/survey (Refereed)
    Abstract [en]

    This article summarises the current evidence on the risk of venous thromboembolism (VTE) with the use of antipsychotics. An increasing number of observational studies indicate an elevated risk of VTE in antipsychotic drug users. Although the use of certain antipsychotics has been associated with VTE, current data can neither conclusively verify differences in occurrence rates of VTE between first- and second-generation antipsychotics or between individual compounds, nor identify which antipsychotic drugs have the lowest risk of VTE. The biological mechanisms involved in the pathogenesis of this adverse drug reaction are still to be clarified but hypotheses such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinaemia and hyperprolactinaemia have been suggested. Risk factors associated with the underlying psychiatric disorder may at least partly explain the increased risk. Physicians should be aware of this potentially serious and even sometimes fatal adverse drug reaction and should consider discontinuing or switching the antipsychotic treatment in patients experiencing a VTE. Even though supporting evidence is limited, prophylactic antithrombotic treatment should be considered in risk situations for VTE.

  • 81.
    Karolak, Justyna A.
    et al.
    Poznan University of Medical Science, Poland; Polish Academic Science, Poland.
    Gambin, Tomasz
    Warsaw University of Technology, Poland; Baylor Coll Med, TX 77030 USA.
    Rydzanicz, Malgorzata
    Medical University of Warsaw, Poland.
    Szaflik, Jacek P.
    Medical University of Warsaw, Poland.
    Polakowski, Piotr
    Medical University of Warsaw, Poland.
    Frajdenberg, Agata
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mrugacz, Malgorzata
    Medical University of Bialystok, Poland.
    Podfigurna-Musielak, Monika
    Medical Centre Vigor Med, Poland.
    Stankiewicz, Pawel
    Baylor Coll Med, TX 77030 USA.
    Gajecka, Marzena
    Poznan University of Medical Science, Poland; Polish Academic Science, Poland.
    Evidence against ZNF469 being causative for keratoconus in Polish patients2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 3, p. 289-294Article in journal (Refereed)
    Abstract [en]

    PurposeKeratoconus (KTCN) is a degenerative disorder characterized by stromal thinning and protrusion of the cornea, resulting in severe impairment of visual function. A recent study proposed that rare heterozygous mutations in ZNF469 determine KTCN aetiology. MethodsTo investigate the contribution of ZNF469 to KTCN, we Sanger sequenced ZNF469 in 42 unrelated Polish patients with KTCN and 49 Polish individuals with high myopia (HM) and compared the results with whole-exome sequencing (WES) data performed in 268 Polish individuals without ocular abnormalities. ResultsThe average number of ZNF469 non-synonymous variants was 16.31 and 16.0 for individuals with KTCN and HM, respectively (p=0.3724). All identified variants were previously reported. Alternative allele frequency (AAF) was determined based on the WES results. Among missense variants, only one (rs528085780) has AAF0.001 and was identified in one patient with sporadic KTCN. However, the resulting Arg1864Lys substitution was not predicted to be deleterious. ConclusionIn summary, we have not found a significant enrichment of sequence variants in ZNF469 in Polish patients with KTCN. High prevalence of ZNF469 variants identified in our KTCN group is typical for a common genetic variation observed in general population. Our findings indicate that variation in ZNF469 is not responsible for KTCN and other genetic variants are involved in the development and progression of this disease in Polish patients.

  • 82.
    Karpul, David
    et al.
    Western Sydney Univ, Australia; Univ Cape Town, South Africa.
    Mcintyre, Sarah
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Western Sydney Univ, Australia; Neurosci Res Australia, Australia.
    van Schaik, Andre
    Western Sydney Univ, Australia.
    Breen, Paul P.
    Western Sydney Univ, Australia.
    Heckmann, Jeannine M.
    Univ Cape Town, South Africa.
    Vibrotactile sensitivity of patients with HIV-related sensory neuropathy: An exploratory study2019In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 9, no 1, article id e01184Article in journal (Refereed)
    Abstract [en]

    Background: HIV-associated distal polyneuropathy (HIV-PN) affects large and small sensory nerve fibers and can cause tactile insensitivity. This exploratory study forms part of an effort to apply subsensory electrical nerve stimulation (SENS) to improve tactile sensitivity of patients with HIV-PN. This work presented an opportunity to use a robust protocol to quantitatively describe the vibrotactile sensitivity of individuals with HIV-PN on effective antiretroviral therapy (ART) and correlate these findings with commonly used clinical vibration testing and scoring grades. Methods: The vibration perception thresholds (VPTs) of 20 patients with HIV-PN at three vibration frequencies (25, 50, and 128 Hz) were measured. We compare the vibration perception threshold (VPT) outcomes to an age- and gender-matched control cohort. We further correlated VPT findings with 128 Hz tuning fork (TF) assessments performed on the HIV-PN participants, accrued as part of a larger study. HIV-PN was defined as having at least one distal symmetrical neuropathic sign, although 18 of 20 had at least two neuropathic signs. Conclusions: HIV-PN participants were found to have lower VPT sensitivity than controls for all three vibration frequencies, and VPT was more sensitive at higher vibration frequencies for both HIV-PN and controls. VPT sensitivity was reduced with older age. Years on ART was correlated with VPT-25 Hz but not with VPT in general. Notably, VPT sensitivity did not correlate with the clinically used 128 Hz TF severity grades. Outcomes of tests for interaction with vibration frequency suggest that HIV-PN pathology does not affect all mechanoreceptors similarly.

