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  • 51.
    Gauffin, Helena
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    van Ettinger-Veenstra, Helene
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet.
    Landtblom, Anne-Marie
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ulrici, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    McAllister, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Logopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Karlsson, Thomas
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutet för handikappvetenskap (IHV). Linköpings universitet, Filosofiska fakulteten.
    Engström, Maria
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet.
    Cognitive problems in young adults with epilepsy: Language deficits correlate to brain activation and self-esteemManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    People with epilepsy often display cognitive decline. Language function in epilepsy has been most thoroughly studied in temporal lobe epilepsy, but the impact of language deficits in epilepsy is not fully understood. The aim of this study was to evaluate the effect of epilepsy on language function with functional magnetic resonance imaging of brain activation, with behavioral methods and to relate language performance to demographic data, self-esteem and Quality of life. We specifically aimed to investigate if variation in epilepsy origin would relate to differences in language performance and if these differences could be associated with specific language activation patterns in the brain. We recruited people with epilepsy (29 in total), with focal onset seizures in either the left or right hemispheres or with generalized epilepsy; and 27 matching healthy controls. The participants’ language skills were measured with a phonemic word fluency test and a broader test measuring higher language functions. Functional magnetic resonance images of the brain were obtained during a word fluency and a sentence reading paradigm. Questionnaires on self-esteem and quality of life were collected. People with epilepsy of both focal and generalized origin had impaired function in semantic and verbal fluency tasks compared to the controls. The causes of language impairment were multifactorial; the most important determinants were education and onset age of epilepsy. Impaired language function was correlated to low self-esteem for participants with focal onset seizures; however Quality of life did not seem to be affected by language impairment. The functional magnetic resonance imaging investigation demonstrated altered functional activity during language tasks for participants with epilepsy compared to healthy controls. In epilepsy with focal seizures originating in the left hemisphere we found increased bilateral  activation of supporting areas in the anterior mid-cingulate cortex and the left anterior ventral insula, indicating a compensational functional reorganization. In generalized epilepsy, the functional language network showed an imbalance expressed as an inadequate  suppression of activation in the left anterior temporal lobe during semantic processing. Our study shows not only that reduced language functioning is present in people with epilepsy other than in the temporal lobe, but also that frequency of convulsive seizures correlates to language impairment. For patients with focalized seizures, low self esteem correlated also to language impairment. Our results highlight the importance of addressing the negative consequences of language decline in people with epilepsy of both focal and generalized origin.

  • 52.
    Gauffin, Helena
    et al.
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    van Ettinger-Veenstra, Helene
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet.
    Landtblom, Anne-Marie
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ulrici, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    McAllister, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Logopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Karlsson, Thomas
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten.
    Engström, Maria
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet.
    Impaired language function in generalized epilepsy: Inadequate suppression of the default mode network2013Ingår i: Epilepsy & Behavior, ISSN 1525-5050, E-ISSN 1525-5069, Vol. 28, nr 1, s. 26-35Artikel i tidskrift (Refereegranskat)
    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.

  • 53.
    Gauffin, Håkan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Child murder and maltreatment in epilepsy2009Ingår i: in EUROPEAN JOURNAL OF NEUROLOGY, vol 16, 2009, Vol. 16, s. 484-484Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 54.
    Gordh, T.E.
    et al.
    Multidisciplinary Pain Center, Uppsala University Hospital, S-751 85 Uppsala, Sweden.
    Stubhaug, A.
    Department of Anaesthesiology, University of Oslo, Rikshospitalet University Hospital, 0027 Oslo, Norway.
    Jensen, T.S.
    Department of Neurology, Danish Pain Research Centre, Aarhus University Hospital, Aarhus, 8000, Denmark.
    Arner, S.
    Arnèr, S., Pain Clinic, Department of Anaesthesiology, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden.
    Biber, B.
    Department of Anaestesiology, Umeå University Hospital, S-901 85 Umeå, Sweden.
    Boivie, Jörgen
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Mannheimer, C.
    Multidisciplinary Pain Center, Department of Medicine, Sahlgrenska University Hospital, Östra, 41685 Göteborg, Sweden.
    Kalliomaki, J.
    Kalliomäki, J., Department of Rehabilitation, Lund University Hospital, S-221 85 Lund, Sweden.
    Kalso, E.
    Pain Clinic, Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Haartmaninkatu 2A, 00029 HUS, Finland.
    Gabapentin in traumatic nerve injury pain: A randomized, double-blind, placebo-controlled, cross-over, multi-center study2008Ingår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 138, nr 2, s. 255-266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks' washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p = 0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p = 0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p = 0.0016). Both the Patient (p = 0.023) and Clinician (p = 0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness. © 2007 International Association for the Study of Pain.

  • 55.
    Gunnarsson, Martin
    et al.
    Orebro University Hospital.
    Malmestrom, Clas
    Sahlgrens University Hospital.
    Axelsson, Markus
    Sahlgrens University Hospital.
    Sundstrom, Peter
    Norrlands University Hospital.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Olsson, Tomas
    Karolinska Institute.
    Piehl, Fredrik
    Karolinska Institute.
    Norgren, Niklas
    UmanDiagnostics, Umea.
    Rosengren, Lars
    Sahlgrens University Hospital.
    Svenningsson, Anders
    Norrlands University Hospital.
    Lycke, Jan
    Sahlgrens University Hospital.
    Axonal Damage in Relapsing Multiple Sclerosis is Markedly Reduced by Natalizumab2011Ingår i: ANNALS OF NEUROLOGY, ISSN 0364-5134, Vol. 69, nr 1, s. 83-89Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The impact of present disease-modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain-specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients. Methods: CSF samples from 92 patients with relapsing forms of MS were collected in a prospective manner prior to natalizumab treatment and after 6 or 12 months. In 86 cases, natalizumab was used as second-line DMT due to breakthrough of disease activity. The levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were determined using highly sensitive in-house developed enzyme-linked immunosorbent assays. Results: Natalizumab treatment led to a 3-fold reduction of NFL levels, from a mean value of 1,300 (standard deviation [SD], 2,200) to 400 (SD, 270) ng/l (p andlt; 0.001). The later value was not significantly different from that found in healthy control subjects (350ng/l; SD, 170; n = 28). Subgroup analysis revealed a consistent effect on NFL release, regardless of previous DMT or whether patients had relapses or were in remission within 3 months prior to natalizumab treatment. No differences between pre- and post-treatment levels of GFAP were detected. Interpretation: Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.

  • 56.
    Hagell, Peter
    et al.
    Department of Health Sciences, Lund University, Sweden.
    Hoglund, Arja
    Department of Neurology, University Hospital, Lund, Sweden.
    Reimer, Jan
    Department of Neurology, Swedish Institute for Health Science, Lund University, Sweden.
    Eriksson, Brita
    Department of Neurological Rehabilitation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Knutsson, Ingmari
    Division of Neuroscience and Locomotion, Arvid Carlsson Institute of Neuroscience, Sahlgrenska University Hospital, Go¨teborg, Sweden.
    Widner, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Cella, David
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Linköpings universitet, Hälsouniversitetet.
    Measuring fatigue in Parkinsons disease: A psychometric study of two brief generic fatigue questionnaires2006Ingår i: Journal of Pain and Symptom Management, ISSN 0885-3924, E-ISSN 1873-6513, Vol. 32, nr 5, s. 420-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study evaluated and compared the measurement properties of the 13-item Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and the 9-item Fatigue Severity Scale (FSS) in 118 consecutive Parkinsons disease (PD) patients, using traditional and Rasch measurement methodologies. Both questionnaires exhibited excellent data quality and reliability (coefficient alpha greater than= 0.9), and acceptable rating scale functionality, and both discriminated between fatigued and nonfatigued patients. factor and Rasch analyses provided general support for unidimensionality of both FACIT-F and FSS, although they do not appear to measure identical aspects of fatigue. No signs of differential item functioning (DIF) were found for the FACIT-F, whereas potential age DIF, was detected for two FSS items. These results support the measurement validity of both questionnaires in PD, although the FACIT-F displayed better measurement precision and modest psychometric advantages over the FSS. Availability of psychometrically sound fatigue measures that are applicable across disorders provides a sound basis for advancing the understanding of this common and distressing complaint.

