Disease steps in multiple sclerosis: a longitudinal study comparing Disease Steps and EDSS to evaluate disease progression

1999 ◽  
Vol 5 (5) ◽  
pp. 349-354 ◽  
Author(s):  
M J Hohol ◽  
E J Orav ◽  
H L Weiner
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Event Analysis ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Practical Tool ◽  
Therapeutic Decision Making ◽  
Over Time

Clinical assessment of outcome in Multiple Sclerosis (MS) patients is problematic since the disease can affect different aspects of the central nervous system and follow a variable course. Recently, we developed Disease Steps, a simple approach for evaluating disease progression. Previously, we found that Disease Steps was easy to use, had uniformly distributed scores and low inter-rater variability. Our current objective was to test the long-term use of Disease Steps together with the most widely utilized clinical outcome measure in MS, the Expanded Disability Status Scale (EDSS) in assessing clinical progression. Over 4 years, 804 patients were classified using both EDSS and Disease Steps. Each patient was assessed at least twice. Follow-up results included annual status and time-to-event analysis examining median staying times within a level of Disease Steps or EDSS. We found that the two scales behaved similarly and correlated strongly with each other. For both Disease Steps and EDSS, patients with milder levels of disability and relapsing-remitting disease demonstrated a higher likelihood of changing scores over time and shorter median staying times compared to more disabled, chronic progressive patients. These findings have important implications for patient selection in clinical trials and for the design of future measurements of clinical outcome in MS. Furthermore, Disease Steps may serve as a simple, practical tool for the nonspecialty neurologist to follow patients over time and serve as a guide in therapeutic decision making. Our findings further document the general progressive nature of MS when a large cohort is followed in an MS specialty clinic over time.

Disease progression in multiple sclerosis: combining physicians’ and patients’ perspectives?

2010 ◽  
Vol 17 (2) ◽  
pp. 234-240 ◽  
Author(s):  
JJ Kragt ◽  
JM Nielsen ◽  
FAH van der Linden ◽  
CH Polman ◽  
BMJ Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Outcome Measures ◽  
Added Value ◽  
Impact Scale ◽  
Disability Status ◽  
The Impact ◽  
Nine Hole Peg Test ◽  
Combine Outcome

Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS. Objective: To explore combining different clinical outcome measures in the evaluation of disease progression in MS. Methods: In 553 patients we studied the presence of relevant changes according to standard definitions on the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW) and the Multiple Sclerosis Impact Scale (MSIS-29). We examined ‘exclusive worsening’ (worsening on one measure while not worsening on any other measure) and ‘opposing changes’ (worsening on one measure while improving on another measure). Finally, we investigated the impact of combining assessments. Results: Based on the EDSS alone, 140 patients progressed. However, almost twice as many (275) showed worsening on any of the clinical outcome measures. Exclusive worsening was observed in 37 patients on the EDSS, 13 on the 9HPT, 39 on the T25FW and 44 on the MSIS physical. Of all worsened patients 76 (28%) showed opposing changes, a phenomenon predominantly observed when combining physician-based and patient-derived outcome measures. Conclusion: When assessing disease progression in MS, sensitivity to change can be increased by combining different outcome measures. The added value is especially present when combining measures from different perspectives. However, further research is needed to evaluate the optimal way to combine outcome measures before implementing this strategy in clinical studies.

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression

2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
In Cis

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

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 Clinical and epidemiological profile of patients with multiple sclerosis in Uberaba, Minas Gerais, Brazil

2011 ◽  
Vol 69 (2a) ◽  
pp. 184-187 ◽  
Author(s):  
Sônia Beatriz Félix Ribeiro ◽  
Danilo Fonseca Maia ◽  
João Batista Ribeiro ◽  
Fabrízio Antônio Gomide Cardoso ◽  
Cátia Silva
Keyword(s):  
Multiple Sclerosis ◽  
College Education ◽  
Average Score ◽  
Initial Symptom ◽  
Immune Mediated ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Epidemiological Profile ◽  
Brazilian Studies

Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. Clinical presentation and prevalence vary widely around the world. OBJECTIVE: To describe the clinical and epidemiological aspects of patients with MS in Uberaba (MG). METHOD: We conducted a transversal descriptive study, with data analysis of 35 patients with MS. RESULTS: Prevalence of MS was 12.5 cases/100,000 inhabitants, with a predominance in females (71.4%) and Caucasoid (85.7%). The current average age was (43.8 ys). The most common initial symptom was sensory (40%), followed by optical neuritis (25.7%). Expanded Disability Status Scale average score was 2.4. The relapsing-remitting form was predominant (88.6%), most (74.3%) were on immunomodulatory treatment and (40%) had college education. CONCLUSION: Prevalence of MS in Uberaba (MG) is considered average in accordance to Kurtzke and Page and clinical features are consistent with most Brazilian studies.

Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis

2014 ◽  
Vol 21 (10) ◽  
pp. 1271-1279 ◽  
Author(s):  
Antonio Checa ◽  
Mohsen Khademi ◽  
Daniel G Sar ◽  
Jesper Z Haeggström ◽  
Jon O Lundberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Neurological Diseases ◽  
Control Groups ◽  
Promising Candidate ◽  
Fatty Acid Chain ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Liquid Chromatography Tandem Mass

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.

scholarly journals Serum Anti-oligodendrocyte Autoantibodies in Patients With Multiple Sclerosis Detected by a Tissue-Based Immunofluorescence Assay

2021 ◽  
Vol 12 ◽  
Author(s):  
Yukino Miyachi ◽  
Takayuki Fujii ◽  
Ryo Yamasaki ◽  
Daisuke Tsuchimoto ◽  
Kyoko Iinuma ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Immunofluorescence Assay ◽  
Mature Oligodendrocyte ◽  
Myelin Sheaths ◽  
Mental Disturbance ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Cns Proteins

Multiple sclerosis (MS), the most prevalent inflammatory disease of the central nervous system (CNS), is characterized by damaged to myelin sheaths and oligodendrocytes. Because MS patients have variable clinical courses and disease severities, it is important to identify biomarkers that predict disease activity and severity. In this study, we assessed the frequencies of serum autoantibodies against mature oligodendrocytes in MS patients using a tissue-based immunofluorescence assay (IFA) to determine whether anti-oligodendrocyte antibodies are associated with the clinical features of MS patients and whether they might be a biomarker to assess CNS tissue damage in MS patients. We assessed the binding of serum autoantibodies to mouse oligodendrocytes expressing Nogo-A, a reliable mature oligodendrocyte marker, by IFA with mouse brain and sera from 147 MS patients, comprising 103 relapsing–remitting MS (RRMS), 22 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS) patients, 38 neuromyelitis optica spectrum disorder (NMOSD) patients, 23 other inflammatory neurological disorder (OIND) patients, and 39 healthy controls (HCs). Western blotting (WB) was performed using extracted mouse cerebellum proteins and IgG from anti-oligodendrocyte antibody-positive MS patients. Tissue-based IFA showed that anti-oligodendrocyte antibodies were positive in 3/22 (13.6%) PPMS and 1/22 (4.5%) SPMS patients but not in RRMS, NMOSD, and OIND patients or HCs. WB demonstrated the target CNS proteins recognized by serum anti-oligodendrocyte antibodies were approximately 110 kDa and/or 150 kDa. Compared with anti-oligodendrocyte antibody-negative MS patients, MS patients with anti-oligodendrocyte antibodies were significantly older at the time of serum sampling, scored significantly higher on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and had a higher frequency of mental disturbance. Although the clinical significance of anti-oligodendrocyte antibodies is still unclear because of their low frequency, anti-oligodendrocyte autoantibodies are potential biomarkers for monitoring the disease pathology and progression in MS.

Mediators of apoptosis Fas and FasL predict disability progression in multiple sclerosis over a period of 10 years

2006 ◽  
Vol 12 (6) ◽  
pp. 704-709 ◽  
Author(s):  
L Lopatinskaya ◽  
J Zwemmer ◽  
B Uitdehaag ◽  
K Lucas ◽  
C Polman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Mrna Levels ◽  
Mild Disease ◽  
Tnf Α ◽  
Disability Status ◽  
Fas Mrna ◽  
Relapsing Remitting ◽  
Post Hoc ◽  
Fasl Mrna

TNF-α, IL-12p35, IL-12p40, IL-4, IL-10, TGF-β1, CCR3, CXCR3, CCR5, Fas and FasL mRNA levels in PBMC of 25 multiple sclerosis (MS) patients were quantified at baseline by real-time PCR according to a post-hoc study design. The baseline values of the different markers were analysed with respect to their correlation with the increase in disability over a period of 10 years. High levels of Fas mRNA were associated with a favourable disease course in relapsing-remitting (RR) MS (R2 = 0.74, P = 0.0001, n = 13), as measured by the Expanded Disability Status Scale (EDSS); high levels of FasL mRNA were associated with relatively mild disease progression (R2 = 0.86, P = 0.0001, n = 12) in secondary progressive (SP) MS. These findings suggest that Fas-mediated apoptosis plays a major role in the mechanism underlying long-term disease progression in MS.

