Immune profiling in multiple sclerosis: a single-center study of 65 cytokines, chemokines, and related molecules in cerebrospinal fluid and serum

IntroductionThe understanding of the pathophysiology of multiple sclerosis (MS) has evolved alongside the characterization of cytokines and chemokines in cerebrospinal fluid (CSF) and serum. However, the complex interplay of pro- and anti-inflammatory cytokines and chemokines in different body fluids in people with MS (pwMS) and their association with disease progression is still not well understood and needs further investigation. Therefore, the aim of this study was to profile a total of 65 cytokines, chemokines, and related molecules in paired serum and CSF samples of pwMS at disease onset.MethodsMultiplex bead-based assays were performed and baseline routine laboratory diagnostics, magnetic resonance imaging (MRI), and clinical characteristics were assessed. Of 44 participants included, 40 had a relapsing–remitting disease course and four a primary progressive MS.ResultsThere were 29 cytokines and chemokines that were significantly higher in CSF and 15 in serum. Statistically significant associations with moderate effect sizes were found for 34 of 65 analytes with sex, age, CSF, and MRI parameters and disease progression.DiscussionIn conclusion, this study provides data on the distribution of 65 different cytokines, chemokines, and related molecules in CSF and serum in newly diagnosed pwMS

Diagnostic value of kappa free light chain index in patients with primary progressive multiple sclerosis – a multicentre study

BackgroundKappa free light chains (κ-FLC) in the cerebrospinal fluid (CSF) are an emerging biomarker in multiple sclerosis (MS).ObjectiveTo investigate whether κ-FLC index has similar diagnostic value in patients with primary progressive multiple sclerosis (PPMS) compared to oligoclonal bands (OCB).MethodsPatients with PPMS were recruited through 11 MS centres across 7 countries. κ-FLC were measured by immunonephelometry/-turbidimetry. OCB were determined by isoelectric focusing and immunofixation.ResultsA total of 174 patients (mean age of 52±11 years, 51% males) were included. κ-FLC index using a cut-off of 6.1 was positive in 161 (93%) and OCB in 153 (88%) patients.Conclusionκ-FLC index shows similar diagnostic sensitivity than OCB in PPMS

Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

Background: An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Methods: Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. Results: HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Conclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic value. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies

Cerebrospinal fluid oligoclonal bands in Neuroborreliosis are specific for Borrelia burgdorferi.

BackgroundCerebrospinal fluid (CSF) oligoclonal bands (OCB) occur in chronic or post-acute phase of inflammatory diseases of the central nervous system.ObjectiveTo determine whether CSF OCB in patients with neuroborreliosis (NB) are specific for borrelia burgdorferi senso lato.MethodsWe performed isoelectric focusing followed by immunoblotting in CSF of 10 NB patients and 11 controls (7 patients with multiple sclerosis, 2 patients with neuromyelitis optica spectrum disease, 1 patient with dementia and 1 patient with monoclonal gammopathy). Immunoblotting was performed using an uncoated as well as a borrelia antigen pre-coated nitrocellulose membrane (NCM). OCB were counted by visual inspection and photometric analysis. OCB were compared between uncoated und pre-coated NCM both in the NB and control group. For validation purposes inter-assay precision was determined by calculating the coefficient of variation (CV).ResultsBorrelia-specific OCB were found in the CSF of 9 NB patients and in none of the control subjects resulting in a sensitivity of 90% and a specificity of 100%. Number of NB specific OCB were 11±7 bands by photometric analyses compared to 9±5 bands by visual inspection. Validation experiments revealed an inconsistent inter-assay precision between visual and photometric analyses (NB uncoated: visual 28% versus photometric 14%, control subject uncoated: visual 16% versus photometric 24%).ConclusionsIn CSF samples with positive OCB, Borrelia-specific bands were detected in almost all NB patients and in none of the control subjects. Inconsistent inter-assay precision may be explained by a poor comparability of visual and photometric approach

