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  • 1.
    Ahlstrom, G.
    et al.
    Ahlström, G., Department of Health Sciences, University of Örebro, SE-701 82 Örebro, Sweden.
    Lindvall, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Wenneberg, S.
    Department of Health Sciences, University of Örebro, SE-701 82 Örebro, Sweden.
    Gunnarsson, L.G.
    Department of Neurology and Neurophysiology, Örebro University Hospital, Örebro, Sweden.
    A comprehensive rehabilitation programme tailored to the needs of adults with muscular dystrophy2006In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 20, no 2, p. 132-141Article in journal (Refereed)
    Abstract [en]

    Objective: To assess if activities of daily living (ADL), coping and quality of life could be improved in adults with muscular dystrophy through a comprehensive rehabilitation programme. Design: Quasi-experimental, controlled clinical study comparing patients with similar age and disease aspects. Setting: Two different counties in Sweden, being either study or control setting. Subjects: The study group comprised 37 adults (21 women, 16 men, mean age 50 years), while the control group comprised 39 people (25 women, 14 men, mean age 46 years). Interventions: Four rehabilitation sessions tailored to different medical, physical and psychosocial needs of the patients, comprising a total of 10 days over a period of 18 months. Main measures: ADL, the Mental Adjustment to Cancer Scale measuring coping strategies, the Sickness Impact Profile measuring health-related quality of life, the Hospital Anxiety and Depression Scale, and the Psychosocial Well-being Questionnaire. Results: No significant differences were found between groups with regard to the outcome measures. There was increased dependence on others in ADL after 18 months in both groups, but it was more pronounced in the control group. Furthermore, a clear trend was observed in the data with regard to coping patterns, the control group using more coping strategies such as 'Helplessness/hopelessness' (P = 0.057), 'Anxious preoccupation' (P = 0.085) and 'Fatalistic' (P = 0.073) when being compared to the study group. Conclusions: No apparent effects on ADL were found from the rehabilitation programme, although there was a tendency of reduction of maladaptive coping patterns in the study group. This initial study may provide the rationale and basis for a randomized controlled trial. © 2006 Edward Arnold (Publishers) Ltd.

  • 2.
    Almen-Christensson, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Lindh-Åstrand, Lotta
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Prevention of menstrual migraine with perimenstrual transdermal 17-beta-estradiol: a randomized, placebo-controlled, double-blind crossover study2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, no 2, p. 498-500Article in journal (Refereed)
    Abstract [en]

    he effect of treatment with percutaneous E(2) (100 mu g/24 h) during 2 weeks perimenstrually on the number and severity of menstrual migraine attacks was studied in 27 women in a randomized, placebo-controlled, double-blind, crossover trial. We were not able to demonstrate any difference between E(2) supplementation and placebo on the number or severity of migraine attacks, but both regimens showed significant effects compared with before treatment.

  • 3.
    Baad-Hansen, Lene
    et al.
    University of Aarhus.
    Leijon, Göran
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Department of Clinical and Experimental Medicine, Neurology .
    Svensson, Peter
    University of Aarhus.
    List, Thomas
    University of Aarhus.
    Comparison of clinical findings and psychosocial factors in patients with atypical odontalgia and temporomandibular disorders2008In: Journal of Orofacial Pain, ISSN 1064-6655, E-ISSN 1945-3396, Vol. 22, no 1Article in journal (Refereed)
    Abstract [en]

    Aims: To systematically compare clinical findings and psychosocial factors between patients suffering from atypical odontalgia (AO) and an age- and gender-matched group of patients with temporomandibular disorders (TMD).Methods: Forty-six AO patients (7 men and 39 women, mean age, 56 years) were compared with 41 TMD patients (8 men and 33 women, mean age, 58 years). Results: Mean pain intensity at the time of inclusion in the study was similar between the groups (TMD: 5.3 ± 0.4, AO: 5.0 ± 0.3), but pain duration was longer in AO patients (AO: 7.7 ± 1.1 years, TMD: 4.5 ± 0.1 years). Eighty-three percent of the AO patients and 15% of TMD patients reported pain onset in relation to dental/surgical procedures. Episodic tension-type headache (TTH) occurred equally in both groups (TMD: 46%, AO: 46%), but TMD patients more frequently experienced chronic TTH (TMD: 35%, AO: 18%), myofascial TMD (TMD: 93%, AO: 50%), and temporomandibular joint disorders (TMD: 66%, AO: 2%). Overall, TMD patients had lower pressure pain thresholds and poorer jaw function than AO patients. Mean depression and somatization scores were moderate to severe in both groups, and widespread pain was most common in TMD patients.Conclusion: AO and TMD share some characteristics but differ significantly in report of dental trauma, jaw function, pain duration, and pain site.

  • 4.
    Baron, R.
    et al.
    Universitätsklinikum Schleswig-Holstein.
    Mayoral, V.
    Hospital Universitari de Bellvitge.
    Leijon, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Binder, A.
    Universitätsklinikum Schleswig-Holstein.
    Steigerwald, I.
    Grünenthal GmbH.
    Serpell, M.
    Gartnavel General Hospital.
    Efficacy and safety of 5% lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: Interim analysis from an open-label, two-stage adaptive, randomized, controlled trial2009In: Clinical Drug Investigation, ISSN 1173-2563, Vol. 29, no 4, p. 231-241Article in journal (Refereed)
    Abstract [en]

    Background and objective: Postherpetic neuralgia (PHN) and diabetic polyneuropathy (DPN) are two common causes of peripheral neuropathic pain. Typical localized symptoms can include burning sensations or intermittent shooting or stabbing pains with or without allodynia. Evidence-based treatment guidelines recommend the 5% lidocaine (lignocaine) medicated plaster or pregabalin as first-line therapy for relief of peripheral neuropathic pain. This study aimed to compare 5% lidocaine medicated plaster treatment with pregabalin in patients with PHN and patients with DPN. Methods: The study was a two-stage, adaptive, randomized, controlled, open-label, multicentre trial that incorporated a drug wash-out phase of up to 2 weeks prior to the start of the comparative phase. At the end of the enrolment phase, patients who fulfilled the eligibility criteria were randomized to either 5% lidocaine medicated plaster or pregabalin treatment and entered the 4-week comparative phase. The interim analysis represents the first stage of the two-stage adaptive trial design and was planned to include data from the comparative phase for the first 150 randomized patients of the 300 total planned for the trial. Patients aged =18 years with PHN or DPN were recruited from 53 investigational centres in 14 European countries. For this interim analysis, 55 patients with PHN and 91 with DPN (full-analysis set [FAS}), randomly assigned to the treatment groups, were available for analysis. Topical 5% lidocaine medicated plaster treatment was administered by patients to the area of most painful skin. A maximum of three or four plasters were applied for up to 12 hours within each 24-hour period in patients with PHN or DPN, respectively. Pregabalin capsules were administered orally, twice daily. The dose was titrated to effect: all patients received 150 mg/day in the first week and 300 mg/day in the second week of treatment. After 1week at 300 mg/day, the dose of pregabalin was further increased to 600 mg/day in patients with high pain intensity scores. The pre-planned primary study endpoint was the rate of treatment responders, defined as completing patients experiencing a reduction from baseline of =2 points or an absolute value of =4 points on the 11-item numerical rating scale of recalled average pain intensity over the last 3 days (NRS-3), after 4 weeks of treatment. Secondary endpoints included =30% and =50% reductions in NRS-3 scores, changes in neuropathic pain symptom inventory (NPSI) scores and allodynia severity ratings. Results: Overall, 65.3% of patients treated with the 5% lidocaine medicated plaster and 62.0% receiving pregabalin responded to treatment with respect to the primary endpoint. A higher proportion of PHN patients responded to plaster treatment compared with pregabalin (63.0% vs 37.5%), whereas in the larger DPN group treatments were comparable. Both treatments improved NPSI scores and reduced allodynia severity. Patients administering lidocaine plaster experienced fewer drug-related adverse events (3.9% vs 39.2%) and there were substantially fewer discontinuations due to drug-related adverse events (1.3% vs 20.3%). Conclusion: After 4 weeks, 5% lidocaine medicated plaster treatment was associated with similar levels of analgesia in patients with PHN or DPN but substantially fewer frequent adverse events than pregabalin.

