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  • 1.
    Berntsson, S. G.
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, A.
    Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Feresiadou, A.
    Uppsala Univ, Sweden.
    Burman, J.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden Outlier or predecessor?2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 327-331Article in journal (Refereed)
    Abstract [en]

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

  • 2.
    Björnevik, Kjetil
    et al.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Casetta, Ilaria
    University of Ferrara, Italy.
    Cortese, Marianna
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Granieri, Enrico
    University of Ferrara, Italy.
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway.
    Kampman, Margitta T.
    University Hospital North Norway, Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Magalhaes, Sandra
    McGill University, Canada.
    Pugliatti, Maura
    University of Bergen, Norway; University of Ferrara, Italy.
    Wolfson, Christina
    McGill University, Canada; McGill University, Canada.
    Myhr, Kjell-Morten
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 7, p. 1018-1024Article in journal (Refereed)
    Abstract [en]

    Background: Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. Objectives: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. Methods: Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. Results: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis (p=0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66-1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): -0.98, 95% CI: -2.05-0.15, p=0.09). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

  • 3.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Berling, P.
    UCB Pharma, Denmark.
    Morberg, S.
    UCB Pharma, Denmark.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Uppsala University, Sweden.
    Patterns of antiepileptic drug prescription in Sweden: A register-based approach2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 5, p. 521-527Article in journal (Refereed)
    Abstract [en]

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

  • 4.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Prevalence and cost of epilepsy in Sweden - a register-based approach2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 1, p. 37-44Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Does the changing sex ratio of multiple sclerosis give opportunities for intervention?2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, p. 42-45Article, review/survey (Refereed)
    Abstract [en]

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

  • 6.
    Bruhn, H.
    et al.
    Cty Hosp Ryhov, Sweden.
    Strandeus, M.
    Cty Hosp Ryhov, Sweden.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lind, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Improved survival of Swedish glioblastoma patients treated according to Stupp2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 332-337Article in journal (Refereed)
    Abstract [en]

    ObjectivesThe median survival in glioblastoma (GBM) patients used to be less than 1year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jonkoping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. Material and MethodThis study includes all patients from the county of Jonkoping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. ResultsThe mean survival was 110days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344days, Pamp;lt;.001) than in the 2006-2012 cohort (mean 220 vs 397days, P=.02). ConclusionSurvival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.

  • 7.
    Danielsson, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindvall, Björn
    University Hospital Örebro, Sweden.
    Hallert, Claes
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Increased prevalence of celiac disease in idiopathic inflammatory myopathies2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 10, article id e00803Article in journal (Refereed)
    Abstract [en]

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

  • 8.
    Eleftheriou, Andreas
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Rashid, Avan Sabir
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Late Transient Contrast-Induced Encephalopathy after Percutaneous Coronary Intervention2018In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 27, no 6, p. E104-E106Article in journal (Refereed)
    Abstract [en]

    n/a

  • 9.
    Eleftheriou, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Circadian rhythm in idiopathic normal pressure hydrocephalus2018In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 164, p. 72-74Article in journal (Refereed)
    Abstract [en]

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

  • 10.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. 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, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Swedish Institute for Disability Research.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Craig, Arthur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Barrow Neurol Institute, AZ 85013 USA.
    Evidence of conjoint activation of the anterior insular and cingulate cortices during effortful tasks2015In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 8, no 1071Article in journal (Refereed)
    Abstract [en]

    The ability to perform effortful tasks is a topic that has received considerable interest in the research of higher functions of the human brain. Neuroimaging studies show that the anterior insular and the anterior cingulate cortices are involved in a multitude of cognitive tasks that require mental effort. In this study, we investigated brain responses to effort using cognitive tasks with task-difficulty modulations and functional magnetic resonance imaging (fMRI). We hypothesized that effortful performance involves modulation of activation in the anterior insular and the anterior cingulate cortices, and that the modulation correlates with individual performance levels. Healthy participants performed tasks probing verbal working memory capacity using the reading span task, and visual perception speed using the inspection time task. In the fMRI analysis, we focused on identifying effort-related brain activation. The results showed that working memory and inspection time performances were directly related. The bilateral anterior insular and anterior cingulate cortices showed significantly increased activation during each task with common portions that were active across both tasks. We observed increased brain activation in the right anterior insula and the anterior cingulate cortex in participants with low working memory performance. In line with the reported results, we suggest that activation in the anterior insular and cingulate cortices is consistent with the neural efficiency hypothesis (Neubauer).

  • 11.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    New hypothesis on pontine-frontal eye field connectivity in Kleine-Levin syndrome2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, no 6, p. 716-719Article in journal (Refereed)
    Abstract [en]

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

  • 12.
    Engström, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Latini, Francesco
    Department of Neuroscience, Section of Neurosurgery, Uppsala University, Uppsala, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Department of Neuroscience, Section of Neurology, Uppsala University, Uppsala, Sweden.
    Neuroimaging in the Kleine-Levin Syndrome2018In: Current Neurology and Neuroscience Reports, ISSN 1528-4042, E-ISSN 1534-6293, Vol. 18, no 9, article id 58Article, review/survey (Refereed)
    Abstract [en]

    The purpose was to review the most recent literature on neuroimaging in the Kleine-Levin syndrome (KLS). We aimed to investigate if frontotemporal and thalamic dysfunction are key KLS signatures, and if recent research indicates other brain networks of interest that elucidate KLS symptomatology and aetiology. In a comprehensive literature search, we found 12 original articles published 2013-2018. Most studies report deviations related to cerebral perfusion, glucose metabolism, or blood-oxygen-level-dependent responses in frontotemporal areas and/or the thalamus. Studies also report dysfunction in the temporoparietal junction and the oculomotor network that also were related to clinical parameters. We discuss these findings based on recent research on thalamocortical networks and brain stem white matter tracts. The hypothesis of frontotemporal and thalamic involvement in KLS was confirmed, and additional findings in the temporoparietal junction and the oculomotor system suggest a broader network involvement, which can be investigated by future high-resolution and multimodal imaging.

