Hayrettin Tumani
University of Ulm, Neurology, Faculty Member
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ZusammenfassungDie Multiple Sklerose (MS) geht als chronisch-entzündliche Erkrankung des zentralen Nervensystems (ZNS) mit typischen Veränderungen im Liquor einher. In der Diagnostik der MS ist die Liquoruntersuchung daher neben der... more
ZusammenfassungDie Multiple Sklerose (MS) geht als chronisch-entzündliche Erkrankung des zentralen Nervensystems (ZNS) mit typischen Veränderungen im Liquor einher. In der Diagnostik der MS ist die Liquoruntersuchung daher neben der Magnetresonanztomographie ein zentrales Verfahren, welches einerseits die Diagnose einer MS untermauern und andererseits hilfreich in der Abgrenzung von Differenzialdiagnosen sein kann. Der wichtigste Liquorbefund bei der MS ist der Nachweis einer persistierenden polyspezifischen intrathekalen Immunglobulinsynthese. Diese Übersichtsarbeit gibt einen Überblick über Liquorbefunde bei der MS, weist auf praxisrelevante Aspekte und diagnostische Fallstricke hin und stellt neue Entwicklungen in der Liquordiagnostik bei der MS dar.AbstractAs a chronic inflammatory disease of the central nervous system (CNS), multiple sclerosis (MS) is associated with characteristic abnormalities in cerebrospinal fluid (CSF). Thus, in addition to magnetic resonance imaging, CSF examination is a central diagnostic procedure in patients with MS, which can corroborate a diagnosis of MS and may also help to discern differential diagnoses. The most important CSF finding in MS is the detection of persistent polyspecific intrathecal immunoglobulin synthesis. This review summarizes CSF findings of patients with MS and addresses issues of relevance for clinical practice, potential diagnostic pitfalls as well as new developments in CSF diagnostics of MS.
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Tracking cognition in patients with multiple sclerosis (MS) is important for detection of disease progression but it is often not performed in routine settings due to time constraints. This exploratory cohort study aims to develop a very... more
Tracking cognition in patients with multiple sclerosis (MS) is important for detection of disease progression but it is often not performed in routine settings due to time constraints. This exploratory cohort study aims to develop a very brief repeatable tracking tool with comparable test quality criteria to the current gold standard, the Brief International Cognitive Assessment for MS (BICAMS). The study included 88 participants (22 healthy controls, 66 MS patients) who were examined at baseline and at one-year follow-up. As a validity criterion for the six administered cognitive tests, we assessed the difference between MS patients and HC, and the correlation with MS-related disability. Combining the two tests with the highest validity—the Controlled Oral Word Association Test and Symbol Digit Modalities Test—yielded an administration time of 5 min. Comparing this new TRACK-MS test battery with the 15 min BICAMS indicated that TRACK-MS showed larger differences between MS patients...
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Background and ObjectivesCSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies... more
Background and ObjectivesCSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated protein 1 antibodies (LGI1-E) represent opposite ends of this spectrum: NMDAR-E with typically frequent/robust and LGI1-E with rare/mild CSF inflammation. For a more in-depth analysis, we characterized CSF findings in acute, therapy-naive NMDAR-E and LGI1-E in a multicentric, retrospective, cross-sectional setting.MethodsEighty-two patients with NMDAR-E and 36 patients with LGI1-E from the GErman NEtwork for Research of AuToimmune Encephalitis (GENERATE) with lumbar puncture within 90 days of onset and before immunotherapy were included. CSF parameters comprised leukocytes, oligoclonal bands (OCBs), and CSF/serum ratios for albumin, immunoglobulin G (IgG), A (IgA), and M (IgM), the latter 3 converted to Z scor...
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Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but... more
Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum. GFAP and CHI3L1 expression was studied in post-mortem brain tissue in additional cases. CSVD cases with higher serum NfL and GFAP levels had a higher modified Rankin Scale (mRS) and NIHSS score and lower CSF Aβ1-42 levels, whereas the CSF NfL and CHI3L1 levels were positively correlated with the WMH load. Moreover, the serum GFAP levels significantly correlated with the neurocognitive functions. Pa...