Intrathecal chitotriosidase and the outcome of multiple sclerosis

2006 ◽  
Vol 12 (5) ◽  
pp. 551-557 ◽  
Author(s):  
S Sotgiu ◽  
R Barone ◽  
G Arru ◽  
M L Fois ◽  
M Pugliatti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Clinical Severity ◽  
Activated Macrophages ◽  
Expanded Disability Status Scale ◽  
Lesion Formation ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Neurological Patients ◽  
The Central Nervous System

Activated macrophages are major effectors at all stages of lesion formation in multiple sclerosis (MS) brain. Here, we report that the macrophage enzyme chitotriosidase (Chit) is significantly elevated both in plasma and cerebrospinal fluid (CSF) of patients with MS as compared to healthy controls and other neurological patients ( P< 0.001). Furthermore, the Chit activity in blood significantly associates with the MS clinical course (higher in secondary progressive relative to relapsing remitting, P = 0.01) and the clinical severity as measured by Kurtkze’s Expanded Disability Status Scale ( P<0.001). Also, we found that Chit activity is compartmentalized in the central nervous system of early MS patients and that its CSF/plasma quotient, in the presence of a preserved albumin quotient, correlates with the extent of future clinical deterioration ( r = 0.91; P<0.001). These findings confirm that innate immunity, here represented by Chit, is clinically relevant in MS and allows, if confirmed, reconsidering novel MS therapeutic strategies specifically aimed at this branch of the immune response.

scholarly journals Diagnosis and Management of Progressive Multiple Sclerosis

Biomedicines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 56 ◽  
Author(s):  
Gabrielle Macaron ◽  
Daniel Ontaneda
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Current Evidence ◽  
Steady Increase ◽  
Trial Methodology ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Active Inflammation

Multiple sclerosis is a chronic autoimmune disease of the central nervous system that results in varying degrees of disability. Progressive multiple sclerosis, characterized by a steady increase in neurological disability independently of relapses, can occur from onset (primary progressive) or after a relapsing–remitting course (secondary progressive). As opposed to active inflammation seen in the relapsing–remitting phases of the disease, the gradual worsening of disability in progressive multiple sclerosis results from complex immune mechanisms and neurodegeneration. A few anti-inflammatory disease-modifying therapies with a modest but significant effect on measures of disease progression have been approved for the treatment of progressive multiple sclerosis. The treatment effect of anti-inflammatory agents is particularly observed in the subgroup of patients with younger age and evidence of disease activity. For this reason, a significant effort is underway to develop molecules with the potential to induce myelin repair or halt the degenerative process. Appropriate trial methodology and the development of clinically meaningful disability outcome measures along with imaging and biological biomarkers of progression have a significant impact on the ability to measure the efficacy of potential medications that may reverse disease progression. In this issue, we will review current evidence on the physiopathology, diagnosis, measurement of disability, and treatment of progressive multiple sclerosis.

scholarly journals Level of kisspeptin-10 in patients with multiple sclerosis and the association between third ventricle diameter size and vitamin D level

2021 ◽  
Author(s):  
T. Akdag ◽  
A.U. Uca ◽  
M. Altas ◽  
F.O. Odabas ◽  
F. Aktas
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Third Ventricle ◽  
Diagnostic Value ◽  
Enzyme Linked Immunosorbent Assay ◽  
Significant Difference ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri

AbstractObjectiveMultiple sclerosis (MS) is a chronic and progressive neurological disease affecting the central nervous system (CNS). Some studies report an association between MS pathogenesis and cytokines. Here, we aimed to determine and evaluate serum kisspeptin-10 level in MS patients and its related clinic parameters.Materials and MethodsA total of 92 participants, 46 patients with relapsing-remitting MS (mean age, 38.92 ± 14.76; 22 men and 24 women) and 46 healthy controls (mean age, 37.04 ± 15.49; 22 men and 24 women) were enrolled in the study. All MS patients were neurologically examined, and magnetic resonance imaging (MRI) was performed. Clinical data (neuropathic pain, expanded disability status scale (EDSS) score, etc.) and the patients' demographic characteristics were recorded. The serum level of kisspeptin-10 was analyzed by enzyme-linked immunosorbent assay (ELISA) method.ResultsThe level of kisspeptin-10 was measured as 2.305 ± 2.781 ng/mL in MS patients and 9.342 ± 9.483 ng/mL in controls. MS patients had significantly lower kisspeptin-10 levels than controls (P = 0.000). Kisspeptin-10 has the highest diagnostic value [Area under curve (AUC) = 0.881, 95% confidence interval (CI), 0.812–0.950] as cut-off value (2.470), sensitivity (80.40%) and specificity (72.87%) in the MS group. Furthermore, the kisspeptin-10 level was negatively correlated with third ventricle diameter (TVD) (P = 0.048) and vitamin D concentration (P = 0.004). No significant difference was determined between kisspeptin-10 and other clinical parameters.ConclusionAs a potential prognostic biomarker, serum kisspeptin-10 level was significantly lower in patients with MS than in those without. Moreover, we observed negative correlations between vitamin D, TVD size, and kisspeptin-10. We think comprehensive studies are needed to verify and elucidate this issue.

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