  • 57.
    Hellqvist, Eva
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Kvarnström, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Söderberg, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Wrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Rosén, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Myelin protein zero is naturally processed in IgM MGUS B cells: Aberrant triggering of patient T cells2010Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 95, nr 4, s. 627-636Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objectives: Monoclonal gammopathy of undetermined significance (MGUS) of IgM isotype is a condition with clonally expanded B cells, recently suggested having an infectious origin. MGUS is frequently associated with polyneuropathy and antibodies against myelin protein zero (P0), whereas the role of the T cells remains largely unknown. Here we have analyzed P0-specific B cells, as antigen-presenting cells, and their capacity to activate T helper cells.

    Design and Methods: We used a well-characterized MGUS-derived B cell line, TJ2, expressing anti-P0 IgM. The ability of TJ2 cells to bind, endocytose, process, and present P0 was investigated by receptor-clustering and immunofluorescence. The activation of P0-specific autologous T cells was studied by measuring IL2 and IFNγ with flow cytometry, immunobeads, and ELISPOT.

    Results: Surface-receptor clustering and endocytosis of receptor-ligand (IgM/P0) complexes were pronounced after P0 exposure. Naturally processed or synthetic P0 peptide (194-208)-pulsed TJ2 cells significantly induced IL2 secretion from autologous T cells compared to control antigen pulsed cells (p<0 .001). The numbers of IFNγ producing T helper cells, including CD4+/CD8+ cells, were also significantly increased (p=0.0152). Affinity-isolated naturally processed myelin peptides were potent IFNγ stimulators for autologous PBMCs, but not for control PBMCs.

    Interpretation and conclusions: We show for the first time that myelin P0 is naturally processed in IgM MGUS B cells, acting as aberrant antigen-presenting cells in activation of patients T helper cells. Our findings cast new light on the important role of autoreactive P0-specific B cells in he induction of the pathogenic T cell responses found in nerve lesions of MGUS patients with peripheral neuropathy.

  • 58.
    Helmers, S.B.
    et al.
    Karolinska University Hospital, Rheumatology Unit, CMM L8:04, SE-171 76 Stockholm, Sweden, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden, Karolinska Institutet, Stockholm, Sweden.
    Dastmalchi, M.
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden, Karolinska Institutet, Stockholm, Sweden.
    Alexanderson, H.
    Karolinska Institutet, Stockholm, Sweden, Rheumatology Unit, Department of Physical Therapy, Karolinska University Hospital, Solna, Sweden.
    Nennesmo, I.
    Karolinska Institutet, Stockholm, Sweden, Department of Pathology, Karolinska University Hospital, Huddinge, Sweden.
    Esbjornsson, M.
    Esbjörnsson, M., Karolinska Institutet, Stockholm, Sweden, Division of Clinical Physiology, Department of Medical Laboratory Medicine, Karolinska University Hospital, Huddinge, Sweden.
    Lindvall, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Lundberg, I.E.
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden, Karolinska Institutet, Stockholm, Sweden.
    Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies2007Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, nr 10, s. 1276-1283Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients. Methods: Thirteen treatment-resistant patients, 6 PM, 4 DM, 2 IBM and 1 juvenile DM, were treated with 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24-48 h after the first infusion. Results: Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (MAC) deposits on capillaries were present to an equal degree in biopsies before and after MG treatment. No correlation between the clinical response and molecular changes was found. Conclusions: The clinical effects of high-dose IVIG on muscle function in patients with refractory inflammatory active myositis did not correspond to effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question a role for IVIG as an immune-modulating therapy in patients with inflammatory myopathies.

  • 59.
    Hensing, Gunnel K. E.
    et al.
    Department of Community Medicine and Public Health, Göteborg University, Sahlgrenska Academy, Goteborg, Social Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
    Sverker, Annette M.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Leijon, Göran S.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Experienced dilemmas of everyday life in chronic neuropathic pain patients: results from a critical incident study2007Ingår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 21, nr 2, s. 147-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neuropathic pain is a disabling chronic condition with limited therapeutic options. Few studies have addressed patient's experience and strategies. The aim of this study was to explore dilemmas experienced in order to improve care and rehabilitation. An interview study with 39 patients suffering from neuropathic pain of different origin was performed. We used the critical incident technique to collect data. Questions on occasions when patients had been hindered by or reminded of their neuropathic pain were included, and the self-perceived consequences and management of such occasions. The interviews were transcribed verbatim and analysed qualitatively. A broad range of experiences categorised into dilemmas, disturbances, consequences and managements from most parts of everyday life was identified. The dilemmas were ‘housework’, ‘sitting’, ‘physical activity’, ‘personal hygiene’, ‘sleeping difficulties’, ‘hypersensitivity to external stimuli’, ‘social relationships’, ‘transportation’ and ‘leisure time’. Disturbances were ‘failures’, ‘inabilities’ and ‘restrictions’. Consequences were ‘increased pain’, ‘psychological reactions’ and ‘physical symptoms’. The majority of the patients used activity-oriented strategies to manage their pain such as alternative ways of performing the task, a cognitive approach or simply ignoring the pain. This is one of the first studies presenting detailed data on everyday dilemmas, disturbances and consequences of patients with chronic neuropathic pain. Such information is important in clinical settings to improve care and rehabilitation.

  • 60.
    Holmqvist, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Brynhildsen, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis2010Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, nr 7, s. 2835-2837Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to evaluate whether age of onset of multiple sclerosis is related to use of combined oral contraceptives and/or timing of childbirth. The results showed that use of combined oral contraceptives and childbirth before the first multiple sclerosis symptom was correlated to a higher mean age at the onset of the disease.

  • 61.
    Holmqvist, Per
    et al.
    County Hospital Sundsvall.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Brynhildsen, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Symptoms of multiple sclerosis in women in relation to cyclical hormone changes.2009Ingår i: The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, ISSN 1473-0782, Vol. 14, nr 5, s. 365-370Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To prospectively investigate if women with multiple sclerosis (MS) experience changes in MS-symptoms in relation to cyclical hormonal changes. METHODS: Sixty-three women with MS, either with regular, spontaneous menstrual cycles or taking combined oral contraceptives (COCs), were asked to score their MS symptoms every day during three cycles. Symptom scores were analysed in relation to different phases of the spontaneous menstrual- or pill-driven cycle. RESULTS: Twenty-three women completed the score record. Among the 16 women who were not using a COC there were no significant differences in symptom scores between the phases of the menstrual cycle. The seven women taking a COC reported significantly higher symptom score points for weakness, numbness and tiredness during the pill-free interval compared with the phase during which they took the COC daily. CONCLUSIONS: This prospective study appears to contradict earlier retrospective studies regarding variations in MS symptoms in relation to the menstrual cycle in women who are not using a COC. The lower symptom scores during the three weeks of pill taking suggest a positive effect of the steroids on the manifestations of MS. Further studies concerning both short- and long-term effects of OC-use on MS symptoms are needed.

  • 62.
    Israelsson, Hanna
    et al.
    Umeå University, Sweden.
    Carlberg, Bo
    Umeå University, Sweden.
    Wikkelso, Carsten
    University of Gothenburg, Sweden.
    Laurell, Katarina
    Umeå University, Sweden.
    Kahlon, Babar
    Lund University, Sweden.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Linköpings universitet, Medicinska fakulteten.
    Eklund, Anders
    Umeå University, Sweden.
    Malm, Jan
    Umeå University, Sweden.
    Vascular risk factors in INPH A prospective case- control study (the INPH-CRasH study)2017Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, nr 6, s. 577-585Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and populationbased controls to determine the extent to which vascular disease influences INPH pathophysiology. Methods: All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age-and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity. Results: In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%. Conclusions: Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.

  • 63.
    Jaworski, J
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet.
    Tisell, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Radiofysikavdelningen.
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Radiofysikavdelningen. Östergötlands Läns Landsting, Bildmedicinskt centrum, Röntgenkliniken i Linköping.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Treatment with glatiramer acetate (Copaxone (R)) prevents neurodegeneration in patients with multiple sclerosis2009Ingår i: in MULTIPLE SCLEROSIS, vol 15, issue 9, 2009, Vol. 15, nr 9, s. S140-S141Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 64.
    Kvarnström, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Ydrefors, J
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Longitudinal interferon-β effects in multiple sclerosis: differential regulation of IL-10 and IL-17A, while no sustained effects on IFN-γ, IL-4 or IL-132013Ingår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 325, nr 1-2, s. 79-85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    Recent studies in experimental models and in vitro indicate lowering of IL-17/Th17 as an important mechanism of interferon-beta (IFN-β) treatment in multiple sclerosis (MS).