  • 5.
    Baron, Ralf
    et al.
    University Klinikum Schleswig Holstein.
    Mayoral, Victor
    Hospital Llobregat.
    Leijon, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Binder, Andreas
    University Klinikum Schleswig Holstein.
    Steigerwald, Ilona
    Grunenthal GmbH.
    Serpell, Michael
    University of Glasgow.
    5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study2009In: CURRENT MEDICAL RESEARCH AND OPINION, ISSN 0300-7995, Vol. 25, no 7, p. 1663-1676Article in journal (Refereed)
    Abstract [en]

    Objective: To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). Study design and methods: This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of greater than= 2 points or an absolute value of less than= 4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs). Results: Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (cor-responding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin. Conclusion: 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.

  • 6.
    Baron, Ralf
    et al.
    University Klinikum Schleswig Holstein.
    Mayoral, Victor
    Hospital Llobregat.
    Leijon, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Binder, Andreas
    University Klinikum Schleswig Holstein.
    Steigerwald, Ilona
    Grunenthal GmbH.
    Serpell, Michael
    University of Glasgow.
    Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy2009In: CURRENT MEDICAL RESEARCH AND OPINION, ISSN 0300-7995, Vol. 25, no 7, p. 1677-1687Article in journal (Refereed)
    Abstract [en]

    Objective: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). Methods: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patients satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs. Clinical trial registration: EudraCT No. 2006-003132-29. Results: Of 229 patients in the per-protocol set(PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated. Conclusions: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.

  • 7.
    Blystad, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Jan Bertus Marcel
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    SyntheticMRI compared with conventional MRI of the brain in a clinical setting: a pilot study, ESMRMB 2012, Lisbon, Portugal.2012Conference paper (Other academic)
  • 8.
    Blystad, Ida
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Warntjes, Jan Bertus Marcel
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Larsson, Elna-Marie
    Uppsala University, Sweden .
    Synthetic MRI of the brain in a clinical setting2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 10, p. 1158-1163Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Conventional magnetic resonance imaging (MRI) has relatively long scan times for routine examinations, and the signal intensity of the images is related to the specific MR scanner settings. Due to scanner imperfections and automatic optimizations, it is impossible to compare images in terms of absolute image intensity. Synthetic MRI, a method to generate conventional images based on MR quantification, potentially both decreases examination time and enables quantitative measurements.

    PURPOSE:

    To evaluate synthetic MRI of the brain in a clinical setting by assessment of the contrast, the contrast-to-noise ratio (CNR), and the diagnostic quality compared with conventional MR images.

    MATERIAL AND METHODS:

    Twenty-two patients had synthetic imaging added to their clinical MR examination. In each patient, 12 regions of interest were placed in the brain images to measure contrast and CNR. Furthermore, general image quality, probable diagnosis, and lesion conspicuity were investigated.

    RESULTS:

    Synthetic T1-weighted turbo spin echo and T2-weighted turbo spin echo images had higher contrast but also a higher level of noise, resulting in a similar CNR compared with conventional images. Synthetic T2-weighted FLAIR images had lower contrast and a higher level of noise, which led to a lower CNR. Synthetic images were generally assessed to be of inferior image quality, but agreed with the clinical diagnosis to the same extent as the conventional images. Lesion conspicuity was higher in the synthetic T1-weighted images, which also had a better agreement with the clinical diagnoses than the conventional T1-weighted images.

    CONCLUSION:

    Synthetic MR can potentially shorten the MR examination time. Even though the image quality is perceived to be inferior, synthetic images agreed with the clinical diagnosis to the same extent as the conventional images in this study.

  • 9.
    Boivie, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Central pain and the role of quantitative sensory testing (QST) in research and diagnosis2003In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 7, no 4, p. 339-343Conference paper (Other academic)
    Abstract [en]

    [No abstract available]

  • 10.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Epidemiological Studies of Multiple Sclerosis in Sweden with focus on the County of Värmland2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to study the frequency of MS in the suggested high-risk area of Värmland county by investigating the current prevalence and analyzing the development over time; secondly to investigate some aetiological factors – the pattern of industry, both in relation to MS in Värmland and in the whole country, and also to examine the possible relation between the distribution of MS and ALS, as it has previously shown a positive correlation in two studies; finally to analyze the women-to-men ratio of MS in Sweden because of international reports of an increasing ratio.

    Clinical data was collected from hospitals and other health care units in the county of Värmland, to calculate the prevalence ratio. The prevalence was 170.07 per 100,000 population on the prevalence day, 31 December 2002. The incidence rates analysed during ten years was 6.46 per 100,000 personyears (1991-1995) and 6.39 (1996-2000).

    The ecological study used data from the beginning of the 20th century on industries in Värmland and in all Sweden, which were correlated with the two MS prevalence studies (1925-1934 and 2002), and the mortality study on the time period 1952-1990. There was a statistical significant association between large sawmills and the prevalence 1925-1934 (p = 0.022). For all Sweden, wood-pulp factories and papermills correlated significantly with MS mortality 1952-1990 (p = <0.05).

    Collected data from Causes of death Register and from the Total Population Register were used when analysing mortality from ALS and MS. The previously shown correlation between ALS and MS mortality distribution in the Swedish counties was not confirmed in this study. However, the mean MS mortality rate was still highest in the county in Värmland. The mean MS mortality rates for whole Sweden was increased from 1.65 per 100,000 person-years (1952-1992) to 2.04 (1990-2010).

    For analysing sex ratio in MS, data from the Swedish Multiple Sclerosis Register and data from Total Population Register of the Swedish Statistics Office were used. These data was analysed by birth day cohort and by year of onset. The sex ratios in Sweden showed a stable women-to-men ratio.

    These investigations give indication that Värmland is a high-risk region of multiple sclerosis, and particularly the municipality of Säffle.

    We conclude that Värmland is a suitable area for continued epidemiological studies with both an environment and genetic focus.

    List of papers
    1. High prevalence of multiple sclerosis in the Swedish county of Värmland
    Open this publication in new window or tab >>High prevalence of multiple sclerosis in the Swedish county of Värmland
    2009 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 15, no 11, p. 1253-1262Article in journal (Refereed) Published
    Abstract [en]

    Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991—1995, 1996—2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

    Keywords
    epidemiological, risk, aetiological, genetics, environment
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51888 (URN)10.1177/1352458509345909 (DOI)
    Available from: 2009-11-23 Created: 2009-11-23 Last updated: 2017-12-12Bibliographically approved
    2. An ecological study of industry in a high-risk region of multiple sclerosis
    Open this publication in new window or tab >>An ecological study of industry in a high-risk region of multiple sclerosis
    2011 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 311, no 1-2, p. 50-57Article in journal (Refereed) Published
    Abstract [en]

    The county of Varmland, Sweden, has shown a high frequency of multiple sclerosis in several investigations. It has been presented in three studies: a period prevalence study in 1925-1934, a mortality study during 1952-1992 and a prevalence investigation in 2002. The aim of this study was to investigate the pattern of industry in this high-risk area for multiple sclerosis. The three investigations were correlated with industry in 1913 and in the 1950s, all analyzed by the Kruskall-Wallis test. Select industries from wood-pulp, paper and iron/mechanical sectors were tested also in whole Sweden. The Spearman rank correlation was used for these data and forestry data in Varmland. In Varmland, industrial data from 1913 revealed that large sawmills were associated with the period prevalence in 1925-1934 and there was a possible correlation with the prevalence for 2002. Wood-pulp factories showed a possible association with the prevalence 1925-1934 and the mortality 1952-1992. Some industries in the 1950s were correlated with the prevalence 2002. Wood and paper industries in Sweden 1913 showed an association with the MS mortality 1952-1992. In summary, data on MS prevalence in Varmland and mortality both in Varmland and all Sweden from the past 100 years suggest an association with wood-related industries in 1913 and in the 1950s, whereas no consistent association was found for other industries.

    Place, publisher, year, edition, pages
    Elsevier, 2011
    Keywords
    Multiple sclerosis; Prevalence; Mortality; Environmental; Ecological; Pollutions; Industry
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-73732 (URN)10.1016/j.jns.2011.09.005 (DOI)000297893400009 ()
    Available from: 2012-01-12 Created: 2012-01-12 Last updated: 2017-12-08
    3. Mortality Statistics Studies of Multiple Sclerosis and Amyotrophic Lateral Sclerosis in Sweden
    Open this publication in new window or tab >>Mortality Statistics Studies of Multiple Sclerosis and Amyotrophic Lateral Sclerosis in Sweden
    2012 (English)In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 38, no 4, p. 245-249Article in journal (Refereed) Published
    Abstract [en]

    Background: Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic neurologic diseases where distinct explanations of the pathogenesis are lacking. Two large Swedish register studies have rather unexpectedly detected a correlation between MS and ALS.