  • 83.
    King, Madeleine T.
    et al.
    Univ Sydney, Australia; Univ Sydney, Australia.
    Stockler, Martin R.
    ANZGOG, Australia.
    OConnell, Rachel L.
    Univ Sydney, Australia.
    Buizen, Luke
    Univ Sydney, Australia.
    Joly, Florence
    Ctr Francois Baclesse, France.
    Lanceley, Anne
    UCL, England.
    Hilpert, Felix
    Krankenhaus Jerusalem Hamburg, Germany.
    Okamoto, Aikou
    Jikei Univ, Japan.
    Aotani, Eriko
    Kanagawa Acad Sci and Technol, Japan.
    Bryce, Jane
    IRCCS, Italy.
    Donnellan, Paul
    Galway Univ Hosp, Ireland.
    Oza, Amit
    Univ Toronto, Canada.
    Åvall-Lundqvist, Elisabeth
    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 Oncology. Karolinska Inst, Sweden.
    Berek, Jonathan S.
    Stanford Comprehens Canc Inst, CA USA.
    Sehouli, Jalid
    AGO Study Grp, Germany.
    Feeney, Amanda
    UCL, England.
    Berton-Rigaud, Dominique
    GINECO, France.
    Costa, Daniel S. J.
    Univ Sydney, Australia.
    Friedlander, Michael L.
    ANZGOG, Australia.
    Measuring what matters MOST: validation of the Measure of Ovarian Symptoms and Treatment, a patient-reported outcome measure of symptom burden and impact of chemotherapy in recurrent ovarian cancer2018In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 27, no 1, p. 59-74Article in journal (Refereed)
    Abstract [en]

    Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit. GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with aeamp;lt;yenamp;gt; 3 lines of prior chemotherapy (PPS-ROC aeamp;lt;yenamp;gt; 3). Patients completed MOSTv1, QLQ-C30, QLQ-OV28, and FACT-O/FOSI at baseline and before cycle 3 of chemotherapy (pre-C3), and global assessments of change (MOST-Change) pre-C3. Clinicians rated patients cancer-related symptoms, performance status, and adverse events. Convergent and divergent validity (Spearmans correlations), discriminative validity (effect sizes between groups classified by clinician-rated characteristics), and responsiveness (paired t tests in patients expected to experience clinically meaningful change) were assessed. Of 948 recruits, 903 completed PROMs at baseline and 685 pre-C3. Baseline symptom burden was substantial for PRR-ROC and PPS-ROC aeamp;lt;yenamp;gt; 3. MOSTv2 has 24 items and five multi-item scales: abdominal symptoms (MOST-Abdo), disease or treatment-related symptoms (MOST-DorT), chemotherapy-related symptoms (MOST-Chemo), psychological symptoms (MOST-Psych), and MOST-Well-being. Correlations confirmed concurrent and divergent validity. Discriminative validity was confirmed by effect sizes that conformed with a priori hypotheses. MOST-Abdo was responsive to improvements in abdominal symptoms and MOST-Chemo detected the adverse effects of chemotherapy. The MOSTv2 validly quantifies patient-reported symptom burden, adverse effects, and symptom benefit in ROC, and as such is fit-for-purpose for clinical trials of palliative chemotherapy in ROC. Further research is required to assess test-retest reliability.

  • 84.
    Klefbeck, B
    et al.
    Department of Physical Therapy, Karolinska Institute, Stockholm, Sweden.
    Sternhag, M
    Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
    Weinberg, J
    Department of Neurology, Huddinge Hospital, Huddinge, Sweden.
    Levi, Richard
    Spinalis SCI Research Unit, Karolinska Institute, Stockholm, Sweden.
    Hultling, C
    Spinalis SCI Research Unit, Karolinska Institute, Stockholm, Sweden.
    Borg, J
    Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
    Obstructive sleep apneas in relation to severity of cervical spinal cord injury.1998In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 36, no 9, p. 611-628Article in journal (Refereed)
    Abstract [en]

    Thirty-three subjects (28 men, five women) with complete or incomplete cervical cord injury representing a wide range of neurological impairment were investigated with regard to the prevalence of Obstructive Sleep Apnea (OSA). The relation between OSA and neurological function, respiratory capacity, body mass index and symptoms associated with OSA were studied. Overnight sleep recordings employed combined oximetry and respiratory movement monitoring. Pulmonary function tests included static and dynamic spirometry, maximal static inspiratory and expiratory pressures at the mouth. The subjects answered a questionnaire concerning sleep quality and tiredness. The prevalence of OSA was 15% (5/33) in this nonobese cervical cord injury study population. Nine percent of the subjects (3/33) fulfilled the criteria for obstructive sleep apnea syndrome, but daytime sleepiness or fatigue were also common in subjects without OSA. There was an inverse correlation between oxygen desaturation index and American Spinal Injury Association (ASIA) motor score in the subjects with complete injury, while there was no such correlation in the whole study group. There were significant correlations between maximal inspiratory and expiratory pressures and vital capacity and between ASIA motor score and vital capacity.

  • 85.
    Kosek, Eva
    et al.
    Karolinska University Hospital, Sweden; Lowenstromska Hospital, Sweden.
    Martinsen, Sofia
    Karolinska University Hospital, 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.
    Mannerkorpi, Kaisa
    University of Gothenburg, Sweden.
    Löfgren, Monika
    Danderyd Hospital, Sweden.
    Bileviciute-Ljungar, Indre
    Danderyd Hospital, Sweden.
    Fransson, Peter
    Karolinska University Hospital, Sweden.
    Schalling, Martin
    Karolinska Institute, Sweden.
    Ingvar, Martin
    Karolinska University Hospital, Sweden.
    Ernberg, Malin
    Karolinska Institute, Sweden.
    Jensen, Karin B.
    Karolinska University Hospital, Sweden.
    The translocator protein gene is associated with symptom severity and cerebral pain processing in fibromyalgia2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 58, p. 218-227Article in journal (Refereed)
    Abstract [en]

    The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n = 126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n = 24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p = 0.016) and fibromyalgia symptoms (p = 0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p amp;lt; 0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception. (C) 2016 The Authors. Published by Elsevier Inc.

  • 86.
    Levi, Richard
    et al.
    Karolinska Institute, Sweden.
    Ertzgaard, Per
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Förvärvade ryggmärgsskador2015In: Rehabiliteringsmedicin: teori och praktik / [ed] Jörgen Borg, Kristian Borg, Björn Gerdle, Katharina Stibrant Sunnerhagen, Lund: Studentlitteratur AB, 2015, 1, p. 375-388Chapter in book (Other academic)
    Abstract [sv]

    Rehabiliteringsmedicinsk kunskap är relevant vid alla sjukdomar och skador som medför långvariga, komplexa funktionshinder och är därför relevant inom stora delar av sjukvården. Inom den rehabiliteringsmedicinska specialiteten handläggs idag främst patienter med skador och sjukdomar i nervsystemet respektive med långvariga smärttillstånd.

