scholarly journals Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Isobel A. Scarisbrick ◽  
Rachel Linbo ◽  
Alexander G. Vandell ◽  
Mark Keegan ◽  
Sachiko I. Blaber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Neurons ◽  
Serine Proteases ◽  
Serum Levels ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Neurite Retraction ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Potential Activity

Abstract Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

Effect of drugs in secondary disease progression in patients with multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S46-S55 ◽  
Author(s):  
Ludwig Kappos
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Positive Effects ◽  
Secondary Progressive ◽  
The North ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Effect Of Therapy ◽  
Almost All

Secondary progressive multiple sclerosis (SPMS) is a form of MS characterized by continuously worsening disability with or without superimposed relapses that occurs after a variable period of relapsing remitting disease and results in limited ambulation for almost all patients. The use of interferon beta (IFN b) for immunomodulation in patients with SPMS has been evaluated in four recent clinical trials: The European multicentre trial on IFN b-1b in SPMS (EUSPMS), the Secondary Progressive Efficacy Trial of Rebif (IFN b-1a) in MS (SPEC TRIMS), the North A merican Study of IFN b-1b in SPMS (NA SPMS), and the Internatio nal MS Secondary Progressive Avonex C linical Trial (IMPAC T). EUSPMS was the only trial to demonstrate a significant positive effect of therapy on disease progression as measured by the expanded disability status scale (EDSS). However, results from all studies demonstrated significant positive effects of treatment on relapse, T2 lesion load, and gadolinium enhancement. Immunomodulation with IFN b has the potential to significantly slow disease progression and improve quality of life for patients with SPMS. While results with monthly IV Ig were disappointing, positive effects on disease progression have been reported with the applicatio n of immunosuppressants, especially Mitoxantrone. The risk-benefit ratio of these cytostatic agents remains controversial. New strategies addressing the important neurodegenerative aspects of the disease are urgently needed.

scholarly journals BDNF and Tau as biomarkers of severity in Multiple Sclerosis

2017 ◽  
Author(s):  
Islas-Hernandez Azul ◽  
Aguilar-Talamantes Hugo Seacatl ◽  
Bertado-Cortes Brenda ◽  
Mejia-delCastillo Georgina de Jesus ◽  
Carrera-Pineda Raul ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Western Blot ◽  
Severity Score ◽  
Active Role ◽  
Serum Levels ◽  
Expanded Disability Status Scale ◽  
Secondary Progressive ◽  
Total Tau ◽  
Disability Status ◽  
Relapsing Remitting

AbstractAimsDetermine if serum levels of tau and brain-derived neurotrophic factor (BDNF) can be used as severity biomarkers in multiple sclerosis (MS).Patients and methodsSubjects with MS, older than 18 and younger than 55 years were included; 74 patients with a diagnosis of relapsing-remitting MS (RRMS), 11 with secondary-progressive MS (SPMS), and 88 controls were included. Total tau and BDNF were measured by western blot.ResultsIncreased tau and decreased BDNF in MS patients compared to controls was found. Total-tau has a peak in RRMS, the second decile of the Multiple Sclerosis Severity Score, and in the lowest Expanded Disability Status Scale and is no different than controls for SPMS patients and the most severe cases of MS.ConclusionBDNF is a good biomarker for diagnosis of MS but not for severity or progression. Tau appears to have a more active role in the progression of MS.

scholarly journals Should We Use Clinical Tools to Identify Disease Progression?

2021 ◽  
Vol 11 ◽  
Author(s):  
Hernan Inojosa ◽  
Undine Proschmann ◽  
Katja Akgün ◽  
Tjalf Ziemssen
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Markers ◽  
Disability Progression ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Secondary Progressive ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Clinical Tools

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.

scholarly journals Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731878334 ◽  
Author(s):  
Francisco Coret ◽  
Francisco C Pérez-Miralles ◽  
Francisco Gascón ◽  
Carmen Alcalá ◽  
Arantxa Navarré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

scholarly journals Enlarged perivascular spaces are not associated with vascular co-morbidities, clinical outcomes, and brain volumes in people with secondary progressive multiple sclerosis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732096450
Author(s):  
Lindsey Wooliscroft ◽  
Erin Boespflug ◽  
Andrea Hildebrand ◽  
Kathleen Shangraw ◽  
Elizabeth Silbermann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Perivascular Spaces ◽  
Centrum Semiovale ◽  
Informative Marker ◽  
Brain Volumes ◽  
Secondary Progressive ◽  
Disability Status

