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  • 1
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    Online Resource
    A Case of Progressive Multifocal Leukoencephalopathy in a Fumaric Acid-Treated Psoriasis Patient With Severe Lymphopenia Among Other Risk Factors
    SAGE Publications ; 2021
    In:  Journal of Central Nervous System Disease Vol. 13 ( 2021-01), p. 117957352110377-
    Details
    In: Journal of Central Nervous System Disease, SAGE Publications, Vol. 13 ( 2021-01), p. 117957352110377-
    Abstract: Progressive multifocal leukoencephalopathy (PML) is a potentially fatal condition caused by a brain infection with JC polyomavirus (JCV), which occurs almost exclusively in immunocompromised patients. Modern immunosuppressive and immunomodulatory treatments for cancers and autoimmune diseases have been accompanied by increasing numbers of PML cases. We report a psoriasis patient treated with fumaric acid esters (FAEs) with concomitant hypopharyngeal carcinoma and chronic alcohol abuse who developed PML. Grade 4 lymphopenia at the time point of PML diagnosis suggested an immunocompromised state. This case underscores the importance of immune cell monitoring in patients treated with FAEs, even more so in the presence of additional risk factors for an immune dysfunction.
    Type of Medium: Online Resource
    ISSN: 1179-5735 , 1179-5735
    URL: Article
    DOI: 10.1177/11795735211037798
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 2
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    Online Resource
    Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis
    SAGE Publications ; 2019
    In:  Multiple Sclerosis Journal Vol. 25, No. 5 ( 2019-04), p. 678-686
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 25, No. 5 ( 2019-04), p. 678-686
    Abstract: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p  〈  0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p  〈  0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458518765666
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
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  • 3
    Online Resource
    Online Resource
    Evidence for early, non-lesional cerebellar damage in patients with multiple sclerosis: DTI measures correlate with disability, atrophy, and disease duration
    SAGE Publications ; 2016
    In:  Multiple Sclerosis Journal Vol. 22, No. 1 ( 2016-01), p. 73-84
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 22, No. 1 ( 2016-01), p. 73-84
    Abstract: Common symptoms of multiple sclerosis (MS) such as gait ataxia, poor coordination of the hands, and intention tremor are usually the result of dysfunctionality in the cerebellum. Magnetic resonance imaging (MRI) has frequently failed to detect cerebellar damage in the form of inflammatory lesions in patients presenting with symptoms of cerebellar dysfunction. Objective: To detect microstructural cerebellar tissue alterations in early MS patients with a “normal appearing” cerebellum using diffusion tensor imaging (DTI). Methods: A total of 68 patients with relapsing–remitting MS (RRMS) and without cerebellar lesions and 26 age-matched healthy controls were admitted to high-resolution MRI and DTI to assess microstructure and volume of the cerebellar white matter (CBWM). Results: We found cerebellar fractional anisotropy (FA) and CBWM volume reductions in the group of 68 patients. Interestingly, a subgroup of these patients that was derived by including only patients with early and mild MS ( N=23, median age 30 years, median Expanded Disability Status Scale =1.5, median duration 28 months) showed already cerebellar FA but no CBWM volume reductions. FA reductions were correlated with disability, atrophy, and disease duration. Conclusion: “Normal appearing” cerebellar white matter can be damaged in a very early stage of RRMS. DTI seems to be a sensitive tool for detecting this hidden cerebellar damage.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458515579439
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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  • 4
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    Online Resource
    Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis
    SAGE Publications ; 2019
    In:  Multiple Sclerosis Journal Vol. 25, No. 3 ( 2019-03), p. 338-343
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 25, No. 3 ( 2019-03), p. 338-343
    Abstract: Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Objective: Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. Methods: We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Results: Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSF IgA and CSF IgM showed higher functional disability at follow-up. Conclusion: CSF markers of blood–brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517748474
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
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  • 5
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    Online Resource
    Studying the blood–brain barrier will provide new insights into neurodegeneration – Commentary
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 8 ( 2018-07), p. 1026-1028
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 8 ( 2018-07), p. 1026-1028
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458518759430
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 6
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    Online Resource
    Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort
    SAGE Publications ; 2023
    In:  Therapeutic Advances in Neurological Disorders Vol. 16 ( 2023-01)
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 16 ( 2023-01)
    Abstract: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce. Objectives: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort. Design: Cross-sectional analysis within a multicenter observational study. Methods: Baseline data of n = 781 adults with newly diagnosed clinically isolated syndrome or relapsing-remitting MS qualified for analysis. Global and region-specific magnetic resonance imaging (MRI)-volumetry parameters were available for n = 327 patients. Association of demographic factors, MS characteristics and risk factors [sex, age, smoking, disease course, presence of current relapse, expanded disability status scale (EDSS) score, fatigue (fatigue scale motor cognition), 25-OH-VD serum concentration, EBV nuclear antigen-1 IgG (EBNA1-IgG) serum levels] and depressive symptoms (Beck Depression Inventory-II, BDI-II) was tested as a primary outcome by multivariable linear regression. Non-parametric correlation and group comparison were performed for associations of MRI parameters and depressive symptoms. Results: Mean age was 34.3 years (95% confidence interval: 33.6–35.0). The female-to-male ratio was 2.3:1. At least minimal depressive symptoms (BDI-II  〉  8) were present in n = 256 (32.8%), 25-OH-VD deficiency ( 〈 20 ng/ml) in n = 398 (51.0%), n = 246 (31.5%) participants were smokers. Presence of current relapse [coefficient ( c) = 1.48, p = 0.016], more severe fatigue ( c = 0.26, p  〈  0.0001), lower 25-OH-VD ( c = −0.03, p = 0.034) and smoking ( c = 0.35, p = 0.008) were associated with higher BDI-II scores. Sex, age, disease course, EDSS, month of visit, EBNA1-IgG levels and brain volumes at baseline were not. Conclusion: Depressive symptoms need to be assessed in early MS. Patients during relapse seem especially vulnerable to depressive symptoms. Contributing factors such as fatigue, vitamin D deficiency and smoking, could specifically be targeted in future interventions and should be investigated in prospective studies.
