Effectiveness and side effects of dimethyl fumarate in multiple sclerosis after 12 months of follow up: An Iranian clinical trial

Dimethyl Fumarate ◽

Liver Function Tests ◽

First Year ◽

Medical Sciences ◽

Disability Status ◽

Background: Multiple sclerosis (MS) is a neurologic disorder with a considerable global burden. During the last decades, some pharmaceutical treatments have been approved for patients with MS. Dimethyl fumarate (DMF) is one of these drugs which has been reported to have early promising results in recent studies, but the efficacy of this drug in patients with MS is still being studied in different parts of the world. In the present study, we evaluated the effectiveness of DMF therapy on reducing relapses, lesions, and disability in Iranian patients with MS. Methods: The present single-arm before-after study was approved by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran [Iranian Registry of Clinical Trial (IRCT) code: IRCT20190121042439N1]. Every patient who was diagnosed with relapsing MS was considered eligible to enroll in the present clinical trial. Before receiving DMF therapy, the baseline liver function tests and complete blood count were obtained from all individuals. Also, a baseline brain magnetic resonance imaging (MRI) was obtained and Expanded Disability Status Scale (EDSS) was documented from all patients. After receiving 240 mg DMF twice daily for 12 months, the laboratory and imaging measurements as well as EDSS were repeated. Furthermore, the total number of relapses within the study period was recorded. Satisfaction with DMF treatment was determined by answering a yes-no question. Results: A total number of 50 patients enrolled in the study and most of them were female (80%). There was a significant decrease in EDSS score and gadolinium (GD)-enhancing lesions after the study period (P < 0.001 for each). Moreover, the attacks significantly dropped after the study period (P < 0.001) and 86% of patients were satisfied with their treatment. Conclusion: The findings of this study showed that 240 mg DMF administered twice daily can effectively reduce disability and provide satisfaction within the first year of therapy in patients with MS.

Correlation Between Disability Measure and Black Hole (T1 Hypointense Lesion) Lesion Load in Brain Magnetic Resonance Imaging (MRI) of Patients With Multiple Sclerosis (MS): Protocol for a Systematic Review and Meta-analysis

10.21203/rs.3.rs-194103/v3 ◽

2021 ◽

Author(s):

Amir Valizadeh ◽

Elham Barati ◽

Mohammad Ali Sahraian ◽

Mohammad Reza Fattahi ◽

Mana Moassefi

Keyword(s):

Multiple Sclerosis ◽

Meta Analysis ◽

Rank Correlation ◽

Lesion Volume ◽

Spearman’S Rank Correlation ◽

Spearman’S Rank Correlation Coefficient ◽

Disability Status ◽

Formation And Evolution ◽

Abstract Introduction: As the role of neurodegeneration in the pathophysiology of multiple sclerosis (MS) has become more prominent, the formation and evolution of chronic or persistent T1-hypointense lesions (Black Holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. However, findings regarding this subject are controversial. In this study we aim to clarify the level of importance of T1 hypointense lesions for estimating the prognosis of patients.Methods: We will search MEDLINE (through PubMed), Embase and Web of Science for relevant studies. We will extract the Spearman's rank correlation coefficient (SRCC) between the T1 hypointense lesion volume and Extended Disability Status Scale (EDSS) in participants. All included studies will be evaluated for the risk of bias. We will also perform a meta-analysis on the data. The risk of publication bias will be evaluated using Funnel plots. Finally, we will assess the confidence in cumulative evidence using an adapted version of GRADE.

Real-world effectiveness of dimethyl fumarate versus fingolimod in a cohort of patients with multiple sclerosis using standardized, quantitative outcome metrics

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/20552173211069852 ◽

2022 ◽

Vol 8 (1) ◽

pp. 205521732110698

Author(s):

Carrie M Hersh ◽

Arman Altincatal ◽

Nicholas Belviso ◽

Shivani Kapadia ◽

Carl de Moor ◽

...