    The aim of this study was to investigate if an association between ALS and MS could be demonstrated as has been shown earlier.

    Material and methods: Data on mortality from ALS and MS, 1990-2010 were collected from the Swedish national statistics office. In all there were 5,696 deaths due to ALS and 3,941 deaths due to MS. Age- and sex-adjusted mortality rates were calculated.

    Results: There was no correlation between the mortality rates of ALS and MS in the 21 counties of Sweden for the period 1990 to 2010 (Spearman’s rho = - 0.052; p = 0.822; n = 21).

    The national mean mortality rate for ALS throughout the period of 1990 to 2010 was 2.98 per 100 000 person-years (95% CI 2.87 – 3.08). For MS the national mean mortality rate was 2.04 per 100 000 person-years (95% CI 1.95 – 2.12). Both ALS and MS mortality showed significant variation between the counties. Conclusion: This study did not confirm the previously shown association between MS and ALS in Sweden.

    Place, publisher, year, edition, pages
    S. Karger, 2012
    Keywords
    Amyotrophic lateral sclerosis; multiple sclerosis; mortality; correlation, epidemiology, genetics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74175 (URN)10.1159/000338031 (DOI)000305659200008 ()
    Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08Bibliographically approved
    4. Sex ratio of multiple sclerosis in Sweden
    Open this publication in new window or tab >>Sex ratio of multiple sclerosis in Sweden
    2013 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, no 1, p. 46-52Article in journal (Other academic) Published
    Abstract [en]

    Sex ratio of multiple sclerosis has been reported from several areas. The disease is more common in women. In Europe the women-to-men ratio varies from 1.1 to 3.4. Recently a study in Canada has reported a significant increased female-to-male ratio in multiple sclerosis.

    Our objective was to analyse the development of sex ratio in multiple sclerosis in the Swedish population.

    Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset.

    In analyse of sex ratio by year of birth there were 8,834 patients (6,271 women and 2,563 men) born during 1931 to 1985. The mean value of women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p=0.298, n=11). Patients analysed by year of onset was 9,098 (6,452 women and 2,646 men) during the study time period 1946 until 2005. The mean women-to-men ratio was 2.57. There was no significant change of the women-to-men ratio (Spearman’s rho = -0.007, p = 0.983, n = 12).

    Conclusion: In the Swedish patients there was no evidence for an increased womento-men ratio in multiple sclerosis.

    Keywords
    Multiple sclerosis, sex ratio, incidence rate, prevalence proportion, SMSreg
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74176 (URN)10.1177/1352458512446169 (DOI)000313272100009 ()
    Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08Bibliographically approved
  • 11.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Callander, Margarita
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kurtzke, John F
    Department of Neurology, Georgetown University, Washington, DC, USA.
    Landtblom, Anne-Marie
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    High prevalence of multiple sclerosis in the Swedish county of Värmland2009In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 15, no 11, p. 1253-1262Article in journal (Refereed)
    Abstract [en]

    Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991—1995, 1996—2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

  • 12.
    Boström, Inger
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Lauer, Klaus
    Epidemiologist, Greishiem.
    An ecological study of industry in a high-risk region of multiple sclerosis2011In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 311, no 1-2, p. 50-57Article in journal (Refereed)
    Abstract [en]

    The county of Varmland, Sweden, has shown a high frequency of multiple sclerosis in several investigations. It has been presented in three studies: a period prevalence study in 1925-1934, a mortality study during 1952-1992 and a prevalence investigation in 2002. The aim of this study was to investigate the pattern of industry in this high-risk area for multiple sclerosis. The three investigations were correlated with industry in 1913 and in the 1950s, all analyzed by the Kruskall-Wallis test. Select industries from wood-pulp, paper and iron/mechanical sectors were tested also in whole Sweden. The Spearman rank correlation was used for these data and forestry data in Varmland. In Varmland, industrial data from 1913 revealed that large sawmills were associated with the period prevalence in 1925-1934 and there was a possible correlation with the prevalence for 2002. Wood-pulp factories showed a possible association with the prevalence 1925-1934 and the mortality 1952-1992. Some industries in the 1950s were correlated with the prevalence 2002. Wood and paper industries in Sweden 1913 showed an association with the MS mortality 1952-1992. In summary, data on MS prevalence in Varmland and mortality both in Varmland and all Sweden from the past 100 years suggest an association with wood-related industries in 1913 and in the 1950s, whereas no consistent association was found for other industries.

  • 13.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Riise, Trond
    Dept of Public Health and Primary Health Care, University of Bergen, BERGEN, Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mortality Statistics Studies of Multiple Sclerosis and Amyotrophic Lateral Sclerosis in Sweden2012In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 38, no 4, p. 245-249Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic neurologic diseases where distinct explanations of the pathogenesis are lacking. Two large Swedish register studies have rather unexpectedly detected a correlation between MS and ALS.

    The aim of this study was to investigate if an association between ALS and MS could be demonstrated as has been shown earlier.

    Material and methods: Data on mortality from ALS and MS, 1990-2010 were collected from the Swedish national statistics office. In all there were 5,696 deaths due to ALS and 3,941 deaths due to MS. Age- and sex-adjusted mortality rates were calculated.

    Results: There was no correlation between the mortality rates of ALS and MS in the 21 counties of Sweden for the period 1990 to 2010 (Spearman’s rho = - 0.052; p = 0.822; n = 21).

    The national mean mortality rate for ALS throughout the period of 1990 to 2010 was 2.98 per 100 000 person-years (95% CI 2.87 – 3.08). For MS the national mean mortality rate was 2.04 per 100 000 person-years (95% CI 1.95 – 2.12). Both ALS and MS mortality showed significant variation between the counties. Conclusion: This study did not confirm the previously shown association between MS and ALS in Sweden.

  • 14.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Stawiarz, Leszek
    Division of Neurology, Dept of Clinical Neuroscience, Karolinska Institute, STOCKHOLM, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Sex ratio of multiple sclerosis in Sweden2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, no 1, p. 46-52Article in journal (Other academic)
    Abstract [en]

    Sex ratio of multiple sclerosis has been reported from several areas. The disease is more common in women. In Europe the women-to-men ratio varies from 1.1 to 3.4. Recently a study in Canada has reported a significant increased female-to-male ratio in multiple sclerosis.

    Our objective was to analyse the development of sex ratio in multiple sclerosis in the Swedish population.

    Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset.

    In analyse of sex ratio by year of birth there were 8,834 patients (6,271 women and 2,563 men) born during 1931 to 1985. The mean value of women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p=0.298, n=11). Patients analysed by year of onset was 9,098 (6,452 women and 2,646 men) during the study time period 1946 until 2005. The mean women-to-men ratio was 2.57. There was no significant change of the women-to-men ratio (Spearman’s rho = -0.007, p = 0.983, n = 12).

    Conclusion: In the Swedish patients there was no evidence for an increased womento-men ratio in multiple sclerosis.

  • 15.
    Caceres, R
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Edston, E
    Swedish Word Forensic Pathology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Cardiac fibrosis in six SUDEP cases2009In: in EUROPEAN JOURNAL OF NEUROLOGY, vol 16, 2009, Vol. 16, p. 471-471Conference paper (Refereed)
    Abstract [en]

    n/a

  • 16.
    Caceres, R.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Richter, J.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Säfström, Kåge
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Editorial: Application of a vagal nerve stimulator in an epilepsy patient with cardiac pacemaker after post-ictal cardiac arrest2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 120, no 2, p. 139-142Article in journal (Other academic)
    Abstract [en]

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

  • 17.
    Caceres, R
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Richter, J
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Säfström, Kåge
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Letter: Increased need for combinated nervus vagus-stimulators and electronic cardiac devices: aspects on methods and safety2010In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 121, no 4, p. 287-288Article in journal (Other academic)
    Abstract [en]

    n/a

  • 18.
    Callander, Margarita
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Epidemiological and genetic studies of muliple sclerosis with focus on the Swedish county of Värmland2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this study was to perform detailed investigations of a presumed high-risk area, namely the county of Värmland, to see if previous results from our group indicating a high frequency of multiple sclerosis (MS) could be confirmed. We soon identified an aggregation of MS cases in the parish of Lysvik located in the north of Värmland and initiated epidemiological and genetical analyses of the population. We also extended our genetic research to include studies of a possible association between MS immunopathic trait and the MS susceptibility gene HLA-DR(2)15 type, but in another geographic area.

