Papers by Sten Fredrikson
American Journal of Neuroradiology, May 11, 2017
BACKGROUND AND PURPOSE: Gadolinium-based contrast agents have been associated with lasting high T... more BACKGROUND AND PURPOSE: Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis. MATERIALS AND METHODS: The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age-and sex-matched controls. Participants also underwent comprehensive neuropsychological testing. RESULTS: Patients with MS had a higher Signal Intensity Index in the dentate nucleus (P Ͻ .001), but not in the globus pallidus (P ϭ .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadoliniumbased contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus ( ϭ 0.45, P Ͻ .001) and globus pallidus ( ϭ 0.60, P Ͻ .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus ( ϭ 0.43, P ϭ .001) and globus pallidus ( ϭ 0.58, P Ͻ .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity ( ϭ Ϫ0.40 P ϭ .013). CONCLUSIONS: Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition and gadolinium-based contrast agent administration.
American Journal of Neuroradiology, Feb 4, 2016
BACKGROUND AND PURPOSE: Incidental MR imaging findings resembling MS in asymptomatic individuals,... more BACKGROUND AND PURPOSE: Incidental MR imaging findings resembling MS in asymptomatic individuals, fulfilling the Okuda criteria, are termed "radiologically isolated syndrome." Those with radiologically isolated syndrome are at high risk of their condition converting to MS. The epidemiology of radiologically isolated syndrome remains largely unknown, and there are no population-based studies, to our knowledge. Our aim was to study the population-based incidence of radiologically isolated syndrome in a high-incidence region for MS and to evaluate the effect on radiologically isolated syndrome incidence when revising the original radiologically isolated syndrome criteria by using the latest radiologic classification for dissemination in space. MATERIALS AND METHODS: All 2272 brain MR imaging scans in 1907 persons obtained during 2013 in the Swedish county of Västmanland, with a population of 259,000 inhabitants, were blindly evaluated by a senior radiologist and a senior neuroradiologist. The Okuda criteria for radiologically isolated syndrome were applied by using both the Barkhof and Swanton classifications for dissemination in space. Assessments of clinical data were performed by a radiology resident and a senior neurologist. RESULTS: The cumulative incidence of radiologically isolated syndrome was 2 patients (0.1%), equaling an incidence rate of 0.8 cases per 100,000 person-years, in a region with an incidence rate of MS of 10.2 cases per 100,000 person-years. There was no difference in the radiologically isolated syndrome incidence rate when applying a modified version of the Okuda criteria by using the newer Swanton classification for dissemination in space. CONCLUSIONS: Radiologically isolated syndrome is uncommon in a high-incidence region for MS. Adapting the Okuda criteria to use the dissemination in space-Swanton classification may be feasible. Future studies on radiologically isolated syndrome may benefit from a collaborative approach to ensure adequate numbers of participants.
European Journal of Neurology, Aug 19, 2019
Article type : Original Article Epilepsy in second-generation immigrants: a cohort study of all c... more Article type : Original Article Epilepsy in second-generation immigrants: a cohort study of all children up to 18 years of age in Sweden
PLOS ONE, Jul 5, 2019
RebiQoL was a phase IV multicenter randomized study to assess the impact of a telemedicine patien... more RebiQoL was a phase IV multicenter randomized study to assess the impact of a telemedicine patient support program (MSP) on health-related quality of life (HRQoL) in patients with relapsing-remitting MS (RRMS) being administered with Rebif with the RebiSmart device. The primary endpoint was to assess the impact of MSP compared to patients only receiving technical support for RebiSmart on HRQoL at 12 months, using the psychological part of Multiple Sclerosis Impact Scale (MSIS-29), in patients administered with Rebif. A total of 97 patients diagnosed with RRMS were screened for participation in the study of which 3 patients did not fulfill the eligibility criteria and 1 patient withdrew consent. Of the 93 randomized patients, 46 were randomized to MSP and 47 to Technical support only. The demographic characteristics of the patients were well-balanced in the two arms. There were no statistical differences (linear mixed model) in any of the primary (difference of 0.48, 95% CI:-8.30-9.25, p = 0.91) or secondary outcomes (p>0.05). Although the study was slightly underpowered, there was a trend towards better adherence in the MSP group (OR 3.5, 95% CI 0.85-14.40, p = 0.08) although not statistically significant. No unexpected adverse events occurred. This study did not show a statistically significant effect of the particular form of teleintervention used in this study on HRQoL as compared to pure technical support, for MS patients already receiving Rebif with the RebiSmart device. Trial Registration: ClinicalTrials.gov: NCT01791244.