    Material and methods:

    In this longitudinal study of MS patients (n = 25), spontaneous and myelin antigen-induced secretion of IL-4, IFN-γ and IL-10 (ELISPOT), mitogen stimulated secretion of IL-13 and IL-17A (ELISA) and circulating cytokine levels (Luminex) were recorded at inclusion and after 1.5, 3, 6 and 12 months of IFN-β treatment.

    Results:

    Early changes were noted for IL-4, while after one year of treatment the only recorded significant effects were a decrease in secreted IL-17A levels and an increase in IL-10 secreting cells. While IL-17A levels tended to be higher in non-responders (n = 8), the decrease in IL-17A levels seemed to be more pronounced in responders (n = 17) showing significantly lower IL-17A levels after one year as compared with non-responders.

    Conclusion:

    IFN-β treatment seems to mainly affect IL-17/IL-10-associated pathways rather than the IFN-γ/IL-4 axis.

  • 65.
    Landtblom, Anne-Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Boivie, Jörgen
    ­Akademiska sjukhuset, Uppsala.
    Utred alltid förstagångsinsjuknande i åskknallshuvudvärk2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 29-31, s. 1446-1446Artikel i tidskrift (Övrigt vetenskapligt)
  • 66.
    Landtblom, Anne-Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Fazio, Patrik
    University Ferrara.
    Fredrikson, Sten
    Karolinska Institute.
    Granieri, Enrico
    University Ferrara.
    The first case history of multiple sclerosis: Augustus dEst, (1794-1848)2010Ingår i: NEUROLOGICAL SCIENCES, ISSN 1590-1874, Vol. 31, nr 1, s. 29-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The personal diary of Sir Augustus dEst,, born 1794 grandson of King George III of England, reveals a medical history strongly suggesting that Augustus suffered from multiple sclerosis (MS). It could well be the first record of a person having this disease. Charcot coined the term scl,rose en plaques 20 years after the death of this patient in 1848. The onset of this mans MS seems to have been in 1822 with bilateral optic neuritis, the disease gradually developing in the classic manner with bouts derived from different loci in the central nervous system and eventually a secondary progressive form with paraparesis, sphincter incontinence, urinary problems and impotence. In 1941, Firth highlighted the case of Augustus dEst, and later wrote a description of the pathology including a discussion on the aetiology of MS. No previous medical records have given such a characteristic picture of MS as this.

  • 67.
    Landtblom, Anne-Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    Lindehammar, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk neurofysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurofysiologiska kliniken US.
    Karlsson, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Craig, A D (Bud)
    Barrow Neurol Institute.
    Insular cortex activation in a patient with "sensed presence"/ecstatic seizures2011Ingår i: EPILEPSY and BEHAVIOR, ISSN 1525-5050, Vol. 20, nr 4, s. 714-718Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Seizures with an aura of a "sensed presence," a religious emotion, or feelings of euphoria (ecstatic seizures) are characterized by heightened self-awareness. A previous case report on a patient with epilepsy and "sensed presence" as an aura described hypoperfusion in both temporal lobes and a local ictal increase in the left frontoparietal area. A reexamination of the data was suggested by a recent study of patients with ecstatic seizures, which proposed that hyperactivation of the left anterior insula might be a potential cause. Methods: We reanalyzed the laboratory data on the case with "sensed presence" aura using a fusion of SPECT and MR images of the brain, which had not previously been available, and a close examination of the subdural ictal EEG registrations. Results: Examination of the ictal EEG recordings from subdural strip electrodes implanted subtemporally and temporally on both sides showed that seizure activity occurred first at the most medial subtemporal electrode on the left side. From an anatomical point of view, this electrode position is close to the ventral aspect of the left anterior insula, and it is possible that the seizure activity was initiated there. Reexamination of the SPECT data after fusion with contemporary MR images clearly indicated that the region of strong hyperactivation overlies the left anterior insula. Hyperactive regions also appear on the midinsula bilaterally. Together with the neurophysiological ictal EEG, this evidence supports a reinterpretation that this aura of "sensed presence" can be attributed to hyperactivation of the left anterior insula. Conclusion: The present findings support the proposal that ecstatic seizures or "sensed presence" auras can originate from the left anterior insula, a region that has been suggested to engender self-awareness associated with positive feelings.

  • 68.
    Landtblom, Anne-Marie
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Lindvall, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ledin, Torbjörn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Berlin, Gösta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    A case report of plasmapheresis treatment in a patient with paraneoplastic cerebellar degeneration and high anti-Yo antibody titers2008Ingår i: Therapeutic Apheresis and Dialysis, ISSN 1744-9979, Vol. 12, nr 1, s. 82-85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A patient with paraneoplastic cerebellar degeneration due to anti-Purkinje cell antibodies (anti-Yo) arising from ovarian carcinoma with metastases was treated with three plasmapheresis (PP) series (a total of 22 PP treatments) over one year and was monitored by repeated otoneurological testing, balance tests and clinical investigations. Blood samples for antibody titers were checked on several occasions. Initially there was a weak clinical response and significantly improved test results regarding the caloric response, as well as a possible effect on visual suppression of the vestibulo-ocular reflex after caloric ear irrigation. After the first series of PP treatment, new metastases were found. A half year later there was a progressive course with increasing general symptoms. Serology tests showed continuously high titers of anti-Yo antibody, although somewhat lower after PP. We thus report a minor and short-lived effect of PP, possibly inhibited by the natural course of metastatic disease. © 2008 International Society for Apheresis.

  • 69.
    Liedberg, Gunilla Margareta
    et al.
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Hälsa, Aktivitet, Vård (HAV). Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Polyneuropathy, with and without neurogenic pain, and its impact on daily life activities - a descriptive study2009Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 31, nr 17, s. 1402-1408Artikel i tidskrift (Refereegranskat)
    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.

  • 70.
    Lindehammar, Hans
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk neurofysiologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Neurofysiologiska kliniken US.
    Lindvall, Björn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Muscle involvement in juvenile idiopathic arthritis2004Ingår i: Rheumatology, ISSN 1462-0324, Vol. 43, nr 12, s. 1546-1554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: An observational study of changes in muscle structure and the relation to muscle strength in juvenile idiopathic arthritis (JIA).

    METHODS: Fifteen children and teenagers (eight girls and seven boys) with JIA, aged 9-19 yr (mean age 16.1), were studied. Muscle biopsies were obtained from the anterior tibial muscle and were examined using histopathological and immunohistochemical methods. Muscle fibre types were classified and fibre areas measured. As markers of inflammation, the major histocompatibility complex (MHC) class I and class II and the membrane attack complex (MAC) were analysed. Results were compared with biopsies from the gastrocnemius muscle in 33 young (19-23 yr) healthy controls. Isometric and isokinetic muscle strengths were measured in ankle dorsiflexion. Strength was compared with reference values for healthy age-matched controls. Nerve conduction velocities were recorded in the peroneal and sural nerves.

    RESULTS: Four of the 15 muscle biopsies were morphologically normal. Eleven biopsies showed minor unspecific changes. Two of these also showed minor signs of inflammation. MHC class II expression was found in 4/15 patients, which was significantly more than in the healthy controls (P = 0.0143). The expression of MHC class I and MAC did not differ from that in the controls. The mean area of type I fibres was lower than that of type IIA fibres in 12/13 biopsies. Muscle strength was significantly reduced in the patient group. There was a significant positive correlation between muscle fibre area and muscle strength. Nerve conduction studies were normal in all cases.

    CONCLUSIONS: Changes in leg muscle biopsies appear to be common in children and teenagers with JIA. The presence of inflammatory cells in the muscle and expression of MHC class II on muscle fibres may be a sign of inflammatory myopathy. There are no findings of type II muscle fibre hypotrophy or neuropathy, as in adults with RA.

