Publications by authors named "Magnus Vrethem"

42 Publications

Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis - a presymptomatic case-control study.

Eur J Neurol 2021 Jun 9. Epub 2021 Jun 9.

Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.

Background: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.

Methods: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).

Results: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).

Conclusions: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ene.14961DOI Listing
June 2021

Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients.

Ann Neurol 2020 05 9;87(5):688-699. Epub 2020 Mar 9.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.

Objective: Novel, highly effective disease-modifying therapies have revolutionized multiple sclerosis (MS) care. However, evidence from large comparative studies on important safety outcomes, such as cancer, is still lacking.

Methods: In this nationwide register-based cohort study, we linked data from the Swedish MS register to the Swedish Cancer Register and other national health care and census registers. We included 4,187 first-ever initiations of rituximab, 1,620 of fingolimod, and 1,670 of natalizumab in 6,136 MS patients matched for age, sex, and location to 37,801 non-MS general population subjects. Primary outcome was time to first invasive cancer.

Results: We identified 78 invasive cancers among treated patients: rituximab 33 (incidence rate [IR] per 10,000 person-years = 34.4, 95% confidence interval [CI] = 23.7-48.3), fingolimod 28 (IR = 44.0, 95% CI = 29.2-63.5), and natalizumab 17 (IR = 26.0, 95% CI = 15.1-41.6). The general population IR was 31.0 (95% CI = 27.8-34.4). Adjusting for baseline characteristics, we found no difference in risk of invasive cancer between rituximab, natalizumab, and the general population but a possibly higher risk with fingolimod compared to the general population (hazard ratio [HR] = 1.53, 95% CI = 0.98-2.38) and rituximab (HR = 1.68, 95% CI = 1.00-2.84).

Interpretation: In this first large comparative study of 3 highly effective MS disease-modifying therapies, no increased risk of invasive cancer was seen with rituximab and natalizumab, compared to the general population. However, there was a borderline-significant increased risk with fingolimod, compared to both the general population and rituximab. It was not possible to attribute this increased risk to any specific type of cancer, and further studies are warranted to validate these findings. ANN NEUROL 2020;87:688-699.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25701DOI Listing
May 2020

Leptin levels are associated with multiple sclerosis risk.

Mult Scler 2021 01 7;27(1):19-27. Epub 2020 Feb 7.

Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.

Background: Obesity early in life has been linked to increased risk of developing multiple sclerosis (MS). Leptin and insulin are both associated with obesity, making them suitable candidates for investigating this connection.

Objective: To determine if leptin and insulin are risk factors for relapsing-remitting multiple sclerosis (RRMS).

Methods: In this nested case-control study using blood samples from Swedish biobanks, we compared concentrations of leptin and insulin in 649 individuals who later developed RRMS with 649 controls matched for biobank, sex, age and date of sampling. Only pre-symptomatically drawn samples from individuals below the age of 40 years were included. Conditional logistic regression was performed on -scored values to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

Results: A 1-unit leptin -score increase was associated with increased risk of MS in individuals younger than 20 years (OR = 1.4, 95% CI = 1.1-1.9) and in all men (OR = 1.4, 95% CI = 1.0-2.0). In contrast, for women aged 30-39 years, there was a lower risk of MS with increased leptin levels (OR = 0.74, 95% CI = 0.54-1.0) when adjusting for insulin levels.

Conclusion: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520905033DOI Listing
January 2021

Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis.

J Neuroimmunol 2020 03 9;340:577147. Epub 2020 Jan 9.

Centre of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≤ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2020.577147DOI Listing
March 2020

High serum concentration of vitamin D may protect against multiple sclerosis.

Mult Scler J Exp Transl Clin 2019 Oct-Dec;5(4):2055217319892291. Epub 2019 Dec 6.

Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden.

Background: High 25-hydroxyvitamin D concentrations have been associated with a reduced risk of multiple sclerosis, with indications of a stronger effect among young individuals.

Objective: Investigate the 25-hydroxyvitamin D association with multiple sclerosis and test if this association is age dependent.

Methods: Prospectively drawn blood samples from individuals later developing relapsing-remitting multiple sclerosis and controls matched for biobank, sex, age and date of sampling, were analysed with liquid chromatography tandem mass spectrometry.

