Tau protein seems not to be a useful routine clinical marker of axonal damage in multiple sclerosis

2006 ◽  
Vol 12 (3) ◽  
pp. 354-356 ◽  
Author(s):  
J Guimarães ◽  
M J Cardoso ◽  
M J Sá

Background The descriptions of early axonal damage in patients with multiple sclerosis (MS) prompted the search of body fluid markers. However, the studies addressing this issue in MS present conflicting results. Aim To assess the levels of tau protein in patients with definite MS. Patients and methods Cerebrospinal fluid (CSF) samples from 50 patients with definite diagnosis of MS (33 F, 17 M; mean age: 33.6 years) and from 19 age-matched individuals without organic neurological diseases (11 F, 8 M), entered this study. With regard to the clinical course, the MS patients were classified as follows: 32 relapsing-remitting (RR); two secondary progressive (SP), and four primary progressive (PP). Twelve patients had clinical isolated syndromes (CIS). The mean duration was 36.1 months (range: 15 days to 20 years). Tau protein was measured in the CSF by double antibody sandwich ELISA. Results The median tau and the cut-off values of the controls were 104.9 and 175.3 pg/mL, respectively. We found that most MS patients presented normal values. In addition, the clinical features-course, duration, Expanded Disability Status Scale (EDSS) value, Poser index of progression, Multiple Sclerosis Severity Score-did not significantly influence the tau levels in the MS group. Conclusion Our study showed similar CSF tau concentrations in MS patients with different clinical characteristics. This suggests that tau protein does not seem to be a useful routine clinical marker of axonal damage.

2002 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
A Ghezzi ◽  
C Pozzilli ◽  
M Liguori ◽  
M G Marrosu ◽  
N Milani ◽  
...  

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.


2010 ◽  
Vol 17 (3) ◽  
pp. 335-343 ◽  
Author(s):  
Mohsen Khademi ◽  
Ingrid Kockum ◽  
Magnus L Andersson ◽  
Ellen Iacobaeus ◽  
Lou Brundin ◽  
...  

Background: Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments. Objective: Here we validate the potential role of CSF CXCL13 as a biomarker for aspects of MS in a large amount of clinical material, the majority collected at early diagnostic work-up. Methods: CXCL13 was measured by ELISA in 837 subjects: relapsing–remitting MS (RRMS; n = 323), secondary progressive MS (SPMS; n = 40), primary progressive MS (PPMS; n = 24), clinically isolated syndrome (CIS; n = 79), other neurological diseases (ONDs; n = 181), ONDs with signs of inflammation or viral/bacterial infections (iONDs; n = 176) and healthy controls ( n = 14). Results: Subjects with viral/bacterial infections had extremely high CXCL13 levels compared to all included groups ( p < 0.0001). CXCL13 was otherwise significantly higher in MS compared to the remaining controls ( p < 0.0001), and CIS ( p < 0.01). A significant and positive correlation between CXCL13 and relapse rate, the results obtained for the Expanded Disability Status Scale (EDSS) and the number of lesions detected by MRI was demonstrated. CXCL13 was increased in CIS conversion to clinically definite MS ( p < 0.001). Oligoclonal immunoglobulin band (OCB)-positive CIS or MS had significantly increased CXCL13 levels compared to OCB-negative CIS or MS ( p < 0.001 and p < 0.0001, respectively). Conclusion: CXCL13 was associated with disease exacerbations and unfavourable prognosis in RRMS. Increased CXCL13 was not specific for MS since subjects with viral/bacterial infections exhibited even higher levels. High levels predicted CIS conversion to MS. We suggest that measurement of CSF CXCL13 can be part of the armamentarium in the diagnostic and prognostic work-up in MS and be of help in future treatment decisions.


Author(s):  
Paolo Angelo Cortesi ◽  
Paolo Cozzolino ◽  
Ruggero Capra ◽  
Giancarlo Cesana ◽  
Lorenzo Giovanni Mantovani

INTRODUCTION: Poor specific economic information are available for the different Multiple Sclerosis (MS) courses: relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS). This study aims to fill this gap.METHODS: A cost of illness study was conducted. Clinical information of patients treated in a major MS Center located in Lombardy, in the period 2004-2010, were linked with administrative data of Lombardy Healthcare System. We assessed the mean cost per patient-year and its association with different MS characteristics.RESULTS: The study identified 869 patients (83.9% RRMS, 8.5% SPMS, 7.2% PPMS). RRMS reported the highest cost per patient-year with a mean of € 5,623 in Expanded Disability Status Scale (EDSS) 0-3, € 8,675 in EDSS 3.5-6.5, and € 7,451 in EDSS 7-9. The PPMS patients reported the lower annual mean cost per patient in all EDSS categories. The mul-tivariate analysis reported a significant association between cost per patient-year and EDSS categories, relapse and use of Disease Modifying Therapies but not to MS courses, age and sex.CONCLUSION: This study provides a complete picture of MS courses direct costs at the different disability levels. The results can help to better understand the burden of each MS courses and the cost-effectiveness of different interventions.


