Epilepsy as a predictor of disease progression in multiple sclerosis

2021 ◽  
pp. 135245852110467
Author(s):  
Matthias Grothe ◽  
David Ellenberger ◽  
Felix von Podewils ◽  
Alexander Stahmann ◽  
Paulus S Rommer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Disease Onset ◽  
Walking Distance ◽  
Disability Status ◽  
Cortical Pathology ◽  
Underlying Mechanisms ◽  
Patients With Epilepsy

Background: Epilepsy development during the course of multiple sclerosis (MS) is considered to be the result of cortical pathology. However, no long-term data exist on whether epilepsy in MS also leads to increasing disability over time. Objective: To examine if epilepsy leads to more rapid disease progression. Methods: We analyzed the data of 31,052 patients on the German Multiple Sclerosis Register in a case–control study. Results: Secondary progressive disease course (odds ratio (OR) = 2.23), age (OR = 1.12 per 10 years), and disability (OR = 1.29 per Expanded Disability Status Scale (EDSS) point) were associated with the 5-year prevalence of epilepsy. Patients who developed epilepsy during the course of the disease had a higher EDSS score at disease onset compared to matched control patients (EDSS 2.0 vs 1.5), progressed faster in each dimension, and consequently showed higher disability (EDSS 4.4 vs 3.4) and lower employment status (40% vs 65%) at final follow-up. After 15 years of MS, 64% of patients without compared to 54% of patients with epilepsy were not severely limited in walking distance. Conclusion: This work highlights the association of epilepsy on disability progression in MS, and the need for additional data to further clarify the underlying mechanisms.

scholarly journals Brain atrophy at onset and physical disability in multiple sclerosis

2012 ◽  
Vol 70 (10) ◽  
pp. 765-768 ◽  
Author(s):  
Juan Ignacio Rojas ◽  
Liliana Patrucco ◽  
Cristina Besada ◽  
Laura Bengolea ◽  
Edgardo Cristiano
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Brain Atrophy ◽  
Physical Disability ◽  
Disease Onset ◽  
First Year ◽  
Expanded Disability Status Scale ◽  
Disability Status

The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS) patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS) was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003). DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

Walking capacities in multiple sclerosis measured by global positioning system odometer

2007 ◽  
Vol 13 (2) ◽  
pp. 220-223 ◽  
Author(s):  
A Créange ◽  
I Serre ◽  
M Levasseur ◽  
D Audry ◽  
A Nineb ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Global Positioning System ◽  
Walking Speed ◽  
Walking Distance ◽  
Expanded Disability Status Scale ◽  
Satellite Technology ◽  
Promising Tool ◽  
Disability Status ◽  
Global Positioning

We used a global positioning satellite technology odometer to determine the maximum objective walking distance capacity (MOWD) of patients with multiple sclerosis (MS). The MOWD correlated with Expanded Disability Status Scale (EDSS) score (r2 =0.41; P < 0.0001), the MSWS-12 scale (r2 = 0.46; P < 0.0001), time to walk 10 m (r2 = 0.51; P < 0.02) and walking speed (r2 =0.75; P < 0.001). Limitation of walking capacities was measurable up to 4550 m, strikingly above the 500-m limit of the EDSS. This objective odometer is a promising tool for evaluation and follow-up of patients with MS. Multiple Sclerosis 2007; 13: 220–223. http://msj.sagepub.com

scholarly journals Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study

2021 ◽  
Vol 10 (21) ◽  
pp. 5207
Author(s):  
Konrad Rejdak ◽  
Adriana Zasybska ◽  
Aleksandra Pietruczuk ◽  
Dariusz Baranowski ◽  
Sebastian Szklener ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cumulative Dose ◽  
Induction Dose ◽  
Disability Status ◽  
Risk Of Progression ◽  
Dosing Regimens ◽  
Favorable Safety ◽  
Relapsing Multiple Sclerosis

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5–20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.

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.