Results: High levels of 25-hydroxyvitamin D (top quintile) were associated with a reduced multiple sclerosis risk (odds ratio 0.68, 95% confidence interval 0.50-0.93).

Conclusion: These findings further support a role for vitamin D in MS aetiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2055217319892291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900627PMC
December 2019

Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies.

JAMA Neurol 2020 02;77(2):184-191

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden.

Objective: To examine the risk of serious infections associated with disease-modifying treatments for MS.

Design, Setting, And Participants: This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included.

Exposures: Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA.

Main Outcomes And Measures: Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions.

Results: A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]).

Conclusions And Relevance: Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2019.3365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784753PMC
February 2020

Fatigue scores correlate with other self-assessment data, but not with clinical and biomarker parameters, in CIS and RRMS.

Mult Scler Relat Disord 2019 Nov 1;36:101424. Epub 2019 Oct 1.

Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Fatigue is common in multiple sclerosis and is associated with reduced quality of life. This study aimed to assess the correlation between fatigue scores and data from other self-assessment questionnaires, neuropsychological tests and neuroimaging, as well as data on neuroimmunological markers in cerebrospinal fluid (CSF) and serum/plasma, in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS).

Methods: Modified fatigue impact scale (MFIS) scores were determined in 38 patients with newly diagnosed CIS or RRMS at baseline and after one year in a prospective longitudinal cohort study. Non-parametric correlation analyses were used to assess associations between MFIS scores and other self-assessment questionnaire data (Hospital Anxiety and Depression scale (HAD), Multiple Sclerosis Impact Scale 29 (MSIS-29) and Short Form 36 (SF-36)), as well as with neuropsychological test performances (e.g. Auditory Consonant Trigram Test (ACTT)), clinical parameters (e.g. disease duration and expanded disability status scale (EDSS)), magnetic resonance imaging (MRI) data (number of T2 lesions in brain MRI and total brain volume) and several neurodegenerative/neuroinflammatory markers in CSF and serum/plasma (IL-1β, IL-6, CXCL1, CXCL10, CXCL13, CCL-22 in plasma; neurofilament light chain (NFL) in serum; IL-6, CXCL1, CXCL10, CXCL13, CCL22, NFL and chitinase-3-like-1 (CHI3L1) in CSF. CSF and serum/plasma from 21 age- and sex-matched healthy controls were available for comparison.

Results: At both baseline and one-year follow-up, fatigue scores correlated significantly with HAD, MSIS-29 and SF-36 scores and ACTT performance (Spearman´s rho 0.45-0.78, all p ≤ 0.01) but not with the other neuropsychological test results, disease duration, EDSS ratings, number of T2 lesions, total brain volume or neurodegenerative/neuroinflammatory markers, including neurofilament light chain levels in CSF and serum. In group comparisons, MFIS scores were similar in patients fulfilling no evidence of disease activity-3 (NEDA-3) (n = 18) and patients not fulfilling NEDA-3 (n = 20) during one year of follow-up (p > 0.01).

Conclusions: In this cohort of patients with newly diagnosed CIS and RRMS, fatigue scores were associated with mood, disease impact on daily life and quality of life as well as with alterations of attentive functions. Study results indicate that subjective fatigue scores are not well reflected by some commonly used and objectively measurable disease parameters like EDSS, T2 lesions and NFL levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2019.101424DOI Listing
November 2019

Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS.

Mult Scler 2020 10 8;26(12):1532-1539. Epub 2019 Aug 8.

Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.

Background: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited.

Objective: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden.

Methods: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF ( = 641) or interferons/glatiramer acetate (IFN/GA;  = 555) as the initial therapy, or DMF ( = 703) or fingolimod (FGL;  = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016.

Results: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58,  < 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09,  < 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13;  < 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04;  = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy ( < 0.05 and  = 0.20, respectively).

Conclusion: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458519866600DOI Listing
October 2020

Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing remitting multiple sclerosis.

Prostaglandins Other Lipid Mediat 2018 09 15;138:41-47. Epub 2018 Aug 15.