Keyword(s):

Multiple Sclerosis ◽

Sensitivity Analysis ◽

Real World ◽

Dimethyl Fumarate ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Brain Volume Loss ◽

Disability Status ◽

Background Prior studies suggest comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapse, Expanded Disability Status Score (EDSS), and magnetic resonance imaging (MRI) lesion metrics. Objective Compare the real-world effectiveness of DMF versus FTY using quantitative, validated neuroperformance tests, MRI, and serum neurofilament light chain (sNfL) outcomes while controlling for between-group differences. Methods Patients were eligible if on DMF or FTY when first enrolled in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network and had ≥1-year follow-up in MS PATHS. Sensitivity analysis included a subgroup who started DMF/FTY ≤2 years from enrolment. After propensity score weighting, differences in means and in mean 1-year change of neuroperformance and MRI outcomes were compared. sNfL levels were assessed. This was a non-randomized comparison. Results In the overall cohort, no significant differences were observed between DMF ( n = 702) and FTY ( n = 600) in neuroperformance or MRI outcomes including brain volume loss; mean time (SD) since treatment initiation was 1.98 (0.68) years for DMF and 2.02 (0.75) years for FTY. A sensitivity analysis controlling for DMF and FTY treatment duration yielded similar results. Conclusion In this study, DMF and FTY demonstrated similar effects on physical and cognitive neuroperformance and MRI outcomes. Direct comparisons to other fumarates and S1P receptor modulators were not conducted.

Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis

10.1177/1352458507085759 ◽

2008 ◽

Vol 14 (5) ◽

pp. 663-670 ◽

Cited By ~ 60

Author(s):

T Vollmer ◽

H Panitch ◽

A Bar-Or ◽

J Dunn ◽

MS Freedman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Glatiramer Acetate ◽

Induction Therapy ◽

Short Term ◽

Disability Status ◽

Mri Scans ◽

Magnetic Resonance Imaging Mri ◽

Multiple Sclerosis Patients ◽

Relapsing Multiple Sclerosis

Forty relapsing multiple sclerosis patients with 1–15 gadolinium (Gd)-enhancing lesions on screening brain magnetic resonance imaging (MRI) and Expanded Disability Status Scale (EDSS) scores 0–6.5 were randomized to receive short-term induction therapy with mitoxantrone (three monthly 12 mg/m2 infusions) followed by 12 months of daily glatiramer acetate (GA) therapy 20 mg/day subcutaneously for a total of 15 months (M-GA, n = 21) or daily GA 20 mg/day for 15 months (GA, n = 19). MRI scans were performed at months 6, 9, 12 and 15. The primary measure of outcome was the incidence of adverse events; secondary measures included number of Gd-enhanced lesions, confirmed relapses and EDSS changes. Except age, baseline demographic characteristics were well matched in both treatment arms. Both treatments were safe and well tolerated. M-GA induction produced an 89% greater reduction (relative risk (RR) = 0.11, 95% confidence interval (CI): 0.04–0.36, p = 0.0001) in the number of Gd-enhancing lesions at months 6 and 9 and a 70% reduction (RR = 0.30, 95% CI: 0.11–0.86, p = 0.0147) at months 12 and 15 versus GA alone. Mean relapse rates were 0.16 and 0.32 in the M-GA and GA groups, respectively. Short-term immunosuppression with mitoxantrone followed by daily GA for up to 15 months was found to be safe and effective, with an early and sustained decrease in MRI disease activity.

Mean upper cervical cord area (MUCCA) measurement in long-standing multiple sclerosis: Relation to brain findings and clinical disability

10.1177/1352458514533399 ◽

2014 ◽

Vol 20 (14) ◽

pp. 1860-1865 ◽

Cited By ~ 43

Author(s):

Marita Daams ◽

Florian Weiler ◽

Martijn D Steenwijk ◽

Horst K Hahn ◽

Jeroen JG Geurts ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Cervical Cord ◽

Healthy Controls ◽

Spinal Cord Atrophy ◽

Disability Status ◽

Upper Cervical ◽

Male Patients ◽

Background: The majority of patients with multiple sclerosis (MS) present with spinal cord pathology. Spinal cord atrophy is thought to be a marker of disease severity, but in long-disease duration its relation to brain pathology and clinical disability is largely unknown. Objective: Our aim was to investigate mean upper cervical cord area (MUCCA) in patients with long-standing MS and assess its relation to brain magnetic resonance imaging (MRI) measures and clinical disability. Methods: MUCCA was measured in 196 MS patients and 55 healthy controls using 3DT1-weighted cervical images obtained at 3T MRI. Clinical disability was measured using the Expanded Disability Status Scale (EDSS), Nine-Hole-Peg test (9-HPT), and 25 feet Timed Walk Test (TWT). Stepwise linear regression was performed to assess the association between MUCCA and MRI measures, and between MUCCA and clinical disability. Results: MUCCA was smaller (mean 11.7%) in MS patients compared with healthy controls (72.56±9.82 and 82.24±7.80 mm2 respectively; p<0.001), most prominently in male patients. MUCCA was associated with normalized brain volume, and number of cervical cord lesions. MUCCA was independently associated with EDSS, TWT, and 9-HPT. Conclusion: MUCCA was reduced in MS patients compared with healthy controls. It provides a relevant marker for clinical disability in long-standing disease, independent of other MRI measures.