    Denna reviderade upplaga inleds med en sektion som avhandlar rehabiliteringsmedicinens utveckling och nuvarande plats i sjukvården, centrala rehabiliteringsmedicinska koncept, mät- och arbetsmetoder. Följande sektioner omfattar rehabiliteringsmedicinsk funktionsdiagnostik, läkningsmekanismer och behandling vid långvariga smärttillstånd respektive vid skador och kroniska sjukdomar i nervsystemet. Bokens omfång har ökat något. Några kapitel har fått större utrymme och nya kapitel om beteendestörning och medicinska komplikationer efter svår hjärnskada liksom om anoxisk hjärnskada har tillkommit. Andra kapitel, som inte rör dagens kärnverksamhet inom praktisk rehabiliteringsmedicin, har utgått.

    Rehabiliteringsmedicin är avsedd för grundutbildning av läkare, arbetsterapeuter och sjukgymnaster, logopeder samt för läkare under ATtjänstgöring. Den är också lämplig som introduktion i specialistutbildningen i rehabiliteringsmedicin, geriatrik, neurologi och smärtlindring, i vidareutbildningar av olika vårdyrkesgrupper och som referenslitteratur av yrkesverksamma med intresse för rehabiliteringsmedicin.

  • 87.
    Levi, Richard
    et al.
    Solberga Spinal Cord Injury Research Project, Karolinska Institute Huddinge University Hospital, Stockholm, Sweden.
    Hultling, C
    Solberga Spinal Cord Injury Research Project, Karolinska Institute Huddinge University Hospital, Stockholm, Sweden.
    Nash, M S
    Solberga Spinal Cord Injury Research Project, Karolinska Institute Huddinge University Hospital, Stockholm, Sweden.
    Seiger, A
    Solberga Spinal Cord Injury Research Project, Karolinska Institute Huddinge University Hospital, Stockholm, Sweden.
    The Stockholm spinal cord injury study: 1. Medical problems in a regional SCI population.1995In: Paraplegia, ISSN 0031-1758, Vol. 33, no 6, p. 308-315Article in journal (Refereed)
    Abstract [en]

    Out of a regional traumatic spinal cord injury population consisting of 379 individuals, 353 (93.1%) participated in the present study. Subjects were individually interviewed using semi-structured protocols. In addition, previous medical records were available for over 96% of subjects, and were used in all these cases to minimise recall bias. Cause of injury, prevalence of present medical symptoms and occurrence of medical complications in the post-acute, post-discharge phase were recorded. Neurological classification was verified by physical examination according to ASIA/IMSOP standards. Many subjects had experienced complications since discharge from initial hospitalisation, especially urinary tract infections, decubitus ulcers, urolithiasis, and neurological deterioration. Prevalence of medical symptoms was also high. More than 41% of subjects with spastic paralysis reported excessive spasticity to be associated with additional functional impairment and/or pain. Almost two-thirds of subjects reported significant pain, with a predominance of neurogenic-type pain. Bladder and bowel dysfunction were each rated by nearly 41% of subjects as a moderate to severe life problem. As expected, sexual dysfunction was also commonly reported. Prevalence of reported symptoms by general systems review was high, particularly fatigue, constipation, ankle oedema, joint and muscle problems, and disturbed sleep. However, lack of adequate normative data precludes comparison with the general population. The frequent occurrence of reported medical problems and complications support advocacy of comprehensive, life-long care for SCI patients. The commonly reported problems of neurogenic pain and neurological deterioration, in particular, require more attention, as these symptoms are not seldom ominous, either by virtue of their impact on quality of life, or because of underlying pathology.

  • 88.
    Levi, Richard
    et al.
    Solberga SCI Research Project, Stockholm, Sweden.
    Hultling, C
    Solberga SCI Research Project, Stockholm, Sweden.
    Seiger, A
    Solberga SCI Research Project, Stockholm, Sweden.
    The Stockholm Spinal Cord Injury Study: 2. Associations between clinical patient characteristics and post-acute medical problems.1995In: Paraplegia, ISSN 0031-1758, Vol. 33, no 10, p. 585-594Article in journal (Refereed)
    Abstract [en]

    The Stockholm Spinal Cord Injury Study (SSCIS) is an extensive evaluation of a sample of 353 subjects with traumatic SCI, constituting 93% of the known regional prevalence population with this diagnosis. In a previous analysis of this group, symptoms such as pain, incontinence, sexual dysfunction and neurological deterioration, as well as secondary complications, such as decubitus ulcers, urinary tract infections, spinal deformity and fractures, were found to be common. In the present report, we investigate associations between a few commonly used patient characteristics, ie gender, age at injury, duration of injury and extent of neurological compromise, and the occurrence of such problems, to assess differences in vulnerability in SCI subgroups. Results generally indicate an increased vulnerability in subjects with extensive neurological deficits, as well as a cumulation of complications with the increasing duration of injury. However, some exceptions are found, possibly indicating differences in temporal patterns of the occurrence of various complications, as well as certain gender-, age-, and lesion-associated variations in vulnerability. Symptoms directly related to the spinal cord lesion, eg neurogenic pain and neurological deterioration, seem to present rather soon post-injury. Males are more prone to experience excessive spasticity and sexual problems. Females experience more fractures and spinal deformity. Younger age at injury is associated with more spinal deformity but less severe pain problems. Higher age at injury is not found to be associated with more medical problems, with the exception of neurogenic pain, among post-acute, post-discharge survivors. The latter finding does not, however, preclude more such problems in the acute stage, since the present study neither addresses the pre-discharge period, nor includes information about mortality. Finally, the ASIA/IMSOP Impairment Scale Grade E-rated subjects were found to report problems to an extent that underlines the restricted sensorimotor sense in which this rating reflects recovery.