  • 13.
    Fardell, Camilla
    et al.
    Univ Gothenburg, Sweden.
    Zettergren, Anna
    Univ Gothenburg, Sweden.
    Ran, Caroline
    Karolinska Inst, Sweden.
    Belin, Andrea Carmine
    Karolinska Inst, Sweden.
    Ekman, Agneta
    Univ Gothenburg, Sweden.
    Sydow, Olof
    Karolinska Univ Hosp, Sweden.
    Backman, Lars
    Karolinska Inst, Sweden.
    Holmberg, Bjorn
    Univ Gothenburg, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nissbrandt, Hans
    Univ Gothenburg, Sweden.
    S100B polymorphisms are associated with age of onset of Parkinsons disease2018In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 19, article id 42Article in journal (Refereed)
    Abstract [en]

    Background: In this study we investigated the association between SNPs in the S100B gene and Parkinsons disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD. Methods: The SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar (R) PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset. Results: The S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population. Conclusions: rs9722, a functional SNP in the 3-UTR of the S100B gene, was strongly associated with age of onset of PD.

  • 14.
    Georgakis, Marios K.
    et al.
    University of Athens, Greece.
    Papathoma, Paraskevi
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. University of Athens, Greece.
    Ryzhov, Anton
    National Cancer Registry Ukraine, Ukraine.
    Zivkovic-Perisic, Snezana
    Institute Public Health Serbia, Serbia.
    Eser, Sultan
    Izmir and Hacettepe University, Turkey.
    Taraszkiewicz, Lukasz
    Greater Poland Cancer Centre, Poland.
    Sekerija, Mario
    Croatian Institute Public Heatlh, Croatia.
    Zagar, Tina
    Cancer Registry Republ Slovenia, Slovenia.
    Antunes, Luis
    Portuguese Oncology Institute Porto, Portugal.
    Zborovskaya, Anna
    Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology, Childhood Cancer Subregistry of Belarus, Minsk, Belarus.
    Bastos, Joana
    Portuguese Oncology Institute Coimbra, Portugal.
    Florea, Margareta
    National Institute Public Heatlh, Romania.
    Coza, Daniela
    Ion Chiricuta Oncology Institute, Romania.
    Demetriou, Anna
    Childhood Cancer Subregistry Belarus, Byelarus; Minist Heatlh, Cyprus.
    Agius, Domenic
    Malta National Cancer Registry, Malta.
    Strahinja, Rajko M.
    Institute Public Heatlh, Montenegro.
    Themistocleous, Marios
    Aghia Sophia Childrens Hospital, Greece.
    Tolia, Maria
    University of Athens, Greece.
    Tzanis, Spyridon
    Errikos Dunant Hospital Centre, Greece.
    Alexiou, George A.
    Ioannina University, Greece.
    Papanikolaou, Panagiotis G.
    Gen Nikaia Piraeus Hospital, Greece.
    Nomikos, Panagiotis
    Hygeia Hospital, Greece.
    Kantzanou, Maria
    University of Athens, Greece.
    Dessypris, Nick
    University of Athens, Greece.
    Pourtsidis, Apostolos
    Panagiotis and Aglaia Kyriakou Childrens Hospital, Greece.
    Petridou, Eleni T.
    University of Athens, Greece; Karolinska Institute, Sweden.
    Malignant Central Nervous System Tumors Among Adolescents and Young Adults (15-39 Years Old) in 14 Southern-Eastern European Registries and the US Surveillance, Epidemiology, and End Results Program: Mortality and Survival Patterns2017In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 123, no 22, p. 4458-4471Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15-39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern-Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program. METHODS: Malignant CNS tumors diagnosed in AYAs during the period spanning 1990-2014 were retrieved from 14 population-based cancer registries in the SEE region (n = 11,438). Age-adjusted mortality rates were calculated and survival patterns were evaluated via Kaplan-Meier curves and Cox regression analyses, and they were compared with respective 1990-2012 figures from SEER (n = 13,573). RESULTS: Mortality rates in SEE (range, 11.9-18.5 deaths per million) were higher overall than the SEER rate (9.4 deaths per million), with decreasing trends in both regions. Survival rates increased during a comparable period (2001-2009) in SEE and SEER. The 5-year survival rate was considerably lower in the SEE registries (46%) versus SEER (67%), mainly because of the extremely low rates in Ukraine; this finding was consistent across age groups and diagnostic subtypes. The highest 5-year survival rates were recorded for ependymomas (76% in SEE and 92% in SEER), and the worst were recorded for glioblastomas and anaplastic astrocytomas (28% in SEE and 37% in SEER). Advancing age, male sex, and rural residency at diagnosis adversely affected outcomes in both regions. CONCLUSIONS: Despite definite survival gains over the last years, the considerable outcome disparities between the less affluent SEE region and the United States for AYAs with malignant CNS tumors point to health care delivery inequalities. No considerable prognostic deficits for CNS tumors are evident for AYAs versus children. (c) 2017 American Cancer Society.

  • 15.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Davidsson, Anette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed)
    Abstract [en]

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

  • 16.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Centre Diagnost Radiol Carouge SA, Switzerland; Uppsala University, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Haller, Sven
    Affidea CDRC Ctr Diagnost Radiol Carouge SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    Olfactory fMRI: Implications of Stimulation Length and Repetition Time2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

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

  • 18.
    Ghaderi Berntsson, Shala
    et al.
    Uppsala University, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Flensner, Gullvi
    University of West, Sweden.
    Cerebellar ataxia and intrathecal baclofen therapy: Focus on patients experiences2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0180054Article in journal (Refereed)
    Abstract [en]

    Elucidating patients A experiences of living with chronic progressive hereditary ataxia and the symptomatic treatment with intrathecal baclofen (ITB) is the objective of the current study. A multicenter qualitative study with four patients included due to the rare combination of hereditary ataxia and ITB therapy was designed to elucidate participants experiences through semi-structured interviews. The transcribed text was analyzed according to content analysis guidelines. Overall we identified living in the present/taking one day at a time as the main theme covering the following categories: 1) Uncertainty about the future as a consequence of living with a hereditary disease; The disease; 2) Impact on life as a whole, 3) Influence on personal life in terms of feeling forced to terminate employment, 4) Limiting daily activities, and 5) ITB therapy, advantages, and disadvantages. Uncertainty about the future was the category that affected participants personal life, employment, and daily activities. The participants experience of receiving ITB therapy was expressed in terms of improved quality of life due to better body position and movement as well as better sleep and pain relief.