2007 ◽  
Vol 13 (5) ◽  
pp. 626-631 ◽  
Author(s):  
M. Debouverie ◽  
L. Taillandier ◽  
S. Pittion-Vouyovitch ◽  
S. Louis ◽  
H. Vespignani

The objectives of this study were to assess the benefits of 1) mitoxantrone after three years of follow-up and 2) disease-modifying treatment (DMT) after stopping mitoxantrone. A retrospective analysis was performed on 304 patients with active relapsing-remitting (RR) or progressive multiple sclerosis (PMS) who were treated with mitoxantrone. After mitoxantrone therapy, some patients received DMT (interferon-beta or glatiramer acetate) while others did not. The disease course of the two groups was evaluated by the Expanded Disability Status Scale (EDSS) before and after mitoxantrone and then every year for three years. The mean EDSS score at starting mitoxantrone and three years after stopping mitoxantrone respectively, were: 3.3 (1.3) and 3.2 (1.7) for the RRMS patients and 5.9 (1.2) and 6.4 (1.4) for the PMS patients. Before starting mitoxantrone, demographic and clinical parameters of predictive disability were not significantly different between patients who received DMT or not. The variation of EDSS between time of stopping mitoxantrone and three years later was significantly different (+0.9 versus +0.3; P=0.03) for patients with RRMS. We found that mitoxantrone treatment induces stable disease up to two years after discontinuation of mitoxantrone therapy. In the third year, patients without DMT deteriorated. Multiple Sclerosis 2007; 13: 626-631. http://msj.sagepub.com


2014 ◽  
Vol 21 (10) ◽  
pp. 1271-1279 ◽  
Author(s):  
Antonio Checa ◽  
Mohsen Khademi ◽  
Daniel G Sar ◽  
Jesper Z Haeggström ◽  
Jon O Lundberg ◽  
...  

Background: Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS). Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression. Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart. Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS ( p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND ( p<0.001), iOND ( p<0.05) and EarlyMS ( p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies ( p=0.048; p=0.027). Conclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.


2003 ◽  
Vol 9 (1) ◽  
pp. 36-38 ◽  
Author(s):  
Hossein Kalanie ◽  
Kurosh Gharagozli ◽  
Amir Reza Kalanie

C linical findings of 200 patients in Iran with definite multiple sclerosis (MS) according to Poser et al.’s criteria and positive findings on magnetic resonance imaging (MRI) have been reviewed. The clinical course was relapsing-remitting (RR) for 88%, primary progressive (PP) for 7% and secondary progressive (SP) for 5% of cases. The mean age of onset was 27±7.4 years for the whole group and 37.1±8.8 years for PPMS. The gender ratio was 2.5:1 female:male. Involvement of the pyramidal system was the most common mode of presentation. Five per cent of patients had positive family history for the disease, 14% of patients had benign MS and 12% with disease duration longer than five years had an Expanded Disability Status Scale-2. The optico-spinal form was not a common form of presentation in the group.


2011 ◽  
Vol 18 (5) ◽  
pp. 592-599 ◽  
Author(s):  
J Frederiksen ◽  
K Kristensen ◽  
JMC Bahl ◽  
M Christiansen

Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. Methods: A total of 66 patients with MS and/or ON from the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased concentration of tau protein in CSF from patients with relapsing–remitting MS and patients monosymptomatic at onset who progressed to MS, but interestingly no increased tau protein concentration in monosymptomatic ON. The concentration of tau protein was significantly correlated to Expanded Disability Status Scale score. No 14-3-3 protein was detected in any CSF sample. Conclusions: The results of this study invite further exploration of the possible role of tau protein as a prognostic factor to predict progression from ON to MS in future studies.


2021 ◽  
pp. jnnp-2020-325421
Author(s):  
Lukas Haider ◽  
Karen Chung ◽  
Giselle Birch ◽  
Arman Eshaghi ◽  
Stephanie Mangesius ◽  
...  

ObjectiveTo determine 30-year brain atrophy rates following clinically isolated syndromes and the relationship of atrophy in the first 5 years and clinical outcomes 25 years later.MethodsA cohort of 132 people who presented with a clinically isolated syndrome suggestive of multiple sclerosis (MS) were recruited between 1984–1987. Clinical and MRI data were collected prospectively over 30 years. Widths of the third ventricle and the medulla oblongata were used as linear atrophy measures.ResultsAt 30 years, 27 participants remained classified as having had a clinically isolated syndrome, 34 converted to relapsing remitting MS, 26 to secondary progressive MS and 16 had died due to MS. The mean age at baseline was 31.7 years (SD 7.5) and the mean disease duration was 30.8 years (SD 0.9). Change in medullary and third ventricular width within the first 5 years, allowing for white matter lesion accrual and Expanded Disability Status Scale increases over the same period, predicted clinical outcome measures at 30 years. 1 mm of medullary atrophy within the first 5 years increased the risk for secondary progressive MS or MS related death by 30 years by 583% (OR 5.83, 95% CI 1.74 to 19.61, p<0.005), using logistic regression.ConclusionsOur findings show that brain regional atrophy within 5 years of a clinically isolated syndrome predicts progressive MS or a related death, and disability 25 years later.


2018 ◽  
Vol 12 (01) ◽  
pp. 144-148 ◽  
Author(s):  
Lucas Senra Correa Carvalho ◽  
Osvaldo José Moreira Nascimento ◽  
Luciane Lacerda Franco Rocha Rodrigues ◽  
Andre Palma Da Cunha Matta

ABSTRACTObjectives: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. Materials and Methods: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. Statistical Analysis Used: Fisher’s exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. Results: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). Conclusions: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.


2021 ◽  
Vol 3 (3) ◽  
pp. 366-376
Author(s):  
Lorenzo Tonetti ◽  
Federico Camilli ◽  
Sara Giovagnoli ◽  
Vincenzo Natale ◽  
Alessandra Lugaresi

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.


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