There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of ...the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.
Background and purpose
The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO ...Diagnosis (IPND) criteria.
Methods
A retrospective population‐based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re‐evaluation from multiple sources. Crude and sex‐ and serostatus‐specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person‐years) from 2006 to 2015 were estimated and age‐adjusted rates were determined.
Results
Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 95% confidence interval (CI) 1.52–2.28 per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person‐years provided an incidence rate of 1.32 (95% CI 1.08–1.61) per 1 000 000 person‐years. Age‐adjusted prevalence was 1.87 (95% CI 1.56–2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98–1.46) per 1 000 000 person‐years.
Conclusions
In this first report of a large population‐based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.
Stroke can lead to lasting sensorimotor deficits of the upper limb (UL) persisting into the chronic phase despite intensive rehabilitation. A major impairment of reaching after stroke is a decreased ...range of active elbow extension, which in turn leads to the use of compensatory movements. Retraining movement patterns relies on cognition and motor learning principles. Implicit learning may lead to better outcomes than explicit learning. Error augmentation (EA) is a feedback modality based on implicit learning resulting in improved precision and speed of UL reaching movements in people with stroke. However, accompanying changes in UL joint movement patterns have not been investigated. The objective of this study is to determine the capacity for implicit motor learning in people with chronic stroke and how this capacity is affected by post-stroke cognitive impairments.
Fifty-two subjects who have chronic stroke will practice reaching movements 3×/wk. for 9 wk. in a virtual reality environment. Participants will be randomly allocated to 1 of 2 groups to train with or without EA feedback. Outcome measures (pre-, post- and follow-up) will be: endpoint precision, speed, smoothness, and straightness and joint (UL and trunk) kinematics during a functional reaching task. The degree of cognitive impairment, lesion profile, and integrity of descending white matter tracts will be related to training outcomes.
The results will inform us which patients can best benefit from training programs that rely on motor learning and utilize enhanced feedback.
Trial status: Ethical approval for this study was finalized in May 2022. Recruitment and data collection is actively in progress and is planned to finish in 2026. Data analysis and evaluation will occur subsequently, and the final results will be published.
•A novel intervention for stroke recovery using enhanced feedback.•A new strategy for the reduction of UL impairment.•A brand-new program to promote UL recovery after stroke.
Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. ...The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient's death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.
Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease.
We evaluated 1,083 families with > ...or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs.
There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading.
Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid ...were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing–remitting MS patients receiving long‐term and acute interferon‐β (IFN‐β) treatment. Twenty‐four hours post‐administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long‐term IFN MS, P = 0.036) were found. The long‐term IFN MS group had higher K/T ratios at 4 and 12 h post‐administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine‐2,3‐dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.
Abstract Background The ‘Multiple Sclerosis Quality of Life Instrument’ (MSQOL-54) was recently validated in Hungarian, on more than 400 multiple sclerosis (MS) patients. The aim of the present study ...was to examine the impact on their overall quality of life (QoL) of the demographic and clinical data on these patients, and their scores on different QoL scales. Methods The Hungarian version of MSQOL-54 was given to patients at the outpatient units at the Department of Neurology, University of Szeged, and two other Hungarian MS centres. Additional data, including the EDSS scores of the patients, and relevant clinical and demographic data, were also collected. Results The questionnaire scales relating to social function, general health, mental health and satisfaction with the sexual function mostly determined the overall QoL ratings. 62.1% of the patients indicated at least one comorbid condition. Depressed patients had a significantly worse quality of life ( p < 0.0001). Conclusions MSQOL-54 is a useful tool for the recognition of possibly treatable factors influencing the QoL, but not assessed by the EDSS. Quality of life data have emerged on more than 400 patients, i.e. a considerable proportion of the Hungarian MS patient population.
The mutual involvement of dopamine and its metabolites in the nervous and immune systems has the potential to provide information on the interaction of these two systems. During a 24-hour period, we ...used capillary electrophoresis with electrochemical detection to repeatedly measure the intracellular catecholamine concentrations in the peripheral blood lymphocytes of relapsing-remitting multiple sclerosis (RRMS) patients receiving interferon (IFN)-beta-1b (n = 13), and those of IFN-naïve RRMS patients receiving their first IFN-beta-1a injection (n = 19) during this study, and compared them with the levels in healthy controls (n = 12). At baseline, the norepinephrine level was significantly decreased (P = 0.003) in the long-term IFN MS patients compared with the controls. The Time × Group interactions for dopamine (P= 0.5854) and norepinephrine (P = 0.6192) were not significant. The group effects for the individual drugs were P = 0.3529 and 0.1282, respectively. The lower norepinephrine level at baseline in the long-term IFN MS group suggests an immunologically stable phase, in line with our previous findings. This is the first report of the effects of IFN-beta administration on intracellular catecholamines in MS patients. Further studies are necessary to elucidate the immune reactions affected by the catecholamines in MS and to evaluate the roles of these potential immunotransmitters.
Health-related quality of life measurements are gaining more importance in the study and clinical practice of multiple sclerosis. The aim of our study was the adaptation of the Multiple Sclerosis ...Quality of Life Instrument (MSQOL-54) in Hungarian. The study was carried out at the Department of Neurology, University of Szeged and two other multiple sclerosis centers. The Hungarian translation of the questionnaire was given to patients at the outpatient units of the neurology departments. The EDSS score of the patients were determined and data concerning the onset and the clinical form of the disease was collected. Altogether 438 patients filled out the questionnaire. We enrolled patients with all clinical forms of the disease. Cronbach's alpha coefficients were over 0.8 in case of all scales except `Rolelimitations — emotional' (0.794), indicating a good internal consistency reliability for group comparisons. The instrument was able to distinguish between known clinical group differences. The Hungarian version of the MSQOL-54 instrument shows good psychometric properties similar to the original questionnaire. Multiple Sclerosis 2008; 14: 391—398. http://msj.sagepub.com
Background and objective:
We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large ...international cohort.
Methods:
Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS.
Results:
At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres.
Conclusions:
We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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