Department of Chemistry, Umeå University, Umeå, Sweden; Department of Entomology and Nematology, University of California, Davis, USA.

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 naïve 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 < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prostaglandins.2018.08.003DOI Listing
September 2018

Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis.

J Neuroinflammation 2018 Jul 18;15(1):209. Epub 2018 Jul 18.

Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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®) 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 < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-018-1249-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052680PMC
July 2018

Increased prevalence of celiac disease in idiopathic inflammatory myopathies.

Brain Behav 2017 10 5;7(10):e00803. Epub 2017 Sep 5.

Department of Clinical and Experimental Medicine Linköping University Linköping Sweden.

Objectives: Idiopathic 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 Östergötland, Sweden.

Material And Methods: We 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.

Results: Four 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 Östergötland was 7.3 per million/year.

Conclusions: The results highlight the high frequency of associated inflammatory and malignant diseases and confirm an increased prevalence of celiac disease in IIM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651387PMC
October 2017

Determination of loss of consciousness: a comparison of clinical assessment, bispectral index and electroencephalogram: An observational study.

Eur J Anaesthesiol 2016 Dec;33(12):922-928

From the Department of Medical and Health Sciences, Division of Drug Research, Linköping University (E-LZ, HG, AO, SV, CE), Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine (HG), Department of Clinical and Experimental Medicine, Division of Clinical Neurophysiology, Linköping University (MV), and Department of Anaesthesia and Intensive Care, Linköping University, Kalmar Hospital, Linköping, Sweden (M-LL).

Background: Computer-processed algorithms of encephalographic signals are widely used to assess the depth of anaesthesia. However, data indicate that the bispectral index (BIS), a processed electroencephalography monitoring system, may not be reliable for assessing the depth of anaesthesia.

Objective: The aim of this study was to evaluate the ability of the BIS monitoring system to assess changes in the level of unconsciousness, specifically during the transition from consciousness to unconsciousness, in patients undergoing total intravenous anaesthesia with propofol. We compared BIS with the electroencephalogram (EEG), and clinical loss of consciousness (LOC) defined as loss of verbal commands and eyelash reflex.

Design: This was an observational cohort study.

Setting: University Hospital Linköping, University Hospital Örebro, Finspång Hospital and Kalmar Hospital, Sweden from October 2011 to April 2013.

Patients: A total of 35 ASA I patients aged 18 to 49 years were recruited.

Interventions: The patients underwent total intravenous anaesthesia with propofol and remifentanil for elective day-case surgery. Changes in clinical levels of consciousness were assessed by BIS and compared with assessment of stage 3 neurophysiological activity using the EEG. The plasma concentrations of propofol were measured at clinical LOC and 20 and 30 min after LOC.

Main Outcome Measures: The primary outcome was measurement of BIS, EEG and clinical LOC.

Results: The median BIS value at clinical LOC was 38 (IQR 30 to 43), and the BIS values varied greatly between patients. There was no correlation between BIS values and EEG stages at clinical LOC (r = -0.1, P = 0.064). Propofol concentration reached a steady state within 20 min.

Conclusion: There was no statistically significant correlation between BIS and EEG at clinical LOC. BIS monitoring may not be a reliable method for determining LOC.

Clinical Trials Registry: This trial was not registered because registration was not mandatory at the time of the trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EJA.0000000000000532DOI Listing
December 2016

The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis.

Mult Scler 2017 Jul 6;23(8):1137-1147. Epub 2016 Oct 6.

Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.

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 ( p < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458516671818DOI Listing
July 2017

Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis.

Cell Rep 2016 09;16(11):2928-2939

Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, 581 83 Linköping, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2016.08.036DOI Listing
September 2016

Improved working ability in a contemporary MS population compared with a historic non-treated MS population in the same geographic area of Sweden.

Mult Scler J Exp Transl Clin 2015 Jan-Dec;1:2055217315608203. Epub 2015 Sep 22.

Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden.

Background: Multiple sclerosis (MS) often causes a reduced ability to work. Improved disease control as well as adjustment of working conditions may improve work ability in MS.

Objectives: The objective of this article is to compare the degree of sickness absence in two MS populations that either have or have not received disease-modifying drug (DMD) treatments or active work-promoting measures.