Acta Neurologica Scandinavica, Jul 1, 1996
VOIDING FUNCTION AND DYSFUNCTION, AND FEMALE UROLOGY pressures, area under rest profile and press... more VOIDING FUNCTION AND DYSFUNCTION, AND FEMALE UROLOGY pressures, area under rest profile and pressure transmission ratio in the second quarter of urethral length were increased in failed cases (P (0.02). Conclusions In successful cases the increased area and pressure transmission ratio in the first quarter of the functional urethral length suggest that collagen placement occurs at the bladder neck or proximal urethra. Cure appears to be due to prevention of bladder neck opening during stress and not obstruction. In addition the cephalad elongation of the urethra caused by collagen probably accounts for the increased abdominal pressure transmission in the first quarter of the urethra. In failures, there is an increased length and increased area to peak pressure suggesting collagen is deposited more distally. This study confirms the role of certain urethral pressure profilometry variables in the prediction and analysis of mechanism of cure. Editorial Comment: If one equates lower urethral profilometry parameters with more severe sphincteric incontinence, w h a t this article indicates is that periurethral bulking is more apt to help patients with mild to moderate incontinence more than those with severe incontinence. Although this finding w a r r a n t s confirmation at other centers using not only parameters of urethral profilometry but Valsalva leak point pressures, it seems logical and is essentially what w e noted in patients after prostatectomy.' Alan J. Wein, M.D.
Acta Neurologica Scandinavica, Jan 29, 2009
Cerebrospinal fluid (CSF) and serum from 15 patients with narcolepsy were examined regarding pres... more Cerebrospinal fluid (CSF) and serum from 15 patients with narcolepsy were examined regarding presence of oligoclonal bands on isoelectric focusing, IgG index elevation as indicator of intrathecal IgG production and CSF/serum albumin ratios. Two of 15 patients (13%) showed oligoclonal IgG bands in CSF, one of whom had increased IgG index. Slight disturbance of blood-brain-barrier function as reflected by elevated CSF/serum albumin ratios was present in 4 other patients. The frequency of oligoclonal IgG bands in CSF from patients with narcolepsy is within the range of what is found in other neurological, non-inflammatory diseases. These findings do not support the hypothesis of an immune-mediated pathogenesis of narcolepsy.
Italian Journal of Neurological Sciences, 1997
Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barre Syndrome (GBS) inciden... more Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barre Syndrome (GBS) incident in SouthWest Stockholm (SWS) during the period from January 1973 to June 1992, we identified three major clinicoepidemiological subgroups. The first subgroup, 25.5 % of the cases (26.7 6.7 years), recorded a peak incidence at ages 20-29 years and presented significant differences from other subgroups, a high proportion of cases with onset at low age preceded by respiratory infection (83.3%) and with normal motor conduction velocity (50.0%). Also found, were less affected biological parameters, a rapidly progressive course and independence in gait at one month after onset. A second subgroup, 27.7% of cases, was severely affected, clinically and functionally. It consisted predominantly of young individuals (22.7 t 1 1.1 years), with a high incidence (69.2% of cases) in autumn. A third subgroup, comprising 40.47; of cases, was older (61.1 _+ 11.0 years) and, in general, also severely affected. The incidence of this form appeared to be invariant with time.
European Journal of Neurology, Mar 1, 2000
Myasthenia gravis (MG) is characterized by T cell-dependent autoantibodies to the acetylcholine r... more Myasthenia gravis (MG) is characterized by T cell-dependent autoantibodies to the acetylcholine receptor on the post-synaptic membrane of the neuromuscular junction. The production of autoantibodies is regulated by T cells via cytokines. To investigate the involvement of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4) and interleukin-10 (IL-10) in MG, the mRNA levels of these cytokines in peripheral blood mononuclear cells without stimulation in vitro were quantified by competitive reverse transcription polymerase chain reaction technique. The mRNA level of TNF-alpha was significantly lower (P = 0.0004) in the overall group of MG patients compared with controls. IL-10 was also lower in MG patients (P = 0.008), most markedly in non-thymectomized patients (P = 0.016). There were no significant differences in IFN-gamma and IL-4 between patients and healthy controls, but the mRNA levels of IL-4 in non-thymectomized patients was significantly lower than in controls (P = 0.02) and in thymectomized patients (P = 0.03). These results, reflecting the in vivo expression pattern of these cytokines in the periphery, suggest an altered cytokine expression at the systemic level in MG.