Transient impairment of olfactory threshold in acute multiple sclerosis relapse

BACKGROUND Impairment of olfactory threshold is a feature of early and active relapsing remitting multiple sclerosis (RRMS). It predicts inflammatory disease activity and was reported to be transient. However, the timing of onset and resolve of olfactory threshold impairment remains unclear. OBJECTIVE To prospectively assess the development of olfactory threshold in acute MS relapse over time in comparison to stable MS patients. METHODS In a prospective observational design, we measured olfactory threshold by performing the Sniffin' Sticks test (minimum score 0, maximum score 16 reflecting optimal olfactory function) at baseline and after 4, 12 and 24 weeks. We included 30 RRMS patients with acute MS relapse and 30 clinically stable RRMS patients (defined as no relapse within the last 12 months) as a control group. RESULTS Olfactory threshold was impaired in patients with acute MS relapse at baseline (median difference = -3.5; inter-quartile range [IQR] -4.5- - 2.5; p < 0.001), week 4 (-2.5; IQR -3.0 - -2.0; p < 0.001), week 12 (-1.5; IQR -2.0 - -0.5; p = 0.002) and week 24 (-0.5; IQR -1.0 - 0.0; p = 0.159) compared to stable MS patients. Of note, in relapsing patients in whom disease-modifying treatment was initiated or escalated after relapse, threshold did not differ anymore from stable patients at week 12 (-0.5; IQR -1.0 - 0.5; p = 0.247) and week 24 (0.0; IQR -1.0 - 1.0; p = 0.753). CONCLUSIONS Olfactory threshold impairment seems to be a transient bystander feature of MS relapse. It may be correlated to the level of inflammation within the CNS and might be a useful biomarker in this regard

The Journal of Headache and Pain / Prevalence, management and burden of episodic and chronic headaches : a cross-sectional multicentre study in eight Austrian headache centres

Background Episodic and chronic headaches (EH, CH) are highly prevalent disorders. Severely affected patients are usually referred to headache centres. In Austria, at least one headache centre is available in seven of nine states, but detailed multicentre data are missing. Therefore we studied prevalence rates, use of medication and health care services, impact of headaches, and comorbid depression and anxiety. Methods We included consecutive patients from eight Austrian outpatient headache centres. The patients filled-in the Eurolight questionnaire. In addition, the treating neurologist completed a questionnaire on clinical diagnoses and ever-before prophylactic medications. Results Of 598 patients screened, 441 questionnaires were analysed (79 % female, mean age 41.1 years). According to the Eurolight algorithm, 56.4 % of the patients had EH, 38.3 % had CH and 5.2 % did not give their headache frequency. The prevalence rates of migraine, tension-type headache, and probable medication overuse headache (pMOH) were 48.5 %, 6.3 % and 15.9 %, respectively. The concordance between clinical and Eurolight diagnoses was good for EH and moderate for CH. During the preceding month, acute medication was used by 90.9 % of the patients and prophylactic medication by 34 %. Ever-before use of five standard prophylactic drugs was recorded in 52.3 %. The proportion of patients with current pharmacoprophylaxis did not differ in EH and CH, whereas ever-before use was more common in CH (62.5 % was 45,3 %, p = 0.02). Patients with CH significantly more often consulted general practitioners and emergency departments, had a lower quality of life and more often signs of depression and anxiety. Conclusion This study provides comprehensive data from eight Austrian headache centres for the first time. We found a substantial number of patients with CH including pMOH and its association with more common utilization of health care facilities and greater burden. The low use of prophylactic medication requires further examination.(VLID)484316

Change of olfactory function as a marker of inflammatory activity and disability progression in MS

BACKGROUND Impaired olfactory threshold has been reported in early inflammatory phases of MS, while impaired odor identification was associated with more widespread disability. OBJECTIVE To prospectively assess the development of olfactory function and its correlation with relapse and disability progression. METHODS In this prospective, 3-year longitudinal study on 151 MS patients and 30 healthy controls, three different qualities of olfactory function (threshold, discrimination, and identification) were quantified using the Sniffin' Sticks test. The influence of relapses and disability on olfactory function was analyzed at different time points and in a multivariate model. RESULTS Discrimination and identification capability significantly worsened over 3 years, while threshold did not. Threshold was markedly impaired in patients with relapse activity within 12 months, recovered in the absence of relapse, and was associated with a 2.5-fold increased risk of relapse. Deterioration of discrimination and identification was irreversible and both strongly associated with and predictive of EDSS progression. CONCLUSION Olfactory function changes over time in MS. Threshold impairment is transient and predicts inflammatory disease activity, while odor identification and discrimination are associated with disability progression. Olfactory dysfunction might be a useful and easily obtainable parameter to monitor patients with regard to inflammation and neurodegeneration in MS