C A Vedeler

University of Bergen, Bergen, Hordaland, Norway

Are you C A Vedeler?

Claim your profile

Publications (162)444.69 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fingolimod (FTY720) is approved for treatment of relapsing-remitting multiple sclerosis. In vitro studies have found that fingolimod stimulates remyelination in cerebellar slices, but in vivo animal studies have not detected any positive effect on cerebral remyelination. The discrepant findings could be a result of different mechanisms underlying cerebral and cerebellar remyelination. The cuprizone model for de- and remyelination was used to evaluate whether fingolimod had an impact on cerebellar remyelination in vivo. We found that fingolimod did not have any effect on cerebellar remyelination, number of mature oligodendrocytes, microglia or astrocytes when fed after cuprizone exposure.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Paraneoplastic neurological syndromes (PNS) are poorly described in patients without onconeural antibodies and in patients with non-small cell lung cancer (NSCLC). We compared the clinical characteristics of PNS in lung cancer patients with and without onconeural antibodies. Medical records from patients with lung cancer and neurological symptoms referred for onconeural antibody analysis in the period 1995-2004 were analyzed and well-established diagnostic criteria used for the retrospective diagnosis of PNS. Thirty-one patients were diagnosed with PNS and included in the study. Data from the Cancer Registry of Norway and follow-up medical data were analyzed. Small-cell lung cancer (SCLC) was the most common lung cancer in the 31 PNS patients (77%, P<0.01). Onconeural antibodies were found in 18 of the PNS patients (58%). Paraneoplastic encephalomyelitis (PEM) was the most common PNS among the seropositive patients (11 of 18 patients), of which 10 had SCLC. Various types of PNS were found in the 13 seronegative patients. Approximately 40% of PNS patients with lung cancer do not have onconeural antibodies. PEM was the most common PNS in the seropositive patients. Our results underline the importance of recognizing PNS in patients with NSCLC and those without onconeural antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of the Neurological Sciences 11/2014; 348(1-2). DOI:10.1016/j.jns.2014.10.040 · 2.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anti interferon-beta (IFN-β) neutralizing antibodies (NAb) affect efficacy of treatment of multiple sclerosis patients, but exactly when the detrimental effects of NAbs offset therapeutic efficacy is debated. Quantification of intracellular pathway-specific phosphorylation by phospho-specific flow cytometry (phosphoflow) is a promising tool for evaluation of these effects in primary immune cells from treated patients at the single-cell level. Samples for phosphoflow and gene expression changes were collected before administration of IFN-β and at four, six, and eight hours thereafter. Patients were NAb negative (n = 3) or were NAb positive with low/medium (n = 1) or high (n = 2) NAb titers. Levels of phosphorylation of six Stat transcription factors (pStat) in seven cell subtypes and expression levels of 71 pathway-specific genes in whole blood were measured. The data was subjected to principal component analysis (PCA), fifty-fifty MANOVA, ANOVA, and partial least square regression (PLSR). PCA of pStat levels clustered patients according to NAb class independently of time. PCA of gene expression data clustered patients according to NAb class but was affected by time and treatment. In the fifty-fifty MANOVA, NAb class was significant for both pStat levels and gene expression data. The ANOVA identified pStat1 protein in several cell subtypes as significantly affected by NAb class. The best fitting model for NAb prediction based on PLSR included pStat1 in monocytes, T cells, or lymphocytes and pStat3 in monocytes (r = 0.97). Gene expression data were slightly less predictive of NAb titers. Based on this proof of concept study, we hypothesize that NAb effects can be monitored by evaluation of a single biomarker, pStat1, in either monocytes or T cells by phosphoflow directly after IFN-β administration. The method will significantly reduce cost relative to labor intensive in vitro methods and offers a patient-specific approach to NAb evaluation.
    PLoS ONE 02/2014; 9(2):e88632. DOI:10.1371/journal.pone.0088632 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Onconeural antibodies are important in the detection of paraneoplastic neurological syndromes (PNS). The avidity of Hu, Yo, and CRMP5 antibodies from 100 patients was determined by immunoprecipitation (IP), and 13 of the Yo positive sera were also tested by surface plasmon resonance (SPR). There was a significant association between the results from IP and SPR. Yo antibodies had higher avidity than Hu and CRMP5 antibodies, and both high- and low-avidity antibodies were associated with tumors and PNS. High-avidity Yo antibodies were mainly associated with ovarian cancer, whereas high-avidity Hu and CRMP5 antibodies were mainly associated with small-cell lung cancer. Low-avidity CRMP5 and Yo antibodies were less often detected by a commercial line blot than high-avidity antibodies. The failure to detect low-avidity onconeural antibodies may result in under diagnosis of PNS.
