Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment

2004 ◽  
Vol 10 (4) ◽  
pp. 462-468 ◽  
Author(s):  
Alfredo Romani ◽  
Roberto Bergamaschi ◽  
Elisa Candeloro ◽  
Enrico Alfonsi ◽  
Roberto Callieco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Test Scores ◽  
Rating Scale ◽  
Symptomatic Treatment ◽  
Cognitive Test ◽  
Treatment Groups ◽  
Impact Scale ◽  
Relapsing Remitting ◽  
Fatigue Severity ◽  
Relapsing Remitting Multiple Sclerosis

Sixty relapsing-remitting multiple sclerosis (MS) patients were selected on the basis of their score on the Fatigue Severity Scale (FSS) and formed two groups: 40 patients (fatigued MS; MSf) scored above the 75th percentile of a previously assessed representative MS sample (100 patients), and 20 age- and sex-matched patients (nonfatigued MS patients; MSnf) scored below the 25th percentile. The patients underwent clinical evaluation (Expanded Disability Status Scale (EDSS)), further assessment of fatigue (Fatigue Impact Scale), scales evaluating depression (Hamilton Depression Rating Scale (HDRS) and Beck’s Depression Inventory (BDI)) and neuropsychological tests. All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction; they also underwent somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS). The patients of the MSf subgroup were then randomized to one of the following two treatments: 4-aminopyridine (4-AP) 24 mg/day and fluoxetine (FLX) 20 mg/day. After a one-week titration this treatment proceeded for 8 weeks. At the end of the treatment, EDSS, fatigue and depression scores were further evaluated. At baseline, fatigue test scores consistently correlated with depression and cognitive test scores, but not with the fatigability test. Fatigue scores decreased in both treatment groups in a similar way. Due to the design of the study, this cannot be disjoined from a placebo effect. The changes of fatigue scores could not be predicted in the FLX group, whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores.

Hypothalamic involvement assessed by T1 relaxation time in patients with relapsing—remitting multiple sclerosis

2009 ◽  
Vol 15 (12) ◽  
pp. 1442-1449 ◽  
Author(s):  
Francesco Zellini ◽  
Graham Niepel ◽  
Christopher R Tench ◽  
Cris S Constantinescu
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Relaxation Time ◽  
Magnetic Resonance ◽  
Resonance Imaging ◽  
T1 Relaxation Time ◽  
T1 Relaxation ◽  
Relapsing Remitting ◽  
Fatigue Severity ◽  
Relapsing Remitting Multiple Sclerosis

Recent work in multiple sclerosis, focusing on neuropathological abnormalities, found a frequent and severe hypothalamic involvement. The possible clinical implications are disturbances in sleep and sexual activity, depression, memory impairment and fatigue. Despite this there are no magnetic resonance imaging studies focusing on in vivo hypothalamic pathology in multiple sclerosis. Our objective was to investigate magnetic resonance imaging-detectable abnormalities related to pathological changes in the hypothalamus of patients with multiple sclerosis, and to subsequently explore the relationship with fatigue. We used T1 relaxation time as a sensitive measure of pathology. Using region of interest analysis, median T1 values in the hypothalamus were measured in 44 relapsing—remitting multiple sclerosis patients and in 13 healthy controls. Fatigue was assessed using the Fatigue Severity Scale, and patients were divided in two subgroups, fatigued and non-fatigued, according to Fatigue Severity Scale scores. We found a significantly higher T1 relaxation time in the hypothalamus of multiple sclerosis patients compared with controls ( p = 0.027). There was a significant correlation between T1 values and fatigue severity (rho 0.437, p = 0.008), and median T1 values were different among the study groups. Our results show that pathological involvement of the hypothalamus in relapsing—remitting multiple sclerosis is detectable using magnetic resonance imaging, and that the pathology measured by quantitative T1 might reflect fatigue.

scholarly journals A Controlled Trial of Mitoxantrone in Multiple Sclerosis: Serial MRI Evaluation at One Year

1994 ◽  
Vol 21 (3) ◽  
pp. 266-270 ◽  
Author(s):  
S. Bastianello ◽  
C. Pozzilli ◽  
F. D’Andrea ◽  
E. Millefiorini ◽  
M. Trojano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gadolinium Dtpa ◽  
Treatment Groups ◽  
Number Of Patients ◽  
Significant Difference ◽  
Relapsing Remitting ◽  
The Mean ◽  
Remitting Multiple Sclerosis ◽  
One Year ◽  
Relapsing Remitting Multiple Sclerosis