Detecting clinically-relevant changes in progressive multiple sclerosis

2014 ◽  
Vol 21 (2) ◽  
pp. 171-179 ◽  
Author(s):  
LVAE Bosma ◽  
JM Sonder ◽  
JJ Kragt ◽  
CH Polman ◽  
BMJ Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measurement ◽  
Progressive Multiple Sclerosis ◽  
Meaningful Change ◽  
Disability Scale ◽  
Impact Scale ◽  
Disability Status ◽  
Disease Impact

Objective: To investigate which changes in different clinical outcome measures contribute most to increased disease impact, as reported by the patient, in progressive multiple sclerosis (MS). Methods: From a cohort of prospectively-followed MS patients, we selected progressive patients with two visits, 4–6 years apart. We assessed long-term changes on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and Guy’s Neurological Disability Scale (GNDS). We defined the presence or absence of clinically meaningful change by using the Multiple Sclerosis Impact Scale (MSIS-29) as an anchor measure. We also studied change on recently identified sub-scales of GNDS. Results: Change on GNDS (especially the spinal-plus subscale) contributed most to increased disease impact. Also change on the T25FW contributed largely. Specific profiles of change in T25FW and MSIS seemed to exist (generally, a lower increase in disease impact in patients with longer disease duration and higher baseline impact/disability). In some patients a dissociation existed between increased impact, according to the MSIS-29, and objective physical worsening of the T25FW. Conclusion: These results support using GNDS (particularly the spinal-plus domain) and T25FW in outcome measurement in progressive MS. We suggest there is a relation between baseline clinical characteristics and an increased impact at follow-up. This may have implications for patient selection in trials for progressive MS.

scholarly journals Influence of treatment in multiple sclerosis dysability: an open, retrospective, non-randomized long-term analysis

2010 ◽  
Vol 68 (4) ◽  
pp. 511-521 ◽  
Author(s):  
Lineu Cesar Werneck ◽  
Paulo José Lorenzoni ◽  
Vitor A Radünz ◽  
Marco A.T Utiumi ◽  
Cláudia Suemi Kamoi Kay ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Age Of Onset ◽  
Statistical Significance ◽  
Time Period ◽  
Disability Status ◽  
Therapeutic Procedures ◽  
Long Time ◽  
Final Score

The efficacies of immunosuppressive (IMS) and immunomodulatory (IMM) drugs for multiple sclerosis (MS) have been reported in several studies. These agents can reduce relapse rates and lesions observed by magnetic resonance imaging studies. However, the effect of these medications in disability progression over 4 years is rarely examined. OBJECTIVE: To study the disabilities associated with MS patients after a long time period and to analyze the therapeutic influence of different types of treatments in patient disease progression. METHOD: This is an open, uncontrolled, non-randomized, retrospective study of the disease progression using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) in 155 cases of MS, which were 76% female with a mean age of onset of 30.21±9.70. The follow-up period was 115.39±88.08 months (median 92, 3 to 447 months). These cases were submitted to the following 277 different therapeutic procedures: 62 without IMS or IMM therapy (SYT) (just corticosteroids), 53 with azathioprine (AZA), 53 interferon-β (IFNβ)-1b 250 µg (BET), 55 IFNβ-1a 22 µg (R22), 19 IFNβ-1a 30 µg (AVO), 15 IFNβ-1a 44 µg (R44), 15 glatiramer acetate (COP) 20 mg, and 5 cases with mitoxantrone (MIT). RESULTS: The median EDSS group was 2.00 (0 to 5.5, mean 1.89±1.52) at the onset of each treatment and 2.50 (0 to 9, mean 3.06±2.18) at the end. The median initial MSSS was 3.34 (0.25 to 9.50, mean 3.94±2.91) and the final medial was 3.90 (0.05 to 9.88, mean 4.02±2.78). The EDSS between initial and final score for the whole group had statistically significant progression, as well as for the sub-groups SYT, AZA, BET and R22. No statistically significance difference was found in the MSSS between initial and final scores in the whole group or treatment sub-groups. The variation between the initial and final EDSS and MSSS among the types of treatments found no statistical significance for any group. CONCLUSION: In this study series, no statistical difference was found in the long-term progression of disability among the IMS and IMM treated cases, nor in the cases treated only with corticosteroids.