  • 89.
    Liedberg, Gunilla Margareta
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    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.
    Polyneuropathy, with and without neurogenic pain, and its impact on daily life activities - a descriptive study2009In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 31, no 17, p. 1402-1408Article in journal (Refereed)
    Abstract [en]

    Purpose. Few studies on disabilities relate to neurogenic chronic pain conditions and how pain influences the patient's ability to maintain life roles. Polyneuropathy is a condition with muscle weakness, sensory impairment and sometimes additional pain of neurogenic origin. The aim was to investigate disability reported in daily activities and quality of life in patients with polyneuropathy, with and without neurogenic pain. Method. A mail questionnaire designed to collect data on the state of health and impact on daily activities, including the Quality of Life-scale, Swedish version (QOLS-S), were sent to 60 patients with polyneuropathy. Forty-two (72.4%) responded. Results. Twenty-three patients were old-age pensioners (>65 years), ten had disability pension and nine were employed. Twenty-seven patients reported pain in addition to polyneuropathy. The neuropathy symptoms influenced occupational performance at work and leisure and in housework for 72% of the patients. Patients with additional neurogenic pain reported significantly greater performance problems in 55% of the daily activities compared with patients without pain. Quality of life was significantly lower for patients with pain concerning health and participation in active recreation. Conclusions. Symptoms in polyneuropathy, especially when accompanied by pain, give rise to disability that affects daily activities and ought to be considered in planning a successful intervention programme.

  • 90.
    Lind, Jonas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Nordlund, Peter
    Cty Hosp Ryhov, Sweden.
    Intravenous use of valproic acid in status epilepticus is associated with high risk of hyperammonemia2019In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 69, p. 20-24Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the study was to examine the frequency of hyperammonemia secondary to valproic acid treatment in status epilepticus and to describe the characteristics of the patients. Methods: All patients with established status epilepticus during 2014 to 2016 at Ryhov County Hospital were identified in a retrospective case series. Clinical and laboratory findings were collected from electronic medical files and the Metavision database at the intensive care unit (ICU). Hyperammonemia was defined as a concentration of at least 50 mu mol/L. Results: 11 of 40 patients developed hyperammonemia. These patients had a significantly longer stay at the ICU (12.6 vs 2.5 days) and at the hospital (22 vs 11 days). All patients with hyperammonemia were treated at the ICU and all received antibiotics. 12 patients were treated with intravenous valproic acid outside the ICU. Hyperammonemia was not related to Body Mass Index, time to initiation of therapy or laboratory abnormalities except anemia (Hemoglobin 104 vs 122 g/l). There was no difference in mortality between groups. Conclusion: The risk of hyperammonemia is almost 40% in patients receiving intravenous valproic acid in the ICU setting. The underlying mechanisms are probably either individual susceptibility or high metabolic demands. A high vigilance should be recommended. These data require further research via prospective designs in which multiple variables are controlled to explore the effects of individual factors on treatment outcome.

  • 91.
    Lindh, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Cryptogenic Polyneuropathy: Clinical, Environmental, And Genetic Studies2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Objectives: The purpose of this medical thesis was to describe the clinical and neurophysiological features and to evaluate the health related quality of life (HR-QoL) in patients with cryptogenic polyneuropathy. We also wanted to investigate different occupational, and leisure time exposures as determinants for cryptogenic polyneuropathy, and to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1), and Theta-1 (GSTT1), and a low activity genetic variation of epoxide hydrolase (EPHX) affect the risk of developing polyneuropathy. These genes were chosen because their enzymes are important in the metabolism of toxic compounds.

    Methods: The medical records of all patients aged 40–79 years with the diagnosis of cryptogenic polyneuropathy from 1993 to 2000 were analyzed, and data regarding clinical symptoms, laboratory findings, and neurophysiological findings at diagnosis were collected. 255 cases were found. When the medical records were reevaluated assessment to a protocol 168 patients remained as cryptogenic. Two validated instruments (SF-36 and EQ-5D) for measuring HR-QoL were sent to patients, and a reference group from the general population. Additional clinical information, and data on occupational, and leisure time exposure was obtained from postal questionnaires. Crude odds ratios (COR), and logistic regression odds ratios (LOR) were calculated for exposures with five or more exposed cases and referents taken together. We also tested for genetic polymorphisms of GSTM1 and GSTT1, and epoxide hydrolase exon three, EPHX*3.

    Results: 68% of the patients were men. The mean age at first symptom was 61 years and at diagnosis 64 years. Distal numbness was the most common symptom, but pain, pedal paresthesias, and impairment of balance were also common. The most common clinical findings were decreased or lost proprioception or sense of vibration (80%), and loss of ankle jerks (78%). Neurography showed mixed sensorimotor polyneuropathy of axonal or mixed axonal and demyelinating type. QOL was significantly affected concerning motor functions, with 42% of the patients reporting problems to walk, 3% having problems with daily activities, and 85% were suffering from pain. Mental health was preserved. Mobility was declining with increasing age, but was not affected by disease duration. Increased risks were found in men for occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, and herbicides and in women for occupational exposure to lead, nitrous oxide, and insecticides. Interaction between occupational and leisure time exposure were seen for several exposures. No significant correlation was found between GSTM1, GSTT1, and EPHX1 polymorphisms in patients with cryptogenic polyneuropathy compared with controls. A tendency, however, was seen for the GSTT1 null phenotype, which was enhanced among smokers compared to controls (OR 3.7).

    Conclusions: Cryptogenic polyneuropathy is a slowly progressive sensorimotor nerve lesion of mainly axonal type. Patients with cryptogenic polyneuropathy have a lower QOL compared to the general population, although mental health scores did not differ between the groups. Our results show that known determinants could be confirmed, but also some new appeared i.e. sulphur dioxide, hydrogen sulphide, fungicides, and vibrations in the feet. Moreover our results point to a synergistic effect of various exposures. Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances and reactive oxygen that could lead to nerve damage in the peripheral nervous system. Our results are indicating that components in cigarette smoke might increase the risk of axonal neuropathy in genetically predisposed patients.