  • 19.
    Gustafsson, Greta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Broström, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Department of Nursing Science, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Svanborg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation2015In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 126, no 8, p. 1493-1497Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSION:

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

    SIGNIFICANCE:

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

  • 20.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Liljenström, H. Robert I.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 313, article id 313ra178Article in journal (Refereed)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

  • 21.
    Hellberg, Sandra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Köpsén, Mattias
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kockum, Ingrid
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Olsson, Tomas
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Dynamic Response Genes in CD4+T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis2016In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, no 11, p. 2928-2939Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

  • 22.
    Hellqvist, Carina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Support supplied by Parkinson's disease specialist nurses to Parkinson's disease patients and their spouses2015In: Applied Nursing Research, ISSN 0897-1897, E-ISSN 1532-8201, Vol. 28, no 2, p. 86-91Article in journal (Refereed)
    Abstract [en]

    AIM:

    The purpose of the study was to identify the role of the Parkinson's disease specialist nurse in providing support both for people with Parkinson's disease (PD) and their spouses.

    BACKGROUND:

    PD is a neurodegenerative disease with symptoms that affect many aspects of daily life. In Sweden, specialised nurses called Parkinson's disease specialist nurses (PD specialist nurses) have been working for over a decade to support PD patients and their families.

    METHOD:

    A qualitative approach was taken using dyad interviews with each PD patient and spouse. The analysis was conducted using conventional qualitative content analysis.

    FINDINGS:

    The analysis resulted in the identification of one overarching category; competent, professional practice, tailored for the individual. Four categories: professional competence, nursing practice, continuity of contact and emotional support, are distinct but related to each other and show different nuances of the same phenomenon.

    CONCLUSION:

    The work of PD specialist nurses in providing support to PD patients and their relatives should be tailored to individual patients and their families as well as including skilled nursing care to relieve the impact of the disease on daily life

  • 23.
    Hellqvist, Carina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Hagell, Peter
    Kristianstad Univ, Sweden.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sund-Levander, Märtha
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Improving self-management for persons with Parkinsons disease through education focusing on management of daily life: Patients and relatives experience of the Swedish National Parkinson School2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 19-20, p. 3719-3728Article in journal (Refereed)
    Abstract [en]

    Aims and objectiveTo identify and describe experiences valuable formanaging daily life after participation in the NPS self-management intervention. The second part was to explore the applicability of the Self- and family management framework by Grey and colleagues for persons with Parkinsons Disease and their relatives. BackgroundThe impact of PD is evident on the lives of both patients and relatives. The National Parkinson School (NPS) is a Swedish self-management programme designed for patients and relatives, aiming at teaching strategies helpful for the ability of self-management, in order to promote life satisfaction. DesignQualitative explorative with inductive and deductive analysis. MethodsFive group discussions with NPS participants were audio-recorded. Verbatim transcriptions were analysed inductively with thematic analysis according to Braun and Clarke, and the findings were then applied deductively to the existing model for patients with chronic disease. ResultsThrough the first step of inductive analysis, three themes capturing the meaning, value and experience of being a participant at the NPS were identified: exchanging experiences and feeling support, adjustment and acceptance of PD for managing daily life and promoting life satisfaction. The deductive analysis applied the inductive findings to the Self- and family management framework of chronically ill to explore the fit to persons with PD and relatives attending the NPS programme. ConclusionsThe NPS programme is a promising approach for helping persons with PD and their relatives to achieve better self-management of disease and improved life satisfaction. Further evaluations of programme outcomes in clinical practice are warranted. Relevance of clinical practiceSelf-management programmes like the NPS is a promising approach in facilitating a positive mindset and outlook on life and gain knowledge to understand, adapt and handle chronic disease, such as PD, better.

    The full text will be freely available from 2019-05-21 14:44
  • 24.
    Huang-Link, Yu-Min
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Al-Hawasi, Abbas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lindehammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Acute optic neuritis: retinal ganglion cell loss precedes retinal nerve fiber thinning.2015In: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 36, no 4, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Optic neuritis (ON) causes axonal loss as reflected by thinning of retinal nerve fiber layer (RNFL) and can be tracked by optical coherence tomography (OCT) about 6 months after ON onset, when swelling of optic nerve head (ONH) has vanished. Changes of macular ganglion cell layer (GCL) thickness provide another window to track the disease process in ON. GCL thinning over time in relation to RNFL change after ON remains elusive. Using OCT, we followed 4 patients with acute unilateral isolated ON for more than 9 months. A diagnosis of multiple sclerosis (MS) was established in all 4 patients. First follow-up was 2-3 weeks after ON onset, and thereafter every 2-3 months. RNFL swelling peaked during first month after acute ON, followed by rapidly reduced swelling (pseudoatrophy) during following 2 months, and thereafter successively vanished 6 months after ON onset. GCL thinning was observed 1-3 months after ON onset, i.e. already during optic disk swelling and before real RNFL thinning. The results imply that quantifying GCL thickness provides opportunities to monitor early axonal loss and ON-to-MS progression, and facilitates distinguishing real atrophy from pseudoatrophy of RNFL after acute ON.

