liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Vrethem, Magnus
Publications (10 of 59) Show all publications
Alping, P., Piehl, F., Langer-Gould, A., Frisell, T., Burman, J., Fink, K., . . . Vrethem, M. (2019). Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations. Epidemiology, 30(2), 230-233
Open this publication in new window or tab >>Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations
Show others...
2019 (English)In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, no 2, p. 230-233Article in journal (Refereed) Published
Abstract [en]

The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of amp;gt;3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
Multiple sclerosis; Pharmacoepidemiology; Register; Validation
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:liu:diva-154830 (URN)10.1097/EDE.0000000000000948 (DOI)000458417200017 ()30721167 (PubMedID)
Note

Funding Agencies|Patient-Centered Outcomes Research Institute (PCORI) Award [MS-1511-33196]; Swedish Foundation for MS Research; Biogen; Roche; Biogen Idec; Genzyme; Novartis

Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2019-03-05
Gustafsson, G., Broström, A., Ulander, M., Vrethem, M. & Svanborg, E. (2015). Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation. Clinical Neurophysiology, 126(8), 1493-1497
Open this publication in new window or tab >>Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation
Show others...
2015 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 126, no 8, p. 1493-1497Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2015
National Category
Pediatrics Neurology
Identifiers
urn:nbn:se:liu:diva-115914 (URN)10.1016/j.clinph.2014.10.015 (DOI)000357488800008 ()25453612 (PubMedID)
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2017-12-04
Burman, J., Iacobaeus, E., Svenningsson, A., Lycke, J., Gunnarsson, M., Nilsson, P., . . . Fagius, J. (2014). Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. Journal of Neurology, Neurosurgery and Psychiatry, 85(10), 1116-1121
Open this publication in new window or tab >>Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience
Show others...
2014 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 10, p. 1116-1121Article in journal (Refereed) Published
Abstract [en]

Background Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS. Methods Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months. Results At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%). Conclusions HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

Place, publisher, year, edition, pages
BMJ Publishing Group, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112836 (URN)10.1136/jnnp-2013-307207 (DOI)000344456000228 ()24554104 (PubMedID)
Available from: 2015-01-08 Created: 2014-12-17 Last updated: 2017-12-05Bibliographically approved
Johansson, P., Alehagen, U., Vrethem, M., Svanborg, E. & Broström, A. (2014). Difficulties in Identification of Sleep Disordered Breathing in an Outpatient Clinic for Heart Failure– A Case Study. Annals of Nursing and Practice, 1(3), Article ID 1011.
Open this publication in new window or tab >>Difficulties in Identification of Sleep Disordered Breathing in an Outpatient Clinic for Heart Failure– A Case Study
Show others...
2014 (English)In: Annals of Nursing and Practice, ISSN 2379-9501, Vol. 1, no 3, article id 1011Article in journal (Refereed) Published
Abstract [en]

Sleep disordered breathing (SDB) is prevalent in patients with heart failure (HF). The clinical signs of newly diagnosed HF and untreated SDB may overlap and patients in need of SDB treatment can therefore be difficult to identify in patients participating in disease management programmes (DMP). The aim was to describe the care process of two patients with HF involved in a DMP, focusing on the difficulties to identify and initiate treatment of SDB.A prospective case study design was used to follow one male (70 yrs) and one female (74 yrs) patient during 18 months at a Swedish University hospital. It took 5 to 10 months from diagnosis of HF until optimal treatment was reached for their heart conditions and 12 to 17 months until SDB was treated. None of the patients complained of poor sleep, but suffered from fatigue. In the male SDB was detected by the wife’s complaints of her husband’s snoring, apnoeas and restless sleep. In the female, SDB was detected after a detailed assessment of fatigue which was shown to be sleepiness. After optimal treatment of HF but before imitation of SDB treatment both cases cardiac function improved. For the female case improvements also were found in the blood pressure. SDB treatment improved fatigue in both patients. Initiation of HF treatment and self-care routines, as well as identification of SDB is complex and time consuming. Treatment of HF and SDB can improve sleep, cardiac function as well as disturbing associated symptoms.

Place, publisher, year, edition, pages
JSciMedCentral, 2014
National Category
General Practice
Identifiers
urn:nbn:se:liu:diva-115916 (URN)
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2018-01-11Bibliographically approved
Samuelsson, K., Kostulas, K., Vrethem, M., Rolfs, A. & Press, R. (2014). Idiopathic Small Fiber Neuropathy: Phenotype, Etiologies, and the Search for Fabry Disease. Journal of Clinical Neurology, 10(2), 108-118
Open this publication in new window or tab >>Idiopathic Small Fiber Neuropathy: Phenotype, Etiologies, and the Search for Fabry Disease
Show others...
2014 (English)In: Journal of Clinical Neurology, ISSN 1738-6586, Vol. 10, no 2, p. 108-118Article in journal (Refereed) Published
Abstract [en]

Background and Purpose

The etiology of small fiber neuropathy (SFN) often remains unclear. Since SFN may be the only symptom of late-onset Fabry disease, it may be underdiagnosed in patients with idiopathic polyneuropathy. We aimed to uncover the etiological causes of seemingly idiopathic SFN by applying a focused investigatory procedure, to describe the clinical phenotype of true idiopathic SFN, and to elucidate the possible prevalence of late-onset Fabry disease in these patients.