Abstract:We present the results of a randomized double-blinded placebo controlled, multicenter trial, of low-dose mitoxantrone (MX), after one year, in 25 patients with relapsing-remitting multiple sclerosis, who had serial enhanced magnetic resonance imaging (MRI). Treatment groups were balanced for age, gender, duration of illness and neurological disability. Five of the 13 MX patients and 10 of the 12 placebo patients had exacerbations during treatment (p < 0.02). The mean change in the extended disability status scale was not significantly different between the MX and placebo treatment groups. Serial Gadolinium-DTPA enhancedMRIdetected no significant difference between the MX treated and placebo groups in the mean total number of new, enlarging, or Gadolinium-DTPA enhancing lesions; there was a trend toward a reduction of new, enlarging and Gadolinium-DTPA enhancing lesions in MX patients. Despite this ameliorating effect, the results indicate that serial Gadolinium-DTPA enhanced MRI, performed over one year in a limited number of patients, could not provide conclusive evidence for a role of MX therapy in relapsing-remitting multiple sclerosis.

MANAGEMENT OF ADVERSE REACTIONS TO ALEMTUZUMAB INFUSION

2015 ◽  
Vol 86 (11) ◽  
pp. e4.23-e4 ◽  
Author(s):  
Basil Sharrack ◽  
Lori Mayer ◽  
Alasdair Coles ◽  
Hans-Peter Hartung ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Symptomatic Treatment ◽  
Phase 3 ◽  
Prior Therapy ◽  
Link Type ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

In the 2-year, phase 3 CARE-MS studies of alemtuzumab in patients with relapsing-remitting multiple sclerosis, infusion-associated reactions (IARs) were the most common adverse events. Here we report on IARs during 4-year follow-up. Patients who were treatment-naive (CARE-MS I; NCT00530348) or with inadequate efficacy response to prior therapy (CARE-MS II; NCT00548405) received 2 annual courses of alemtuzumab 12 mg, and as-needed retreatment in an extension study (NCT00930553). Patients received methylprednisolone on the first 3 days of each course. IARs were any adverse event occurring between start of infusion and within 24 hours after end of infusion. 742/811 alemtuzumab-treated patients entered extension. Over 4 years, 70.4% received only 2 initial treatment courses; 22.6% and 6.1% received 3 and 4 courses, respectively. IARs were most frequent in Course 1 (84.7%) versus Courses 2 (68.5%), 3 (65.7%), and 4 (71.1%); frequency decreased on infusion Days 2 and 3 versus Day 1. IARs were predominantly mild to moderate; none led to study withdrawal or death. Serious IAR incidence was 3.1%. Most common IARs were skin disorders (predominantly rash), headache, pyrexia, and nausea. One confirmed anaphylaxis and one non-anaphylactoid hypotension event resolved with treatment. Effective IAR management included premedication, infusion monitoring, symptomatic treatment, and infusion interruption/adjustment.

No evidence of disease activity in patients receiving daclizumab versus intramuscular interferon beta-1a for relapsing-remitting multiple sclerosis in the DECIDE study

2016 ◽  
Vol 23 (13) ◽  
pp. 1736-1747 ◽  
Author(s):  
Ludwig Kappos ◽  
Eva Havrdova ◽  
Gavin Giovannoni ◽  
Bhupendra O Khatri ◽  
Susan A Gauthier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Interferon Beta ◽  
Composite Endpoint ◽  
Logistic Regression Models ◽  
Treatment Groups ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: No evidence of disease activity (NEDA) is a composite endpoint being increasingly applied as an outcome measure in clinical trials as well as proposed for individual therapeutic decisions in multiple sclerosis (MS). Objective: Assess the proportion of patients with relapsing-remitting MS achieving NEDA in the DECIDE study of daclizumab 150 mg subcutaneous versus intramuscular interferon beta-1a 30 µg for 96–144 weeks. Methods: NEDA was defined as no relapses, no onset of 12-week confirmed disability progression (CDP), no new/newly enlarging T2 hyperintense lesions (NET2), and no gadolinium-enhancing (Gd+) lesions. Logistic regression models adjusted for baseline covariates compared treatment groups for baseline to week 96, weeks 0–24, and weeks 24–96. Results: From baseline to week 96, more daclizumab versus intramuscular interferon beta-1a patients achieved NEDA (24.6% vs 14.2%; odds ratio (OR; 95% confidence interval): 2.059 (1.592−2.661); p < 0.0001). ORs for clinical NEDA (no relapses, no CDP) and magnetic resonance imaging (MRI) NEDA (no NET2, no Gd+ lesions) were 1.651 (1.357−2.007; p < 0.0001) and 2.051 (1.628−2.582; p < 0.0001), respectively. ORs in favor of daclizumab for weeks 24–96 were consistently higher than for weeks 0–24. Conclusion: More daclizumab versus intramuscular interferon beta-1a patients achieved NEDA early in DECIDE, with effects increasing over time.