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<p>Immunoglobulin kappa free light chain (KFLC) in CSF and serum of patients with MS, CIS, pathogen-related diseases and NIND (for abbreviations see legend of <a... more
<p>Immunoglobulin kappa free light chain (KFLC) in CSF and serum of patients with MS, CIS, pathogen-related diseases and NIND (for abbreviations see legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-t001" target="_blank">table 1</a>). Q KFLC: CSF- serum ratio of KFLC. Data are shown as the median and IQR.</p
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<p>Dashed line indicates the approximately upper reference value of Q KFLC, described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-g002"... more
<p>Dashed line indicates the approximately upper reference value of Q KFLC, described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-g002" target="_blank">figure 2</a>. Black rhomb indicate positive OCBs, white rhomb indicate negative OCBs.</p
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<p>There are five classic patterns of oligoclonal bands <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone.0088680-Andersson1" target="_blank">[48]</a> (type 1, no... more
<p>There are five classic patterns of oligoclonal bands <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone.0088680-Andersson1" target="_blank">[48]</a> (type 1, no bands in CSF and serum; type 2, oligoclonal IgG bands in CSF but not in serum, indicative of intrathecal IgG synthesis; type 3, oligoclonal bands in CSF plus identical oligoclonal bands in serum and CSF, indicative of intrathecal IgG synthesis; type 4, identical pattern of oligoclonal bands in CSF and serum. There was no patient with type 5 (identical patterns of monoclonal bands in CSF and serum) in the study. Horizontal solid line indicates median, Kruskal-Wallis test among groups revealed a significant difference (p<0.001), significant P-values for pairwise comparisons (Mann-Whitney U test) are displayed.</p
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<p>Dashed line indicates the approximately upper reference value of Q KFLC, described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-g002"... more
<p>Dashed line indicates the approximately upper reference value of Q KFLC, described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-g002" target="_blank">figure 2</a>. Black rhomb indicate positive OCBs, white rhomb indicate negative OCBs.</p
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<p>There are five classic patterns of oligoclonal bands <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone.0088680-Andersson1" target="_blank">[48]</a> (type 1, no... more
<p>There are five classic patterns of oligoclonal bands <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone.0088680-Andersson1" target="_blank">[48]</a> (type 1, no bands in CSF and serum; type 2, oligoclonal IgG bands in CSF but not in serum, indicative of intrathecal IgG synthesis; type 3, oligoclonal bands in CSF plus identical oligoclonal bands in serum and CSF, indicative of intrathecal IgG synthesis; type 4, identical pattern of oligoclonal bands in CSF and serum. There was no patient with type 5 (identical patterns of monoclonal bands in CSF and serum) in the study. Horizontal solid line indicates median, Kruskal-Wallis test among groups revealed a significant difference (p<0.001), significant P-values for pairwise comparisons (Mann-Whitney U test) are displayed.</p
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A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic... more
A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the…
Research Interests: Medicine, Neurodegenerative Diseases, Amyotrophic Lateral Sclerosis, Humans, Female, and 15 moreMale, Meta Analysis, Clinical Sciences, Aged, Middle Aged, Imputation, Genotype, GWAS, Neurodegenerative Disease, European Continental Ancestry Group, Genetic Association, Elsevier, Alzheimer Disease, Case Control Studies, and alleles
Epidemiological, clinical and post mortem studies indicate that inflammatory and immune reactions are involved in the pathomechanisms of affective and schizophrenic spectrum disorders. However, in psychiatric patients, only sporadic... more
Epidemiological, clinical and post mortem studies indicate that inflammatory and immune reactions are involved in the pathomechanisms of affective and schizophrenic spectrum disorders. However, in psychiatric patients, only sporadic investigation on immunochemistry has been performed and information about immunofunction derived by investigation of immunocompetent cells in the CSF is not available to date. Here we present an interdisciplinary work of neurologists, psychiatrists and hemato-immunologists focusing on the immunology of psychiatric and neurological disorders. In a first study including 63 patients with therapy resistant affective and schizophrenic spectrum disorders we applied conventional, validated neurological CSF investigation such as analysis of albumin, IgG, IgA, IgM, oligoclonal IgG and specific antibodies, cell count and interpreted the data by Reibergrams. In a second study, we applied the highly sensitive and specific multicolour flowcytometry of paired samples ...