    The onset-adjusted prevalence of MS in Värmland was 170/105 (95% CI: 154-185) in December 2002, which is higher than prevalence previously reported from other Swedish areas. There was a great variation in MS frequency between communities in Värmland. We found a persistently high occurrence of MS in Torsby and Sunne communities. In the community of Årjäng MS frequency had increased substantially since the previous study performed by our group.

    Epidemiological analysis of a cluster of MS cases in Lysvik revealed 27 MS patients, of whom 23 were the descendants of a Finnish family originated from a common ancestor born in Savolaks in Finland in the 16th century and 18 had relatives with MS. Since this cluster was most likely to have a genetic basis (located in an area with a high inbreeding rate) the mode of MS inheritance was investigated. The linkage study using the genome-wide transmission disequilibrium test (TDT) provided several regions of interest, especially on chromosome 14q (14q24-31). The linkage peak on chromosome 17q was also confirmed by this study.

    The frequency of the HLA-DR(2)15 allele was higher in healthy siblings of MS patients without MS immunopathic trait (MSIT) than in siblings with the trait, which provides further support for the hypothesis that MSIT and MS are two independent, albeit, synergistic conditions.

    The prevalence study supports that Värmland County is a high-risk area. Furthermore, the aggregation of MS cases in Lysvik indicates a concentrated risk zone, possibly due to a combination of genetic, environmental and social risk factors. A widely and evenly spread environmental (i.e., infectious) agent together with cultural changes and industrialisation could possibly induce disease in subgroups of genetically more susceptible individuals. The evidence of linkage to chromosome 14 found in this study indicates that further genetic research is required.

    List of papers
    1. A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Värmland
    Open this publication in new window or tab >>A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Värmland
    2004 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, no 1, p. 14-22Article in journal (Refereed) Published
    Abstract [en]

    Objectives – When surveying the county of Värmland in Sweden in order to determine the prevalence of multiple sclerosis (MS), we observed an aggregation of MS cases originating from the parish of Lysvik in the local region called Fryksdalen. Our intention was to analyse this cluster thoroughly, confirming the MS diagnosis and seeing if a hereditary or environmental background was plausible.

    Methods – The medical files were studied and the cases were classified by a neurologist according to Poser's criteria. Hereditary factors were analysed.

    Results – Sixteen living cases of MS were found, either living in the parish (n = 6) or born or raised there and had later moved to another place (n = 10). All patients had clinically definite MS. Eleven patients had relatives with MS, all of these being descendants of the Suhoinen family. Another two cases were Suhoinen descendants who did not have relatives with MS. Other common ancestors were also identified. Two cases were adopted. Eleven deceased MS patients from Lysvik were found, 10 of them had Suhoinen ancestry.

    Conclusion – We report a cluster of MS cases with a common ancestry indicating heredity for MS in 85% of the cases. Lysvik is a parish where Finnish immigration was pronounced in the 17th century and there has been inbreeding to a certain extent through marriage between cousins. Thus, we interpret this aggregation as possibly being genetically based, and neurogenetic studies are now being performed. However, as two of the cases were adopted environmental factors must also be considered.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-28710 (URN)10.1111/j.1600-0404.2004.00266.x (DOI)13879 (Local ID)13879 (Archive number)13879 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    2. Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q
    Open this publication in new window or tab >>Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q
    Show others...
    2003 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 4, no 8, p. 559-563Article in journal (Refereed) Published
    Abstract [en]

    Epidemiological studies show that susceptibility to multiple sclerosis (MS) has a strong genetic component, but apart from the HLA gene complex, additional genetic factors have proven difficult to map in the general population. Thus, localized populations, where MS patients are assumed to be more closely related, may offer a better opportunity to identify shared chromosomal regions. We have performed a genome-wide scan with 834 microsatellite markers in a data set consisting of 54 MS patients and 114 healthy family members. A group of families from a small village were possible to track back to common ancestors living in the 17th century. We used single marker- and haplotype-based transmission disequilibrium test (TDT) analysis and nonparametric linkage analysis to analyze genotyping data. Regions on chromosomes 2q23–31, 6p24–21, 6q25–27, 14q24–32, 16p13–12 and 17q12–24 were found to be in transmission disequilibrium with MS. Strong transmission disequilibrium was detected in 14q24–32, where several dimarker haplotypes were in transmission disequilibrium in affected individuals. Several regions showed modest evidence for linkage, but linkage and TDT were both clearly positive only for 17q12–24. All patients and controls were also typed for HLA class II genes; however, no evidence for a gene–gene interaction was observed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27719 (URN)10.1038/sj.gene.6364024 (DOI)12457 (Local ID)12457 (Archive number)12457 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis
    Open this publication in new window or tab >>Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis
    Show others...
    2007 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, no 4, p. 441-445Article in journal (Refereed) Published
    Abstract [en]

    We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-40847 (URN)10.1177/1352458506070264 (DOI)54299 (Local ID)54299 (Archive number)54299 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
    4. High prevalence of multiple sclerosis in the Swedish county of Värmland
    Open this publication in new window or tab >>High prevalence of multiple sclerosis in the Swedish county of Värmland
    2009 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 15, no 11, p. 1253-1262Article in journal (Refereed) Published
    Abstract [en]

    Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991—1995, 1996—2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

    Keywords
    epidemiological, risk, aetiological, genetics, environment
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51888 (URN)10.1177/1352458509345909 (DOI)
    Available from: 2009-11-23 Created: 2009-11-23 Last updated: 2017-12-12Bibliographically approved
  • 19.
    Dahlqvist Leinhard, Olof
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Jaworski, J,
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Aalto, Anne
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Grönkvist, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Tisell, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Is Increased normal White Matter Glutamate Concentrations a Precursor of Gliosis and Disease Progression in Multiple Sclerosis?2011In: Internationell Society for Magnetic Resonance in Medicin, 2011, 2011, p. 4089-4089Conference paper (Refereed)
  • 20.
    Danielsson, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Gati, Istvan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Lindvall, B
    University Hospital, Neurol Clin, Orebro.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    CLASSIFICATION AND VALUE OF EXTENDED PATHOLOGICAL WORK UP OF 99 CONSECUTIVE PATIENTS WITH MORPHOLOGICAL FINDINGS OF INFLAMMATORY MYOPATHY in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 49-492011In: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2011, Vol. 18, no SI, p. 49-49Conference paper (Refereed)
    Abstract [en]

    n/a

  • 21.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation2012In: IEEE Engineering in Medicine and Biology Society (EMBC), 2012, IEEE , 2012, p. 6438-6441Conference paper (Refereed)
    Abstract [en]

    Microdialysis of the basal ganglia was used in parallel to deep brain stimulation (DBS) for patients with Parkinson’s disease. The aim of this study was to patientspecifically simulate and visualize the maximum tissue volume of influence (TVImax) for each microdialysis catheter and the electric field generated around each DBS electrode. The finite element method (FEM) was used for the simulations. The method allowed mapping of the anatomical origin of the microdialysis data and the electric stimulation for each patient. It  was seen that the sampling and stimulation targets differed among the patients, and the results will therefore be used in the future interpretation of the biochemical data.

  • 22.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis2011In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 49, no 12, p. 1459-1469Article in journal (Refereed)
    Abstract [en]

    Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.

  • 23.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Microdialysis as a Tool in Studies of L-Dopa and Metabolites in Malignant Melanoma and Parkinson’s Disease1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A model with human melanoma xenografts transplanted to athymic mice has been adopted for in vivo studies of 5-S-cysteinyldopa (an intermediate pigment metabolite), glutathione, and cysteine. L-Dopa is an intermediate metabolite in pigment formation and is also important in the treatment of Parkinson's disease, and therefore 1 have also studied the pharmacokinetics of this compound.

    We were first to describe in vivo microdialysis in melanoma tissue and showed that dialysis membranes of cuprophane or polyamide are suitable for studies of interstitial 5-S-cysteinyldopa and selected thiols. Analytical procedures were also improved for quantitation of 5-S-cysteinyldopa, L-dopa, glutathione, cysteine, and N-acetylcysteine (NAC). In the melanoma xenografts the interstitial concentration of 5-S-cysteinyldopa reflected the high intracellular production of this intermediate metabolite. For in vivo manipulation of glutathione in the melanoma tissue we gave intraperitoneal injection of buthionine sulphoximine to the animals and thus reduced the glutathione concentrations substantially. We showed that restitution of glutathione in melanoma tissue occurs spontaneously and is not much improved by treatment with the cysteine deliverers NAC and L-2-oxothiazolidine-4-carboxylate (OTC). 5-S-Cysteinyldopa was not substantially affected by great variations in glutathione concentrations. Transport of NAC from intraperitoneal injection to melanoma tissue occurred rapidly and deacetylation to cysteine in vivo could be detected soon after NAC injection. In vivo formation of cysteine was slower from OTC than from NAC.