    Cancer Immunology and Immunotherapy 06/2013; 62(8). DOI:10.1007/s00262-013-1442-6 · 3.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: We report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity. CASE PRESENTATION: An eighteen year old man presented with a history of childhood-onset, progressive generalized dystonia. Clinical examination revealed a pure generalized dystonia with no cognitive or other neurological findings. Magnetic resonance imaging showed bilateral high T2 signal striatal lesions, which were slowly progressive over a period of nine years. New parts of the lesion showed restricted water diffusion suggesting cytotoxic oedema. Positron emission tomography of the brain showed frontal hypermetabolism and cerebellar hypometabolism. Antibodies against the NR1 subunit of the NMDA receptor were detected in the patient's serum and cerebrospinal fluid. There was no neoplasia or preceding infection or vaccination. CONCLUSION: This is the first report of chronic progressive bilateral striatal necrosis associated with anti-NMDAR antibodies. Our findings expand the clinical spectrum of disease associated with anti-NMDAR antibodies and suggest that these should be included in the work-up of dystonia with striatal necrosis.
    BMC Neurology 05/2013; 13(1):55. DOI:10.1186/1471-2377-13-55 · 2.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND PURPOSE: Our population-based long-term follow-up of young ischaemic stroke patients and controls showed 10-fold increased mortality and fivefold increased arterial event rate nearly 12 years after study inclusion. We now assess memory, anxiety, depression and sleep in relation to employment and functional outcome, treatment goals and results from a last alive-dead survey. METHODS: Patients (n = 232) ≤ 49 years with an index-stroke between 1988 and 1997 were retrospectively selected and compared with age- and sex-matched controls (n = 453). At follow-up from 2004 to 2005, 144 (77%) of 187 patients were clinically examined. Self-assessment information about memory problems, anxiety, depression, sleeping problems, education and employment was compared with answers from standardized questionnaires from 167 controls. Functional outcome was measured by the modified Rankin Scale (mRS). RESULTS: Patients compared with controls had more memory problems (41.0% vs. 5.4%, P < 0.001), anxiety (19.4% vs. 9%, P = 0.009), depression (29.2% vs. 13.2%, P = 0.001) and sleeping problems (36.1% vs. 19.2%, P = 0.001). In the multiple regression analysis male gender (OR 9.3, 95%CI 0.10-0.61, P = 0.002), normal memory (OR 12.7, 95%CI 0.07-0.47, P < 0.001) and mRS 0-1 (OR 15.7, 95%CI 0.002-0.12, P < 0.001) were factors for full-time employment. Blood pressure was < 140/90 mmHg in 39% of patients, 49% stopped smoking and 38.2% used statins. After a mean observation time of 18.3 years, 63 (27.2%) of 232 patients were dead. CONCLUSIONS: Our data show a heterogeneous prognosis and high mortality even for long-time survivors of ischaemic stroke at a young age. Prospective studies of young stroke patients and controls are necessary for direct comparison.
    European Journal of Neurology 01/2013; 20(5). DOI:10.1111/ene.12073 · 3.85 Impact Factor
  • C A Vedeler, E Farbu, S I Mellgren
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic immune-mediated demyelinating polyneuropathies can often lead to severe neurologic disability. Literature review and personal experience with these types of neuropathies. It is important to recognize these immune-mediated neuropathies as they respond to treatment.
    Acta neurologica Scandinavica. Supplementum 01/2013; 127(196):48-51. DOI:10.1111/ane.12049
  • Journal of Neurology 12/2012; 260(3). DOI:10.1007/s00415-012-6800-3 · 3.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system in genetically susceptible persons. Fcγ receptors (FcγR) are involved in autoimmune diseases. Sixteen Norwegian patients with relapsing-remitting MS (RRMS) were studied to see whether treatment with either interferon-beta (INF-β) or glatiramer acetate (GA) influenced the proportion of FcγR1a, FcγR2a, and FcγR3b positive monocytes, granulocytes, or lymphocytes or FcγR1a, FcγR2a, and FcγR2b mRNA levels in leukocytes. One hundred and twenty-seven patients with RRMS and 54 Norwegian healthy blood donors were also analyzed for FcγR2b polymorphisms. Interferon-beta or GA treatment initiated an increase in the proportion of FcγR positive lymphocytes, but did not cause major influence of the long-term proportion of FcγR positive leukocytes or their FcγR mRNA levels. No significant differences were observed between RRMS patients and healthy controls for the genotype and allele frequencies of FcγR2b polymorphisms. INF-β or GA treatment probably has no major role in the regulation of FcγRs on immune cells in RRMS. Furthermore, polymorphisms of the inhibitory FcγR2b do not seem to influence the susceptibility for MS.