  • 25.
    Huang-Link, Yu-Min
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Al-Hawasi, Abbas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Oberwahrenbrock, Timm
    Charite University of Medical Berlin, Germany.
    Jin, Ya-Ping
    University of Toronto, Canada.
    OCT measurements of optic nerve head changes in idiopathic intracranial hypertension2015In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 130, p. 122-127Article in journal (Refereed)
    Abstract [en]

    Objective: Severity of papilledema and vision loss constitute a basis for therapeutic intervention in idiopathic intracranial hypertension (IIH), but both are often subjective and insensitive in guiding clinical management. The aim of this study was to identify reliable and sensitive measurements of optic nerve head (ONH) and macula, to provide objective guidance for prognostic evaluation and treatment in IIH. We analyzed potential of spectral domain optical coherence tomography (SD-OCT), to measure neuro-retinal rim thickness and area, optic cup-to-disc ratio (C/D) and cup volume of ONH which have not previously been reported in IIH. In parallel, thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) together with inner plexiform layer (IPL) (GCL-IPL) were examined. Results: All 7 enrolled IIH patients had increased neuro-retinal rim thickness (p less than 0.01 for both eyes) and rim area (p less than 0.05), decreased C/D (p less than 0.01) and optic cup volume (p less than 0.01) when compared to findings in 18 sex- and age-matched healthy controls (HC). In a longitudinal study, two IIH patients were followed repetitively by SD-OCT before and after measurement of intracranial pressure (ICP) and removal of cerebrospinal fluid (CSF) by lumbar puncture. Rim thickness and area, C/D and optic cup volume remained altered. RNFL thickness may change with very high ICP, but not immediately after CSF removal. GCL-IPL thickness was unchanged irrespective of ICP change or CSF removal. Conclusion: SD-OCT allows detection of ONH changes even in subtle IIH without papilledema and has potential for routine use in IIH.

  • 26.
    Huang-Link, Yu-Min
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Link, Hans
    Karolinska Institute, Sweden.
    Benign Multiple Sclerosis is Associated with Reduced Thinning of the Retinal Nerve Fiber and Ganglion Cell Layers in Non-Optic-Neuritis Eyes2015In: JOURNAL OF CLINICAL NEUROLOGY, ISSN 1738-6586, Vol. 11, no 3, p. 241-247Article in journal (Refereed)
    Abstract [en]

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

  • 27.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Gouveia-Figueira, Sandra
    Umea Univ, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Nording, Malin
    Umea Univ, Sweden; Univ Calif Davis, CA 95616 USA.
    Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing remitting multiple sclerosis2018In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 138, p. 41-47Article in journal (Refereed)
    Abstract [en]

    Although oxylipins are involved in inflammation, data on these lipid mediators in multiple sclerosis are sparse. In this study, a panel of oxylipins were analysed swith liquid chromatography tandem mass spectrometry in cerebrospinal fluid (CSF) from 41 treatment naive patients with clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) and 22 healthy controls. CSF levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were significantly higher in patients than in healthy controls (9-HODE median 380 nM (interquartile range 330-450 nM) in patients and 290 nM (interquartile range 250-340 nM) in controls, 13-HODE median 930 nM (interquartile range 810-1080 nM) in patients and 690 nM (interquartile range 570-760 nM) in controls, p amp;lt; 0.001 in Mann-Whitney U tests). 9-HODE and 13-HODE performed well for separation of patients and healthy controls (AUC 0.85 and 0.88, respectively, in ROC curve analysis). However, baseline CSF levels of the oxylipins did not differ between patients with signs of disease activity during one, two and four years of follow-up and patients without. In conclusion, this study indicates that 9-HODE and 13-HODE levels are increased in CSF from CIS and RRMS patients compared with healthy controls, but does not support 9-HODE or 13-HODE as prognostic biomarkers of disease activity in patients during follow-up.

  • 28.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Askmark, Håkan
    University of Uppsala Hospital, Sweden.
    Pirskanen, Ritva
    Karolinska Institute, Sweden.
    Carlson, Kristina
    University Hospital, Sweden.
    Piehl, Fredrik
    Karolinska Institute, Sweden.
    Hägglund, Hans
    University Hospital, Sweden.
    Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 1, p. 90-93Article in journal (Refereed)
    Abstract [en]

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

  • 29.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Blennow, K.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Zetterberg, H.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; UCL Institute Neurol, England.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 5, p. 703-712Article in journal (Refereed)
    Abstract [en]

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

  • 30.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England; UCL, England.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis2018In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 15, article id 209Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Israelsson, Hanna
    et al.
    Umeå University, Sweden.
    Carlberg, Bo
    Umeå University, Sweden.
    Wikkelso, Carsten
    University of Gothenburg, Sweden.
    Laurell, Katarina
    Umeå University, Sweden.
    Kahlon, Babar
    Lund University, Sweden.
    Leijon, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Anders
    Umeå University, Sweden.
    Malm, Jan
    Umeå University, Sweden.
    Vascular risk factors in INPH A prospective case- control study (the INPH-CRasH study)2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 6, p. 577-585Article in journal (Refereed)
    Abstract [en]

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

  • 32.
    Jonsson Gauffin, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Flensner, Gullvi
    University of West, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Being parents with epilepsy: thoughts on its consequences and difficulties affecting their children2015In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 11, p. 1291-1298Article in journal (Refereed)
    Abstract [en]

    Objective: Parents with epilepsy can be concerned about the consequences of epilepsy affecting their children. The aim of this paper is to describe aspects of what it means being a parent having epilepsy, focusing the parents perspectives and their thoughts on having children. Methods: Fourteen adults aged 18-35 years with epilepsy and subjective memory decline took part in focus-group interviews. The interviews were conducted according to a semi-structured guideline. Material containing aspects of parenthood was extracted from the original interviews and a secondary analysis was done according to a content-analysis guideline. Interviews with two parents for the Swedish book Leva med epilepsi [To live with epilepsy] by AM Landtblom (Stockholm: Bilda ide; 2009) were analyzed according to the same method. Results: Four themes emerged: (1) a persistent feeling of insecurity, since a seizure can occur at any time and the child could be hurt; (2) a feeling of inadequacy - of not being able to take full responsibility for ones child; (3) acknowledgment that ones children are forced to take more responsibility than other children do; and (4) a feeling of guilt - of not being able to fulfill ones expectations of being the parent one would like to be. Conclusion: The parents with epilepsy are deeply concerned about how epilepsy affects the lives of their children. These parents are always aware that a seizure may occur and reflect on how this can affect their child. They try to foresee possible dangerous situations and prevent them. These parents were sad that they could not always take full responsibility for their child and could not live up to their own expectations of parenthood. Supportive programs may be of importance since fear for the safety of the child increases the psychosocial burden of epilepsy. There were also a few parents who did not acknowledge the safety issue of their child - the authors believe that it is important to identify these parents and provide extra information and support to them.