    Pharmacokinetic studies of L-dopa in human subjects indicated a slight to moderate protein binding. Plasma free L-dopa had similar elimination T½ as interstitial L-dopa, but in some cases the elimination of total L-dopa was slower. Difficulties in intestinal absorption of L-dopa were revealed by microdialysis in blood and subcutaneous tissue. Studies showed that this was due to delayed emptying of the stomach. L-Dopa intake increased 5-S-cysteinyldopa concentrations in blood within 30 min in patients with Parkinson's disease and a history of melanoma. No melanoma activation occurred during long-term treatment with L-dopa.

    Microdialysis is thus a safe and easily applied method for in vivo studies of both pigment metabolites from human melanoma tissue transplanted to nude mice and for pharmacokinetic studies of L-dopa.

    List of papers
    1. Microdialysis of 5-S-cysteinyldopa from interstitial fluid in cutaneous human melanoma transplanted to athymic mice
    Open this publication in new window or tab >>Microdialysis of 5-S-cysteinyldopa from interstitial fluid in cutaneous human melanoma transplanted to athymic mice
    Show others...
    1991 (English)In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, p. 23-32Article in journal (Refereed) Published
    Abstract [en]

    Microdialysis was investigated as a tool for the determination of the extracellular concentration of the pigment metabolite 5-S-cysteinyldopa in human melanoma transplanted to athymic mice. Histology of the tumour with the microdialysis probes in situ showed no tissue damage. With probes equipped with polycarbonate membranes (20 kD) extraction (relative recovery) was approximately 50% at pH 4.0 and flow rates of 1 microliter/min, but at pH 7.0 recoveries were markedly lower, particularly from serum. In a first series of human melanomas transplanted to athymic mice low concentrations of 5-S-cysteinyldopa were detected in only two out of ten dialysates and were not detected in the other eight. Utilizing devices constructed for comparison of membrane characteristics in vitro we found about 4-fold higher recoveries with cuprophane and polyamide membranes than with polycarbonate membranes. Therefore newly constructed microdialysis probes (CMA/11) with cuprophane membranes were tested in vitro and gave recoveries of 38-48% from Ringer-Acetate solutions and 22-31% from serum, and the pH effects were low. When these probes were utilized in a second series of melanomas transplanted to athymic mice, 5-S-cysteinyldopa could easily be quantified in 10/10 experiments. A steady-state level of the dialysate 5-S-cysteinyldopa concentration was reached after 45 min.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13524 (URN)
    Available from: 1999-05-21 Created: 1999-05-21
    2. A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.
    Open this publication in new window or tab >>A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.
    1991 (English)In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, p. 33-42Article in journal (Refereed) Published
    Abstract [en]

    A high-performance liquid chromatographic method with fluorometric detection is described which is suitable for determination of glutathione in small samples. Reduced glutathione (GSH) and total glutathione obtained as GSH after reduction with glutathione reductase is derivatized with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) and subjected to chromatography. The detection limit for the GSH-DACM derivative was 5-10 fmol/injection, and analytical recovery was quantitative. The method is suitable for determination of both reduced and total glutathione in samples from microdialysis of melanoma tumours, and cysteine can be quantified in the same chromatogram. Application is shown also for glutathione determinations in cultured melanoma cells, melanoma homogenates and plasma.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13525 (URN)
    Available from: 1999-05-21 Created: 1999-05-21 Last updated: 2018-01-12
    3. Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants
    Open this publication in new window or tab >>Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants
    1997 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 7, no 4, p. 322.-328Article in journal (Refereed) Published
    Abstract [en]

    Using microdialysis of human melanoma transplants in athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-S-cysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after either N-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-S-cysteinyldopa remained unaltered after both the NAC and the OTC injections.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13526 (URN)
    Available from: 1999-05-21 Created: 1999-05-21 Last updated: 2018-01-12Bibliographically approved
    4. Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice
    Open this publication in new window or tab >>Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice
    2000 (English)In: Cancer chemotherapy and pharmacology, ISSN 0344-5704, Vol. 45, no 3, p. 192-198Article in journal (Refereed) Published
    Abstract [en]

    Purpose: Glutathione is an important cellular compound which affects detoxification of electrophiles and may have direct or indirect effects on pigment formation. It is therefore of importance to study interstitial concentrations in melanoma tissue while decreasing its formation with an enzyme inhibitor and increasing its amount with cysteine deliverers. Method: Glutathione formation was inhibited by intraperitoneal (i.p.) injection of BSO. N-Acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) were then given i.p. to subgroups of the animals. Intratumoral microdialysis was performed during BSO treatment, during BSO treatment combined with NAC or OTC and after discontinuation of BSO but ongoing NAC or OTC treatment. Results: Glutathione formation was inhibited during BSO treatment. The dialysate concentrations of both glutathione and cysteine decreased during concomitant treatment with BSO and NAC or OTC. Recovery of the amounts of the two compounds was seen in both groups after discontinuation of BSO treatment. In the NAC group we also observed an acute increase in dialysate concentrations of cysteine after NAC injection. The 5-S-cysteinyldopa concentrations were unaffected by variations in glutathione and cysteine concentrations. Conclusions: 5-S-Cysteinyldopa in melanoma is not formed from glutathione in vivo to any appreciable extent. The intracellular amount of cysteine is probably not a limiting factor for cysteinyldopa formation. It seems that both NAC and OTC can be used as cysteine deliverers to melanoma cells in vivo to produce recovery of glutathione levels after synthesis inhibition by BSO treatment.

    Keywords
    N-Acetylcysteine, Athymic mice, Buthionine 4-sulphoximine, 5-S-Cysteinyldopa, Microdialysis, Glutathione, l-2-Oxothiazolidine-4-carboxylate
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13527 (URN)10.1007/s002800050029 (DOI)
    Available from: 1999-05-21 Created: 1999-05-21 Last updated: 2018-01-12
    5. Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis
    Open this publication in new window or tab >>Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis
    Show others...
    1999 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 45, no 10, p. 1813-1820Article in journal (Refereed) Published
    Abstract [en]

    Background: Intravenous and subcutaneous microdialysis was performedto compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine(L-dopa) in blood and tissue in healthy subjects and in patientswith Parkinson disease.

    Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide),and the microdialysis was continued for another 210 min. Bloodsamples were obtained at 30-min intervals.

    Results: The serum samples gave a significantly higher meanarea under the curve (AUC; 491 ± 139 µmol ·min/L) than that for intravenous dialysates (235 ± 55.3µmol · min/L), suggesting a protein binding of50%. The L-dopa concentrations from the subcutaneous dialysatesmatched those from the intravenous dialysates, indicating rapiddistribution of L-dopa to the tissues.

    Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13528 (URN)
    Available from: 1999-05-21 Created: 1999-05-21 Last updated: 2018-01-12Bibliographically approved
    6. L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma
    Open this publication in new window or tab >>L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma
    Show others...
    1999 (English)In: Acta neurologica Scandinavica, ISSN 0001-6314, Vol. 100, no 4, p. 231-237Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients.

    METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time.

    RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy.

    CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13529 (URN)10.1111/j.1600-0404.1999.tb00386.x (DOI)
    Available from: 1999-05-21 Created: 1999-05-21 Last updated: 2018-01-12
  • 24.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Granerus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Hannestad, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Ljungdahl, Å.
    Department of Neurology, Huddinge Hospital, Stockholm.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma1999In: Acta neurologica Scandinavica, ISSN 0001-6314, Vol. 100, no 4, p. 231-237Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients.

    METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time.

    RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy.

    CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.