Methods: We investigated the occurrence of sickness absence in MS patients living in Västerbotten County, Sweden, in 2013, in which the majority of MS patients receive DMD treatment. The result was compared with a previous survey in the same area during a period when no DMD was available and no work-promoting measures for MS patients were practiced.

Results: The proportion of MS patients active in the labor market or studying increased from 38% to 70% in the contemporary compared with the historic population ( < 0.001). The proportion of MS patients with a full-time disability pension decreased from 27% to 12% ( < 0.001). There was a significant decrease of sickness absence in several individual EDSS grades.

Conclusions: Our data indicate that treatment with DMDs combined with active work-promoting measures lead to improved work ability in MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2055217315608203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433506PMC
September 2015

Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation.

Clin Neurophysiol 2015 Aug 18;126(8):1493-7. Epub 2014 Oct 18.

Department of Clinical Neurophysiology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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 1-16 years 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 1-4 years 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 9-12 years 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2014.10.015DOI Listing
August 2015

Idiopathic small fiber neuropathy: phenotype, etiologies, and the search for fabry disease.

J Clin Neurol 2014 Apr 23;10(2):108-18. Epub 2014 Apr 23.

Department of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3988/jcn.2014.10.2.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017013PMC
April 2014

Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience.

J Neurol Neurosurg Psychiatry 2014 Oct 19;85(10):1116-21. Epub 2014 Feb 19.

Department of Neuroscience, Uppsala University, Uppsala, Sweden Department of Neurology, Uppsala University Hospital, Uppsala, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2013-307207DOI Listing
October 2014

Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial.

Mult Scler 2014 07 30;20(8):1095-101. Epub 2013 Dec 30.

Department of Pharmacology and Clinical Neuroscience, Section of Neuroscience, Umeå University, Sweden

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458513517590DOI Listing
July 2014

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

PLoS One 2013 2;8(12):e81685. Epub 2013 Dec 2.

Neurology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, and Department of Neurology, County Council of Östergötland, Linköping, Sweden.

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

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

Results: Absolute numbers of all major lymphocyte populations 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(-)CD56(dim) cytotoxic NK cells, whereas CD3(-)CD56(bright) regulatory NK cells decreased. The increase in cell numbers was further associated with a restored T cell responsiveness to recall antigens and mitogens in functional assays.

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 finding supports reduction of lymphocyte extravasation as a main mode of action, although the differential effects on subpopulation composition suggests that cell-signalling may also be affected. The systemic increase in T cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses may become correspondingly decreased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081685PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847051PMC
September 2014

Taurine and glutathione in plasma and cerebrospinal fluid in olanzapine treated patients with schizophrenia.

Psychiatry Res 2013 Dec 7;210(3):819-24. Epub 2013 Oct 7.

Division of Psychiatry, Department of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden. Electronic address:

Oxidative stress has been implicated in the pathophysiology of schizophrenia. Taurine and glutathione (GSH) have antioxidant and central nervous system protective properties, and are proposed to be involved in the pathology of schizophrenia. The aim of this study was to compare the blood and cerebrospinal fluid (CSF) levels of taurine and GSH in patients with schizophrenia, medicated with oral olanzapine, compared with controls. In total, 37 patients with schizophrenia and 45 healthy volunteers were recruited. We found the plasma taurine levels to be elevated in patients compared with controls. No differences were, however, found between patients and controls regarding taurine in CSF or GSH concentrations in plasma and CSF. Moreover, in the patient group no correlations between taurine and GSH levels and the symptoms or function of the disorder were found. The higher levels of plasma but not CSF taurine in patients with schizophrenia treated with OLA may implicate the involvement of taurine in the pathophysiology of the disease. The absence of GSH differences both in plasma and CSF between patients and controls is interesting in the perspective of earlier research proposing a dysregulation of GSH metabolism as a vulnerability factor for the development of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2013.09.014DOI Listing
December 2013

Urinary 2,5-hexanedione excretion in cryptogenic polyneuropathy compared to the general Swedish population.

J Occup Med Toxicol 2013 Jul 30;8(1):21. Epub 2013 Jul 30.