  • 71.
    Lindh, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Cryptogenic Polyneuropathy: Clinical, Environmental, And Genetic Studies2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. Cryptogenic polyneuropathy: Clinical and neurophysiological findings
    Öppna denna publikation i ny flik eller fönster >>Cryptogenic polyneuropathy: Clinical and neurophysiological findings
    2005 (Engelska)Ingår i: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 10, nr 1, s. 31-37Artikel i tidskrift (Refereegranskat) 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.

    Nyckelord
    Axonal, Electromyography, Idiopathic, Neurophysiology, Peripheral neuropathies
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-45496 (URN)10.1111/j.1085-9489.2005.10106.x (DOI)
    Tillgänglig från: 2009-10-11 Skapad: 2009-10-11 Senast uppdaterad: 2017-12-13
    2. Occupational determinants of cryptogenic polyneuropathy
    Öppna denna publikation i ny flik eller fönster >>Occupational determinants of cryptogenic polyneuropathy
    Visa övriga...
    2006 (Engelska)Ingår i: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 26, nr 4, s. 187-194Artikel i tidskrift (Refereegranskat) 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.

    Nyckelord
    Environmental exposure, Epidemiological factors, Polyneuropathy, cryptogenic, Solvents
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-48033 (URN)10.1159/000092405 (DOI)
    Tillgänglig från: 2009-10-11 Skapad: 2009-10-11 Senast uppdaterad: 2017-12-13
    3. Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population
    Öppna denna publikation i ny flik eller fönster >>Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population
    2011 (Engelska)Ingår i: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 33, nr 7, s. 617-623Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    Informa Healthcare, 2011
    Nyckelord
    Activities of daily living, EuroQol, polyneuropathy, neurological disease, neuropathy
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-67316 (URN)10.3109/09638288.2010.505996 (DOI)000287451200008 ()
    Tillgänglig från: 2011-04-08 Skapad: 2011-04-08 Senast uppdaterad: 2011-10-10
    4. Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study
    Öppna denna publikation i ny flik eller fönster >>Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study
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    2011 (Engelska)Ingår i: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 1, nr 2, s. 135-141Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    Hoboken, New Jersey, USA: John Wiley & Sons, Inc, 2011
    Nyckelord
    Polyneuropathy
    Nationell ämneskategori
    Neurologi
    Identifikatorer
    urn:nbn:se:liu:diva-70979 (URN)10.1002/brb3.26 (DOI)000209173700009 ()
    Projekt
    kryptogen polyneuropati
    Tillgänglig från: 2011-10-03 Skapad: 2011-09-23 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
  • 72.
    Lindh, Jonas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Hosseininia, Shahzad
    Yrkes och miljömedicin, Medicinska fakulteten, Teherans universitet, Teheran, Iran.
    Tondel, Martin
    Arbets- och miljömedicin, Sahlgrenska Universitetssjukhuset, Göteborg.
    Persson, Bodil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk neurofysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study2011Ingår i: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 1, nr 2, s. 135-141Artikel i tidskrift (Refereegranskat)
    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.

  • 73.
    Lindh, Jonas
    et al.
    Section of Neurology, Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden, Department of Internal Medicine, Ryhov County Hospital, S-551 85 Jönköping, Sweden.
    Tondel, Martin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Östergötlands Läns Landsting, Medicincentrum, Smärt- och rehabiliteringscentrum.
    Osterberg, A.
    Österberg, A., Section of Neurology, Department of Internal Medicine, Motala Hospital, Motala, Sweden.
    Vrethem, Magnus
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Cryptogenic polyneuropathy: Clinical and neurophysiological findings2005Ingår i: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 10, nr 1, s. 31-37Artikel i tidskrift (Refereegranskat)
    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.

  • 74.
    Lindh, Jonas
    et al.
    Ryhov County Hospital.
    Tondel, Martin
    University of Gothenburg.
    Persson, Bodil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Arbets- och miljömedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population2011Ingår i: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 33, nr 7, s. 617-623Artikel i tidskrift (Refereegranskat)
    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.

  • 75. List, Thomas
    et al.
    Leijon, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Helkimo, Martti
    Oster, Anders
    Dworkin, Samuel F.
    Svensson, Peter
    Clinical findings and psychosocial factors in patients with atypical odontalgia: A case-control study2007Ingår i: Journal of Orofacial Pain, ISSN 1064-6655, E-ISSN 1945-3396, Vol. 21, nr 2, s. 89-98Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To provide a systematic description of clinical findings and psychosocial factors in patients suffering from atypical odontalgia (AO). Methods: Forty-six consecutive AO patients (7 men and 39 women, mean age, 56 years, range, 31 to 81 years) were compared with 35 control subjects (11 men and 24 women, mean age, 59 years, range, 31 to 79 years). Results: The pain of the AO patients was characterized by persistent, moderate pain intensity (mean, 5.6 +/- 1.9) with long pain duration (mean, 7.7 +/- 7.8 years). Eighty-three percent reported that onset of pain occurred in conjunction with dental treatment. No significant difference was found between the groups in number of remaining teeth or number of root fillings. Temporomandibular disorder (TMD) pain (P < .001), tension-type headache (P < .002), and widespread pain (P < .001) were significantly more common among AO patients than controls. Significantly higher scores for somatization (P < .01) and depression (P < .01) and limitations in jaw function (P < .001) were found for the AO group compared with the control group. Significant differences between groups were found in 4 general health domains: role-physical (P < .001), bodily pain (P < .001), vitality (P < .004), and social functioning (P < .001). Conclusion: A majority of the AO patients reported persistent, moderately intense intraoral pain that in most cases had an onset in conjunction with dental treatment. AO patients had more comorbid pain conditions and higher scores for depression and somatization. Significant limitation in jaw function and significantly lower scores on quality of life measures were found for AO patients compared with controls.

  • 76.
    List, Thomas
    et al.
    Malmö University.
    Leijon, Göran
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Svensson, Peter
    University of Aarhus.
    Somatosensory abnormalities in atypical odontalgia: A case-control study2008Ingår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 139, nr 2, s. 333-341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Somatosensory function in patients with persistent idiopathic types of orofacial pain like atypical odontalgia (AO) is not well described. This study tested the hypothesis that AO patients have significantly more somatosensory abnormalities than age- and sex-matched controls. Forty-six AO patients and 35 controls participated. Inclusion criteria for AO were pain in it region where a tooth had been endodontically Or surgically treated, persistent pain >6 months, and kick of clinical and radiological findings. The examination included qualitative tests and a battery of intraoral quantitative sensory testing (QST). Most AO patients (85%) had qualitative somatosensory abnormality compared with few controls (14%). The most common qualitative abnormalities in AO patients were found with pin-prick 67.4%, cold 47.8%, and touch 46.5%, compared with 11.4%, 8.6%, and 2.9%, respectively. in the control group (P < 0.001). Between-group differences were seen for many intraoral QST: mechanical detection threshold, mechanical pain threshold (pinprick), dynamic mechanical allodynia (brush), dynamic mechanical allodynia (vibration), wind-up ratio. and pressure pain threshold (P < 0.01). In the trigeminal area, between-group differences in thermal thresholds were nonsignificant while differences in cold detection at the thenar eminence were significant. Individual somatosensory profiles revealed complex patterns with hyper- and hyposensitivity to intraoral QST. Between-group differences in pressure pain thresholds (P < 0.022) were observed at the thenar eminence. In conclusion, significant abnormalities in intraoral somatosensory function were observed in AO. which may reflect peripheral and central sensitization of trigerminal pathways. More generalized sensitization of the nociceptive system may also be part of AO pathophysiology.

  • 77.
    Lundin, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Idiopathic Normal Pressure Hydrocephalus: Aspects on Pathophysiology, Clinical Characteristics and Evaluation Methods2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Introduction. Idiopathic normal pressure hydrocephalus (iNPH) is a condition with enlargement of the cerebral ventricular system and an intracranial pressure (ICP) within normal limits. Cerebrospinal fluid circulation is disturbed but the mechanisms behind the symptoms: gait and balance difficulties, cognitive dysfunction and micturition problems, are as yet mostly unexplained.

    Aim. In Studies I and II the aim was to investigate cerebral metabolism in the frontal deep white matter (FDWM) and the thalamus in iNPH using Magnetic Resonance Spectroscopy (MRS) before and after shunt surgery and to compare this with healthy individuals (HI). In Study III the aim was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in iNPH patients before and after shunt surgery, in comparison with HI. In Study IV the aim was to study postural function using computerised dynamic posturography (CDP) before and after shunt surgery as well as in comparison with HI.