Low degree of cortical pathology is associated with benign course of multiple sclerosis

10.1177/1352458512463767 ◽

2012 ◽

Vol 19 (7) ◽

pp. 904-911 ◽

Cited By ~ 22

Author(s):

Massimiliano Calabrese ◽

Alice Favaretto ◽

Valentina Poretto ◽

Chiara Romualdi ◽

Francesca Rinaldi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Duration ◽

Cortical Thinning ◽

Low Degree ◽

Disability Status ◽

Relapsing Remitting ◽

Cortical Pathology ◽

Magnetic Resonance Imaging Mri ◽

Normal Cognition

Background: Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association. Materials and Methods: We followed 95 early relapsing–remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly. Results: At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients ( p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients ( p ranging between 0.001–0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal ( p = 0.036) and superior parietal gyrus ( p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume ( p = 0.006) and the cortical thickness of the temporal middle ( p < 0.001), insular long ( p < 0.001), superior frontal ( p < 0.001) and middle frontal gyri ( p < 0.001) as the most sensitive independent predictors of a favorable disease course. Conclusions: Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.

Correlation between disability measure and Black Hole (T1 hypointense lesion) lesion load in brain Magnetic Resonance Imaging (MRI) of patients with multiple sclerosis (MS): Protocol for a systematic review and meta-analysis

10.21203/rs.3.rs-194103/v4 ◽

2021 ◽

Author(s):

Amir Valizadeh ◽

Elham Barati ◽

Mohammad Ali Sahraian ◽

Mohammad Reza Fattahi ◽

Mana Moassefi

Keyword(s):

Multiple Sclerosis ◽

Meta Analysis ◽

Rank Correlation ◽

Lesion Volume ◽

Spearman’S Rank Correlation ◽

Spearman’S Rank Correlation Coefficient ◽

Disability Status ◽

Formation And Evolution ◽

Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04820-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Helda Tutunchi ◽

Majid Mobasseri ◽

Samira Pourmoradian ◽

Hamid Soleimanzadeh ◽

Behnam Kafil ◽

...

Keyword(s):

Clinical Trial ◽

Sample Size ◽

Complete Blood Count ◽

Controlled Clinical Trial ◽

Medical Sciences ◽

Boron Compounds ◽

Double Blind ◽

Link Type ◽

Nutrition Research ◽

Full Protocol

Abstract Objectives In this study, we investigate the effect of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19. Trial design The current study is a single-center, randomized, double-blind, placebo-controlled clinical trial with parallel groups. Participants The inclusion criteria include male and female patients≥18 years of age, with a confirmed diagnosis of SARS-CoV-2 infection via polymerase chain reaction (PCR) and/or antibody test and with written informed consent to participate in this trial. The exclusion criteria include regular use of any other supplement, severe and critical COVID-19 pneumonia, pregnancy and breastfeeding. This study is being conducted at Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. Intervention and comparator Patients are randomly assigned to four groups. The first group (A) will take one capsule containing 5 mg of boron compounds twice a day for two weeks. The second group (B) will take one capsule containing 200 mg oleoylethanolamide twice a day for two weeks. The third group (C) will take one capsule containing 5 mg boron compounds with 200 mg oleoylethanolamide twice a day for two weeks, and the fourth group (D) does not receive any additional treatment other than routine treatments. Boron-containing compounds and oleoylethanolamide capsules will be synthesized at Nutrition Research Center of Tabriz University of Medical Sciences. Main outcomes The primary end point of this study is to investigate the recovery rate of clinical symptoms, including fever, dry cough, and fatigue, as well as preclinical features, including complete blood count (CBC), the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) profiles within two weeks of randomization. Randomisation Patients are randomized into four equal groups in a parallel design (allocation ratio 1:1). A randomized block procedure is used to divide subjects into one of four treatment blocks (A, B, C, and D) by a computer-generated allocation schedule. Blinding (masking) The participants and investigators (enrolling, assessing, and analyzing) are blinded to the intervention assignments until the end of the study and data analysis. Numbers to be randomised (sample size) The calculated total sample size is 40 patients, with 10 patients in each group. Trial Status The protocol is Version 1.0, May 17, 2020. Recruitment began May 19, 2020, and is anticipated to be completed by October 19, 2020. Trial registration This clinical trial has been registered by the title of “Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in Patients with COVID-19: A double-blind randomized placebo-controlled clinical trial” in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20090609002017N35”, https://www.irct.ir/trial/48058. The registration date is 17 May 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Prospective study of multiple sclerosis with early onset

10.1191/1352458502ms786oa ◽

2002 ◽

Vol 8 (2) ◽

pp. 115-118 ◽

Cited By ~ 93

Author(s):

A Ghezzi ◽

C Pozzilli ◽

M Liguori ◽

M G Marrosu ◽

N Milani ◽

...