  • 33.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Brain circuitries involved in sleep disorders2015In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, no UNSP 66Article in journal (Refereed)
    Abstract [en]

    n/a

  • 34.
    Lill, Christina M.
    et al.
    University of Lubeck, Germany; Max Planck Institute Molecular Genet, Germany.
    Rengmark, Aina
    Oslo University Hospital, Norway.
    Pihlstrom, Lasse
    Oslo University Hospital, Norway.
    Fogh, Isabella
    Kings Coll London, England.
    Shatunov, Aleksey
    Kings Coll London, England.
    Sleiman, Patrick M.
    Childrens Hospital Philadelphia, PA 19104 USA; Childrens Hospital Philadelphia, PA 19104 USA; University of Penn, PA 19104 USA; University of Turin, Italy.
    Wang, Li-San
    University of Penn, PA 19104 USA; University of Turin, Italy.
    Liu, Tian
    Max Planck Institute Human Dev, Germany.
    Lassen, Christina F.
    Danish Cancer Soc, Denmark.
    Meissner, Esther
    Max Planck Institute Molecular Genet, Germany.
    Alexopoulos, Panos
    Technical University of Munich, Germany.
    Calvo, Andrea
    University of Turin, Italy.
    Chio, Adriano
    University of Turin, Italy; Neurosci Institute Turin, Italy.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Faltraco, Frank
    Goethe University of Frankfurt, Germany.
    Forsgren, Lars
    Umeå University, Sweden.
    Kirchheiner, Julia
    University of Ulm, Germany.
    Kurz, Alexander
    Technical University of Munich, Germany.
    Larsen, Jan P.
    Stavanger University Hospital, Norway.
    Liebsch, Maria
    Max Planck Institute Molecular Genet, Germany.
    Linder, Jan
    Umeå University, Sweden.
    Morrison, Karen E.
    University of Birmingham, England; University Hospital Birmingham, England.
    Nissbrandt, Hans
    University of Gothenburg, Sweden.
    Otto, Markus
    University of Ulm, Germany.
    Pahnke, Jens
    University of Oslo, Norway; Oslo University Hospital, Norway; University of Lubeck, Germany.
    Partch, Amanda
    University of Penn, PA 19104 USA.
    Restagno, Gabriella
    Azienda Osped Citta Salute and Science, Italy.
    Rujescu, Dan
    University of Halle Wittenberg, Germany.
    Schnack, Cathrin
    University of Ulm, Germany.
    Shaw, Christopher E.
    Kings Coll London, England.
    Shaw, Pamela J.
    University of Sheffield, England.
    Tumani, Hayrettin
    University of Ulm, Germany.
    Tysnes, Ole-Bjorn
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Valladares, Otto
    University of Penn, PA 19104 USA.
    Silani, Vincenzo
    IRCCS Ist Auxol Italiano, Italy; University of Milan, Italy.
    van den Berg, Leonard H.
    University of Medical Centre Utrecht, Netherlands.
    van Rheenen, Wouter
    University of Medical Centre Utrecht, Netherlands.
    Veldink, Jan H.
    University of Medical Centre Utrecht, Netherlands.
    Lindenberger, Ulman
    Max Planck Institute Human Dev, Germany.
    Steinhagen-Thiessen, Elisabeth
    Charite, Germany.
    Teipel, Stefan
    German Centre Neurodegenerat Disease DZNE, Germany; University of Rostock, Germany.
    Perneczky, Robert
    Technical University of Munich, Germany; University of London Imperial Coll Science Technology and Med, England; West London Mental Health Trust, England.
    Hakonarson, Hakon
    Childrens Hospital Philadelphia, PA 19104 USA; Childrens Hospital Philadelphia, PA 19104 USA; University of Penn, PA 19104 USA.
    Hampel, Harald
    AXA Research Fund, France; University of Sorbonne, France.
    von Arnim, Christine A. F.
    University of Ulm, Germany.
    Olsen, Jorgen H.
    Danish Cancer Soc, Denmark.
    Van Deerlin, Vivianna M.
    University of Penn, PA 19104 USA; University of Turin, Italy.
    Al-Chalabi, Ammar
    Kings Coll London, England.
    Toft, Mathias
    Oslo University Hospital, Norway.
    Ritz, Beate
    ICM, France.
    Bertram, Lars
    Max Planck Institute Molecular Genet, Germany; University of Calif Los Angeles, CA USA.
    The role of TREM2 R47H as a risk factor for Alzheimers disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinsons disease2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 12, p. 1407-1416Article in journal (Refereed)
    Abstract [en]

    A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimers disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinsons disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2s role in AD may involve tau dysfunction. (C) 2015 The Alzheimers Association. Published by Elsevier Inc. All rights reserved.

  • 35.
    Magalhaes, Sandra
    et al.
    McGill University, Canada; McGill University, Canada.
    Pugliatti, Maura
    University of Sassari, Italy; University of Bergen, Norway; McGill University, Canada.
    Casetta, Ilaria
    University of Ferrara, Italy.
    Drulovic, Jelena
    University of Belgrade, Serbia.
    Granieri, Enrico
    University of Ferrara, Italy.
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway.
    Kampman, Margitta T.
    University Hospital North Norway, Norway.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Lauer, Klaus
    Darmstadt, Germany.
    Myhr, Kjell-Morten
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Parpinel, Maria
    University of Udine, Italy.
    Pekmezovic, Tatjana
    University of Belgrade, Serbia.
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Wolfson, David
    McGill University, Canada.
    Zhu, Bin
    McGill University, Canada.
    Wolfson, Christina
    McGill University, Canada; McGill University, Canada; McGill University, Canada.
    The EnvIMS Study: Design and Methodology of an International Case-Control Study of Environmental Risk Factors in Multiple Sclerosis2015In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 44, no 3, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, often resulting in significant neurological disability. The causes of MS are not known; however, the incidence of MS is increasing, thereby suggesting that changes in lifestyle and/or environmental factors may be responsible. On this background, the Environmental Risk Factors in MS Study or EnvIMS study was designed to further explore the etiology of MS. The design and methodology are described, providing details to enable investigators to (i) use our experiences to design their own studies; (ii) take advantage of, and build on the methodological work completed for, the EnvIMS study; (iii) become aware of this data source that is available for use by the research community. Methods: EnvIMS is a multinational case-control study, enrolling 2,800 cases with MS and 5,012 population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study was designed to investigate the most commonly implicated risk factors for MS etiology using a self-report questionnaire. Results/Conclusions:The use of a common methodology to study MS etiology across several countries enhances the comparability of results in different geographic regions and research settings, reduces the resources required for study design and enhances the opportunity for data harmonization.