    Acta neurologica Scandinavica. Supplementum 12/2012; 126(195):84-9. DOI:10.1111/ane.12026
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to identify proteins in cerebrospinal fluid (CSF) with different abundance between patients with relapsing-remitting multiple sclerosis (RRMS) and controls. Such proteins may be diagnostic biomarkers and contribute with novel information about the disease pathogenesis. Cerebrospinal fluid from patients with RRMS (n = 17) and controls (n = 17) were trypsin digested and analyzed in a label-free fashion using liquid chromatography mass spectrometry. The resulting data were analyzed using SearchGUI, PeptideShaker, and the Progenesis software. Two hundred and ninety-one proteins were identified, of which 32 were significantly differentially abundant between the patients with RRMS and controls (P-value ≤ 0.05, two or more peptides quantified). Among these were proteins which previously have been linked to MS, including immunoglobulin subunits, vitamin D-binding protein, apolipoprotein D, kallikrein-6, neuronal pentraxin receptor, Dickkopf-related protein 3, and contactin-1. The study provides an overview of differentially abundant proteins between RRMS and controls, and a few of these are further discussed. It should be stressed that a larger verification study is needed to reveal the potential value of these proteins as biomarkers for RRMS and their involvement in the disease pathogenesis.
    Acta neurologica Scandinavica. Supplementum 12/2012; 126(195):90-6. DOI:10.1111/ane.12029
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we aimed to discover cerebrospinal fluid (CSF) proteins with significant abundance difference between early multiple sclerosis patients and controls, and do an initial verification of these proteins using selected reaction monitoring (SRM). iTRAQ and Orbitrap MS were used to compare the CSF proteome of patients with clinically isolated syndrome (CIS) (n=5), patients with relapsing-remitting multiple sclerosis that had CIS at the time of lumbar puncture (n=5), and controls with other inflammatory neurological disease (n=5). Of more than 1200 identified proteins, five proteins were identified with significant abundance difference between the patients and controls. In the initial verification using SRM we analyzed a larger patient and control cohort (n=132) and also included proteins reported as differentially abundant in multiple sclerosis in the literature. We found significant abundance difference for 11 proteins after verification, of which the five proteins alpha-1-antichymotrypsin, contactin-1, apolipoprotein D, clusterin, and kallikrein-6 were significantly differentially abundant in several of the group comparisons. This initial study form the basis for further biomarker verification studies in even larger sample cohorts, to determine if these proteins have relevance as diagnostic or prognostic biomarkers for multiple sclerosis.
    Journal of proteomics 10/2012; 78. DOI:10.1016/j.jprot.2012.09.037 · 3.93 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunogenicity of recombinant interferon-β (IFN-β) is a known complication in the therapy of relapsing-remitting multiple sclerosis (RRMS). Neutralizing antibodies (NAbs) that can interfere with efficacy are quantified using in vitro bioassays; however, these assays do not reveal the immunogenic state of the patient and are not predictive of treatment outcome. Assessment of the impact of NAbs on IFN-β responsive cells and signalling pathways in peripheral blood mononuclear cells (PBMCs) with phospho-specific flow cytometry. PBMCs from 10 IFN-β-treated patients with RRMS, two untreated patients, and two healthy controls were re-stimulated in autologous sera and media with a serial dilution of IFN-β (0-8000 U/ml) and levels of phosphorylation of STAT1/3/4/5/6 transcription factors were quantified in PBMC subtypes (NAb titres 0 to > 6000 neutralizing units). Data was subjected to principal component analysis, Hotelling's T (2), and partial least squares analysis. Three significantly distinct clusters of individuals were revealed in autologous sera: therapy-naïve and healthy, treated NAb-negative, and treated NAb-positive. Compared with controls STATs signalling patterns were modulated in treated NAb-negative patients and inhibited in all treated NAb-positive patients independently of NAb titres. In media no clustering of patients could be found. The predictability of NAb titres based on the phospho-flow data was 74%. Phospho-specific flow cytometry can delineate subset-specific cell responses that can act as surrogates for NAb exposure in blood. Immunogenic effects alter the response in primary cells even at low NAb levels. Cell line-based immunogenicity testing is not readily transferable to the immunogenic response in patients.