Background In secondary progressive multiple sclerosis (SPMS) significance of enlarged perivascular spaces (ePVS) is unknown. Objectives, Methods: Analysis of associations between vascular co-morbidities, clinical outcomes, and volumetrics with categorical ePVS scores in midbrain, basal ganglia (BG), and centrum semiovale (CSO) in SPMS(n-46). Results, Conclusion: In BG, advancing age (Z = 2.68) and lower Expanded Disability Status Scale (Z = −2.04) were associated with increasing ePVS score. In CSO, advancing age (Z = 2.66) and male gender (Z = 2.45) were associated with increasing ePVS score. No associations between ePVS score and vascular co-morbidities or volumetrics existed; ePVS may not be an informative marker for SPMS.

Hopelessness Ratings in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis

2002 ◽  
Vol 32 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Scott B. Patten ◽  
Luanne M. Metz
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Interferon Beta ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Exact Probability ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Trial Participants ◽  
Over Time

Objective: Two recent randomized double-blind placebo controlled clinical trials of interferon beta-1a in multiple sclerosis have obtained hopelessness ratings using the Beck Hopelessness Scale (BHS). One of these studies, the PRISMS trial, evaluated interferon beta-1a in relapsing remitting multiple sclerosis (RRMS). Another, the SPECTRIMS trial, evaluated the same medication in secondary progressive (SP) MS. The objective of this analysis was to compare levels of hopelessness in persons with RRMS and SPMS, and to describe changes over time in the clinical trial participants. Method: Raw data from each clinical trial was obtained from the sponsor of the trials (Serono). Median BHS ratings, and the proportions at or above the BHS cut-point of 10 were calculated over a two (PRISMS) or three (SPECTRIMS) year period. Results: The analysis included n = 532 clinical trial participants. Ratings of hopelessness were higher in SPMS clinical trial participants (SPECTRIMS) than in the RRMS group (PRISMS) at baseline (Fisher's exact test, p = 0.0035). Furthermore, ratings of hopelessness were higher during follow-up than at baseline, in the SPMS group (McNemar's exact probability, p = 0.0015), but not in the RRMS group (McNemar's exact probability, p = 0.65). Depression was strongly associated with hopelessness in both RRMS ( z = 4.13, p < 0.001) and SPMS ( z = 5.24, p < 0.001). Conclusions: Hopelessness is associated with SPMS, and may increase over time in this group. Hopelessness may influence suicide risk in people with MS and may potentially have an impact on coping and quality of life. Additional research is necessary to define the clinical implications of hopelessness in persons with this condition.

T1 relaxation maps allow differentiation between pathologic tissue subsets in relapsing-remitting and secondary progressive multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 556-561 ◽  
Author(s):  
A Castriota-Scanderbeg ◽  
F Fasano ◽  
M Filippi ◽  
C Caltagirone
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Relaxation Times ◽  
Brain Regions ◽  
Progressive Multiple Sclerosis ◽  
Clinical Group ◽  
Secondary Progressive ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Normal White Matter

In an attempt to clarify whether T1 relaxation time mapping may assist in characterizing the pathological brain tissue substrate of multiple sclerosis (MS), we compared the T1 relaxation times of lesions, areas of normal-appearing white matter (NAWM) located proximal to lesions, and areas of NAWM located distant from lesions in 12 patients with the relapsing-remitting and 12 with the secondary progressive (SP) subtype of disease. Nine healthy volunteers served as controls. Calculated mean T1 values were averaged across all patients within each clinical group, and comparisons were made by means of the Mann-Whitney U-test. Significant differences were found between all investigated brain regions within each clinical subgroup. Significant differences were also detected for each investigated brain region among clinical subgroups. While T1 values of NAWM were significantly higher in patients with SP disease than in normal white matter (NWM) of controls, no differences were detected when corresponding brain areas of patients with RR MS were compared with NWM of controls. T1 maps identify areas of the brain that are damaged to a different extent in patients with MS, and may be of help in monitoring disease progression.

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