Methods

Forty-seven adults younger than 60 years with seemingly idiopathic pure or predominantly small fiber sensory neuropathy underwent a standardized focused etiological and clinical investigation. The patients deemed to have true idiopathic SFN underwent genetic analysis of the alpha-galactosidase A gene (GLA) that encodes the enzyme alpha-galactosidase A (Fabry disease).

Results

The following etiologies were identified in 12 patients: impaired glucose tolerance (58.3%), diabetes mellitus (16.6%), alcohol abuse (8.3%), mitochondrial disease (8.3%), and hereditary neuropathy (8.3%). Genetic alterations of unknown clinical significance in GLA were detected in 6 of the 29 patients with true idiopathic SFN, but this rate did not differ significantly from that in healthy controls (n=203). None of the patients with genetic alterations in GLA had significant biochemical abnormalities simultaneously in blood, urine, and skin tissue.

Conclusions

A focused investigation may aid in uncovering further etiological factors in patients with seemingly idiopathic SFN, such as impaired glucose tolerance. However, idiopathic SFN in young to middle-aged Swedish patients does not seem to be due to late-onset Fabry disease.

Place, publisher, year, edition, pages
Korean Neurological Association, 2014
Keywords
etiology; Fabry disease; idiopathic; impaired glucose tolerance; small fiber neuropathy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106282 (URN)10.3988/jcn.2014.10.2.108 (DOI)000333775100005 ()
Available from: 2014-05-06 Created: 2014-05-05 Last updated: 2014-10-29Bibliographically approved
Wickström, A., Dahle, C., Vrethem, M. & Svenningsson, A. (2014). Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial. Multiple Sclerosis, 20(8), 1095-1101
Open this publication in new window or tab >>Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial
2014 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 8, p. 1095-1101Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

In a retrospective study, we have previously shown that work ability was improved after the initiation of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS). In another prospective trial (TYNERGY) the effect on MS-related fatigue was evaluated after 12 months of treatment with natalizumab. A comprehensive Capacity for Work Questionnaire (CWQ) was used to collect data regarding number of working hours and sickness absence. The predefined intention-to-treat analysis regarding work ability did not, however, show significant results.

OBJECTIVES:

The objective of this paper is to assess the amount of sick leave in RRMS before and after one year of natalizumab treatment and correlate it to fatigue and walking ability.

METHODS:

This is a post-hoc analysis of the complete data from the CWQ used in the TYNERGY trial.

RESULTS:

MS patients receiving sickness benefit before start of treatment reduced their sickness benefit by an absolute change of 33% after one year of natalizumab treatment. Younger age and improvement of walking ability correlated significantly with reduction of sick leave.

CONCLUSIONS:

This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

Place, publisher, year, edition, pages
Sage Publications, 2014
Keywords
Multiple sclerosis; work ability; fatigue; motor fatigue; walking distance; biological drugs; natalizumab
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-109239 (URN)10.1177/1352458513517590 (DOI)000338819400012 ()24378984 (PubMedID)
Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved
Edström, M., Dahle, C., Vrethem, M., Gustafsson, M., Benson, M., Jenmalm, M. & Ernerudh, J. (2014). Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines.
Open this publication in new window or tab >>Regulatory T cells in Multiple Sclerosis – Indications of impaired function of suppressive capacity and a role for chemokines
Show others...
2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND Regulatory T cells (Treg) are critical for immune regulation and homeostasis. In multiple sclerosis (MS), the function of these cells has been shown to be impaired, although the underlying mechanism has yet to be shown. In the current study, we aimed to characterize and assess the phenotypical, functional and transcriptional characteristics of memory and naïve Treg in MS patients and controls.

MATERIAL AND METHODS 27 patients with relapsing-remitting disease were included, along with 29 healthy controls. Flow cytometry was used for detailed phenotyping of Treg subpopulations CD4+CD45RA+/- and CD4dimCD25++ and their expression of FOXP3, CD39 and HELIOS. CFSE (proliferation marker) and CD69 (activation marker) were used to investigate the functional capacity of Treg. A microarray was employed for genome-wide transcriptional characterization of isolated Treg.

RESULTS CD4+CD45RA–CD25++ activated Treg displayed a higher expression of FOXP3 and CD39 than resting CD4+CD45RA+CD25+ Treg, while no significant phenotypical differences were observed in Treg subpopulations between patients and controls. However, a lower anti-proliferative capacity was observed in activated Treg of MS patients compared with those of controls (p<0.05), while suppression of activation was similar to controls. Gene set enrichment analysis (GSEA) of microarray data revealed enrichment for the GO gene set ‘chemokine receptor binding’ in MS Treg.