scholarly journals Fatigue after a first attack of suspected multiple sclerosis

2017 ◽  
Vol 24 (7) ◽  
pp. 974-981 ◽  
Author(s):  
Roos M van der Vuurst de Vries ◽  
Jan JA van den Dorpel ◽  
Julia Y Mescheriakova ◽  
Tessel F Runia ◽  
Naghmeh Jafari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Depression Scale ◽  
Common Symptom ◽  
Disability Status ◽  
Definite Multiple Sclerosis ◽  
Fatigue Severity ◽  
Clinically Definite Multiple Sclerosis ◽  
In Cis

Background: Fatigue is reported by more than 75% of multiple sclerosis (MS) patients. In an earlier study, we showed that fatigue is not only a common symptom in patients at time of clinically isolated syndrome (CIS; fatigued 46%) but also predicts subsequent diagnosis of clinically definite multiple sclerosis (CDMS). The course of fatigue after CIS is unknown. Objective: We aimed to explore the long-term course of fatigue after CIS. Methods: In this study, 235 CIS patients, aged 18–50 years, were prospectively followed. Patients filled in the Krupp’s Fatigue Severity Scale (FSS) and the Hospital Anxiety and Depression Scale (HADS) at baseline and annually. After reaching CDMS diagnosis, Expanded Disability Status Scale (EDSS) was obtained annually. Mixed-effects models were used to analyse longitudinal FSS measurements. Results: Fatigue at baseline was an independent predictor for CDMS diagnosis (hazard ratio (HR): 2.6, 95% confidence interval (CI): 1.6–4.4). The evolution of FSS was the same in CIS patients who remained monophasic and patients who were diagnosed with CDMS during follow-up. However, FSS increased by 0.86 units after reaching CDMS diagnosis ( p = 0.01). After this increase, the FSS course remained unaltered ( p = 0.44). Conclusion: Fatigue, which is often present at time of CIS, probably persists over time and increases after a second attack.

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 contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis

2021 ◽  
pp. 135245852110100
Author(s):  
Zoë YGJ van Lierop ◽  
Luuk Wieske ◽  
Marleen JA Koel-Simmelink ◽  
Madhurima Chatterjee ◽  
Iris Dekker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Odds Ratio ◽  
Prognostic Biomarker ◽  
Disability Progression ◽  
Lower Baseline ◽  
Relapsing Remitting ◽  
Natalizumab Treatment

Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). Objective: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. Methods: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. Results: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04–1.45) ( p = 0.017) for progression during follow-up. Conclusion: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS.

scholarly journals Predicting Long-term Disability in Multiple Sclerosis: A Narrative Review of Current Evidence and Future Directions

2021 ◽  
Author(s):  
Bianca Weinstock-Guttman ◽  
Maria Pia Sormani ◽  
Pavle Repovic
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Panel Discussion ◽  
Current Evidence ◽  
Future Directions ◽  
Current State ◽  
Published Evidence ◽  
Disability Status ◽  
Insight Into

Abstract The ability to reliably monitor disease progression in patients with multiple sclerosis (MS) is integral to patient care. The Expanded Disability Status Scale (EDSS) is a commonly used tool to assess the disability status of patients with MS; however, it has limited sensitivity in detecting subtle changes in disability levels and, as a result, does not consistently provide clinicians with accurate insight into disease progression. At the 2019 European Committee for Treatment and Research in Multiple Sclerosis meeting in Stockholm, Sweden, a panel of neurologists met to discuss the limitations of the EDSS as a short-term predictor of MS progression. Prior to this panel discussion, a targeted literature review was conducted to evaluate published evidence on prognostic measures such as fatigue, physical assessments, and measures that are more taxing for patients, all of which may be useful to clinicians at different stages of the course of MS. This article summarizes currently available evidence in support of these measures. In addition, this article highlights the current state of expert clinical consensus regarding the current approaches used to predict and monitor disease progression and offers insight for future studies to assist clinicians in accurately monitoring disease progression in patients with MS.

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