    Patients and Methods. In all studies the patients had a neurological examination and baseline bedside assessments of motor, balance and cognitive function were performed. Motor function was assessed using a motor score (MOS) consisting of the following items: 10 metre walk time in seconds and number of steps and TUG time in seconds and number of steps. MOS was considered significant if there was an increase of 5% or more. The HI were also tested for motor, balance and cognitive function. In Study I the patients (n=16) and the HI (n=15) were examined with MRS (absolute quantification) with voxels placed in the thalamus and in FDWM and compared with one another. In Studies III and IV the preoperative results of actigraphy and CDP respectively in patients (Study III n=33; study IV n=35) were compared with the HI: Study III, n=17; Study IV, n=16. The HI performed these examinations twice and the average was calculated. In Study II, 14 patients, and in Studies III and IV, 20 patients underwent shunt surgery and new MRS/actigraphy/CDP examinations were performed three months postoperatively and compared with the preoperative results.

    Results. In the patients decreased total N-acetyl compounds (tNA) and N-acetyl aspartate (NAA) were found in the thalamus compared to the HI. No metabolic differences were seen in the FDWM between the groups. Postoperatively there were no metabolic changes in the thalamus but an increased total Choline (tCho) and a borderline significant decrease in myo-inositol (mIns).During the day the patients took fewer steps and had also lower total energy expenditure (TEE) than the HI. There was no difference concerning resting/sleeping time between patients and the HI. Postoperatively there were no differences of either number of steps, TEE or time spent resting or sleeping compared with the preoperative state. Postural function was worse in the patients compared to the HI, this difference being more pronounced in tests measuring vestibular function, where loss of balance (LOB) was frequent. There was only a slight improvement in balance after shunt surgery. A positive response to the shunt operation was seen in 86% in Study II, 85% in Study III and 90% in Study IV.

    Conclusions. Our results suggest that the thalamus may be involved in the pathogenesis of iNPH. In contrast to others, we did not find any metabolic abnormalities in the FDWM, nor detect an increment of tNA or NAA postoperatively in the thalamus. The postoperative increase in tCho and borderline decrease in mIns in the FDWM might reflect a state of metabolic recovery since high tCho, a major component of the cell membrane, may be a sign of increased membrane turnover, and a decrease in mIns may indicate diminished gliosis.

    The low gait capacity seen in the iNPH patients was not surprising but well that time spent resting/sleeping did not differ from the HI. Another unexpected finding was the unchanged ambulatory activity after shunt surgery despite improvement in a point test to determine capacity to walk a short distance. We believe this could be due to strong habits that are difficult to break and/or shortage of rehabilitation after surgery.

    There was a profound postural dysfunction in the patients with many falls, especially in test situations intended to measure vestibular function. This implies that there is a central vestibular disturbance. The discrete improvement in postural function postoperatively was lower than previously reported.

    Delarbeten
    1. Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification
    Öppna denna publikation i ny flik eller fönster >>Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification
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    2011 (Engelska)Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, nr 7, s. 772-778Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). Subjects and methods 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. 1 H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. Results INPH patients had lower NAA (p = 0.02) and lower tNA (p = 0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myoinositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Conclusion Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

    Ort, förlag, år, upplaga, sidor
    BMJ Publishing Group, 2011
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-69842 (URN)10.1136/jnnp.2010.223529 (DOI)000291429200016 ()
    Anmärkning

    Original Publication: Fredrik Lundin, Anders Tisell, Olof Dahlqvist Leinhard, M. Tullberg, C. Wikkelso, Peter Lundberg and Göran Leijon, Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification, 2011, Journal of Neurology, Neurosurgery and Psychiatry, (82), 7, 772-778. http://dx.doi.org/10.1136/jnnp.2010.223529 Copyright: BMJ Publishing Group http://group.bmj.com/

    Tillgänglig från: 2011-08-10 Skapad: 2011-08-08 Senast uppdaterad: 2019-06-14
    2. Pre-Postoperative 1H-MRS-Changes in Frontal Deep White Matter and the Thalamus in Idiopathic Normal Pressure Hydrocephalus
    Öppna denna publikation i ny flik eller fönster >>Pre-Postoperative 1H-MRS-Changes in Frontal Deep White Matter and the Thalamus in Idiopathic Normal Pressure Hydrocephalus
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    In a previous study we found a significantly decreased N-acetylaspartate (NAA) and total N-acetyl groups (tNA) in the thalamus in patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM.

    Subjects and Methods: Fourteen iNPH-patients, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of motor scores was performed before and after shunt surgery. Absolute quantitative 1H-MRS (1.5 T, VOI 2.5-3 mL) was performed on the patients in the FDWM and in the thalamus, before and three months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine (tCr), total choline (tCho), myo-inositol (mIns), glutamate (Glu), and lactate (Lac) concentrations. MRI volumetric calculations of the lateral ventricles were also performed.

    Results: At three months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between motor score (MOS) and ventricular reduction was observed.

    Conclusion: Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.

    Nyckelord
    Normal Pressure Hydrocephalus, Magnetic Resonance Spectroscopy, Postoperative, Thalamus, Frontal lobe
    Nationell ämneskategori
    Radiologi och bildbehandling
    Identifikatorer
    urn:nbn:se:liu:diva-84236 (URN)
    Tillgänglig från: 2012-10-02 Skapad: 2012-10-02 Senast uppdaterad: 2019-06-14Bibliografiskt granskad
    3. How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.
    Öppna denna publikation i ny flik eller fönster >>How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.
    Visa övriga...
    2012 (Engelska)Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, nr 2, s. 192-196Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    INTRODUCTION: Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI).

    SUBJECTS AND METHODS: 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively.

    RESULTS: During daytime the patients took fewer steps (p<0.001) and their total energy expenditure (TEE) was lower (p<0.01) than in the HI. Twenty patients were evaluated pre- and post-operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery.

    CONCLUSION: Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84239 (URN)10.1016/j.clineuro.2012.05.009 (DOI)000314447500013 ()22673042 (PubMedID)
    Tillgänglig från: 2012-10-02 Skapad: 2012-10-02 Senast uppdaterad: 2017-12-07
    4. Postural Function in Idiopathic Normal Pressure Hydrocephalus Before and After Shunt Surgery: A Controlled Study Using Computerised Dynamic Posturography (EquiTest)
    Öppna denna publikation i ny flik eller fönster >>Postural Function in Idiopathic Normal Pressure Hydrocephalus Before and After Shunt Surgery: A Controlled Study Using Computerised Dynamic Posturography (EquiTest)
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Postural dysfunction is one of the major features of idiopathic Normal Hydrocephalus (iNPH). With computerised dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP.

    Subjects and methods: Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval.

    Results: Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organising Test (SOT) score in every condition (p= 0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients did undergo shunt surgery and 18/20 (90%) were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67 %). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions.

    Conclusion: CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.

    Nyckelord
    idiopathic Normal Pressure Hydrocephalus, Postural Function, Computerised Dynamic Posturography, Shunt surgery
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84240 (URN)
    Tillgänglig från: 2012-10-02 Skapad: 2012-10-02 Senast uppdaterad: 2012-10-03Bibliografiskt granskad
  • 78.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Wikkelsø, C.
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Postural Function in Idiopathic Normal Pressure Hydrocephalus Before and After Shunt Surgery: A Controlled Study Using Computerised Dynamic Posturography (EquiTest)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Postural dysfunction is one of the major features of idiopathic Normal Hydrocephalus (iNPH). With computerised dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP.

    Subjects and methods: Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval.

    Results: Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organising Test (SOT) score in every condition (p= 0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients did undergo shunt surgery and 18/20 (90%) were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67 %). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions.

    Conclusion: CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.

  • 79.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US.
    Wikkelsø, C.
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Postural function in idiopathic normal pressure hydrocephalus before and after shunt surgery: a controlled study using computerized dynamic posturography (EquiTest)2013Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, nr 9, s. 1626-1631Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction

    Postural dysfunction is one of the major features of idiopathic normal pressure hydrocephalus (iNPH). With computerized dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP.

    Subjects and methods

    Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49–81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62–89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval.