CONCLUSION Although numerical phenotypical assessment of resting and activated Tregs did not reveal any significant difference between patients and controls, functional co-culturing experiments showed an impaired function in activated Treg of MS patients. Furthermore, GSEA revealed immune-related gene sets overexpressed in Treg of MS patients, possibly containing clues to the functional impairment. In particular over-activity in chemokine signalling in Treg would be of interest for further investigation.

Keywords
EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-108908 (URN)
Available from: 2014-07-11 Created: 2014-07-11 Last updated: 2018-01-11Bibliographically approved
Mellergård, J., Edström, M., Jenmalm, M., Dahle, C., Vrethem, M. & Ernerudh, J. (2013). An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients. PLoS ONE, 8(12), Article ID e81685.
Open this publication in new window or tab >>An Increase in B cell and Cytotoxic NK cell Proportions and Increased T cell Responsiveness in Blood of Natalizumab-treated Multiple Sclerosis Patients
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81685Article in journal (Refereed) Published
Abstract [en]

Background

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

Objectives

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

Material and methods

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

Results

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

Conclusions

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

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science, 2013
Keywords
Multiple sclerosis, natalizumab, flow cytometry, T-cells, NK-cells, B-cells, lymphocyte proliferation
National Category
Neurology Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-84268 (URN)10.1371/journal.pone.0081685 (DOI)000327944500088 ()24312575 (PubMedID)2-s2.0-84891420120 (Scopus ID)
Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2018-01-12Bibliographically approved
Vrethem, M., Lindh, J., Tondel, M., Persson, B. & Dahle, C. (2013). IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy. Acta Neurologica Scandinavica, 127(2), 109-115
Open this publication in new window or tab >>IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy
Show others...
2013 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 109-115Article in journal (Refereed) Published
Abstract [en]

Objectives To study the prevalence of antibodies of IgA class against tissue transglutaminase (tTG), endomysium (EMA) and gliadin (AGA) in patients with chronic idiopathic axonal polyneuropathy (CIAP) and to characterize the patients clinically and neurophysiologically. Methods Of 182 patients, 126 patients agreed to blood sampling. Sera were analysed by ELISAs detecting anti-tTG and AGA, whereas EMA was analysed by indirect immunofluorescence (IF) microscopy. Gastrointestinal symptoms were assessed by data from medical records and patient interviews. Results Nine of 126 patients (7%) were seropositive in at least one test (five with positive anti-tTG and/or EMA and four with positive AGA only). One patient with elevated levels of all specificities had laboratory signs of malabsorption and gastrointestinal complaints with abdominal pain and diarrhoea. Conclusions Elevated levels of IgA-AGA were slightly more frequent in patients with CIAP (4%) compared to 2.5% in 1866 healthy blood donors. Highly specific serological markers indicative of coeliac disease (CD) (anti-tTG and EMA) were somewhat more common in our patients with CIAP (4%) than expected from normal reference values and from studies of the prevalence of CD in the general population. Even though these findings may indicate a relationship, the aetiological importance is unclear.

Place, publisher, year, edition, pages
John Wiley and Sons, 2013
Keywords
neuropathy, idiopathic, gluten sensitivity, coeliac disease, anti-tissue transglutaminase, anti-gliadin, anti-endomysium
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-89742 (URN)10.1111/j.1600-0404.2012.01687.x (DOI)000313886700007 ()
Note

Funding Agencies|Swedish Council for Work Life and Social Research||Medical Research Council of Southeast Sweden (FORSS)||

Available from: 2013-03-07 Created: 2013-03-05 Last updated: 2017-12-06
Kvarnström, M., Ydrefors, J., Ekerfelt, C., Vrethem, M. & Ernerudh, J. (2013). Longitudinal interferon-β effects in multiple sclerosis: differential regulation of IL-10 and IL-17A, while no sustained effects on IFN-γ, IL-4 or IL-13. Journal of the Neurological Sciences, 325(1-2), 79-85
Open this publication in new window or tab >>Longitudinal interferon-β effects in multiple sclerosis: differential regulation of IL-10 and IL-17A, while no sustained effects on IFN-γ, IL-4 or IL-13
Show others...
2013 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 325, no 1-2, p. 79-85Article in journal (Refereed) Published
Abstract [en]

Background:

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

Material and methods:

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

Results:

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

Conclusion:

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

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Multiple sclerosis, Interferon-beta, Cytokines, IL-4, IL-17, IL-10, Responder
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90199 (URN)10.1016/j.jns.2012.12.001 (DOI)000315323000016 ()
Note

Funding Agencies|Biogen Idec||Network for Inflammation research||Swedish Foundation for Strategic Research||Swedish Association of Neurologically Disabled||County Council of Ostergotland||University Hospital of Linkoping and Lions Ostergotland||

Available from: 2013-04-03 Created: 2013-03-21 Last updated: 2017-12-06Bibliographically approved
Organisations

Search in DiVA

Show all publications