  • 25.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice2000In: Cancer chemotherapy and pharmacology, ISSN 0344-5704, Vol. 45, no 3, p. 192-198Article in journal (Refereed)
    Abstract [en]

    Purpose: Glutathione is an important cellular compound which affects detoxification of electrophiles and may have direct or indirect effects on pigment formation. It is therefore of importance to study interstitial concentrations in melanoma tissue while decreasing its formation with an enzyme inhibitor and increasing its amount with cysteine deliverers. Method: Glutathione formation was inhibited by intraperitoneal (i.p.) injection of BSO. N-Acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) were then given i.p. to subgroups of the animals. Intratumoral microdialysis was performed during BSO treatment, during BSO treatment combined with NAC or OTC and after discontinuation of BSO but ongoing NAC or OTC treatment. Results: Glutathione formation was inhibited during BSO treatment. The dialysate concentrations of both glutathione and cysteine decreased during concomitant treatment with BSO and NAC or OTC. Recovery of the amounts of the two compounds was seen in both groups after discontinuation of BSO treatment. In the NAC group we also observed an acute increase in dialysate concentrations of cysteine after NAC injection. The 5-S-cysteinyldopa concentrations were unaffected by variations in glutathione and cysteine concentrations. Conclusions: 5-S-Cysteinyldopa in melanoma is not formed from glutathione in vivo to any appreciable extent. The intracellular amount of cysteine is probably not a limiting factor for cysteinyldopa formation. It seems that both NAC and OTC can be used as cysteine deliverers to melanoma cells in vivo to produce recovery of glutathione levels after synthesis inhibition by BSO treatment.

  • 26.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants1997In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 7, no 4, p. 322.-328Article in journal (Refereed)
    Abstract [en]

    Using microdialysis of human melanoma transplants in athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-S-cysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after either N-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-S-cysteinyldopa remained unaltered after both the NAC and the OTC injections.

  • 27.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Norlander, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis1999In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 45, no 10, p. 1813-1820Article in journal (Refereed)
    Abstract [en]

    Background: Intravenous and subcutaneous microdialysis was performedto compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine(L-dopa) in blood and tissue in healthy subjects and in patientswith Parkinson disease.

    Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide),and the microdialysis was continued for another 210 min. Bloodsamples were obtained at 30-min intervals.

    Results: The serum samples gave a significantly higher meanarea under the curve (AUC; 491 ± 139 µmol ·min/L) than that for intravenous dialysates (235 ± 55.3µmol · min/L), suggesting a protein binding of50%. The L-dopa concentrations from the subcutaneous dialysatesmatched those from the intravenous dialysates, indicating rapiddistribution of L-dopa to the tissues.

    Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.

  • 28.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Smeds, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.1991In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, p. 33-42Article in journal (Refereed)
    Abstract [en]

    A high-performance liquid chromatographic method with fluorometric detection is described which is suitable for determination of glutathione in small samples. Reduced glutathione (GSH) and total glutathione obtained as GSH after reduction with glutathione reductase is derivatized with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) and subjected to chromatography. The detection limit for the GSH-DACM derivative was 5-10 fmol/injection, and analytical recovery was quantitative. The method is suitable for determination of both reduced and total glutathione in samples from microdialysis of melanoma tumours, and cysteine can be quantified in the same chromatogram. Application is shown also for glutathione determinations in cultured melanoma cells, melanoma homogenates and plasma.

  • 29.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Nezirevic, Dzeneta
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Letter: Untitled2013In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 212, no 2, p. 363-363Article in journal (Refereed)
    Abstract [en]

    n/a

  • 30.
    Edström, Måns
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Press, Rayomand
    Karolinska Hospital.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Th1/Th2/Th17 and Treg related transcription factors and cytokines in multiple sclerosis2008In: JOURNAL OF NEUROIMMUNOLOGY, 2008, Vol. 203, no 2, p. 131-132Conference paper (Refereed)
  • 31.
    Edström, Måns
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Press, R
    Huddinge University Hospital.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood2011In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, no 1, p. 57-66Article in journal (Refereed)
    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.

  • 32.
    Ekdahl, Kristina N
    et al.
    Kalmar University.
    Blomberg, Carolina
    Kalmar University.
    Henningsson, Anna J
    Ryhov County Hospital.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Hakansson, Irene
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology .
    Sandholm, Kerstin
    Kalmar University.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Systemic and intrathecal complement activation in multiple sclerosis and Guillan-Barre syndrome2009In: in MOLECULAR IMMUNOLOGY, vol 46., issue 14, 2009, Vol. 46, no 14, p. 2848-2848Conference paper (Refereed)
    Abstract [en]

    n/a

  • 33.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Flensner, Gullvi
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. University West, Trollhättan, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Thalamo-striato-cortical determinants to fatigue in multiple sclerosis2013In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 3, no 6, p. 715-728Article in journal (Refereed)
    Abstract [en]

    Background

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

    Methods

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

    Conclusions

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

  • 34.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Karlsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Crone, Marie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, The Institute of Technology.
    Ragnehed, Mattias
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Antepohl, Wolfram
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Rehabilitation Medicine UHL.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Clinical fMRI of language function in aphasic patients: Reading paradigm successful, while word generation paradigm fails2010In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 51, no 6, p. 679-686Article in journal (Refereed)
    Abstract [en]

    Background: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients ability to perform the required cognitive tasks during fMRI must be taken into account. Purpose: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. Material and Methods: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. Results: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. Conclusion: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

  • 35.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Abnormal thalamic activation and complex working memory in Kleine-Levin Syndrome2013Conference paper (Other academic)
  • 36.
    Engström, Maria
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Karlsson, Thomas
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Craig, A. D. (Bud)
    Atkinson Research Laboratory, Barrow Neurological Institute, Phoenix, AZ.
    Mental energy – an fMRI investigation of the anterior insular and the anterior cingulate network2012Conference paper (Other academic)
  • 37.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology.
    Craig, A. D. (Bud)
    Atkinson Research Laboratory, Barrow Neurological Institute, Phoenix, AZ.
    Mental energy: graded co-activation of the anterior insular and anterior cingulate cortices during challenging working memory,  visual perception and motor speed tasks.Manuscript (preprint) (Other academic)
  • 38.
    Engström, Maria
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Karlsson, Thomas
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Brain and effort: brain activation and effort-related working memory in healthy participants and patients with working memory deficits2013In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 7, no 140, p. 1-17Article in journal (Refereed)
    Abstract [en]

    Despite the interest in the neuroimaging of working memory, little is still known about the neurobiology of complex working memory in tasks that require simultaneous manipulation and storage of information. In addition to the central executive network, we assumed that the recently described salience network [involving the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC)] might be of particular importance to working memory tasks that require complex, effortful processing.

    Method: Healthy participants (n = 26) and participants suffering from working memory problems related to the Kleine–Levin syndrome (KLS) (a specific form of periodic idiopathic hypersomnia; n = 18) participated in the study. Participants were further divided into a high- and low-capacity group, according to performance on a working memory task (listening span). In a functional magnetic resonance imaging (fMRI) study, participants were administered the reading span complex working memory task tapping cognitive effort.

    Principal findings: The fMRI-derived blood oxygen level dependent (BOLD) signal was modulated by (1) effort in both the central executive and the salience network and (2) capacity in the salience network in that high performers evidenced a weaker BOLD signal than low performers. In the salience network there was a dichotomy between the left and the right hemisphere; the right hemisphere elicited a steeper increase of the BOLD signal as a function of increasing effort. There was also a stronger functional connectivity within the central executive network because of increased task difficulty.

    Conclusion: The ability to allocate cognitive effort in complex working memory is contingent upon focused resources in the executive and in particular the salience network. Individual capacity during the complex working memory task is related to activity in the salience (but not the executive) network so that high-capacity participants evidence a lower signal and possibly hence a larger dynamic response.

  • 39.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Pihlsgård, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Axelsson Söderfeldt, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Functional Magnetic Resonance Imaging of Hippocampal Activation During Silent Mantra Meditation2010In: Journal of Alternative and Complementary Medicine, ISSN 1075-5535, E-ISSN 1557-7708, Vol. 16, no 12, p. 1253-1258Article in journal (Refereed)
    Abstract [en]

    Objectives: The objective of the present study was to investigate whether moderately experienced meditators activate hippocampus and the prefrontal cortex during silent mantra meditation, as has been observed in earlier studies on subjects with several years of practice. Methods: Subjects with less than 2 years of meditation practice according to the Kundalini yoga or Acem tradition were examined by functional magnetic resonance imaging during silent mantra meditation, using an on-off block design. Whole-brain as well as region-of-interest analyses were performed. Results: The most significant activation was found in the bilateral hippocampus/parahippocampal formations. Other areas with significant activation were the bilateral middle cingulate cortex and the bilateral precentral cortex. No activation in the anterior cingulate cortex was found, and only small activation clusters were observed in the prefrontal cortex. Conclusions: In conclusion, the main finding in this study was the significant activation in the hippocampi, which also has been correlated with meditation in several previous studies on very experienced meditators. We propose that the hippocampus is activated already after moderate meditation practice and also during different modes of meditation, including relaxation. The role of hippocampal activity during meditation should be further clarified in future studies, especially by investigating whether the meditation-correlated hippocampal activity is related to memory consolidation.