    Results

    Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organizing Test (SOT) score in every condition (p = 0.01 in SOT 1 and p < 0.001 in SOT 2–6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients were evaluated three months after shunt surgery and 18/20 (90%) of them were considered shunt responders, with a mean improvement of motor score of 26% (range 5–67%). There was an improvement post-operatively in the weighted composite SOT score (p < 0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions.

    Conclusion

    CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5–6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.

  • 80.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Personne, Mark
    Giftinformationscentralen, Stockholm, Sweden.
    Hanberger, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Botulism är en behandlingsbar, mycket sällsynt förgiftning2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 12-13, s. 551-552Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Botulism är en sällsynt förgiftning orsakad av botulinumtoxin från bakterien Clostridium botulinum.

    Bakterien tillväxer under anaeroba förhållanden och återfinns på våra breddgrader oftast i bristfälligt tillagad fisk.

    Botulism ska misstänkas vid snabbt progredierande symmetrisk nedåtstigande muskelparalys och autonoma symtom – framför allt vid pupillpåverkan (mydriasis). Behandlingen består i tillförsel av antitoxin för att förhindra symtomprogress samt symtomatiskt omhändertagande, speciellt med avseende på andningsunderstöd.Långvarig intensivvårdsbehandling kan bli aktuell, men på sikt är prognosen relativt god.

  • 81.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Tisell, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Hälsouniversitetet.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet.
    Davidsson, Leif
    Östergötlands Läns Landsting, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Grönkvist, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Wikkelsö, C
    University of Gothenburg.
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Östergötlands Läns Landsting, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Idiopathic Normal Pressure Hydrocephalus Pre -Postoperative 1H -MRS  changes in Frontal Deep White Matter and the Thalamus2011Konferensbidrag (Refereegranskat)
  • 82.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Tisell, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet.
    Tullberg, M.
    University of Gothenburg.
    Wikkelso, C.
    University of Gothenburg.
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Östergötlands Läns Landsting, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification2011Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, nr 7, s. 772-778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). Subjects and methods 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. 1 H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. Results INPH patients had lower NAA (p = 0.02) and lower tNA (p = 0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myoinositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Conclusion Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

  • 83.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Tisell, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Davidsson, L.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Grönqvist, A.
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Wikkelsø, C.
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Lundberg, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Pre-Postoperative 1H-MRS-Changes in Frontal Deep White Matter and the Thalamus in Idiopathic Normal Pressure HydrocephalusManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    In a previous study we found a significantly decreased N-acetylaspartate (NAA) and total N-acetyl groups (tNA) in the thalamus in patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM.

    Subjects and Methods: Fourteen iNPH-patients, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of motor scores was performed before and after shunt surgery. Absolute quantitative 1H-MRS (1.5 T, VOI 2.5-3 mL) was performed on the patients in the FDWM and in the thalamus, before and three months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine (tCr), total choline (tCho), myo-inositol (mIns), glutamate (Glu), and lactate (Lac) concentrations. MRI volumetric calculations of the lateral ventricles were also performed.

    Results: At three months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between motor score (MOS) and ventricular reduction was observed.

    Conclusion: Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.

  • 84.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Tisell, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Davidsson, Leif
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Grönqvist, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Medicinsk strålningsfysik.
    Wikkelso, Carsten
    University of Gothenburg, Sweden .
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Östergötlands Läns Landsting, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Preoperative and postoperative H-1-MR spectroscopy changes in frontal deep white matter and the thalamus in idiopathic normal pressure hydrocephalus2013Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, nr 2, s. 188-193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background In a previous study we found significantly decreased N-acetyl aspartate (NAA) and total N-acetyl (tNA) groups in the thalamus of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). less thanbrgreater than less thanbrgreater thanObjective The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM. less thanbrgreater than less thanbrgreater thanSubjects and methods Fourteen patients with iNPH, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of a motor score (MOSs) was performed before and after shunt surgery. Absolute quantitative H-1-MR spectroscopy (1.5 T, volumes of interest 2.5-3 ml) was performed on the patients in the FDWM and in the thalamus, before and 3 months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine, total choline (tCho), myo-inositol (mIns), glutamate and lactate concentrations. MRI volumetric calculations of the lateral ventricles were also performed. less thanbrgreater than less thanbrgreater thanResults At 3 months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in the FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between MOS and ventricular reduction was seen. less thanbrgreater than less thanbrgreater thanConclusions Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.

  • 85.
    Lundin, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk neurofysiologi. Linköpings universitet, Hälsouniversitetet.
    Svanborg, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk neurofysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurofysiologiska kliniken US.
    Wikkelsø, C.
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.2012Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, nr 2, s. 192-196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI).

    SUBJECTS AND METHODS: 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively.

    RESULTS: During daytime the patients took fewer steps (p<0.001) and their total energy expenditure (TEE) was lower (p<0.01) than in the HI. Twenty patients were evaluated pre- and post-operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery.

    CONCLUSION: Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed.

  • 86.
    Malm, J
    et al.
    Umeå University.
    Sundstrom, N
    Umeå University.
    Cesarini, K G
    Uppsala University.
    Edsbagge, M
    University of Gothenburg.
    Kristensen, B
    University of Aalborg.
    Leijon, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Eklund, A
    Umeå University.
    Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients2012Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, nr 3, s. 199-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives - The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study. Methods -Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered. Results Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Postinvestigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed. Conclusion Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.

  • 87.
    Mazya, Michael
    et al.
    Vrinnevisjukhuset Norrköping.
    Rossitti, Sandro
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurokirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Neurokirurgiska kliniken US.
    Andersson, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    New endovascular treatment of intracranial arterial stenosis in clinical practice. Good result in a patient with high risk of cerebral ischemia2008Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 37, s. 2486-2487Artikel i tidskrift (Refereegranskat)
    Abstract [en]

       

  • 88.
    Mellergård, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Immunological Mechanisms and Natalizumab Treatment in Multiple Sclerosis: Studies on lymphocytes, inflammatory markers and magnetic resonance spectroscopy2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system (CNS), and a frequent cause of neurological disability among young adults. In addition to focal inflammatory demyelinated lesions, diffuse white matter pathology as well as a neurodegenerative component with accumulating axonal damage and gliosis have been demonstrated and contribute to MS disease characteristics. The inflammatory component is considered autoimmune and mediated by auto-reactive T lymphocytes together with other cell populations of the immune system and their respective products like cytokines and chemokines. Treatment with natalizumab, a monoclonal antibody directed against the α4β1-integrin (VLA-4), reduces migration of potential disease-promoting cells to the CNS. The efficacy of natalizumab in reducing relapses and MRI activity is evident, however associated effects on the immune response and the neurodegenerative component in MS are not clear.

    Methods: In total 72 MS patients were included, distributed among paper I-IV. We investigated effects associated with one-year natalizumab treatment in 31 MS patients regarding cytokine and chemokine levels in CSF and blood using multiplex bead assay analyses (paper I), as well as treatment effects on blood lymphocyte composition in 40 patients using flow cytometry, including functional assays of lymphocyte activation (paper II). Normal appearing white matter (NAWM) metabolite concentrations were assessed with proton magnetic resonance spectroscopy (1H-MRS) in 27 MS patients before and after one year of treatment (paper III). We also evaluated the balance between circulating T helper (Th) subsets in 33 MS patients using gene expression analyses of the CD4+ T cell related transcription factors in whole blood (paper IV).

    Results: One-year natalizumab treatment was associated with a marked decline in pro-inflammatory cytokines (IL-1β and IL-6) and chemokines (CXCL8, CXCL9, CXCL10 and CXCL11) intrathecally. Circulating plasma levels of some cytokines (GM-CSF, TNF, IL-6 and IL-10) also decreased after treatment. Natalizumab treatment was further associated with an increase in lymphocyte numbers of major populations in blood (total lymphocytes, T cells, T helper cells, cytotoxic T cells, NK cells and B cells). In addition, T cell responsiveness to recall antigens and mitogens was restored after treatment. As to 1H-MRS metabolite concentrations in NAWM, no change in levels were detected post-to pretreatment on a group level. However, correlation analyses between one-year change in metabolite levels (total creatine and total choline) and levels of pro-inflammatory IL-1β and CXCL8 showed a pattern of high magnitude correlation coefficients (r=0.43-0.67). Gene expression analyses demonstrated a systemically reduced expression of transcription factors related to immunoregulatory T cell populations (regulatory T cells and Th2) in relapsing MS compared with controls.