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Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML). We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with... more
Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML). We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with natalizumab-associated PML (n=37). Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in blood and cerebrospinal fluid. In MS patients treated with natalizumab without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower in cerebrospinal fluid compared with MS patients not treated with natalizumab (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM levels as well as the IgG index dropped in longitudinal samples during natalizumab therapy. Oligoclonal bands persisted, but the total amount of the intrathecally produced IgG fraction, and the polyclonal intrathecal IgG reactivity to measles, rubella, and ...
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Research Interests: Engineering, Chemistry, Biology, Immunohistochemistry, Apoptosis, and 15 moreMedicine, Multidisciplinary, Cerebrospinal Fluid, Mice, Chronic Disease, Animals, Dimensional, High Resolution, Gel electrophoresis, Experimental Autoimmune Encephalomyelitis, Axons, Glutamate decarboxylase, Gene Expression Regulation, Gene expression profiling, and Ciliary Neurotrophic Factor
Research Interests: Immune response, Cerebrospinal Fluid, Identification, Humans, HPLC, and 15 moreFemale, Intestinal barrier function, Male, Astrocyte, Differential Diagnosis, Cohort, International Classification of Diseases, Adult, Elsevier, Immunoglobulins, Affective Disorder, Control Group, Cohort Studies, Cc, and Diagnostic Tool
Research Interests: Immunology, Medicine, Cerebrospinal Fluid, Humans, Cell Death, and 15 moreTemperature, Coefficient of Variation, Neurons, Axonal Degeneration, Optometry and Ophthalmology, Observer Variation, Neuronal Death, Time Factors, Reproducibility of Results, Biological markers, Elsevier, Enzyme Linked Immunosorbent Assay, Light chain, Reference standards, and Neurofilament proteins
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Research Interests: Multiple sclerosis, Magnetic Resonance Imaging, Adolescent, Medicine, Multidisciplinary, and 15 moreCerebrospinal Fluid, Humans, Female, Male, Clinically isolated syndrome, PLoS one, Aged, Middle Aged, Adult, Biological markers, B Lymphocytes, Predictive value of tests, Positive predictive value, Magnetic resonance image, and Cell count
The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application... more
The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in M...
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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing–remitting MS... more
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing–remitting MS (RRMS). The periphery-to-CNS transmission of inflammatory molecules is a major pathophysiological pathway in MS. This could include signalling via extracellular vesicle (EV) microRNAs (miRNAs). In this study, we investigated the serum EV miRNome in CIS and RRMS patients and matched controls, with the aims to identify MS stage-specific differentially expressed miRNAs and investigate their biomarker potential and pathophysiological relevance. miRNA sequencing was conducted on serum EVs from CIS-remission, RRMS-relapse, and viral inflammatory CNS disorder patients, as well as from healthy and hospitalized controls. Differential expression analysis was conducted, followed by predictive power and target-pathway analysis. A moderate number of dysregulated ...
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ZusammenfassungBei Verdacht auf eine Entzündung des ZNS besteht die wichtigste diagnostische Maßnahme in der Liquoranalytik. Gewissenhaft durchgeführt trägt sie dazu bei, inflammatorischen, neoplastischen, hämorrhagischen und... more
ZusammenfassungBei Verdacht auf eine Entzündung des ZNS besteht die wichtigste diagnostische Maßnahme in der Liquoranalytik. Gewissenhaft durchgeführt trägt sie dazu bei, inflammatorischen, neoplastischen, hämorrhagischen und degenerativen Erkrankungen des Nervensystems auf den Grund zu gehen. Dabei kommt es darauf an, alle Einzelbefunde in einen Gesamtbefund zu integrieren. Diese Befundungsstrategie erlaubt sowohl das Erkennen von krankheitstypischen Befundmustern als auch Plausibilitätskontrollen zur Vermeidung von Analytikfehlern.
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Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in... more
Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in particular the kappa isoform of FLC (“KFLC”), has been investigated for more than 40 years. Based on an extensive literature review, we found that an agreement on the correct method for evaluating KFLC concentrations has not yet been reached. KFLC indices with varying cut-off values and blood-CSF-barrier (QAlbumin) related non-linear formulas for KFLC interpretation have been investigated in several studies. All approaches revealed high diagnostic sensitivity and specificity compared with the oligoclonal bands, which are considered the gold standard for the detection of intrathecally synthesized immunoglobulins. Measurement of KFLC is fully automated, rater-independent, and has been shown to be stable against most pre-analytic influencing factors. In conclu...