    List of papers
    1. Cryptogenic polyneuropathy: Clinical and neurophysiological findings
    Open this publication in new window or tab >>Cryptogenic polyneuropathy: Clinical and neurophysiological findings
    2005 (English)In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 10, no 1, p. 31-37Article in journal (Refereed) Published
    Abstract [en]

    The purpose of this study was to describe the clinical and neurophysiological features of cryptogenic polyneuropathy in 168 patients in the neurological departments at three Swedish hospitals. The medical records of all patients aged 40-79 years with the diagnosis of cryptogenic polyneuropathy from 1993 to 2000 were analysed. One hundred and fourteen patients (68%) were men. The mean age at first symptom was 61 years and at diagnosis it was 64 years. Distal numbness (n=115, 68%) was the most common symptom, but some patients complained of pain, pedal paresthesiae, and impairment of balance. The most common clinical findings were decreased or lost proprioception or sense of vibration (n=135, 80%) and loss of ankle jerks (n=131, 78%). Neurography in 139 patients showed mixed sensorimotor polyneuropathy of axonal or mixed axonal and demyelinating type in 97 (70%). Cryptogenic polyneuropathy is a slowly progressive sensorimotor nerve lesion of mainly axonal type. Men are more often affected than women. Most patients have a minor or moderate severe polyneuropathy.

    Keywords
    Axonal, Electromyography, Idiopathic, Neurophysiology, Peripheral neuropathies
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-45496 (URN)10.1111/j.1085-9489.2005.10106.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    2. Occupational determinants of cryptogenic polyneuropathy
    Open this publication in new window or tab >>Occupational determinants of cryptogenic polyneuropathy
    Show others...
    2006 (English)In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 26, no 4, p. 187-194Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The aim was to investigate different occupational and leisure time exposures as determinants for cryptogenic polyneuropathy. Methods: A case-referent study was conducted in Sweden including 232 cases of cryptogenic polyneuropathy 40-79 years of age at diagnosis who were enrolled from the out-patient neurology departments of 3 hospitals. From the population register 853 referents were randomly selected. Information on occupational and leisure time exposure was obtained from a postal questionnaire. The response rate was 71% for cases and for referents. Crude odds ratios (CORs) and logistic regression odds ratios (LORs) were calculated for exposures with 5 or more exposed cases and referents taken together. The reference category was defined as individuals unexposed to any of the occupational or leisure time risk factors in the questionnaire. Results: As expected, male sex and increasing age were significant determinants for cryptogenic polyneuropathy. Occupational exposures in men to Stoddard solvent, petrol exhausts, herbicides or hand and foot vibrations generated significantly increased CORs. LORs >3.50 were found in men for occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, herbicides and in women for occupational exposure to lead, nitrous oxide and insecticides. Only solvent exposure in leisure time remained significant in the regression analysis indicating that not only occupational exposures were of importance. Interactions between occupational and leisure time exposure were seen for several agents. Conclusions: Several known determinants for polyneuropathy, from animal studies and case reports, were confirmed. New determinants were also indicated, i.e. sulphur dioxide, xylene and methyl ethyl ketone. Copyright © 2006 S. Karger AG.

    Keywords
    Environmental exposure, Epidemiological factors, Polyneuropathy, cryptogenic, Solvents
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-48033 (URN)10.1159/000092405 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    3. Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population
    Open this publication in new window or tab >>Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population
    2011 (English)In: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 33, no 7, p. 617-623Article in journal (Refereed) Published
    Abstract [en]

    Purpose. To evaluate the quality of life (QOL) in patients with cryptogenic polyneuropathy. Method. Two validated instruments (SF-36 and EQ-5D) were sent to 86 patients with a 72% response rate (44 men, 18 women). As reference, 2721 individuals (1292 men, 1429 women; 59% response rate) from the general population responded to the same QOL instruments. Results. Compared to the general population, QOL was significantly more affected in patients with polyneuropathy concerning motor functions, with 42% of the patients reporting problems with walking, 7% having difficulties with washing and dressing, and 31% having problems with usual activities (work, study, household work, and family or leisure activities). The EQ-5D results showed that 85% of the patients were suffering from pain compared to 56% of the general population. Mental health was preserved among patients with polyneuropathy. Mobility was declining with increasing age in patients, but was not affected by disease duration. Conclusions. Our study showed that patients with cryptogenic polyneuropathy have a lower QOL compared to the general population, although mental health scores did not differ between the groups. This information may be helpful when explaining the disease and its impact on newly diagnosed patients.

    Place, publisher, year, edition, pages
    Informa Healthcare, 2011
    Keywords
    Activities of daily living, EuroQol, polyneuropathy, neurological disease, neuropathy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-67316 (URN)10.3109/09638288.2010.505996 (DOI)000287451200008 ()
    Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2011-10-10
    4. Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study
    Open this publication in new window or tab >>Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study
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    2011 (English)In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 1, no 2, p. 135-141Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1) and Theta-1 (GSTT1) and a low activity genetic variation of epoxide hydrolase exon three (EPHX*3) affect the risk of developing polyneuropathy. The enzymes of these genes are important in the metabolism of toxic compounds. 79 patients with cryptogenic polyneuropathy (equivalent to chronic idiopathic axonal neuropathy) and 398 controls were tested for the genetic polymorphism. Medical records were reviewed to collect data regarding clinical findings at diagnosis, and exposure data was collected via questionnaires. The odds ratios (OR) for the null forms of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one except GSTT1, which reached 1.86. The highest risk of polyneuropathy was found in smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between genes were analyzed and confirmed the increased odds ratio for GSTT1, which was strongest if the patients had the low activity HH form of EPHX*3 (OR 2.37). Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances that could lead to nerve damage in the peripheral nervous system.