Journal of Medical Economics, Dec 18, 2012
Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing mu... more Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing multiple sclerosis, and are considered by the Committee for Medicinal Products for Human Use (CHMP) to have broadly similar efficacy. A cost-minimization analysis was performed to compare differences in treatment costs between fingolimod and natalizumab from a societal perspective in Sweden. This analysis included costs associated with initiating and following treatment (physician visits and monitoring), continuing therapy (drugs and administration), and lost patient productivity and leisure time. Unit costs (in Swedish krona [SEK]) were based on regional data (median prices for physician visits and monitoring sessions). Natalizumab infusion costs were obtained from the national cost-per-patient database. Drug costs for both therapies were 15,651 SEK/28 days. After 3 years, fingolimod use was associated with savings of 124,823 SEK/patient compared with natalizumab (total cost/patient: 566,718 SEK vs 691,542 SEK). Cost savings with fingolimod were 40,402 SEK/patient after 1 year and 301,730 SEK/patient after 10 years. Treatment with natalizumab was 18% more expensive than fingolimod therapy after 1 year and 23% more expensive after 10 years. Based on the CHMP assessment, it was assumed that fingolimod and natalizumab have similar efficacy. The analysis was conducted for Sweden, and caution is needed in extrapolating the results to other countries. Fingolimod is cost-saving compared with natalizumab for the treatment of relapsing-remitting multiple sclerosis in Sweden.
Acta Neurologica Scandinavica, Jan 29, 2009
Genetic factors influence the susceptibility to multiple sclerosis (MS). This disease is accompan... more Genetic factors influence the susceptibility to multiple sclerosis (MS). This disease is accompanied by augmented T cell responses to CNS myelin components such as myelin basic protein. To evaluate the familial occurrence of such T cell autoreactivity, we have studied 12 M S families including 37 healthy first-degree relatives for occurrence of numbers of interferon-gamma (IFN-y) secreting cells among blood mononuclear after culture in presence of myelin basic protein (MBP), eight synthetic MBP peptides and the control antigen acetylcholine receptor (AChR). There were no differences between MS patients and healthy family members regarding frequencies of autoreactive T cells recognizing MBP, the eight different MBP peptides or AChR. None of the MBP peptides predominated as T cell antigen among the M S patients or their unaffected family members. In some families the highest number of MBP peptide reactive T cells were found among unaffected family members. No correlation was observed between numbers of MBP or MBP peptide reactive T cells in various subjects and their HLA-DR-DQ phenotypes. In conclusion, this study has revealed the presence of MBP and MBP peptide reactive T cells of similar frequencies
Journal of the Neurological Sciences, Nov 1, 2003
Clinical manifestations, outcomes, prognostic indicators, and clinico-epidemiological subgroups w... more Clinical manifestations, outcomes, prognostic indicators, and clinico-epidemiological subgroups were described based on the information of 71 patients with Guillain-Barré syndrome (GBS), who were identified from a prospective survey in Harbin, China during a 1-year period from 1 October 1997 to 30 September 1998. GBS diagnoses of the patients were validated by senior neurologists and most patients were followed up for 6 months after onset. Antecedent events, mainly respiratory infections, were found in 55 (78%) patients during the month before onset. The clinical features, like motor weakness as initial symptoms (82%) and tendon areflexia or hyporeflexia (100%), are similar to those reported from other populations. However, the proportion (70%) of patients reaching to nadir less than 7 days after onset was rather high. Intravenous human immunoglobulin and/or plasmapheresis were used in 45% of the patients and steroids in 58%. At 6 months after onset, 82% of the patients could walk without aid, 46% of the patients had no any residual signs. Four (6%) patients died within 1 month due to respiratory failure. Three subgroups with different clinico-epidemiological characteristics were identified by using cluster analysis. In conclusion, GBS patients in Harbin, China were younger, had shorter time to nadir, frequently preceded by a respiratory infection, and often treated with steroids. Clinical and epidemiological differences of GBS might exist between various populations.
Acta Neurologica Scandinavica, 2010
Fredrikson S. Evaluation of multiple sclerosis diagnostic criteria in Suzhou, China-risk of under... more Fredrikson S. Evaluation of multiple sclerosis diagnostic criteria in Suzhou, China-risk of under-diagnosis in a low prevalence area.