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Serum neurofilament light chain (NfL) has been shown to correlate with neuroaxonal damage in multiple sclerosis (MS) and various other neurological diseases. While serum NfL is now regularly reported in clinical approval studies, there is... more
Serum neurofilament light chain (NfL) has been shown to correlate with neuroaxonal damage in multiple sclerosis (MS) and various other neurological diseases. While serum NfL is now regularly reported in clinical approval studies, there is a lack of longitudinal data from patients treated with established basic immunotherapies outside of study conditions. In total, 34 patients with early relapsing-remitting MS (RRMS) were included. The follow-up period was 24 months with regular follow-up visits after 3, 6, 9, 12 and 18 months. Therapy with glatiramer acetate was initiated in 20 patients and with interferon-beta in 12 patients. The disease course was monitored by the events of relapses, Expanded Disability Status Scale (EDSS) score and MRI parameters. Overall, serum NfL levels were higher at time points with a current relapse event than at time points without relapse (12.8 pg/mL vs. 9.7 pg/mL, p = 0.011). At follow-up, relapse-free patients showed significantly reduced serum NfL leve...
Research Interests: Medicine and biomedicines
Background: Proper identification of disability accumulation in the routine clinical care of progressive multiple sclerosis (PMS) patients is usually a challenging task. Patient-reported outcome measurements (PROMs) can provide a... more
Background: Proper identification of disability accumulation in the routine clinical care of progressive multiple sclerosis (PMS) patients is usually a challenging task. Patient-reported outcome measurements (PROMs) can provide a practical, cost-efficient, and remotely accessible tool to assess disease progression. Methods: EmBioProMS is a prospective, multicentric cohort, conducted in 7 specialized MS centers in Germany. PROMs were evaluated at inclusion and compared between patients with retrospective evidence of disease progression in the last two years and those with stable disease. Patients with either primary or secondary progressive MS according to the McDonald criteria 2017 were included in the analysis, while patients with incomplete PROMs scores, MS relapses, other neurological or systemic inflammatory diseases were excluded. The disease progression was assessed using a combined outcome parameter, including EDSS score, timed 25-foot walk test, and nine-hole-peg test. Resul...
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The assessment and demonstration of a positive benefit-risk balance of a drug is a life-long process and includes specific data from preclinical, clinical development and post-launch experience. However, new integrative approaches are... more
The assessment and demonstration of a positive benefit-risk balance of a drug is a life-long process and includes specific data from preclinical, clinical development and post-launch experience. However, new integrative approaches are needed to enrich evidence from clinical trials and sponsor-initiated observational studies with information from multiple additional sources, including registry information and other existing observational data and, more recently, health-related administrative claims and medical records databases. To illustrate the value of this approach, this paper exemplifies such a cross-package approach to the area of multiple sclerosis, exploring also possible analytic strategies when using these multiple sources of information.
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Tear fluid is receiving growing attention as a source for novel diagnostic biomarkers. Multiple techniques are available for its collection and impact the composition of acquired samples. We sought to provide a direct comparison of two... more
Tear fluid is receiving growing attention as a source for novel diagnostic biomarkers. Multiple techniques are available for its collection and impact the composition of acquired samples. We sought to provide a direct comparison of two collection methods with regard to implementation, acceptance, and impact on sample composition. Tear fluid was collected from fifteen healthy volunteers with capillary tubes and Schirmer strips and analyzed for total protein and IgG concentrations. Sampling parameters and perception by test persons were compared. The use of capillary tubes was more convenient for the participants while causing more effort for the collector. Tear flow rates as well as the relative and absolute amount of IgG were higher when Schirmer strips were used. Consecutive collections with Schirmer strips significantly influenced tear flow rates, IgG, and protein concentrations. A moderate correlation was observed between tear flow rates and IgG concentrations for both methods. S...