  • 36.
    Mellergård, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Blystad, Ida
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Grönqvist, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Blennow,, K.
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Olsson,, B.
    Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 1, p. 112-121Article in journal (Refereed)
    Abstract [en]

    Background and purpose

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

    Methods

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

    Results

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

    Conclusions

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

  • 37.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Szakacs, Attila
    University of Gothenburg, Sweden.
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Wretman, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Ståhlbrandt, Henriettae
    Highland Hospital, Sweden.
    Darin, Niklas
    University of Gothenburg, Sweden.
    Hallbook, Tove
    University of Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Altered Brain Microstate Dynamics in Adolescents with Narcolepsy2016In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 10, no 369Article in journal (Refereed)
    Abstract [en]

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional fMRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics.

  • 38.
    Nord, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Levodopa pharmacokinetics -from stomach to brain: A study on patients with Parkinson’s disease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients.

    In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment.

    To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.

    List of papers
    1. Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
    Open this publication in new window or tab >>Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
    2017 (English)In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 06, no 01Article in journal (Refereed) Published
    Abstract [en]

    Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.

    Place, publisher, year, edition, pages
    Scientific Research Publishing, 2017
    National Category
    Neurology Gastroenterology and Hepatology Anesthesiology and Intensive Care Surgery Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-136685 (URN)10.4236/apd.2017.61001 (DOI)
    Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2018-01-12
    2. The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
    Open this publication in new window or tab >>The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
    Show others...
    2010 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 25, no 3, p. 363-367Article in journal (Refereed) Published
    Abstract [en]

    Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa. shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day I; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg bid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C-max of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C-max in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2010
    Keywords
    Parkinsons Disease, levodopa, continuous infusion, COMT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54855 (URN)10.1002/mds.22613 (DOI)000276136900016 ()
    Available from: 2010-04-16 Created: 2010-04-16 Last updated: 2018-01-12
    3. Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
    Open this publication in new window or tab >>Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
    Show others...
    2014 (English)In: Neurology and Clinical Neuroscience, ISSN 2049-4173, Vol. 2, no 5, p. 149-155Article in journal (Refereed) Published
    Abstract [en]

    Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2014
    Keywords
    deep brain stimulation, levodopa, microdialysis, neurotransmitters, Parkinson
    National Category
    Medical Bioscience Medical Biotechnology Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-113590 (URN)10.1111/ncn3.109 (DOI)
    Available from: 2015-01-23 Created: 2015-01-23 Last updated: 2018-01-12Bibliographically approved
    4. Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
    Open this publication in new window or tab >>Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
    2017 (English)In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 6, no 2, p. 52-66Article in journal (Refereed) Published
    Abstract [en]

    Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.

    Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.

    Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.

    Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.

    Place, publisher, year, edition, pages
    Scientific Research Publishing Inc, 2017
    Keywords
    Parkinson’s Disease, Levodopa, Dopamine, Brain, Microdialysis, Deep Brain Stimulation
    National Category
    Neurology Cardiac and Cardiovascular Systems Gastroenterology and Hepatology Anesthesiology and Intensive Care Other Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-139251 (URN)10.4236/apd.2017.62006 (DOI)
    Available from: 2017-07-07 Created: 2017-07-07 Last updated: 2018-01-12Bibliographically approved
  • 39.
    Nord, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kullman, Anita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Hannestad, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?2017In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 06, no 01Article in journal (Refereed)
    Abstract [en]

    Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.

  • 40.
    Nord, Maria
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease2017In: Advances in Parkinsons Disease, ISSN 2169-9712, Vol. 6, no 2, p. 52-66Article in journal (Refereed)
    Abstract [en]

    Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.

    Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.

    Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.

    Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.

  • 41.
    Pihlstrom, Lasse
    et al.
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Rengmark, Aina
    Oslo University Hospital, Norway.
    Anne Bjornara, Kari
    Drammen Hospital, Norway.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Fardell, Camilla
    University of Gothenburg, Sweden.
    Forsgren, Lars
    Umeå University, Sweden.
    Holmberg, Bjorn
    University of Gothenburg, Sweden.
    Petter Larsen, Jan
    Stavanger University Hospital, Norway.
    Linder, Jan
    Umeå University, Sweden.
    Nissbrandt, Hans
    University of Gothenburg, Sweden.
    Tysnes, Ole-Bjorn
    Haukeland Hospital, Norway.
    Dietrichs, Espen
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Toft, Mathias
    Oslo University Hospital, Norway.
    Fine mapping and resequencing of the PARK16 locus in Parkinsons disease2015In: Journal of Human Genetics, ISSN 1434-5161, E-ISSN 1435-232X, Vol. 60, no 7, p. 357-362Article in journal (Refereed)
    Abstract [en]

    The PARK16 locus, spanning five genes on chromosome 1, was among the first genetic regions to show genome-wide association in Parkinsons disease (PD). Subsequent investigations have found variability in PARK16 top-hits and association patterns across populations, and the implicated genes and mechanisms are currently unclear. In the present study, we aimed to explore the contribution of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17 single-nucleotide polymorphisms in a case-control sample set of 2570 individuals from Norway and Sweden to fine map the locus. Targeted resequencing of the full coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in DNA pools from a subset of 387 patient samples. We find evidence for an association with PD for rs1775143 as well as a haplotype located around the 5 region of RAB7L1, implicating variants which are not in high linkage disequilibrium with the strongest signal from a recent large meta-analysis in Caucasians. We also provide suggestive support for epistasis between RAB7L1 and LRRK2 as previously hypothesized by others. Comparing our results with previous work, allelic heterogeneity at PARK16 appears likely, and further studies are warranted to disentangle the complex patterns of association and pinpoint the functionally relevant variants.