BMJ Open, Nov 1, 2013
The improved availability of MRI in medicine has led to an increase in incidental findings. Unexp... more The improved availability of MRI in medicine has led to an increase in incidental findings. Unexpected brain MRI findings suggestive of multiple sclerosis (MS) without typical symptoms of MS were recently defined as radiologically isolated syndrome (RIS). The prevalence of RIS is uncertain. The aim of this study was to determine the prevalence of RIS at a university hospital in a region with a high prevalence for MS and describe the long-term prognosis of the identified patients.
The Cochrane library, Apr 25, 2017
Treatment with disease modifying drugs for people with a first clinical attack suggestive of mult... more Treatment with disease modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.
Multiple sclerosis and related disorders, Apr 1, 2018
Acta Neurologica Scandinavica, Jan 29, 2009
Tissue Antigens, Jul 1, 1990
The aims of the present study were to investigate if the anterior finding could be confirmed in o... more The aims of the present study were to investigate if the anterior finding could be confirmed in our large material of well-characterized multiple sclerosis (MS) patients and wether any differences in the distribution of MspI HLA-DP RFLPs between primarly chronic progressive MS and relapsing/remitting MS (R/R MS) could be identified
European Journal of Neurology, Dec 1, 2000
We described clinical manifestations, outcomes, prognostic indicators and clinico‐epidemiological... more We described clinical manifestations, outcomes, prognostic indicators and clinico‐epidemiological subgroups for 53 adult patients with Guillain–Barré syndrome (GBS) in Sweden during the period 1996–97. These patients were identified from a population of 2.8 million inhabitants and prospectively followed up for one year by a network of neurologists. An additional 10 cases, of whom five were adults who had not been prospectively followed up, were not included in the analyses. At 6 months after onset 80% of the patients could walk without aid, while at 1 year 46% were fully recovered, 42% had mild residual signs or symptoms, 4% had moderate and 6% severe disabilities, and 2% had died. Intravenous human immunoglobulin or plasmapheresis were used in 72% of the patients. The sum of the Medical Research Council (MRC) score at nadir was found as the only significant predictor for residual signs at 1 year in a multivariate model. Three subgroups, with different clinico‐epidemiological characteristics, were identified by using cluster analysis. In conclusion, GBS in Sweden is frequently preceded by a respiratory infection, is often treated with immunomodulatory therapies, and exhibits a high recovery rate and a low fatality rate.
Journal of Neuroimmunology, Dec 1, 1996
Myasthenia gravis (MG) is a neuromuscular disorder mediated by autoantibodies against the nicotin... more Myasthenia gravis (MG) is a neuromuscular disorder mediated by autoantibodies against the nicotinic acetylcholine receptor (AChR) on the postsynaptic membrane of the neuromuscular junction. The production of antibodies is regulated by T cells by means of immunoregulatory cytokines. To investigate the involvement of TNF-α, lymphotoxin (LT), IL-6, IL-10, IL-12 and perforin in MG, numbers of cytokine mRNA expressing blood mononuclear
Clinical and Experimental Immunology, May 1, 2001
Multiple sclerosis (MS) is assumed to result from autoaggressive T cell-mediated immune responses... more Multiple sclerosis (MS) is assumed to result from autoaggressive T cell-mediated immune responses, in which T helper type 1 (Th1) cells producing cytokines, e.g. IFN-g and lymphotoxin promote damage of oligodendrocyte-myelin units. Dendritic cells (DCs) as potent antigen presenting cells initiate and orchestrate immune responses. Whether phenotype and function of DCs with respect to Th1 cell promotion are altered in MS, are not known. This study revealed that blood-derived DCs from MS patients expressed low levels of the costimulatory molecule CD86. In addition, production of IFN-g by blood mononuclear cells (MNCs) was strongly enhanced by DCs derived from MS patients. IFNb and IL-10 inhibited the costimulatory capacity of DCs in mixed lymphocyte reaction (MLR) and showed additive effects on suppression of IL-12 production by DCs. Correspondingly, DCs pretreated with IFN-b and IL-10 significantly suppressed IFN-g production by MNCs. IFN-b in vitro also upregulated CD80 and, in particular, CD86 expression on DCs. In vitro, anti-CD80 antibody remarkably increased, while anti-CD86 antibody inhibited DC-induced IL-4 production in MLR. We conclude that DC phenotype and function are altered in MS, implying Th1-biased responses with enhanced capacity to induce Th1 cytokine production. In vitro modification of MS patients' DCs by IFN-b and IL-10 could represent a novel way of immunomodulation and of possible usefulness for future immunotherapy of MS.
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Papers by Sten Fredrikson