The inflammatory neuropathies are disabling conditions with diverse immunological mechanisms. In some, a pathogenic role for immunoglobulin G (IgG)-class autoantibodies is increasingly appreciated, and immunoadsorption (IA) may therefore... more
The inflammatory neuropathies are disabling conditions with diverse immunological mechanisms. In some, a pathogenic role for immunoglobulin G (IgG)-class autoantibodies is increasingly appreciated, and immunoadsorption (IA) may therefore be a useful therapeutic option. We reviewed the use of and response to IA or plasma exchange (PLEx) in a cohort of 41 patients with nodal/paranodal antibodies identified from a total of 573 individuals with suspected inflammatory neuropathies during the course of routine diagnostic testing (PNAb cohort). 20 patients had been treated with PLEx and 4 with IA. Following a global but subjective evaluation by their treating clinicians, none of these patients were judged to have had a good response to either of these treatment modalities. Sequential serology of one PNAb+ case suggests prolonged suppression of antibody levels with frequent apheresis cycles or adjuvant therapies, may be required for effective treatment. We further retrospectively evaluated ...
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The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be... more
The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features. (1) Methods: In a multicenter PPMS cohort (n = 81) with known MRZR status, we measured B cell-activating factor (BAFF), chemokine CXC ligand 13 (CXCL-13), soluble B cell maturation antigen (sBCMA), soluble transmembrane activator and CAML interactor (sTACI), and chitinase-3-like protein 1 (CHI3L1) in the CSF with enzyme-linked immunosorbent assays (ELISAs). Glial fi...
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Plasma exchange (PE) and immunoadsorption (IA) are frequently used for treatment of various autoimmune-mediated neurological diseases, including multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and... more
Plasma exchange (PE) and immunoadsorption (IA) are frequently used for treatment of various autoimmune-mediated neurological diseases, including multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and Guillain–Barré syndrome (GBS). Although both methods are generally regarded as well-tolerated treatment options, evidence for safety and tolerability is low for most indications and largely relies on small case series. In this study, we retrospectively analysed adverse events (AEs) and laboratory changes in 284 patients with various neurological indications who received either PE (n = 65, 113 cycles) or IA (n = 219, 435 cycles) between 2013 and 2020 in our Neurology department. One standard treatment cycle for PE as well as IA consisted of five treatments on five consecutive days. During every treatment, the 2.0–2.5-fold individual plasma volume (PV) was treated in IA, while in PE, the 0.7-fold individual PV was replaced by human albumin solution. Overall...
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To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections... more
To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes (p < 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = ...
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Background: Kappa free light chains (KFLC) are a promising new biomarker to detect neuroinflammation. Still, the impact of pre-analytical effects on KFLC concentrations was not investigated. Methods: KFLC concentrations were measured in... more
Background: Kappa free light chains (KFLC) are a promising new biomarker to detect neuroinflammation. Still, the impact of pre-analytical effects on KFLC concentrations was not investigated. Methods: KFLC concentrations were measured in serum and cerebrospinal fluid (CSF) of patients with a newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) before (n = 42) or after therapy with high-dose methylprednisolone (n = 65). In prospective experiments, KFLC concentrations were analyzed in the same patients in serum before and after treatment with high-dose methylprednisolone (n = 16), plasma exchange (n = 12), immunoadsorption (n = 10), or intravenous immunoglobulins (n = 10). In addition, the influence of storage time, sample method, and contamination of CSF with blood were investigated. Results: Patients diagnosed with MS/CIS and treated with methylprednisolone showed significantly lower KFLC concentrations in serum as untreated patients. Repeated longitudinal in...
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Central nervous system inflammation and neurodegeneration are the pathophysiological hallmarks of multiple sclerosis (MS). While inflammation can readily be targeted by current disease modifying drugs, neurodegeneration is by far less... more
Central nervous system inflammation and neurodegeneration are the pathophysiological hallmarks of multiple sclerosis (MS). While inflammation can readily be targeted by current disease modifying drugs, neurodegeneration is by far less accessible to treatment. Based on suggested additional neuroprotective capacities of the orally available non-opioid and centrally acting analgesic drug flupirtine maleate we hypothesized that treatment with flupirtine maleate might be beneficial in MS patients. The upirtine as al treatment n ultiple clerosis (FLORIMS) study was a multi-center, randomized and stratified, placebo-controlled double-blind phase II trial to investigate safety and efficacy in terms of clinical and radiographical activity of flupirtine maleate (300 mg per day) given orally for 12 months, add-on to interferon beta 1b subcutaneously in patients with relapsing remitting MS. Due to a substantial delay in recruitment, enrolment of patients was prematurely terminated after randomi...