    Multiple Sclerosis 01/2012; 18(8):1116-24. DOI:10.1177/1352458511434066 · 4.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is not unusual to observe peripheral nervous system involvement in people with tumours outside the nervous system. Any part of the peripheral nervous system can be involved, from sensory and motor neurons to nerve roots and plexuses, from distal trunks to neuromuscular junctions. Pathogenesis also varies from direct infiltration by cancer cells, to treatment toxicity, to metabolic derangement, cachexia, infections and paraneoplastic syndromes.Paraneoplastic neurological syndromes are symptoms or signs resulting from damage to organs or tissues that are remote from the site of the malignancy or its metastases. The pathogenesis is thought to be immune-mediated as a result of a cross-reaction against antigens shared by the tumour and nervous system cells.Paraneoplastic neuropathies are the most frequently reported paraneoplastic syndromes. They are, however, heterogeneous and require several therapeutic approaches. This review was undertaken to systematically assess any data available from randomised controlled trials (RCTs) on the treatment of paraneoplastic syndromes of the peripheral nervous system and not the whole range of paraneoplastic neurological syndromes. To assess the benefits and harms of treatments for paraneoplastic neuropathies. We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2012), CENTRAL (2012, Issue 1), MEDLINE (January 1966 to February 2012), EMBASE (January 1980 to February 2012) and LILACS (January 1982 to February 2012) for RCTs, quasi-RCTs, historically controlled studies and trials with concurrent controls.We adapted this strategy to search MEDLINE from 1966 and EMBASE from 1980 for comparative cohort studies, case-control studies and case series. We planned to include all RCTs and quasi-RCTs (in which allocation is not random but is intended to be unbiased, for example alternate allocation) of any treatment for paraneoplastic neuropathies. Since we expected there to be few or no included studies, we also planned to assess and summarise observational studies, prospective and retrospective comparative cohort studies, case-control studies and case series that met minimum criteria in the discussion. Three review authors selected the trials for inclusion. When there was any disagreement we reached an agreement by discussion. Two review authors extracted data independently onto a specially designed data extraction form. We would have collected adverse event data from included studies. Despite many reports on paraneoplastic neuropathy, we identified no RCT or quasi-RCTs for inclusion in this review. We found only six studies, involving 54 participants, from among the non-randomised evidence that were judged by predefined criteria to be of suitable quality for inclusion in the discussion. These studies were not readily comparable. The treatments focused on tumour treatment and immunomodulation, mainly intravenous immunoglobulin. At present there are no RCTs or quasi-RCTs of treatment for paraneoplastic neuropathies on which to base practice. There is only evidence from case series, case reports or expert opinion (class IV evidence) for the effect of immunomodulation (intravenous immunoglobulin, plasma exchange, steroid treatment or chemotherapy) on paraneoplastic neuropathy.
    Cochrane database of systematic reviews (Online) 01/2012; 12(12):CD007625. DOI:10.1002/14651858.CD007625.pub2 · 5.94 Impact Factor
  • M Raspotnig, C A Vedeler, A Storstein
    [Show abstract] [Hide abstract]
    ABSTRACT: Onconeural antibodies are strongly associated with cancer and paraneoplastic neurological syndromes (PNS). Most of these antibodies are well-characterized (antibodies against Hu, Yo, Ri, CRMP5, amphiphysin, Ma2 and Tr) and are in common use for the diagnosis of definite PNS. Literature on detection and clinical significance of onconeural antibodies were identified by using relevant search terms in PubMed and reviewed. The onconeural antibodies are directed against intracellular antigens and their pathogenic role is still largely unknown. They are highly specific markers of paraneoplastic aetiology in patients with neurological symptoms. Detection of an onconeural antibody in a patient with neurological symptoms should lead to prompt investigation for cancer. However, absence of detectable onconeural antibodies does not exclude the PNS diagnosis. In particular, failure to detect antibodies in patients without classical PNS symptoms may result in less vigorous cancer screening and diagnostic delay. Neuronal antibodies that are directed to synaptic proteins or proteins of the cell membrane are also associated with neurological symptoms, and probably have pathogenic effects. The association between these antibodies and cancer is less robust, and they are usually not included among the onconeural antibodies.