    Place, publisher, year, edition, pages
    Hoboken, New Jersey, USA: John Wiley & Sons, Inc, 2011
    Keywords
    Polyneuropathy
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-70979 (URN)10.1002/brb3.26 (DOI)000209173700009 ()
    Projects
    kryptogen polyneuropati
    Available from: 2011-10-03 Created: 2011-09-23 Last updated: 2017-12-08Bibliographically approved
  • 92.
    Lindh, Jonas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Hosseininia, Shahzad
    Yrkes och miljömedicin, Medicinska fakulteten, Teherans universitet, Teheran, Iran.
    Tondel, Martin
    Arbets- och miljömedicin, Sahlgrenska Universitetssjukhuset, Göteborg.
    Persson, Bodil
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study2011In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 1, no 2, p. 135-141Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1) and Theta-1 (GSTT1) and a low activity genetic variation of epoxide hydrolase exon three (EPHX*3) affect the risk of developing polyneuropathy. The enzymes of these genes are important in the metabolism of toxic compounds. 79 patients with cryptogenic polyneuropathy (equivalent to chronic idiopathic axonal neuropathy) and 398 controls were tested for the genetic polymorphism. Medical records were reviewed to collect data regarding clinical findings at diagnosis, and exposure data was collected via questionnaires. The odds ratios (OR) for the null forms of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one except GSTT1, which reached 1.86. The highest risk of polyneuropathy was found in smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between genes were analyzed and confirmed the increased odds ratio for GSTT1, which was strongest if the patients had the low activity HH form of EPHX*3 (OR 2.37). Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances that could lead to nerve damage in the peripheral nervous system.

  • 93.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Irritable Bowel Syndrome: Studies of central pathophysiological mechanisms and effects of treatment2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims

    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. The societal costs of the disorder are significant, as are its negative effects on quality of life. Medical treatment options are limited, but psychological treatments such as hypnotherapy have proven to be effective. Important pathophysiological mechanisms include disturbances in brain processing of visceral sensation and expectation of visceral sensation. Increased sensation of stimuli (hypersensitivity) is present in a subset of IBS patients to distensions in the lower part of the gastrointestinal tract, indicating a probable important pathophysiological mechanism in IBS. The overall aim of the thesis was to further study the central pathophysiological mechanisms involved in IBS. Specifically, we aimed to identify differences in brain response to standardized repeated rectal distensions and expectation of these stimuli between IBS patients (with or without perceptual rectal hypersensitivity), and healthy controls. Furthermore, we aimed to investigate IBS patients´ brain responses to standardized rectal distensions and expectation of these stimuli after either a successful course hypnotherapy or educational intervention.

    Methods

    Functional magnetic resonance imaging (fMRI) data were acquired and analyzed from 15 IBS patients with visceral hypersensitivity, and 18 IBS patients with normal visceral sensitivity (papers I and II). In paper III, fMRI data were analyzed from IBS patients who reported significant symptom reduction after either a course of hypnotherapy, or an educational intervention. FMRI data from IBS patients and healthy controls were also compared.

    Results

    The findings reported in papers I and II suggest, that the differences in brain response between IBS patients with and without rectal hypersensitivity, can be explained by changes in brain response during the course of the experiment. Even though the brain responses were similar between groups during the early phase of the experiment, they became substantially different during the late phase. The IBS patients with rectal hypersensitivity demonstrated increased brain response in several brain regions and networks involved in visceral sensation and processing. In contrast, IBS patients with normal rectal sensitivity exhibited reduced brain response during the late phase of the experiment. As reported in paper III, similar symptom reduction was achieved for both treatments. The symptomatic improvement was associated with a reduction of response in the anterior insula, indicating an attenuated awareness of the stimuli. The hypnotherapy group had a reduction of response in the posterior insula, indicating less input to the brain, possibly due to changed activity in endogenous pain modulatory systems. In patients who reported significant symptom reduction following treatment, the brain response to rectal distension got more similar to that observed in healthy controls.

    Conclusions

    The results from papers I and II indicate that a subpopulation of IBS patients lacks the ability to habituate to repeated rectal distensions and expectation of these stimuli. Results from paper III indicate that the abnormal processing of visceral stimuli in IBS can be altered, and that the treatments probably had a normalizing effect on the central processing abnormality of visceral signals in IBS.

    List of papers
    1. Brain Responses to Visceral Stimuli Reflect Visceral Sensitivity Thresholds in Patients With Irritable Bowel Syndrome
    Open this publication in new window or tab >>Brain Responses to Visceral Stimuli Reflect Visceral Sensitivity Thresholds in Patients With Irritable Bowel Syndrome
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    2012 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 3, p. 463-472Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND & AIMS:

    Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences.

    METHODS:

    We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest.

    RESULTS:

    The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls.

    CONCLUSIONS:

    Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Barostat; Visceral Sensitivity; Functional MRI; Anticipation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-73455 (URN)10.1053/j.gastro.2011.11.022 (DOI)000300774700024 ()
    Note

    funding agencies|County Council of Ostergotland, Sweden||Lions Forskningsfond for Folksjukdomar||Bengt Ihresfond, Svenska Lakaresallskapet||Magnus Bergvall fond||National Institutes of Health| DK 64531 DK 48351 K23 DK73451 |

    Available from: 2012-01-04 Created: 2012-01-04 Last updated: 2017-12-08Bibliographically approved
    2. Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity
    Open this publication in new window or tab >>Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity
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    2015 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 27, no 5, p. 646-655Article in journal (Refereed) Published
    Abstract [en]

    Background Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and without visceral hypersensitivity (IBS-N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli.

    Methods Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups.

    Key Results While BOLD response was similar during the early phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs during the late phase of the distension series. IBS-S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS-N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala.

    Conclusions & Inferences These findings are consistent with compromised ability of IBS-S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.