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/17562864231197309
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 7
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    Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Neurological Disorders Vol. 14 ( 2021-01), p. 175628642110034-
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 14 ( 2021-01), p. 175628642110034-
    Abstract: Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods: Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients ( n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes. Results: In our cohort, HON patients had a thinner outer plexiform layer (OPL) volume compared to NHON patients ( B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients ( B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy ( B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning. Conclusions: In summary, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration.
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/17562864211003478
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 8
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    Online Resource
    Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Neurological Disorders Vol. 14 ( 2021-01), p. 175628642110514-
    Details
    In: Therapeutic Advances in Neurological Disorders, SAGE Publications, Vol. 14 ( 2021-01), p. 175628642110514-
    Abstract: The aim was to evaluate the diagnostic potential of serum neurofilament light chain (sNfL) measurements in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Methods: sNfL levels were determined by single molecule array assay in a retrospective cross-sectional cohort of 144 patients with systemic lupus erythematosus (SLE). After log-transformation of sNfL levels, mean sNfL levels were compared between NPSLE patients and SLE patients without neuropsychiatric disease using Student’s t test. Furthermore, the association of different neuropsychiatric manifestations with sNfL levels was assessed using a one-way analysis of variance (ANOVA) with post hoc analysis. Associations of sNfL with clinical and laboratory parameters were assessed by correlation and multiple linear regression analysis. Results: NPSLE patients ( n = 69) had significantly higher sNfL levels than SLE patients without neuropsychiatric disease manifestations ( n = 75; mean difference: 0.13, 95% CI: 0.04–0.22, p = 0.006). With regard to the category of NPSLE manifestation, mean sNfL levels were only increased in NPSLE patients with focal central nervous system (CNS) involvement ( n = 45; mean difference: 0.16, 95% CI: 0.02–0.30, p = 0.019), whereas mean sNfL levels of NPSLE patients with diffuse CNS and peripheral nervous system involvement did not differ from those of SLE patients without neuropsychiatric manifestations. Age and serum creatinine concentrations were identified as relevant contributors to sNfL levels. Conclusion: sNfL is a promising, easily accessible biomarker for neuropsychiatric involvement in SLE patients and might therefore complement the diagnostic workup of SLE patients with suspected involvement of the nervous system.
    Type of Medium: Online Resource
    ISSN: 1756-2864 , 1756-2864
    URL: Article
    DOI: 10.1177/17562864211051497
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 9
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    Online Resource
    Treatment response to dimethyl fumarate is characterized by disproportionate CD8+ T cell reduction in MS
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 5 ( 2018-04), p. 632-641
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 5 ( 2018-04), p. 632-641
    Abstract: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). Objective: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study. Methods: Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Untreated MS patients ( n = 40) were compared to those 6 months after onset of DMF treatment ( n = 51). Clinical and magnetic resonance imaging (MRI) disease activity of DMF-treated patients were assessed in the first year under treatment. Results: Stable patients showed significantly lower lymphocytes, CD4+ and CD8+ T cells as well as CD19+ B cells compared to active patients under DMF treatment. Furthermore, an increased CD4/CD8 ratio ( p 〈 0.025) in stable patients indicated a disproportionate reduction of CD8+ T cells relative to CD4+ T cells. Reduced lymphocytes, CD8+ T cells, and CD19+ B cells 6 months after DMF start allowed prediction of the treatment response in the first year. Conclusion: DMF treatment response is reflected by lower circulating lymphocytes and specific lymphocyte subsets. Changes in the cellular immune profiles under DMF treatment are clinically relevant and might serve as a surrogate marker of treatment response.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517703799
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 10
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    Online Resource
    Natalizumab restores evoked potential abnormalities in patients with relapsing–remitting multiple sclerosis
    SAGE Publications ; 2011
    In:  Multiple Sclerosis Journal Vol. 17, No. 2 ( 2011-02), p. 198-203
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 17, No. 2 ( 2011-02), p. 198-203
    Abstract: Background and Objective: The objective of this study was to examine the effects of natalizumab on functional parameters assessed by evoked potentials (visual [VEP], somatosensory [SEP] and motor evoked potentials [MEP]) in a cohort study in relapsing–remitting multiple sclerosis patients. Methods: EP data of 44 patients examined 12 months prior to natalizumab treatment, at the timepoint of treatment initiation and 1 year later were compared. Sum scores (VEP, MEP, SEP) were evaluated and correlated with the Expanded Disability Status Scale. Results: Improvement of the VEP sum score was found in 33% of natalizumab-treated patients but only in 9% of the same patients prior to treatment ( p = 0.041). A comparable situation was found for SEP (improvement: 32% versus 5%; worsening: 11% versus 37%; p = 0.027). For MEP no significant differences were seen (improvement: 10% versus 18%; worsening: 5% versus 29%; p = 0.60). EP recordings (VEP = SEP  〉  MEP) have the capacity to demonstrate treatment effects of natalizumab on a functional level. Conclusions: Natalizumab therapy increases the percentage of patients showing stable or even ameliorated electrophysiological parameters in the investigated functional systems.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458510386998
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
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