Division of Neurology and Neurophysiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

Background: 2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors.

Methods: Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis.

Results: Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age.

Conclusions: Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1745-6673-8-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733657PMC
July 2013

Association between change in normal appearing white matter metabolites and intrathecal inflammation in natalizumab-treated multiple sclerosis.

PLoS One 2012 17;7(9):e44739. Epub 2012 Sep 17.

Neurology, Department of Clinical and Experimental Medicine, Division of Neuroscience, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

Background: Multiple sclerosis (MS) is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS). Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM.

Methods: Quantitative proton magnetic resonance spectroscopy ((1)H-MRS) was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in (1)H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients.

Results: The group levels of (1)H-MRS metabolite concentrations were unchanged pre- to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43-0.67, p<0.0005-0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1β and CXCL8).

Conclusions: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in (1)H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0044739PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444490PMC
March 2013

A patient with both narcolepsy and multiple sclerosis in association with Pandemrix vaccination.

J Neurol Sci 2012 Oct 28;321(1-2):89-91. Epub 2012 Jul 28.

Division of Neurology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Department of Neurology and Neurophysiology, County Council of Östergötland, Linköping, Sweden.

Narcolepsy with cataplexy is caused by a selective loss of hypocretin-producing neurons, but symptomatic narcolepsy can also result from hypothalamic and brainstem lesions caused by multiple sclerosis (MS). We report a previously healthy man who developed clinical and laboratory verified narcolepsy without having any indication of hypothalamic lesions and MS after vaccination against the influenza H1N1 with Pandemrix. HLA typing showed both DRB1*15:01, associated with MS and DQB1*06:02, associated with narcolepsy. The genetic susceptibility in this patient makes it tempting to speculate upon an immune-mediated mechanism and a common etiology for both diseases in this patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2012.07.025DOI Listing
October 2012

Long-term clinical outcome after Lyme neuroborreliosis in childhood.

Pediatrics 2012 Aug 16;130(2):262-9. Epub 2012 Jul 16.

Center for Clinical Research in Dalarna (CKF), Nissersv. 3, SE-791 82 Falun, Sweden.

Objectives: To determine long-term clinical outcome in children with confirmed Lyme neuroborreliosis (LNB) and to evaluate persistent subjective symptoms compared with a control group.

Methods: After a median of 5 years, 84 children with confirmed LNB underwent a neurologic re-examination, including a questionnaire. Medical records were analyzed, and a control group (n = 84) was included.

Results: The total recovery rate was 73% (n = 61). Objective neurologic findings, defined as "definite sequelae," were found in 16 patients (19%). The majority of these children had persistent facial nerve palsy (n = 11), but other motor or sensory deficits occurred (n = 5). Neurologic signs and/or symptoms defined as "possible sequelae" were found in another 7 patients (8%), mainly of sensory character. Nonspecific subjective symptoms were reported by 35 patients (42%) and 32 controls (38%) (nonsignificant). Affected daily activities or school performance were reported to the same extent in both groups (23% vs 20%, nonsignificant).

Conclusions: The long-term clinical recovery rate was 73% in children with confirmed LNB. Persistent facial nerve palsy occurred in 13%, whereas other motor or sensory deficits were found in another 14%. Neurologic deficits did not affect daily activities or school performance more often among patients than controls and should be considered as mild. Furthermore, nonspecific subjective symptoms such as headache, fatigue, or memory or concentration problems were reported as often among patients as controls and should not be considered as sequelae after LNB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2011-3719DOI Listing
August 2012

Taurine and glutathione levels in plasma before and after ECT treatment.

Psychiatry Res 2012 Jun 26;198(1):53-7. Epub 2012 Mar 26.

Psychiatry, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköpings University, Linköping, Sweden.