  • 42.
    Pålhagen, Sven E.
    et al.
    Karolinska University Hospital, Sweden.
    Sydow, Olof
    Karolinska University Hospital, Sweden.
    Johansson, Anders
    Uppsala University, Sweden.
    Nyholm, Dag
    Uppsala University, Sweden.
    Holmberg, Bjorn
    Sahlgrens University Hospital, Sweden.
    Widner, Hakan
    Skåne University Hospital, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Linder, Jan
    Norrlands University Hospital, Sweden.
    Hauge, Tove
    Molde Hospital HNR, Norway.
    Jansson, Rasmus
    Sundsvall Hospital, Sweden.
    Bergmann, Lars
    AbbVie Inc, IL USA.
    Kjellander, Susanna
    AbbVie AB, Sweden.
    Marshall, Thomas S.
    AbbVie Inc, IL USA.
    Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinsons disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs2016In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 29, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Background: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinsons disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. Methods: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naive (N = 37), or had previous LCIG treatment for amp;lt;2 (N = 22), or amp;gt;= 2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinsons Disease Rating Scale (UPDRS), 39-item Parkinsons Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. Results: Mean monthly costs per patient ( 8226 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naive patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. Conclusions: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naive patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The longterm safety was consistent with the established LCIG profile. (C) 2016 AbbVie Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  • 43.
    Sundström, Nina
    et al.
    Umeå University, Sweden.
    Malm, Jan
    Umeå University, Sweden.
    Laurell, Katarina
    Umeå University, Sweden.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Medicine and Health Sciences.
    Kahlon, Babar
    Lund University Hospital, Sweden.
    Cesarini, Kristina G.
    Uppsala University, Sweden.
    Leijon, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Medicine and Health Sciences.
    Wikkelso, Carsten
    University of Gothenburg, Sweden.
    Incidence and outcome of surgery for adult hydrocephalus patients in Sweden2017In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 31, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

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

  • 44.
    Vigren, Patrick
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    On the Kleine-Levin Syndrome2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [sv]

    Populärvetenskaplig sammanfattning på svenska

    Kleine-Levins syndrom är en sömnsjukdom som beskrevs av Willi Kleine 1925 och därefter utvecklades i fallbeskrivningar av Max Levin och McDonald Chritchley. De symptom som beskrevs var återkommande sömnperioder (periodisk hypersomnia), en tendens att äta mycket i samband med dessa perioder (hyperfagi) och ökad sexdrift i samband med perioderna (hypersexualitet) och, i senare beskrivningar, kognitiva och beteendemässiga störningar. Enligt tidigare beskrivningar var patienterna återställda mellan sömnperioderna. Dessa varade i dagar-veckor och återkom flera gånger årligen. Sjukdomen debuterade vanligtvis i tonåren och beskrevs gå över efter åtta år.

    d avhandling beskriver diagnosens utveckling över tid och sätter forskningen i sitt teoretiska sammanhang. Med det senare menas att det diskuteras hur forskningen förhåller sig till en diagnos som förändras över tid och där olika läkare kan ha olika kunskap kring och förhållningssätt till diagnosen.

    De studier som ingår i avhandlingen har undersökt flera olika aspekter av Kleine-Levins syndrom. Den första studien undersökte arbetsminnet hos patienterna och kunde påvisa att det var nedsatt jämfört med friska försökspersoner, även mellan sömnperioderna, något som inte var visat systematiskt tidigare. Dessutom sågsandra aktiveringsmönster i hjärnan när patienterna försökte klara arbetsminnesuppgiften, jämfört med aktiveringsmönstren hos friska försökspersoner. Hos hälften av patienterna sågs dessutom avvikande blodflöde i delar av hjärnan även när ingen särskild arbetsuppgift utfördes. Detta sågs även hos patienter som tillfrisknat.

    Då det funnits hypoteser i annan forsking att sjukdomen kan ha ett genetiskt/ärftligt inslag undersöktes huruvida patienterna hade en gen som tidigare har kopplats till sjukdomen. I den grupp av patienter som undersöktes i avhandlingens sista artikel kunde dock ingen sådan koppling ses.

    Slutsatsen av forskningsresultaten är att (1) patienter med Kleine-Levins syndrom har en störning av arbetsminnet som verkar konstant. (2) De uppvisar andra hjärnaktiveringsmönster än friska personer som gör samma arbetsminnesuppgift. (3) Hälften av patienterna har ett avvikande blodflödesmönster även i vila och efter tillfrisknande. (4) En eventuell ärftlig komponent kan inte påvisas avseende de undersökta generna.

    List of papers
    1. Working Memory in 8 Kleine-Levin Syndrome Patients: An fMRI Study
    Open this publication in new window or tab >>Working Memory in 8 Kleine-Levin Syndrome Patients: An fMRI Study
    2009 (English)In: SLEEP, ISSN 0161-8105, Vol. 32, no 5, p. 681-688Article in journal (Refereed) Published
    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.

    Keywords
    fMRI, Kleine-Levin Syndrome, working memory, hypersomnia, thalamus
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18262 (URN)000265541900015 ()
    Available from: 2009-05-16 Created: 2009-05-15 Last updated: 2017-09-28
    2. Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
    Open this publication in new window or tab >>Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
    Show others...
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2Article in journal (Refereed) Published
    Abstract [en]

    Background

    Kleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus.

    Methods

    fMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods.

    Results

    There was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activiation.

    Conclusion

    This study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85927 (URN)10.1371/journal.pone.0056279 (DOI)000316849500009 ()
    Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2017-12-07Bibliographically approved
    3. SPECT in the Kleine–Levin syndrome, a possible diagnostic and prognostic aid?
    Open this publication in new window or tab >>SPECT in the Kleine–Levin syndrome, a possible diagnostic and prognostic aid?
    2014 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, no 178Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Kleine–Levin syndrome (KLS) is a rare syndrome of periodic hypersomnia and behavioral and cognitive symptoms based on clinical criteria. In the setting of differential diagnosis of hypersomnia disorders, an objective diagnostic aid is desirable. A promising modality is single photon emission computed tomography (SPECT). As intraepisodal investigations are difficult to perform, an interepisodal investigation would be very helpful. Another aim of the study was to correlate SPECT findings to prognosis.