    Conclusions: Our findings support that an important mode of action of natalizumab is reducing lymphocyte extravasation, although cell-signalling effects through VLA-4 also may be operative. Correlation analyses between changes 1H-MRS metabolite concentrations and inflammatory markers possibly point towards an association between intrathecal inflammation and gliosis development in NAWM. Finally, gene expression analyses indicate a systemic defect at the mRNA level in relapsing MS, involving downregulation of beneficial CD4+ phenotypes.

    Delarbeten
    1. Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid
    Öppna denna publikation i ny flik eller fönster >>Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid
    Visa övriga...
    2010 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 16, nr 2, s. 208-217Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Natalizumab exerts impressive therapeutic effects in patients with multiple sclerosis (MS). The proposed main mode of action is reducing transmigration of leukocytes into the CNS, but other immunological effects may also be operative. Cytokines and chemokines are involved in the regulation of inflammatory responses and may reflect the disease process in MS. The objective of this study was to evaluate the effects of natalizumab treatment on cytokine and chemokine profiles systemically and intrathecally in multiple sclerosis. We used luminex to analyse a panel of cytokines (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma, GM-CSF) and chemokines (CXCL9, CXCL10, CXCL11, CCL17, CCL22) in blood and cerebrospinal fluid (CSF) from 31 patients with relapsing MS before and after one year of natalizumab treatment. There was a marked decline in CSF levels of cytokines and chemokines, thus including pro-inflammatory cytokines (IL-1 beta, IL-6 and IL-8) as well as chemokines associated with both Th1 (CXCL9, CXCL10, CXCL11) and Th2 (CCL22). Circulating plasma levels of some cytokines (GM-CSF, TNF-alpha, IL-6 and IL-10) also decreased after one year of treatment. This is the first study to show that natalizumab treatment is associated with a global decline in cytokine and chemokine levels at a protein level. This finding was most pronounced in CSF, in line with the reduced transmigration of cells into CNS, whereas reduction in plasma levels indicates other possible mechanisms of natalizumab treatment.

    Nyckelord
    cerebrospinal fluid, chemokines, cytokines, luminex, multiple sclerosis, natalizumab, peripheral blood
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-54061 (URN)10.1177/1352458509355068 (DOI)000274326500010 ()
    Anmärkning

    Original Publication: Johan Mellergård, Måns Edström, Magnus Vrethem, Jan Ernerudh and Charlotte Dahle, Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid, 2010, MULTIPLE SCLEROSIS, (16), 2, 208-217. http://dx.doi.org/10.1177/1352458509355068 Copyright: SAGE Publications http://www.uk.sagepub.com/

    Tillgänglig från: 2010-02-22 Skapad: 2010-02-22 Senast uppdaterad: 2017-12-12
    2. An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients
    Öppna denna publikation i ny flik eller fönster >>An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients
    Visa övriga...
    2013 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, artikel-id e81685Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

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

    Objectives

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

    Material and methods

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

    Results

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

    Conclusions

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

    Ort, förlag, år, upplaga, sidor
    San Francisco, USA: Public Library of Science, 2013
    Nyckelord
    Multiple sclerosis, natalizumab, flow cytometry, T-cells, NK-cells, B-cells, lymphocyte proliferation
    Nationell ämneskategori
    Neurologi Immunologi inom det medicinska området
    Identifikatorer
    urn:nbn:se:liu:diva-84268 (URN)10.1371/journal.pone.0081685 (DOI)000327944500088 ()24312575 (PubMedID)2-s2.0-84891420120 (Scopus ID)
    Tillgänglig från: 2012-10-03 Skapad: 2012-10-03 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    3. Association between Change in Normal Appearing White Matter Metabolites and Intrathecal Inflammation in Natalizumab-Treated Multiple Sclerosis
    Öppna denna publikation i ny flik eller fönster >>Association between Change in Normal Appearing White Matter Metabolites and Intrathecal Inflammation in Natalizumab-Treated Multiple Sclerosis
    Visa övriga...
    2012 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 9, s. e44739-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Multiple sclerosis (MS) is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS). Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM.

    Methods: Quantitative proton magnetic resonance spectroscopy (1H-MRS) was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in 1H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients.

    Results: The group levels of 1H-MRS metabolite concentrations were unchanged pre-to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43–0.67, p<0.0005–0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1β and CXCL8).

    Conclusions: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in 1H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84270 (URN)10.1371/journal.pone.0044739 (DOI)000309742800016 ()
    Anmärkning

    funding agencies|Swedish Society of Neurologically Disabled||Swedish Society of Medicine||National Research Council (VR/NT)||University Hospital of Linkoping||County Council of Ostergotland||Teva||Biogen Idec||

    Tillgänglig från: 2012-10-03 Skapad: 2012-10-03 Senast uppdaterad: 2019-06-14
    4. Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood
    Öppna denna publikation i ny flik eller fönster >>Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood
    Visa övriga...
    2011 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, nr 1, s. 57-66Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

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

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

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

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

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

    Ort, förlag, år, upplaga, sidor
    Sage Publications, 2011
    Nyckelord
    EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-64758 (URN)10.1177/1352458510381256 (DOI)000285867200006 ()20847001 (PubMedID)
    Tillgänglig från: 2011-02-04 Skapad: 2011-02-04 Senast uppdaterad: 2017-12-11
  • 89.
    Mellergård, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Edström, Måns
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, artikel-id e81685Artikel i tidskrift (Refereegranskat)
    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.

  • 90.
    Mellergård, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Edström, Måns
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet.
    Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid2010Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 16, nr 2, s. 208-217Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Natalizumab exerts impressive therapeutic effects in patients with multiple sclerosis (MS). The proposed main mode of action is reducing transmigration of leukocytes into the CNS, but other immunological effects may also be operative. Cytokines and chemokines are involved in the regulation of inflammatory responses and may reflect the disease process in MS. The objective of this study was to evaluate the effects of natalizumab treatment on cytokine and chemokine profiles systemically and intrathecally in multiple sclerosis. We used luminex to analyse a panel of cytokines (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma, GM-CSF) and chemokines (CXCL9, CXCL10, CXCL11, CCL17, CCL22) in blood and cerebrospinal fluid (CSF) from 31 patients with relapsing MS before and after one year of natalizumab treatment. There was a marked decline in CSF levels of cytokines and chemokines, thus including pro-inflammatory cytokines (IL-1 beta, IL-6 and IL-8) as well as chemokines associated with both Th1 (CXCL9, CXCL10, CXCL11) and Th2 (CCL22). Circulating plasma levels of some cytokines (GM-CSF, TNF-alpha, IL-6 and IL-10) also decreased after one year of treatment. This is the first study to show that natalizumab treatment is associated with a global decline in cytokine and chemokine levels at a protein level. This finding was most pronounced in CSF, in line with the reduced transmigration of cells into CNS, whereas reduction in plasma levels indicates other possible mechanisms of natalizumab treatment.

  • 91.
    Mellergård, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Tisell, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet.
    Blystad, Ida
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
    Olsson, Bob
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Association between Change in Normal Appearing White Matter Metabolites and Intrathecal Inflammation in Natalizumab-Treated Multiple Sclerosis2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 9, s. e44739-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Multiple sclerosis (MS) is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS). Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM.

    Methods: Quantitative proton magnetic resonance spectroscopy (1H-MRS) was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in 1H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients.

    Results: The group levels of 1H-MRS metabolite concentrations were unchanged pre-to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43–0.67, p<0.0005–0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1β and CXCL8).

    Conclusions: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in 1H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.