  • 40.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Vigren, Patrick
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Working Memory in 8 Kleine-Levin Syndrome Patients: An fMRI Study2009In: SLEEP, ISSN 0161-8105, Vol. 32, no 5, p. 681-688Article in journal (Refereed)
    Abstract [en]

    Study Objectives: The objectives of this study were to investigate possible neuropathology behind the Kleine-Levin Syndrome (KLS), a severe form of hypersomnia with onset during adolescence.

    Design: Functional magnetic resonance imaging (fMRI) applying a verbal working memory task was used in conjunction with a paper-and-pencil version of the task. Participants: Eight patients with KLS and 12 healthy volunteers participated in the study.

    Results: The results revealed a pattern of increased thalamic activity and reduced frontal activity (involving the anterior cingulate and adjacent prefrontal cortex) while performing a reading span task.

    Discussion: This finding may explain the clinical symptoms observed in KLS, in that the thalamus is known to be involved in the control of sleep. Given the increasing access to fMRI, this investigation may aid clinicians in the diagnosis of patients suffering from severe forms of hypersomnia.

  • 41.
    Escobar Kvitting, John-Peder
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Engvall, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Broqvist, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    FranzÉn, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ohlsson, Ulf
    Department of Medicine Oskarshamns Hospital.
    Nielsen, Niels Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Recurrence of myxoma in the left ventricle with concurrent cerebral fusiform aneurysms after previous atrial myxoma surgery2008In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 135, no 5, p. 1172-1173Article in journal (Other academic)
  • 42.
    Fall, Per-Arne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Hansson, Gunilla
    Lindvall, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences.
    Granérus, Ann-Kathrine.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Age standardised incidence and prevalence of Parkinson´s disease in a Swedish community1996In: Journal of Clinical Epidemiology, ISSN 0895-4356, Vol. 49, no 6, p. 637-641Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low -dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.

  • 43.
    Flensner, Gullvi
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Soderhamn, Olle
    University West.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Sensitivity to heat in MS patients: a factor strongly influencing symptomology - an explorative survey2011In: BMC NEUROLOGY, ISSN 1471-2377, Vol. 11, no 27Article in journal (Refereed)
    Abstract [en]

    Background: Many individuals diagnosed with Multiple Sclerosis (MS) are sensitive to increased body temperature, which has been recognized as correlating with the symptom of fatigue. The need to explore this association has been highlighted. The aim of this study was to investigate the occurrence of heat sensitivity and its relations to disease course, disability, common MS-related symptoms and ongoing immunosuppressive treatments among individuals 65 years of age or younger diagnosed with MS. Methods: A cross-sectional designed survey was undertaken. A questionnaire was sent to MS-patients with an Expanded Disability Status Score (EDSS) in the interval of 0-6.5 and who were between 20 and 65 years of age, living in an eastern region of Sweden (n = 334). Besides occurrence of heat sensitivity (Yes/No) and corresponding questions, the Fatigue Severity Scale (FSS), the MS-related symptom checklist and the Perceived Deficit Questionnaire (PDQ) were included. Data were analysed in relation to data level using Chi-square, Mann Whitney U-test, and Students t-test. Pearsons and Spearmans correlations were calculated. In the logistic regression analyses (enter) dichotomized MS-symptoms were used as dependent variables, and EDSS, disease-course, time since onset, heat-sensitivity, age and sex (female/male) were independent variables. In the linear regression analyses, enter, mean FSS and summarized PDQ were entered as dependent variables and EDSS, disease-course, time since onset, heat sensitivity, age and sex (female/male) were independent variables. Results: Of the responding patients (n = 256), 58% reported heat sensitivity. The regression analyses revealed heat sensitivity as a significant factor relating not only to fatigue (p andlt; 0.001), but also to several other common MS symptoms such as pain (p andlt; 0.001), concentration difficulties (p andlt; 0.001), and urination urgency (p = 0.009). Conclusions: Heat sensitivity in MS patients is a key symptom that is highly correlated with disabling symptoms such as fatigue, pain, concentration difficulty and urination urgency.

  • 44.
    Flensner, Gullvi
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Soderhamn, Olle
    University of West, Sweden .
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Work capacity and health-related quality of life among individuals with multiple sclerosis reduced by fatigue: a cross-sectional study2013In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 13Article in journal (Refereed)
    Abstract [en]

    Background: Among individuals diagnosed with the chronic neurologic disease, multiple sclerosis (MS), a majority suffers from fatigue, which strongly influences their every-day-life. The aim of this study was to investigate work capacity and health-related quality of life (HRQoL) in a group of MS patients and also to investigate if work capacity and HRQoL could be predicted by background factors, fatigue, heat sensitivity, cognitive dysfunction, emotional distress or degree of disability. less thanbrgreater than less thanbrgreater thanMethods: A descriptive, cross-sectional, designed survey was undertaken A questionnaire was sent to 323 individuals diagnosed with MS, aged between 20 and 65 years, with physical disability on the expanded disability status score (EDSS) in the interval 0 andgt;= EDSS andlt;= 6.5, living in sterg"tland county in eastern Sweden. Questions on background factors, occupation and work, together with the health-related quality of life short form instrument (SF-36), the fatigue severity scale (FSS), the perceived deficit questionnaire (PDQ) and the hospital anxiety depression scale (HAD) were posed. Associations between variables were analyzed using Pearsons and Spearmans correlations. Differences between groups were tested using the Chi-square test, the Mann Whitney U-test, and the Students t-test. Predictive factors were analyzed using multiple linear and multiple logistic regression analysis. less thanbrgreater than less thanbrgreater thanResults: Of those who completed the questionnaire (n = 257, 79.6%), 59.8% were working. Work capacity was found significantly more among men (p andlt; 0.005), those with a higher level of education (p andlt; 0.001), those reporting less fatigue (p andlt; 0.001), and those having no heat sensitivity (p = 0.004). For work capacity, significant predictors were low physical disability (EDSS), low fatigue, higher level of education, male sex and lower age. Those with work capacity showed significantly higher HRQoL than those who had no work capacity (p andlt; 0.001). Levels of fatigue, cognition and emotional distress were found to be major contributing factors for HRQoL. less thanbrgreater than less thanbrgreater thanConclusions: Work capacity and HRQoL among individuals diagnosed with MS are highly influenced by fatigue which can be considered as a key symptom. Work capacity was influenced by heat-sensitivity, cognitive difficulties and emotional distress and significant predictive factors besides fatigue, were physical disability (EDSS), age, sex, and level of education. Remaining at work also gives a better HRQoL.

  • 45.
    Gati, Istvan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Danielsson, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Betmark, T.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Culturing of diagnostic muscle biopsies as spheroid-like structures: a pilot study of morphology and viability2010In: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 32, no 6, p. 650-655Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to establish three-dimensional cultures originating from muscle biopsies and evaluate the viability and morphology. Method: Muscle biopsies from patients with suspected neuromuscular disorders were obtained and established as primary muscle tissue cultures. Tissue pieces, 1-2 mm of diameters, were placed in culture medium and subjected to sporadic stirring to prevent attachment and outgrowth as monolayer cells. Morphology and ability to attach to the surface were investigated by light microscopy. Viability was evaluated by Tc-99m-tetrofosmin uptake. After 1 month, histology was evaluated by light microscopy and immunocytochemistry. The findings of a healthy muscle and a dystrophic muscle were compared. Results: Initially, the tissue pieces were unshaped but formed spheroid-like structures during the culture period. For dystrophic muscle, attachment capacity to the surface was initially potent and decreased during the culture period, whereas control muscle showed weak attachment from the start that increased during the culture period. The uptake of Tc-99m-tetrofosmin increased in control muscle, while it decreased in dystrophic muscle, during the culture period. The histological investigation demonstrated larger destruction of myofiber, weaker satellite cell activation and reduced myofiber regeneration in the dystrophic muscle as compared to the control muscle. Conclusion: The cellular components of the muscle tissue can survive and proliferate as spheroid-like primary cultures. The cellular composition resembles the in vivo condition, which allows studies of degeneration of the original fibers, and activation and proliferation of the satellite cells. The culture system may provide better understanding of the degeneration and regeneration processes in different muscle disorders and allow investigations of pharmacological interventions.