Both paracetamol and ibuprofen are equally effective in managing flu-like symptoms in relapsing-remitting multiple sclerosis patients during interferon beta-1a (AVONEX®) therapy

2002 ◽  
Vol 8 (1) ◽  
pp. 15-18 ◽  
Author(s):  
J Reeß ◽  
J Haas ◽  
K Gabriel ◽  
A Fuhlrott ◽  
M Fiola
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Open Label ◽  
Treatment Groups ◽  
Significant Difference ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Mild Impairment ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Interferon beta-1a is an established therapy for patients with relapsing-remitting multiple sclerosis (MS). Adverse effects in the first weeks of treatment are common. This open-label, multicenter, randomized, prospective study compared treatment of flu-like symptoms (FLS) with paracetamol versus ibuprofen administered 48 h within interferon injection. The percentage of patients with FLS was comparable between both treatment groups and improved during the course of the study (baseline: paracetamol 92%, ibuprofen 90%; week 12: paracetamol 60%, ibuprofen 57%). More than 75% of patients receiving either paracetamol or ibuprofen reported no or only mild impairment of daily activities. There was no significant difference in general satisfaction or incidence of additional symptoms (weakness, nausea, headache; paracetamol 84.6% patients, ibuprofen 86.0% patients) between the two groups. A significant overall improvement from baseline to week 12 was observed for all parameters studied (paracetamol and ibuprofen groups were pooled). These results indicate that neither the paracetamol nor the ibuprofen treatment regimen is better.

Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing—remitting multiple sclerosis

2010 ◽  
Vol 16 (10) ◽  
pp. 1220-1228 ◽  
Author(s):  
Massimiliano Calabrese ◽  
Francesca Rinaldi ◽  
Paola Grossi ◽  
Irene Mattisi ◽  
Valentina Bernardi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Thickness ◽  
Posterior Parietal Cortex ◽  
Cognitive Domain ◽  
Impact Scale ◽  
Relapsing Remitting ◽  
Cortical Grey Matter ◽  
Fatigue Impact Scale ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Fatigue is one of the most frequent symptoms suffered by patients affected by multiple sclerosis. The patho-physiological basis of multiple sclerosis-related fatigue remains to be elucidated. Objective: Our aim was to investigate whether a particular pattern of deep and/or cortical grey matter atrophy is associated with fatigue in patients with multiple sclerosis. Methods: A total of 152 patients with relapsing—remitting multiple sclerosis were evaluated with the Expanded Disability Status Scale, the Fatigue Severity Status Scale (FSS), the Modified Fatigue Impact Scale and the Beck Depression Inventory. The thalamic and basal ganglia volume and the regional cortical thickness were analysed by means of FreeSurfer. Results: Based on Fatigue Severity Status Scale score, patients were divided into fatigued (FSS ≥ 4, 71 patients, 46.6%) and non-fatigued (FSS < 4, 81 patients, 53.4%). A significant atrophy of striatum, thalamus, superior frontal gyrus and inferior parietal gyrus was observed in fatigued patients compared with non-fatigued patients. The cognitive domain of Modified Fatigue Impact Scale significantly correlated with the volume of the striatum and with the cortical thickness of the posterior parietal cortex and middle frontal gyrus (R = 0.51—0.61), while the physical domain of Modified Fatigue Impact Scale significantly correlated with striatum volume and superior frontal gyrus cortical thickness (R = 0.50—0.54). Conclusions: The regional analysis of deep and cortical grey matter atrophy suggests an association between the neurodegenerative process taking place in the striatum—thalamus—frontal cortex pathway and the development of fatigue in relapsing—remitting multiple sclerosis. The inclusion of the posterior parietal cortex as one of the best predictors of the Modified Fatigue Impact Scale cognitive domain suggests the major role of the posterior attentional system in determining cognitive fatigue in relapsing—remitting multiple sclerosis.