Keyword(s):

Multiple Sclerosis ◽

First Year ◽

Hormonal Changes ◽

Disability Status ◽

Definite Multiple Sclerosis ◽

Relapsing Remitting ◽

Clinically Definite Multiple Sclerosis ◽

The Mean ◽

And Gender

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.

Combined visual and motor evoked potentials predict multiple sclerosis disability after 20 years

10.1177/1352458514525867 ◽

2014 ◽

Vol 20 (10) ◽

pp. 1348-1354 ◽

Cited By ~ 28

Author(s):

Regina Schlaeger ◽

Christian Schindler ◽

Leticia Grize ◽

Sophie Dellas ◽

Ernst W Radue ◽

...

Keyword(s):

Multiple Sclerosis ◽

Motor Evoked Potentials ◽

Rank Correlation ◽

Disease Modifying Therapy ◽

Disability Status ◽

Adaptive Processes ◽

Multivariable Regression ◽

Predictive Relationships ◽

Background: The development of predictors of multiple sclerosis (MS) disability is difficult due to the complex interplay of pathophysiological and adaptive processes. Objective: The purpose of this study was to investigate whether combined evoked potential (EP)-measures allow prediction of MS disability after 20 years. Methods: We examined 28 patients with clinically definite MS according to Poser’s criteria with Expanded Disability Status Scale (EDSS) scores, combined visual and motor EPs at entry (T0), 6 (T1), 12 (T2) and 24 (T3) months, and a cranial magnetic resonance imaging (MRI) scan at T0 and T2. EDSS testing was repeated at year 14 (T4) and year 20 (T5). Spearman rank correlation was used. We performed a multivariable regression analysis to examine predictive relationships of the sum of z-transformed EP latencies ( s-EPT0) and other baseline variables with EDSST5. Results: We found that s-EPT0 correlated with EDSST5 (rho=0.72, p<0.0001) and ΔEDSST5-T0 (rho=0.50, p=0.006). Backward selection resulted in the prediction model: E (EDSST5)=3.91–2.22×therapy+0.079×age+0.057× s-EPT0 (Model 1, R2=0.58) with therapy as binary variable (1=any disease-modifying therapy between T3 and T5, 0=no therapy). Neither EDSST0 nor T2-lesion or gadolinium (Gd)-enhancing lesion quantities at T0 improved prediction of EDSST5. The area under the receiver operating characteristic (ROC) curve was 0.89 for model 1. Conclusions: These results further support a role for combined EP-measures as predictors of long-term disability in MS.

De novo convulsive status epilepticus in patients with multiple sclerosis treated with dalfampridine

10.1177/1352458518790379 ◽

2018 ◽

Vol 25 (4) ◽

pp. 618-621 ◽

Cited By ~ 3

Author(s):

Emilie Panicucci ◽

Mikael Cohen ◽

Veronique Bourg ◽

Fanny Rocher ◽

Pierre Thomas ◽

...

Keyword(s):

Multiple Sclerosis ◽

Status Epilepticus ◽

De Novo ◽

Case Reports ◽

Convulsive Status Epilepticus ◽

Biological Tests ◽

History Of ◽

Magnetic Resonance Imaging Mri ◽

History Of Epilepsy

Background: Dalfampridine extended release (DAL) is a broad-spectrum voltage-gated potassium channel blocker that is indicated in multiple sclerosis to improve the nerve conduction of demyelinated axons. Seizures are a known side effect of DAL, which is contraindicated in patients with a history of epilepsy. Objective: Three cases of multiple sclerosis (MS) with de novo convulsive status epilepticus (CSE) probably related to dalfampridine administration are described. Methods: No patients had a history of seizures or renal impairment. Biological tests were normal. A brain magnetic resonance imaging (MRI) showed diffuse cortical and subcortical atrophy without active inflammatory lesions. Results: All three patients presented with CSE that was attributed to DAL and so was discontinued. Conclusion: These case reports illustrate that, aside from seizures, de novo CSE is a potential complication of MS patients treated with DAL.