  • 46.
    Gati, Istvan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Danielsson, Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Häggqvist, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Fredriksson, Bengt-Arne
    Linköping University, Department of Clinical and Experimental Medicine.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Letter: Bent Spine Syndrome: A Phenotype of Dysferlinopathy or a Symptomatic DYSF Gene Mutation Carrier2012In: European Neurology, ISSN 0014-3022, E-ISSN 1421-9913, Vol. 67, no 5, p. 300-302Article in journal (Other academic)
    Abstract [en]

    n/a

  • 47.
    Gati, Istvan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Danielsson, Olof
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindehammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurophysiology UHL.
    Lindvall, B
    University Örebro, Örebro, Sweden .
    Häggqvist, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Fredriksson, Bengt-Arne
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    SENSORY ATAXIC NEUROPATHY WITH DYSARTHRIA/DYSPHAGIA AND OPHTHALMOPLEGIA (SANDO) - CASE HISTORIES in EUROPEAN JOURNAL OF NEUROLOGY, vol 18, issue SI, pp 282-2822011In: EUROPEAN JOURNAL OF NEUROLOGY, Wiley-Blackwell , 2011, Vol. 18, no SI, p. 282-282Conference paper (Refereed)
    Abstract [en]

    n/a

  • 48.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Epilepsy in young adulthood: medical, psychosocial and functional aspects2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to describe the medical, cognitive and psychosocial consequences of epilepsy in young adulthood. Four studies were carried out with this patient group. The first two papers were based on a follow-up study regarding young adults with epilepsy that investigated medical and psychosocial aspects and compared the present results with those five years earlier. We then conducted focus group interviews with young adults with epilepsy and subjective cognitive decline to assess the deeper meaning of living with epilepsy accompanied by cognitive difficulties. In the fourth study we studied cognitive dysfunction further, choosing the language function in young adults with epilepsy. We firstly examined whether language impairments were associated to functional brain alterations and secondly related the language performance to demographics, clinical data, Quality of Life (QoL) and self-esteem.

    The five-year follow up of 97 young adults with uncomplicated epilepsy revealed no improvement regarding seizure frequency or side effects from anti-epileptic drugs (AEDs) over time, even though many new-generation AEDs had been established during this period. During the study period 21% had recovered from epilepsy, Seizure frequency among those who still had epilepsy had not improved, and 42% had experienced seizures during the past year. New-generation anti-epileptic drugs (AEDs) had been introduced to PWE, especially to women. There is still need for new and more effective treatment options for this group in the future. It is essential to find alternative approaches to develop better treatment options for this group in the future. However QoL was normal compared to the general population, indicating that new options regarding treatment can have made an impact. Lower QoL was correlated to high seizure frequency and to cognitive side effects. Self-esteem and Sence of Coherence were impaired compared to the situation at adolescence. Self-esteem was correlated to seizure frequency and to side-effects of antiepileptic drugs. Sence of Coherence was not correlated to epilepsy-related factors in the same way as QoL, but mirrored the phenomenon of epilepsy.

    The qualitative study showed that the consequences of epilepsy are not only restricted to the consequences of seizures, but also concerns many other aspects of life. The interviews revealed four themes: “affecting the whole person“, “influencing daily life”, ”affecting relations” and ”meeting ignorance in society”. Another important factor was language function; when one loses some language ability, this gives a feeling of losing one’s capability.

    The fourth study examined language by neuropsychological methods and correlated this function to brain activation measured by fMRI. Language functions measured in verbal fluency and abstract language comprehension were impaired in participants with both generalized epilepsy and epilepsy of focal onset. Age at onset of epilepsy and education are the most important factors correlating to language function. An additional factor that impacts abstract language comprehension is the frequency of convulsive seizures, while use of topiramate /zonisamide affect verbal fluency negatively. QoL was not correlated to language impairments, but for patients with focal onset seizures there was a correlation between self-esteem and abstract language comprehension. The fMRI investigation revealed altered activity during language tasks in participants with epilepsy compared to 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 anterior ventral insulae, indicating a compensational functional reorganization. In generalized epilepsy, the functional language network showed an imbalance, as this group expressed an inadequate suppression of activation in the anterior temporal lobe during semantic processing. Subtle language impairment can, even if it does not occur in everyday dialogue, be of importance and have consequences for the person affected. The negative consequences of language decline must be addressed in people with epilepsy of different etiology. Young adults with epilepsy are still substantially affected by the condition. The consequences are not only restricted to the seizures, but concern many aspects of life and there is a great need for new treatment options for this group in the future.

    List of papers
    1. Medical outcome in epilepsy patients of young adulthood-A 5-year follow-up study
    Open this publication in new window or tab >>Medical outcome in epilepsy patients of young adulthood-A 5-year follow-up study
    2009 (English)In: SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, ISSN 1059-1311 , Vol. 18, no 4, p. 293-297Article in journal (Refereed) Published
    Abstract [en]

    The appearance of new anti-epileptic drugs (AED) during the last decade has provided neurologists and their patients with a greater choice, but the proof for their superiority over traditional AEDs is sparse, especially their use in adolescence and Young adulthood. We studied a group Of Young adults (18-27 years) with epilepsy and compared their Situation in 2004 with those 5 years earlier.

    Materials and methods: The participants (n = 97) answered questionnaires regarding seizure-frequency, AED, side-effects and quality-of-life. Information was also taken from medical records.

    Results: The use of new generation AEDs increased during the 5-year study period, particularly among women. However seizure frequency had not changed significantly over time, and compared to men the effectiveness in controlling seizures Was lower in women. The participants reported normal quality-of-life (QOL), which may indicate that the increase in number of AEDs to choose from actually improved the situation for these Young adults with epilepsy. Frequency of seizures and cognitive side-effects of AEDs were associated with a lower QOL.

    Conclusions: More women than men seem to be treated with new AEDs, and that the increase in use of new AEDs does not reduce seizure frequency in young adulthood. The effectiveness in controlling seizures seems to be lower in women in the age group Studied. Further Studies are required to better understand how epilepsy related factors interact.

     

    Keywords
    Epilepsy, Medical outcome, Quality-of-life, Young adults
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18136 (URN)10.1016/j.seizure.2008.11.009 (DOI)
    Available from: 2009-05-09 Created: 2009-05-08 Last updated: 2012-08-24
    2. Self-esteem and sense of coherence in young people with uncomplicated epilepsy: A 5-year follow-up
    Open this publication in new window or tab >>Self-esteem and sense of coherence in young people with uncomplicated epilepsy: A 5-year follow-up
    2010 (English)In: EPILEPSY and BEHAVIOR, ISSN 1525-5050, Vol. 17, no 4, p. 520-524Article in journal (Refereed) Published
    Abstract [en]

    Objective: It is not clear how the psychosocial well-being of young people with epilepsy is affected by growing up with the condition. We studied self-esteem and sense of coherence in a group of young adults with epilepsy and compared the results with those obtained 5 years earlier. Methods: The participants (n = 97) answered questionnaires regarding self-esteem, sense of coherence, and medical characteristics. Results: Self-esteem and sense of coherence both decreased during the 5-year study period. Self-esteem was correlated to epilepsy-related variables. Participants who were seizure free scored higher on sense of coherence, but there was no association between seizure frequency and sense of coherence among participants who still experienced seizures. Conclusion: We found that there was a decline in both sense of coherence and self-esteem over time for young adults with epilepsy. Growing up with epilepsy can lead to impairment of sense of coherence. Sense of coherence does not significantly correlate with epilepsy-related factors, but mirrors the phenomenon of epilepsy. Self-esteem is associated with such epilepsy-related factors as seizure frequency.

    Place, publisher, year, edition, pages
    Elsevier Science B.V., Amsterdam, 2010
    Keywords
    Epilepsy, Seizure-frequency, Self-esteem, Sense of coherence, Young adults, Psychosocial aspects
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-56533 (URN)10.1016/j.yebeh.2010.01.167 (DOI)000277446000017 ()
    Available from: 2010-05-21 Created: 2010-05-21 Last updated: 2012-08-24
    3. Living with epilepsy accompanied by cognitive difficulties: Young adults experiences
    Open this publication in new window or tab >>Living with epilepsy accompanied by cognitive difficulties: Young adults experiences