  • 92.
    Mellergård, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Tisell, Anders
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Hälsouniversitetet.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Landtblom, Anne-Marie
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Lundberg, Peter
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiofysik. Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk radiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    MR spectroscopy and quantitative MRI in multiple sclerosis patients treated with natalizumab: changes in normal appearing white matter are associated to intrathecal inflammation and clinical variables2010Konferensbidrag (Övrigt vetenskapligt)
  • 93.
    Mentesidou, E
    et al.
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Medicinska specialistkliniken .
    ANGINAL PAIN AS EPILEPTIC AURA MANIFESTATION in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 469-4692011Ingår i: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2011, Vol. 18, nr SI, s. 469-469Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 94.
    Mentesidou, E
    et al.
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Richter, J
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Vigren, P
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Säfström, Kåge
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Combination of vagal nerve stimulator and cardiac pace-maker in EUROPEAN JOURNAL OF NEUROLOGY, vol 17, issue SI, pp 456-4562010Ingår i: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2010, Vol. 17, nr SI, s. 456-456Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 95.
    Murray, V
    et al.
    Danderyd Hosp, Div Med, Stockholm, Sweden Reg Hosp, Dept Geriatr Med, Orebro, Sweden Linkoping Univ Hosp, Dept Neurol, S-58185 Linkoping, Sweden Acad Hosp, Dept Med, Uppsala, Sweden Reg Hosp, Dept Neurol, Orebro, Sweden Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden Danderyd Hosp, Dept Rehabil Med, Stockholm, Sweden Linkoping Univ Hosp, Dept Psychiat, S-58185 Linkoping, Sweden.
    Von Arbin, M
    Danderyd Hosp, Div Med, Stockholm, Sweden Reg Hosp, Dept Geriatr Med, Orebro, Sweden Linkoping Univ Hosp, Dept Neurol, S-58185 Linkoping, Sweden Acad Hosp, Dept Med, Uppsala, Sweden Reg Hosp, Dept Neurol, Orebro, Sweden Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden Danderyd Hosp, Dept Rehabil Med, Stockholm, Sweden Linkoping Univ Hosp, Dept Psychiat, S-58185 Linkoping, Sweden.
    Varelius, R
    Danderyd Hosp, Div Med, Stockholm, Sweden Reg Hosp, Dept Geriatr Med, Orebro, Sweden Linkoping Univ Hosp, Dept Neurol, S-58185 Linkoping, Sweden Acad Hosp, Dept Med, Uppsala, Sweden Reg Hosp, Dept Neurol, Orebro, Sweden Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden Danderyd Hosp, Dept Rehabil Med, Stockholm, Sweden Linkoping Univ Hosp, Dept Psychiat, S-58185 Linkoping, Sweden.
    Olsson, Jan-Edvin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Terent, A
    Danderyd Hosp, Div Med, Stockholm, Sweden Reg Hosp, Dept Geriatr Med, Orebro, Sweden Linkoping Univ Hosp, Dept Neurol, S-58185 Linkoping, Sweden Acad Hosp, Dept Med, Uppsala, Sweden Reg Hosp, Dept Neurol, Orebro, Sweden Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden Danderyd Hosp, Dept Rehabil Med, Stockholm, Sweden Linkoping Univ Hosp, Dept Psychiat, S-58185 Linkoping, Sweden.
    Samuelsson, M
    Berggren, AL
    Landtblom, Anne-Marie
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Asberg, M
    Bartfai, A
    Danderyd Hosp, Div Med, Stockholm, Sweden Reg Hosp, Dept Geriatr Med, Orebro, Sweden Linkoping Univ Hosp, Dept Neurol, S-58185 Linkoping, Sweden Acad Hosp, Dept Med, Uppsala, Sweden Reg Hosp, Dept Neurol, Orebro, Sweden Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden Danderyd Hosp, Dept Rehabil Med, Stockholm, Sweden Linkoping Univ Hosp, Dept Psychiat, S-58185 Linkoping, Sweden.
    Bengtsson, F
    Martensson, B
    Sertraline in poststroke depression - A controlled study2002Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 33, nr 1, s. P292-Konferensbidrag (Övrigt vetenskapligt)
  • 96.
    Nyholm, Dag
    et al.
    Uppsala University Hospital.
    Constantinescu, R
    Sahlgrens University Hospital.
    Holmberg, B
    Sahlgrens University Hospital.
    Dizdar Segrell, Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Askmark, H
    Uppsala University Hospital.
    Comparison of apomorphine and levodopa infusions in four patients with Parkinsons disease with symptom fluctuations2009Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, nr 5, s. 345-348Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Motor fluctuations in patients with advanced Parkinsons disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed.

    We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail.

    The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary.

    Ratings in moderate to severe off state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion.

    Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

  • 97.
    Palhagen, S.
    et al.
    Pålhagen, S., Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden, Department of Neurology, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.
    Heinonen, E.
    Research and Development, Orion Pharma, Turku, Finland.
    Hagglund, J.
    Hägglund, J., Department of Medicine, Mälar Hospital, Eskilstuna, Sweden.
    Kaugesaar, Toomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Maki-Ikola, O.
    Mäki-Ikola, O., Research and Development, Orion Pharma, Turku, Finland.
    Palm, R.
    Department of Neurology and Rehabilitation, Central Hospital, Karlstad, Sweden.
    Selegiline slows the progression of the symptoms of Parkinson disease2006Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 66, nr 8, s. 1200-1206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD). Methods: One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy. Results: Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline, after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated. Conclusions: The results of this long-term study confirm earlier findings indicating that selegiline delays the progression of the signs and symptoms of Parkinson disease. Copyright © 2006 by AAN Enterprises, Inc.

  • 98.
    Paues, Jakob
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Fatal progressive multifocal leukoencephalopathy in a patient with non-Hodgkin lymphoma treated with rituximab2010Ingår i: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 48, nr 4, s. 291-293Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We report a case of progressive multifocal leukoencephalopathy (PML) in a woman with non-Hodgkin lymphoma treated with chemotherapy in combination with rituximab. She presented with rapid deterioration of vision and subsequently cognitive decline. Magnetic resonance imaging (MRI) of the brain raised the suspicion of PML. The first PCR analysis of the cerebrospinal fluid (CSF) was negative, but a second sample was positive for JC virus DNA. Anti-viral treatment was ineffective and the patient died 7 months after debut of symptoms. Our case emphasizes the importance of the awareness of PML in patients with progressive neurological symptoms treated with antilymphocytic drugs and that consecutive CSF analyses may be needed to detect the JC virus.

  • 99.
    Persson, Bodil
    et al.
    Skåne University Hospital, Sweden.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Murgia, Nicola
    University of Perugia, Italy.
    Lindh, Jonas
    Ryhov County Hospital, Sweden.
    Hällsten, Anna-Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Tondel, Martin
    Uppsala University, Sweden.
    Urinary 2,5-hexanedione excretion in cryptogenic polyneuropathy compared to the general Swedish population2013Ingår i: Journal of Occupational Medicine and Toxicology, ISSN 1745-6673, E-ISSN 1745-6673, Vol. 8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors.

    Methods

    Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis.

    Results

    Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age.

    Conclusions

    Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.

  • 100.
    Petzold, Axel
    et al.
    University College London.
    Thompson, Edward J
    University College London.
    Keir, Geoffrey
    University College London.
    Quinn, Niall
    University College London.
    Holmberg, Bjorn
    University of Gothenburg.
    Dizdar Segrell, Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Wenning, Gregor K
    Rascol, Olivier
    Hop Purpan.
    Tolosa, Eduardo
    University of Barcelona.
    Rosengren, Lars
    University of Gothenburg.
    Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy2009Ingår i: JOURNAL OF THE NEUROLOGICAL SCIENCES, ISSN 0022-510X, Vol. 279, nr 1-2, s. 76-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Two cerebrospinal fluid (CSF) biomarkers specific for neurodegeneration have recently emerged the neurofilament light (NfL, 68 kDa) and heavy (NfH, 190-210 kDa) chains. This study investigated whether the CSF NfH and NfL levels or their stoichionietric relationship changed over time in a neuroprotective treatment trial.

    Methods: Serial CSF samples (n =95) from 42 patients with multiple system atrophy (MSA), half randomized to treatment with recombinant human growth hormone (r-hGH) and the other half to placebo, were collected at baseline, 6 and 12 months. The concentration of CSF NfL and NfH was determined using standard ELISAs. Results: There was no consistent change in the levels of either protein over the 12 month period, or between treatment with active r-hGH versus placebo. The molar stoichiometry of CSF NfL:NfH was 4:1 (R=0.37, p=0.0002) and increased following treatment with r-hGH (p=0.03).

    Conclusion: These results indicate that CSF levels of both NfL and NfH on their own are not useful markets of disease progression in MSA, at least over a 12-month period. Future work is needed to elucidate whether the CSF stoichiometry and dynamics of Nf subunits in individual patients are a feature of the underlying pathology and of diagnostic or prognostic value.

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