    Keywords
    irritable bowel syndrome, brain-gut interaction, fMRI, visceral sensitivity
    National Category
    Gastroenterology and Hepatology Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-122143 (URN)10.1111/nmo.12537 (DOI)000364742000007 ()25777251 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland, Sweden; National Institute of Health [DK 64531]

    Available from: 2015-10-20 Created: 2015-10-20 Last updated: 2018-01-11Bibliographically approved
    3. Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome
    Open this publication in new window or tab >>Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome
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    2013 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 12, p. 1184-1197Article in journal (Refereed) Published
    Abstract [en]

    Background Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. Aim To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Methods Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45mmHg) and low-intensity (15mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Results Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P=0.006, and cluster size 101, P=0.005 respectively). Moreover HYP responders demonstrated a prepost treatment BOLD attenuation in posterior insula (cluster sizes 59, P=0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P=0.05). Prepost differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. Conclusions The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. Clinical trial number: NCT01815164.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-94599 (URN)10.1111/apt.12319 (DOI)000319295100006 ()
    Note

    Funding Agencies|County Council of Ostergotland||Lions forskningsfond for folksjukdomar||Svenska Lakaresallskapets forskningsfond||NIDDK|DK048351|

    Available from: 2013-06-27 Created: 2013-06-27 Last updated: 2019-02-11
  • 94.
    Lundberg, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Simon
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Stenmark, Jonathan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Lena
    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 Cardiology in Linköping.
    Stress-induced release of matrix metalloproteinase-9 in patients with coronary artery disease: The possible influence of cortisol2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 73, p. 117-124Article in journal (Refereed)
    Abstract [en]

    Stress and inflammation are both important risk factors for coronary artery disease (CAD). However, the susceptibility to stress-induced inflammation and its determinants have been little explored in patients with CAD. Here, our aim was to study the stress-induced inflammatory response, more precisely the early release of matrix metalloproteinase (MMP)-9, and its association with cortisol response in patients with CAD. Sixty-four patients underwent a standardized laboratory stress test. The stress-induced release of MMP-9 was closely associated with the release of other neutrophil-associated proteins, MMP-8 and myeloperoxidase (MPO). It also showed a large variation among patients, as did cortisol. Twenty minutes after stress, a negative association between changes in MMP-9 and cortisol was seen (p amp;lt; 0.01). In vitro, dexamethasone reduced the IL-8-mediated release of MMP-9 from neutrophils, indicating that glucocorticoids may exert rapid effects on neutrophil activation. Further characterization of patients revealed that stress-induced release of MMP-9 was related to leukocyte telomere shortening and increased ultrasound assessed plaque occurrence in the carotid arteries, but not to other characteristics such as age, gender or psychological background factors. The susceptibility to stress-induced release of MMP-9 may thus have impact on disease phenotype. Stress tests can be useful to identify CAD patients in need of novel prevention and treatment strategies. (C) 2016 Published by Elsevier Ltd.

  • 95.
    Lundberg, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Karlsson, Markus
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Forsgren, Mikael
    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). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Leinhard Dahlqvist, Olof
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Norén, Bengt
    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.
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Ekstedt, Mattias
    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 Gastroentorology.
    Kechagias, Stergios
    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 Gastroentorology.
    Mechanistic modeling of qDCE-MRI data reveals increased bile excretion of Gd-EOB-DTPA in diffuse liver disease patients with severe fibrosis2016Conference paper (Refereed)
    Abstract [en]

    Introduction

    Over the past decades, several different non-invasive methods for staging hepatic fibrosis have been proposed. One such method is dynamic contrast enhanced MRI (DCE-MRI) using the contrast agent (CA) Gd-EOB-DTPA. Gd-EOB-DTPA is liver specific, which means that it is taken up specifically by the hepatocytes via the OATP3B1/B3 transporters and excreted into the bile via the MRP2 transporter. Several studies have shown that DCE-MRI and Gd-EOBDTPA can separate patients with advanced (F3-F4) from mild (F0-F2) hepatic fibrosis by measuring the signal intensity, where patients with advanced fibrosis have a lower signal intensity than the mild fibrosis cases.1 However, none of the studies up to date have been able to differentiate if the reduced signal intensity in the liver is because of an decreased uptake of CA or an increased excretion. Analyzing the DCE-MRI data with mechanistic mathematical modelling has the possibility of investigating such a differentiation.

    Subjects and methods

    88 patients with diffuse liver disease were examined using DCE-MRI (1.5 T Philips Achieva, two-point Dixon, TR=6.5 ms, TE=2.3/4.6 ms, FA=13) after a bolus injection of Gd-EOB-DTPA, followed by a liver biopsy. Regions of interest were placed within the liver, spleen and veins and a whole-body mechanistic pharmacokinetic model2 was fitted to the data. The fitted parameters in the model correspond to the rate of CA transport between different compartments, e.g. hepatocytes, blood plasma, and bile (Fig. 1).

    Results

    As can be seen in Fig. 2, the parameter corresponding to the transport of CA from the blood plasma to the hepatocytes, kph, is lower for patients with advanced fibrosis (p=0.01). Fig. 3 shows that the parameter corresponding to the CA excretion into the bile, khb, is higher for patients with advanced fibrosis (p<0.01).

    Discussion/Conclusion

    This work shows that the decreased signal intensity in DCE-MRI images in patients with advanced fibrosis depends on both a decreased uptake of CA in the hepatocytes and an increased excretion into the bile. Similar results have also been observed in a rat study3. In that study, rats with induced cirrhosis had a higher MRP2-activity than the healthy control rats.

    References

    1Norén et al: Eur. Radiol, 23(1), 174-181, 2013.

    2Forsgren et al: PloS One, 9(4): e95700, 2014.

    3Tsuda & Matsui: Radiol, 256(3): 767-773, 2010.

  • 96.
    Lundin, Anna-Carin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tendinosis in Trigger Finger2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.

    We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.

    Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.

    Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.

    We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.

    In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.

    List of papers
    1. Trigger finger and tendinosis
    Open this publication in new window or tab >>Trigger finger and tendinosis
    2012 (English)In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 37, no 3, p. 233-236Article in journal (Refereed) Published
    Abstract [en]

    The pathogenesis of trigger finger has generally been ascribed to primary changes in the pulley. Histological examination of the affected tendons has rarely been done. We studied biopsies from tendons of trigger fingers from 29 patients and compared these to biopsies from six intact tendons. We used a modified Movin score, which describes the tendinosis of the Achilles tendon. Trigger finger tendons had a high score (14.2; SD, 2.2) consistent with tendinosis, while the controls were almost normal (2.5; SD, 1.9). This suggests that the tendon is also affected, and that trigger finger is a form of tendinosis.