scholarly journals Relationship between Fatigue and Physical Activity in a Polish Cohort of Multiple Sclerosis Patients

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 726
Author(s):  
Michalina Rzepka ◽  
Mateusz Toś ◽  
Michał Boroń ◽  
Katarzyna Gibas ◽  
Ewa Krzystanek
Keyword(s):  
Physical Activity ◽  
Multiple Sclerosis ◽  
Severe Depression ◽  
Neurological Impairment ◽  
Common Symptom ◽  
Metabolic Equivalents ◽  
Impact Scale ◽  
Relapsing Remitting ◽  
Fatigue Severity ◽  
Multiple Sclerosis Patients

Background and objectives: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS). It can be defined as a subjective lack of physical and mental energy. The aim of this study was to evaluate the frequency and severity of fatigue in patients with MS and its relationship with overall physical activity and disease-related disability. Materials and Methods: The study included 100 patients with a clinical relapsing-remitting form of MS. Patients with severe depression were excluded. Neurological impairment was rated using the Expanded Disability Status Scale (EDSS). Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), with FSS scores greater than 36 indicating patients with fatigue. Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ) and categorized on three levels: low, moderate, and high, using standard metabolic equivalents (MET). Results: The average FSS and MFIS scores were (mean ± SD) 31.3 ± 15.2 and 30.1 ± 17.0, respectively. The mean EDSS score was 2.5 ± 1.5. 42%. Patients were classified as fatigued based on FSS. Fatigued patients had higher mean EDSS scores than non-fatigued (3.0 ± 1.6 vs. 2.2 ± 1.4, respectively, p = 0.002). Low, moderate, and high levels of physical activity were reported in 35%, 20%, and 45% of patients, respectively. Higher scores of fatigue in FSS and MFIS were inversely correlated with the intensity of physical activity (r = −0.38, p < 0.001 and r = −0.33, p < 0.001, respectively). Conclusions: In patients with MS, fatigue is a common symptom. Patients with lower physical activity and greater MS-related disability have a higher severity of fatigue, which negatively affects cognitive, psychosocial, and physical functioning.

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis

2015 ◽  
Vol 22 (1) ◽  
pp. 85-93 ◽  
Author(s):  
T Frisell ◽  
L Forsberg ◽  
N Nordin ◽  
C Kiesel ◽  
L Alfredsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Drug Discontinuation ◽  
First Year ◽  
Real World Data ◽  
Impact Scale ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Stopping Treatment ◽  
Baseline Characteristics ◽  
Relapsing Remitting Multiple Sclerosis

Background: Natalizumab (NTZ) and fingolimod (FGL) are mainly used second line in relapsing–remitting multiple sclerosis (MS), although pivotal trials included mainly treatment-naïve patients. Objective: This study aims to provide real-world data on safety and discontinuation rates. Methods: Using IMSE, a drug monitoring registry for all newer MS drugs in Sweden, we analysed differences in baseline characteristics and 1-year drug survival for patients registered 2011–2013, initiating treatment with NTZ ( n=640) or FGL ( n=876). Among FGL initiators, n=383 (44%) had previously used NTZ (FGLafterNTZ). Results: Compared with NTZ, the FGL cohort was older and more often male (36/38 years, 24%/33% males). Baseline Expanded Disability Status Scale was similar across groups, but MS Severity Score was higher in NTZ patients, and Symbol Digit Modalities Test and MS Impact Scale (MSIS-29) was higher in FGLafterNTZ versus FGLNTZ-naïve patients. Proportion on drug after 1 year was high, NTZ=87%, FGLNTZ-naïve=83% and FGLafterNTZ=76%. Adverse events was the most frequent reason for discontinuing FGL (FGLNTZ-naïve=9%, FGLafterNTZ=12%), and was significantly higher than on NTZ (3%). In contrast, the proportion of patients stopping treatment due to lack of effect was more similar: NTZ=4%, FGLNTZ-naïve=3%, FGLafterNTZ=8%. Conclusion: FGL and NTZ were both well tolerated, but FGL less so than NTZ, especially in patients switching to FGL from NTZ. Group differences were not explained by differences in recorded baseline characteristics.

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