    Acta neurologica Scandinavica. Supplementum 08/2011; 124(191):83-8. DOI:10.1111/j.1600-0404.2011.01549.x
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0-5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0-4.0%) and transient in 1.0% (95% CI: 0.7-1.3%) of the patients. The frequencies of permanently antibody positive patients did not show statistically significant differences between the four centres, whereas the frequencies of transiently antibody positive patients showed some variations. The frequencies of antibodies appeared to be of the same magnitude in the four centres, but might be less than in the pivotal studies of natalizumab.
    Multiple Sclerosis 04/2011; 17(9):1074-8. DOI:10.1177/1352458511404271 · 4.86 Impact Factor
  • Source
    Christian Vedeler, Laurence Bindoff
    Journal of Neurology 04/2011; 258(10):1888-9. DOI:10.1007/s00415-011-6023-z · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To define the frequency and clinical and immunologic characteristics of patients af- fected by paraneoplastic neurologic syndromes (PNS) and lymphoma. Methods: Patients fulfilling the criteria for PNS associated with lymphoma collected from the European Commission-funded PNS Euronetwork group database were analyzed. Results: Fifty-three patients with Hodgkin lymphoma (HL) (24 patients, mean age 51, range 16– 84) or non-Hodgkin lymphoma (NHL) (29 patients, mean age 64, range 31–82) and PNS were analyzed. The most commonly associated PNS was paraneoplastic cerebellar degeneration, present in 21 cases, with a higher prevalence in HL (16/24 cases). Peripheral nervous system (mainly demyelinating polyradiculopathies) and motor neuron involvement were more common in NHL. Onconeural antibodies were more frequent in patients with paraneoplastic cerebellar de- generation, most commonly against the Tr antigen. Fifty percent of the patients with PNS and HL responded to chemotherapy, whereas neurologic improvement was less frequent (24%) in patients with PNS and NHL. In both groups, the survival rate was good. Overall, 10 out of 53 patients eventually died, with only 2 patients (1 with HL, 1 with NHL) dying from PNS. Conclusions: PNS in patients with lymphoma are relatively rare. Paraneoplastic cerebellar degen- eration, mainly associated with anti-Tr antibodies, is more prevalent in HL and NHL, followed in our study by motor neuron disease in patients with NHL. Involvement of the peripheral nervous system is heterogeneous, with a prevalence of polyradiculoneuritis in patients with NHL.
    Neurology 02/2011; 76:705–710. · 8.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To define the frequency and clinical and immunologic characteristics of patients affected by paraneoplastic neurologic syndromes (PNS) and lymphoma. Patients fulfilling the criteria for PNS associated with lymphoma collected from the European Commission-funded PNS Euronetwork group database were analyzed. Fifty-three patients with Hodgkin lymphoma (HL) (24 patients, mean age 51, range 16-84) or non-Hodgkin lymphoma (NHL) (29 patients, mean age 64, range 31-82) and PNS were analyzed. The most commonly associated PNS was paraneoplastic cerebellar degeneration, present in 21 cases, with a higher prevalence in HL (16/24 cases). Peripheral nervous system (mainly demyelinating polyradiculopathies) and motor neuron involvement were more common in NHL. Onconeural antibodies were more frequent in patients with paraneoplastic cerebellar degeneration, most commonly against the Tr antigen. Fifty percent of the patients with PNS and HL responded to chemotherapy, whereas neurologic improvement was less frequent (24%) in patients with PNS and NHL. In both groups, the survival rate was good. Overall, 10 out of 53 patients eventually died, with only 2 patients (1 with HL, 1 with NHL) dying from PNS. PNS in patients with lymphoma are relatively rare. Paraneoplastic cerebellar degeneration, mainly associated with anti-Tr antibodies, is more prevalent in HL and NHL, followed in our study by motor neuron disease in patients with NHL. Involvement of the peripheral nervous system is heterogeneous, with a prevalence of polyradiculoneuritis in patients with NHL.
    Neurology 02/2011; 76(8):705-10. DOI:10.1212/WNL.0b013e31820d62eb · 8.30 Impact Factor

Publication Stats

3k Citations
444.69 Total Impact Points

Institutions

  • 1987–2014
    • University of Bergen
      • • Department of Clinical Medicine
      • • The Gade Institute
      Bergen, Hordaland, Norway
  • 1989–2012
    • Haukeland University Hospital
      • Department of Neurology
      Bergen, Hordaland, Norway
  • 2011
    • University of Padova
      • Department of Neurosciences
      Padova, Veneto, Italy
  • 2003
    • University Hospital of North Norway
      • Department of Neurology
      Tromsø, Troms Fylke, Norway
  • 1992
    • University of Pennsylvania
      • Department of Neurology
      Philadelphia, Pennsylvania, United States