    Place, publisher, year, edition, pages
    Sage Publications, 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-76086 (URN)10.1177/1753193411421853 (DOI)000300994100007 ()21987275 (PubMedID)
    Available from: 2012-03-26 Created: 2012-03-26 Last updated: 2017-12-07Bibliographically approved
    2. Trigger finger, tendinosis, and intratendinous gene expression
    Open this publication in new window or tab >>Trigger finger, tendinosis, and intratendinous gene expression
    2014 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 24, no 2, p. 363-368Article in journal (Refereed) Published
    Abstract [en]

    The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in comparison to normal tendons in a pattern similar to what is published for Achilles tendinosis. We performed quantitative real-time polymerase chain reaction on biopsies from finger flexor tendons, 13 trigger fingers and 13 apparently healthy control tendons, to assess the expression of 10 genes which have been described to be differently expressed in tendinosis (collagen type 1a1, collagen 3a1, MMP-2, MMP-3, ADAMTS-5, TIMP-3, aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen types 1a1 and 3a1, aggrecan and biglycan were all up-regulated, and MMP-3and TIMP-3 were down-regulated. These changes were statistically significant and have been previously described for Achilles tendinosis. The remaining four genes were not significantly altered. The changes in gene expression support the hypothesis that trigger finger is a form of tendinosis. Because trigger finger is a common condition, often treated surgically, it could provide opportunities for clinical research on tendinosis.

    Place, publisher, year, edition, pages
    Wiley, 2014
    Keywords
    tendinopathy; tendinosis; stenosing tendovaginitis; tendovaginitis stenosans; quantitative real-time PCR; qPCR
    National Category
    Orthopaedics Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-106131 (URN)10.1111/j.1600-0838.2012.01514.x (DOI)000332982700018 ()
    Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2018-01-11
  • 97.
    Magaard, Gustaf
    et al.
    Umea Univ, Sweden.
    Wester, Per
    Umea Univ, Sweden; Karolinska Inst, Sweden.
    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.
    Lindvall, Peter
    Umea Univ, Sweden.
    Gustafsson, Emma
    Umea Univ, Sweden.
    Sedeh, Arzhang Nazemroaya
    Umea Univ, Sweden.
    Lonnqvist, Malin
    Umea Univ, Sweden.
    Berggren, Stina
    Umea Univ, Sweden.
    Nyman, Kristin
    Umea Univ, Sweden.
    Hu, Xiaolei
    Umea Univ, Sweden.
    Identifying Unmet Rehabilitation Needs in Patients After Stroke With a Graphic Rehab-Compass (TM)2018In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 27, no 11, p. 3224-3235Article in journal (Refereed)
    Abstract [en]

    Background: Unmet rehabilitation needs are common among stroke survivors. We aimed to evaluate whether a comprehensive graphic "Rehab-Compass," a novel combination of structured patient-reported outcome measures, was feasible and useful in facilitating a capture of patients rehabilitation needs in clinical practice. Methods: A new graphic overview of broad unmet rehabilitation needs covers deficits in functioning, daily activity, participation, and quality of life. It was constructed by using 5 patient-oriented, well-validated, and reliable existing instruments with converted data into a 0 (worst outcome) to 100 (best outcome) scale but unchanged in terms of variable properties. Satisfaction of the Rehab-Compass (TM) was studied by a qualitative interview of 9 patients with stroke and 3 clinicians. Practical feasibility and capacity of the instrument were evaluated in a cross sectional study with 48 patients at 5-month follow-ups after subarachnoid hemorrhage. Results: The Rehab-Compass (TM) identified and graphically visualized a panoramic view of the multidimensional needs over time which was completed before clinical consultation. The Rehab-Compass (TM) appeared to be feasible and time efficient in clinical use. The interviews of both patients and clinicians showed high satisfaction when using the Rehab-Compass (TM) graph. In the studied stroke patients, the Rehab-Compass (TM) identified memory and processing information, fatigue, mood, and pain after subarachnoid hemorrhage as the most common problems. Conclusions: The graphic Rehab-Compass (TM) seems to be a feasible, useful, and time-saving tool for identification of unmet rehabilitation needs among stroke survivors in clinical practice. Further research is needed to make the Rehab-Compass (TM) more concise and evaluate the instrument among different stroke subgroups.

  • 98.
    Magnusson, Anna K.
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Tham, Richard
    Linköping University, Department of Neuroscience and Locomotion. Linköping University, Faculty of Health Sciences.
    Vestibulo-Oculomotor Behavior in Rats after a Transient Unilateral Vestibular Loss Induced by Lidocaine2003In: THE OCULOMOTOR AND VESTIBULAR SYSTEMS: THEIR FUNCTION AND DISORDERS / [ed] Thomas Brandt, Bernard Cohen, and Christoph Siebold, New York, NY, USA: New York Academy of Sciences, 2003, Vol. 1004, p. 422-423Conference paper (Other academic)
  • 99.
    Mellergård, Johan
    et al.
    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.
    Edström, Måns
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    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.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81685Article in journal (Refereed)
    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.

  • 100.
    Mellergård, Johan
    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.
    Tisell, Anders
    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).
    Blystad, Ida
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Grönqvist, Anders
    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.
    Blennow,, K.
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Olsson,, B.
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg.
    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.
    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. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Lundberg, Peter
    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). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ernerudh, Jan
    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.
    Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 1, p. 112-121Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites.

    Methods

    About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1H MRS). Analyses of inflammatory [interleukin 1β (IL-1β), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up.

    Results

    The mean decline in PBVC was 3% at the 3-year follow-up, although mean 1H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = −0.564, P = 0.012, and r = −0.592, P = 0.010, respectively).

    Conclusions

    A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.

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