Taurine has been shown to be elevated in plasma and lymphocytes of depressed patients, but the level normalises after successful drug therapy. During depression, levels of glutathione (GSH) are decreased in the plasma and blood. This study was performed to examine taurine and GSH levels in depressed patients before and after electroconvulsive therapy (ECT). Fasting blood samples were collected from 23 patients before the first and after the third ECT treatment. The severity of depression was estimated with the Montgomery-Åsberg Depression Rating Scale (MADRS). We analysed GSH in blood and the levels of taurine and total GSH in plasma. After three ECTs, a significant decrease in MADRS scores was found for the entire group. Simultaneously, the decrease in the plasma taurine levels was significant for the seven responders but not for the sixteen non-responders. We observed no differences in blood or plasma GSH levels after three ECT treatments when compared to values before the therapy. Plasma taurine levels decrease significantly after three ECT treatments in patients who respond to treatment. GSH levels were not affected by ECT treatment. The results indicate that taurine may play a role in the pathophysiology of depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2012.02.016DOI Listing
June 2012

Polymorphisms of GSTT1, GSTM1, and EPHX genotypes in patients with cryptogenic polyneuropathy: a case-control study.

Brain Behav 2011 Nov;1(2):135-41

The aim of this study was to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1), Glutathione S-Transferase Theta-1 (GSTT1), and a low-activity genetic variation of epoxide hydrolase exon three (EPHX*3) affect the risk of developing polyneuropathy. The enzymes of these genes are important in the metabolism of toxic compounds. Seventy-nine patients with cryptogenic polyneuropathy (equivalent to chronic idiopathic axonal neuropathy) and 398 controls were tested for the genetic polymorphism. Medical records were reviewed to collect data regarding clinical findings at diagnosis, and exposure data was collected via questionnaires. The odds ratios (ORs) for the null forms of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one except GSTT1, which reached 1.86. The highest risk of polyneuropathy was found in smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between genes were analyzed and confirmed the increased OR for GSTT1, which was strongest if the patients had the low-activity HH form of EPHX*3 (OR 2.37). Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances that could lead to nerve damage in the peripheral nervous system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236538PMC
November 2011

Subacute neuronopathy in a young man: a possible association with tetracycline treatment.

Neurol Int 2011 Nov;3(3):e16

Division of Neurology and.

A young man with subacute neuronopathy following tetracycline treatment is described. The symptoms started as a sensory dorsal root affection but by time also involved motor nerves. He developed a severe sensory ataxia with pseudoathetotic movements. Other possible aetiologies were scrutinized and excluded. Tetracycline induced neuronopathy is hitherto not reported in the literature. We propose a possible association between treatment with tetracycline and the development of sensory neuronopathy in this patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/ni.2011.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286156PMC
November 2011

Clinical, diagnostic and immunological characteristics of patients with possible neuroborreliosis without intrathecal Ig-synthesis against Borrelia antigen in the cerebrospinal fluid.

Neurol Int 2011 Jun 8;3(1):e2. Epub 2011 Apr 8.

Division of Neurology and Neurophysiology, Department of Clinical and Experimental Medicine, University Hospital, Linköping;

The diagnosis of neuroborreliosis is not always straightforward. Intrathecal immunoglobulin (Ig) synthesis against Borrelia antigen may not be detected, at least early in the disease course. Also other neurological and infectious diagnoses have to be considered. We have studied patients with clinical possible neuroborreliosis without intrathecal Ig synthesis against Borrelia antigen in the cerebrospinal fluid (CSF) (n=17). Diagnosis was based on typical clinical history and at least one of the following findings; mononuclear leucocytosis in the CSF (n=4); typical erythema migrans >5 cm in diameter in relation to debut of symptoms (n=8); prompt clinical response to antibiotic teratment (n=14). Also other possible diagnoses had to be excluded. Seventeen patients first investigated because of suspected neuroborreliosis but later confirmed with other diagnoses were used as controls. All patients had a lumbar puncture. Borrelia specific IFN-γ and IL-4 secretion was investigated in peripheral blood (PBL) and CSF with an ELISPOT assay. Polymerase chain reaction (PCR) was used to reveal any Borrelia antigen in the CSF. Six of 17 patients with possible neuroborreliosis showed high IFN-γ secretion in peripheral blood, otherwise we found no statistically significant differences between the groups. PCR did not reveal any Borrelia antigen in CSF. The diagnosis and treatment of possible but not confirmed neuroborreliosis is a clinical challenge. The clinical response to treatment may be the best option in these cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/ni.2011.e2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141113PMC
June 2011