    Methods and Materials: Twenty-four KLS-patients were categorized as severe or non-severe based on clinical characteristics. The clinical characteristics were analyzed in relation to SPECT-examinations performed between hypersomnia periods (interepisodal) or after remission, as a clinical routine investigation.

    Results: Forty-eight percent of the KLS-patients have hypoperfusion in the temporal or fronto-temporal regions. In patients that have undergone remission, 56% show that pattern. There were no specific findings related to prognosis.

    Discussion/Conclusion: SPECT might be a diagnostic aid, in a setting of hypersomnia experience. With a sensitivity of 48%, interepisodal SPECT alone cannot be used for diagnosing KLS.

    Place, publisher, year, edition, pages
    Switzerland: Frontiers Research Foundation, 2014
    Keywords
    single photon emission tomography, sleep disorders, brain perfusion, Kleine–Levin syndrome, sleep
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-110858 (URN)10.3389/fneur.2014.00178 (DOI)25295028 (PubMedID)
    Available from: 2014-09-24 Created: 2014-09-24 Last updated: 2017-12-05Bibliographically approved
  • 45.
    Vågberg, M.
    et al.
    Umeå University, Sweden.
    Axelsson, M.
    University of Gothenburg, Sweden.
    Birgander, R.
    Umeå University, Sweden.
    Burman, J.
    Uppsala University, Sweden.
    Cananau, C.
    Karolinska Institute, Sweden.
    Forslin, Y.
    Karolinska Institute, Sweden.
    Granberg, T.
    Karolinska Institute, Sweden.
    Gunnarsson, M.
    University of Örebro, Sweden.
    von Heijne, A.
    Karolinska Institute, Sweden.
    Jönsson, L.
    Sahlgrens University Hospital, Sweden.
    Karrenbauer, V. D.
    Karolinska Institute, Sweden.
    Larsson, E. -M.
    Uppsala University, Sweden.
    Lindqvist, T.
    Umeå University, Sweden.
    Lycke, J.
    University of Gothenburg, Sweden.
    Lönn, L.
    Karolinska Institute, Sweden.
    Mentesidou, E.
    Karolinska Institute, Sweden.
    Müller, S.
    Karolinska Institute, Sweden.
    Nilsson, P.
    Lund University, Sweden.
    Piehl, F.
    Karolinska Institute, Sweden.
    Svenningsson, A.
    Karolinska Institute, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Wikström, J.
    Uppsala University, Sweden.
    Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, no 1, p. 17-24Article, review/survey (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.

  • 46.
    Wesnes, Kristin
    et al.
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Myhr, Kjell-Morten
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Riise, Trond
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Cortese, Marianna
    Univ Bergen, Norway; Haukeland Hosp, Norway.
    Pugliatti, Maura
    Univ Bergen, Norway; Univ Ferrara, Italy.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden.
    Wolfson, Christina
    McGill Univ, Canada.
    Bjornevik, Kjetil
    Haukeland Hosp, Norway; Univ Bergen, Norway.
    Physical activity is associated with a decreased multiple sclerosis risk: The EnvIMS study2018In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, no 2, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background: The lifestyle factors smoking and obesity have been associated with the risk of multiple sclerosis (MS). Physical activity (PA) may also be of importance. Objective: To examine the association between PA and MS risk in Italy, Norway, and Sweden and to evaluate the possible influence by established risk factors. Methods: In this case-control study, 1904 cases and 3694 controls were asked to report their average weekly amounts of light and vigorous PA during adolescence on a scale ranging from none to more than 3 hours activity. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for potential confounders. Results: Vigorous PA was inversely associated with MS risk in the pooled analysis (p-trend amp;lt; 0.001) with an age-and sex-adjusted OR of 0.74 (95% CI: 0.63-0.87) when comparing the highest and lowest levels. Adjusting for outdoor activity, infectious mononucleosis, body size, and smoking yielded similar results. The association was present in all countries and was not affected by exclusion of patients with early disease onset. Light PA was not associated with the risk of MS. Conclusion: Our findings suggest that vigorous PA can modify the risk of developing MS independent of established risk factors.

  • 47.
    Wickström, Anne
    et al.
    Umeå University, Sweden.
    Fagerström, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center.
    Wickström, Lucas
    Linköping University, Department of Computer and Information Science. Linköping University, Faculty of Science & Engineering.
    Granasen, Gabriel
    Umeå University, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Sundstrom, Peter
    Umeå University, Sweden.
    The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 8, p. 1137-1147Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. Objectives: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Methods: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. Results: The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population (pamp;lt;0.001). The employees in the northern population had significantly lower requirements, greater adapted work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population (p=0.042). Conclusion: Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

  • 48.
    Willows, Thomas
    et al.
    Karolinska University Hospital, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Nyholm, Dag
    Uppsala University, Sweden.
    Widner, Hakan
    Skåne University Hospital, Sweden.
    Grenholm, Peter
    Uppsala University, Sweden.
    Schmiauke, Ursula
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Urbom, Anna
    AbbVie AB, Sweden.
    Groth, Kristina
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Larsson, Jorgen
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Permert, Johan
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Kjellander, Susanna
    AbbVie AB, Sweden.
    Initiation of Levodopa-Carbidopa Intestinal Gel Infusion Using Telemedicine (Video Communication System) Facilitates Efficient and Well-Accepted Home Titration in Patients with Advanced Parkinsons Disease2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 4, p. 719-728Article in journal (Refereed)
    Abstract [en]

    Background: Levodopa-carbidopa intestinal gel (LCIG; Duodopa r) is used for continuous infusion in advanced Parkinsons disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. Objective: Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. Methods: Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. Results: Patient median (range) age was 67 (52-73) years and time since diagnosis was 10 (7-23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0-13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours: minutes) 1 : 14 (0 : 29-1 : 52), 5 : 49 (2 : 46-10 : 3), and 8 : 53 (4 : 11-14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). Conclusions: In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses.

  • 49.
    Witt, Suzanne T
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Drissi, Natasha Morales
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
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    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
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    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Szakács, Attila
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Hallböök, Tove
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Uppsala, Sweden.
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    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).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
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    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Evidence for cognitive resource imbalance in adolescents with narcolepsy2018In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 2, p. 411-424Article in journal (Refereed)
    Abstract [en]

    The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized