Modified Fatigue Impact Scale Score Research Articles

Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial

Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue. This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed. Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy). Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered. Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society.

Impact of Siponimod on Clinical and Radiological Parameters of Secondary Progressive Multiple Sclerosis: A Real-World Prospective Study.

Secondary progressive multiple sclerosis (SPMS) presents with a challenging clinical phenotype, and siponimod has a potential to treat the active clinical phenotype of this disease. This single-center longitudinal study aimed to determine the therapeutic effects of siponimod in patients with active SPMS over 12 months. The clinical and radiological parameters of 50 patients with active SPMS treated using siponimod were assessed at baseline and after a 1-year follow-up period using the annual relapse rate (ARR), the Expanded Disability Status Scale (EDSS), the occurrence of gadolinium-enhanced lesion (GdE+), the Modified Fatigue Impact Scale (MFIS), and the Symbol Digit Modalities Test. The urine bladder postvoid residual (PVR) volume was also measured in a subcohort of 39 participants. Participants with an EDSS score ≥5.0 at baseline were finally assessed separately in prespecified subgroup analyses. There were significant reductions in ARR (p<0.001), GdE+ (p<0.001), and MFIS score (p=0.001) during the follow-up period. The progression of physical and cognitive disabilities remained stable (p>0.05). The PVR-volume analysis revealed a significant decrease in urine bladder PVR volume (p<0.001). These observations were consistent for the subgroup with EDSS score ≥5.0. Siponimod demonstrated efficacy in reducing ARR, GdE+, fatigue levels, and PVR volume, while maintaining stability in the cognitive and physical disability statuses of patients with SPMS. Similar findings were documented in the subgroup with EDSS score ≥5.0.

Spectrum of Cognitive Impairment in Patients with Multiple Sclerosis

Introduction. Cognitive impairment (CI) is a common manifestation of multiple sclerosis (MS), which significantly affects patients’ daily life and professional activity. Despite the development of methods to screen MS patients for CI, data on its prevalence in the Russian population are still lacking. Aim: to comprehensively assess cognitive functions in patients with different types of MS. Materials and methods. The study included MS patients who did not have any other possible causes of CI and no diseases or conditions that confounded this assessment. CI was determined using the Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) test battery and the Stroop test as a decrease in the scores below the mean by at least 1.5 standard deviations. CI was subjectively assessed using the Perceived Deficit Questionnaire; fatigue was subjectively assessed using the Modified Fatigue Impact Scale (MFIS). The Mann–Whitney test and Fisher’s exact test were used for comparison, and the Spearman test was used to evaluate correlations. Results. We evaluated 77 MS patients (30 men; age 40 [30; 48] years; 47 with relapsing-remitting MS, 30 with progressive MS). CI incidence was 23.4% in patients with relapsing-remitting MS and 77% in patients with progressive MS, while multi-domain CI was statistically significantly more common in patients with progressive MS. Impairment of processing speed was the most common. Patients with relapsing-remitting MS and CI were statistically significantly older and had longer disease duration than those without CI. There was a statistically significant correlation of subjective CI severity with MFIS scores but not with testing results. Conclusion. CI incidence in MS patients was relatively high with greater severity and involvement of more domains in patients with progressive MS. No correlation was found between subjective and objective CI assessment results, which may suggest that patients underestimated their deficit.

Effects of a plank-based strength training programme on muscle activation in patients with long COVID: a case series.

This study aimed to analyse the effects of a plank-based strength training programme on muscle activation in patients with long COVID. Case series study that included patients with long COVID who participated in a 12-week trunk and pelvic muscle strength training programme. Clinical variables and the modified fatigue impact scale (MFIS) were used to assess fatigue levels. Percentage of muscle activation during a core muscle plank was measured via surface electromyography. Pre- and post-intervention results were compared using the Wilcoxon signed-rank test and evaluated with Cohen's D effect size (ES). Twenty-one subjects participated in the study; 81% female, mean age 47.5 years (range: 28-55 years), and median duration of symptoms 21 months (range: 5-24 months); 90.5% of the participants experienced fatigue (MFIS score = 38). Muscle activation during plank exercises improved across all muscles after the intervention, with significant increases in the left (p = 0.011, medium ES) and right external oblique (p =0.039, small ES) muscles and the right latissimus dorsi muscle (p = 0.039, small ES). Additionally, significant reductions in fatigue were observed in the total MFIS score (p = 0.004, medium ES) and in the physical (p < 0.001, large ES) and psychosocial subscales (p = 0.033, small ES). Results suggest that a plank-based strength training programme may be effective in enhancing trunk and pelvic muscle activation in individuals with long COVID.

Impact of oral melatonin supplementation on urine and serum melatonin concentrations and quality-of-life measures in persons with relapsing multiple sclerosis

IntroductionMelatonin is an antioxidant and anti-inflammatory agent that modulates the immune system by scavenging free radicals, reducing the upregulation of pro-inflammatory cytokines, and reducing transendothelial cell migration. Therefore, melatonin may play a role in regulating multiple sclerosis (MS) disease activity. However, little is known about how melatonin supplementation effects individuals with MS. ObjectiveDetermine if there was a dose-dependent elevation in urine and serum melatonin concentrations. Determine if melatonin supplementation had an impact on patient reported outcomes. MethodsThis was a randomized, dose-blinded exploratory study. Adults (age 18–65) with relapsing forms of multiple sclerosis (RMS) treated with a stable dose of oral disease modifying therapy for at least 6 months were randomized into melatonin 3 mg or 5 mg daily. Urinary and serum melatonin levels and modified fatigue impact scale (MFIS), multiple sclerosis impact scale (MSIS-29), and Pittsburgh sleep quality index (PSQI), patient determined disease steps (PDDS) and performance scales (PS) were measured at baseline, 3, 6, and 12 months. Urinary and serum melatonin analyses was performed to estimate mean concentrations and their differences between treatment arms over time by a repeated measures linear mixed model. The model included treatment, assessment time, and treatment × time interaction. ResultsThirty patients, randomized 1:1, were analyzed in an intent to treat population. Twenty-three completed the study. The repeated measures linear mixed model analysis of all timepoints revealed higher melatonin concentrations in patients on 5 mg compared to 3 mg melatonin for both urinary 6-SMT (p = 0.03) and serum melatonin (p = 0.04). MFIS, MSIS-29, PSQI, and PDSS-PS scores did not significantly change from baseline to month 12. No significant differences in these measures were seen between the two doses. Five patients stopped melatonin (three on 5 mg and two on 3 mg) due to adverse events, including one patient who developed focal spongiotic dermatitis. One patient experienced three consecutive serious adverse events that were unrelated to melatonin supplementation. ConclusionsThe 5 mg melatonin supplementation group had higher concentrations of urinary 6-SMT and serum melatonin compared to the 3 mg group over 12 months of treatment. There was a correlation between 6-SMT and serum melatonin concentrations. This suggests that measuring serum melatonin is a reliable alternative to measuring urinary 6-SMT. However, no differences in clinical benefit between the two dosage groups were demonstrated in the patient reported outcomes. Trial Registration NumberNCT03498131

THE EFFECTS OF HYBRID FUNCTIONAL ELECTRICAL STIMULATION INTERVAL TRAINING ON AEROBIC FITNESS AND FATIGUE IN PEOPLE WITH ADVANCED MULTIPLE SCLEROSIS

INTRODUCTION &amp; AIMS Improving aerobic fitness in people with multiple sclerosis (MS) can reduce fatigue, and lower the risk of cardiovascular disease. Aerobic training can be challenging due to paresis, access to suitable equipment and fatigue. The aim was to investigate whether functional electrical stimulation (FES) cycling combined with arm crank interval exercise (hybrid FES interval training) is feasible for people with advanced MS, and its effects on aerobic fitness and fatigue. METHODS Hybrid FES interval training was performed 2 d/wk for 12 weeks. Each session consisted of 40 minutes of continuous FES cycling with arm crank intervals of 30 seconds work/30 seconds rest added concurrently for 20 minutes. The intensity target was a minimum of 60% of arm crank power and ‘hard’ measured by rate of perceived exertion (RPE) on a scale of 6-20. Feasibility was measured by attendance, compliance to intensity and time targets, adverse events, and drop outs. Aerobic fitness was assessed by an arm crank maximal test. Fatigue was measured via the Modified Fatigue Impact Scale (MFIS). RESULTS Seven participants (6 female; age 57.1±7.8y; Expanded Disability Status Scale 7.1±0.8) with advanced MS attended 80±10.4% of the scheduled sessions and there were no adverse events or drop outs. Average RPE at the end of each training session was 15±2, representing vigorous intensity exercise. Aerobic fitness did not change pre- to post-intervention [14.2±5.7 to 14.78±6.0 mL/kg/min (p=0.43)]. There was a trend towards a reduction in the MFIS score pre- to post-intervention [31.0±10.4 to 21.7±11.4 (p=0.10)]. CONCLUSION Hybrid FES interval training is feasible for people with advanced MS who need exercise equipment appropriate for their condition, and can represent vigorous intensity exercise. The positive findings support the need for future randomized control trials that can assess the aerobic fitness changes and associated health benefits of hybrid FES interval training.

Rapid Recovery with Physiotherapy in An Adult with Surgically managed Torticollis and Associated Cervical Myelopathy

Torticollis which is a relatively temporary condition rarely seen till adulthood. However, if untreated during childhood may develop complications later which may include musculoskeletal or neurological structures around neck. It may range from contracture of soft tissue to involvement of neural structures. However neurological complications are rare and may require surgical correction. Case description: Here, a 16-year-old male patient who reported physiotherapy department with chief complaint of difficulty in movement of bilateral upper and lower limb difficulty in standing and difficulty in walking independently and breathlessness on exertional activity. Result: After 2 months of physiotherapy treatment berg balance scale score improved from 20/56 to 51/56, dynamic gait index score improved from 10/24 to 15/24, Modified fatigue impact scale score improved from 51/84 to 12/84. Conclusion: Neurological complication of Torticollis in a 16-year-old patient could be reversed partially resulting in functional improvement, with surgery and appropriate Physiotherapy treatment.

Clinical and radiological correlates of apathy in multiple sclerosis

Background: Although apathy has been associated with fronto-striatal dysfunction in several neurological disorders, its clinical and magnetic resonance imaging (MRI) correlates have been poorly investigated in people with multiple sclerosis (PwMS). Objectives: To evaluate clinical variables and investigate microstructural integrity of fronto-striatal grey matter (GM) and white matter (WM) structures using diffusion tensor imaging (DTI). Methods: A total of 123 PwMS (age: 40.25 ± 11.5; female: 60.9%; relapsing–remitting multiple sclerosis: 75.6%) were prospectively enrolled and underwent neurological and neuropsychological evaluation, including Expanded Disability Status Scale (EDSS), Apathy Evaluation Scale (AES-S), Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS) and brain 3T-MRI volumes of whole brain, frontal/prefrontal cortex (PFC) and subcortical regions were calculated. DTI-derived metrics were evaluated in the same GM regions and in connecting WM tracts. Results: Apathetic PwMS (32.5%) showed lower education levels, higher HADS, MFIS scores and WM lesions volume than nonapathetic PwMS. Significant differences in DTI metrics were found in middle frontal, anterior cingulate and superior frontal PFC subregions and in caudate nuclei. Significant alterations were found in the right cingulum and left striatal-frontorbital tracts. Conclusions: Apathy in PwMS is associated with higher levels of physical disability, depression, anxiety and fatigue together with lower educational backgrounds. Microstructural damage within frontal cortex, caudate and fronto-striatal WM bundles is a significant pathological substrate of apathy in multiple sclerosis (MS).

Sedentary behaviour and related factors in people with multiple sclerosis

BackgroundSedentary behaviour is a major problem in persons with multiple sclerosis (pwMS). However, little is known about the related factors of sedentary behaviour in MS. Our study aimed to examine the association between sedentary behaviour and physical activity level, fear of falling, and fatigue. MethodDemographic and clinical data have been recorded. Sedentary behaviour was assessed with the Marshall Sitting Questionnaire, physical activity level was evaluated with the Godin Leisure Time Exercise Questionnaire, fear of falling was evaluated with the Fall Efficacy Scale International, and fatigue was evaluated with the modified fatigue impact scale (MFIS). The Timed 25-Foot Walk, 6-Minute Walk Test, Timed Up and Go Test, and 12-Item Multiple Sclerosis Walking Scale were also used to assess walking and perceived walking disability. ResultsWe recruited 71 pwMS [49 were female (69 %), mean age:38.08 years, median EDSS:1.5]. The mean daily sitting time was 593.54 min (∼10 h). No significant correlation was found between sitting times and demographics, leisure time physical activity, fear of falling, walking, perceived walking disability, and neurological disability level (p > 0.05). Logistic regression analysis indicated that being male increased the risk of sedentary behaviour by 3.08 times, being employed increased the risk of sitting by 4.65 times, and each point increase in MFIS scores resulted in a 1.03-fold elevation in the odds of prolonged sitting. ConclusionThe fact that pwMS, even with a mild disability spend almost 10 h sitting highlights the significance of sedentary behaviour in this population. Developing strategies to address modifiable factors, such as fatigue, may be effective in reducing sedentary behaviour.

Sociodemographic and Clinical Determinants of Fatigue in Multiple Sclerosis.

Fatigue is the most common and disabling symptom in patients with multiple sclerosis (PwMS), representing one of the main determinants of reduced quality of life among PwMS due to its interference with social activities and work capacity. This study aimed to identify the sociodemographic determinants of fatigue in a cohort of 150 PwMS and 100 healthy controls (HCs). Fatigue was assessed using one of the most suitable and appropriate tools for measuring the degree of fatigue: the Modified Fatigue Impact Scale (MFIS). By comparing the median scores for the MFIS, we observed that the PwMS group had significantly higher MFIS scores than the HCs (p = 0.0001). In PwMS, MFIS scores correlated positively with age, total number of relapses, total disease duration, disability status, and Beck Depression Inventory-II score and negatively with cognitive performance. Patients with relapsing-remitting MS had significantly lower fatigue levels than those with secondary progressive MS (p = 0.0010). Fatigue levels were significantly lower among male than female PwMS (p = 0.0120). Other determinant factors of fatigue in our study proved to be the marital and occupational status, as well as the presence of children, but in a linear multivariate regressions analysis with MFIS score as the dependent variable, the fatigue levels were influenced only by sex, occupational status, marital status, children status, and BDI-II test results. Considering the significant impact of fatigue on the quality of life of PwMS, clinicians must diagnose fatigue as early as possible, identify its modifiable determinants, and manage it effectively to increase their quality of life.

Patterns of attention deficit in relapsing and progressive phenotypes of multiple sclerosis

Behavioral aspects and underlying pathology of attention deficit in multiple sclerosis (MS) remain unknown. This study aimed to clarify impairment of attention and its relationship with MS-related fatigue. Thirty-four relapse-remitting MS (RRMS), 35 secondary-progressive MS (SPMS) and 45 healthy controls (HC) were included. Results of psychophysics tasks (attention network test (ANT) and Posner spatial cueing test) and fatigue assessments (visual analogue scale and modified fatigue impact scale (MFIS)) were compared between groups. In ANT, attentional network effects were not different between MS phenotypes and HC. In Posner task, RRMS or SPMS patients did not benefit from valid cues unlike HC. RRMS and SPMS patients had less gain in exogenous trials with 62.5 ms cue-target interval time (CTIT) and endogenous trials with 250 ms CTIT, respectively. Total MFIS was the predictor of gain in 250 ms endogenous blocks and cognitive MFIS predicted orienting attentional effect. Executive attentional effect in RRMS patients with shorter disease duration and orienting attentional effect in longer diagnosed SPMS were correlated with MFIS scores. The pattern of attention deficit in MS differs between phenotypes. Exogenous attention is impaired in RRMS patients while SPMS patients have deficit in endogenous attention. Fatigue trait predicts impairment of endogenous and orienting attention in MS.

Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome

BackgroundChronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.MethodsRandomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2 years and mean duration of CFS 6.3 years) were randomly assigned to receive either FMT from a universal donor (n = 5) or autologous FMT (n = 6) via colonoscopy. Patients’ HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients’ HRQOL was evaluated at baseline, and 1 and 6 months after the FMT.ResultsThe baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p = 0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p = 0.80), 53.5 and 62.0 at 1 month and 58.6 and 56.2 at 6 months. Compared to the baseline scores, differences at 1 and 6 months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported.ConclusionFMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results.Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register.clinicaltrials.gov, date of registration 08/08/2019.

Functional Connectivity Modifications in Monoaminergic Circuits Occur in Fatigued MS Patients Treated With Fampridine and Amantadine (P10-3.008)

<h3>Objective:</h3> To investigate changes over time of fatigue severity and concomitant modifications of resting state (RS) functional connectivity (FC) in monoaminergic networks in 45 fatigued multiple sclerosis (MS) patients after different symptomatic treatments. <h3>Background:</h3> Fatigue is common and disabling in MS. Symptomatic treatments for fatigue rely on drugs reinforcing monoaminergic synaptic transmission, suggesting a role of monoaminergic network abnormalities in fatigue pathogenesis. <h3>Design/Methods:</h3> MS patients were randomly, blindly assigned to treatment with fampridine (n=15), amantadine (n=15) or placebo (n=15) and underwent clinical, neuropsychological and 3T RS fMRI at baseline (T0) and after four weeks (W4) of treatment. Fifteen matched healthy controls (HC) were acquired twice. Dopamine-, noradrenaline- and serotonin-related RS FC was derived by independent component analysis (ICA), constrained to PET atlases for dopamine, noradrenaline and serotonin transporters, obtained in HCs’ brain. Changes in modified fatigue impact scale (MFIS) score and monoaminergic-related RS FC were assessed. <h3>Results:</h3> MS patients showed baseline abnormalities <i>vs</i> HC in all three networks, with decreased monoamine-related RS FC in temporal, occipital, insular and cerebellar regions, and increased RS FC in frontal, parietal and subcortical areas. At W4, MFIS scores decreased in all patients’ groups, with no time-by-treatment interaction. At W4, fampridine and amantadine patients showed increased dopamine- and noradrenaline-related RS FC in the insular cortex, as well as increased serotonin-related RS FC in the precuneus/posterior cingulate cortex. Amantadine patients also showed increased dopamine- and noradrenaline-related RS FC in the anterior cingulate cortex (ACC). Conversely, placebo patients mostly showed increased noradrenaline-related RS FC in the precuneus and middle cingulate cortex. Fampridine and placebo groups showed trends towards significant correlations between RS FC modifications and MFIS improvements (r=−0.49: −0.52, p=0.07–0.08). <h3>Conclusions:</h3> Fatigue improved in all groups. Concomitant monoaminergic-related RS FC modifications were found in insular, ACC and parietal regions for fampridine and amantadine MS patients, and in medial parietal regions for placebo patients. <b>Disclosure:</b> Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Dr. Lamanna has nothing to disclose. Bruno Colombo has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Neural effects of fatigue on cognition in relapsing multiple sclerosis detected by magnetoencephalography: Towards an imaging biomarker (P11-3.007)

<h3>Objective:</h3> Determining functional differences in MS patients during a task, compared to controls. <h3>Background:</h3> Fatigue affects 80% of patients with MS. Fatigue can also have adverse effects on cognitive abilities. MEG is a noninvasive functional brain imaging technique that measures the magnetic brain waves arising from neuronal activity during rest or during a cognitive task. MEG may help detect functional changes that happen in MS patients with fatigue and cognitive difficulties. <h3>Design/Methods:</h3> This study examined the effects of fatigue on cognition in patients with MS using the modified fatigue impact scale(MFIS) and symbol digits modalities test(SDMT) before and during MEG study respectively. MEG data from 6 patients with MS were compared to 3 control subjects. MEG data were filtered into 4 different frequency bands: theta, alpha, beta, and gamma. Network brain activity for each frequency band was mapped for the strength of connectivity across 27 regions in each hemisphere, resulting in 1431 pairings in the brain. The false discovery rate was used to adjust for multiple testing. Only the most statistically significant connections were based on a p-value of less than 0.05. <h3>Results:</h3> MS patients had most coherent beta and gamma connectivity in the fusiform and frontal regions respectively. The control subjects had more coherent connections in the frontal-parietal, frontal-temporal, and frontal-occipital regions. Individual MFIS scores in MS-patients were higher than the controls and correlated with lower SDMT scores in the MS patients. <h3>Conclusions:</h3> MEG was able to detect clear differences in active networks during SDMT tasks in patients with MS compared to controls. Slow processing speed has been associated with reduced frontal lobe activation in younger adults. Our study cohort supported the lack of coherent beta activity in the frontal lobe. The limitation of our study is a small sample size. The complete data analysis of 10 patients will be presented at AAN-2023. <b>Disclosure:</b> Dr. Memon has nothing to disclose. Mr. Hammami has nothing to disclose. Mr. Memon has nothing to disclose. Dr. Bowyer has nothing to disclose.

Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study.

Fatigue is one of the most frequent and disabling symptoms of the post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue. We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The modified fatigue impact scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck depression inventory) and quality of life (EuroQol-5D). Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); the mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since the acute infection was 20.68 ± 6.34 months. Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and 1 month as compared with sham stimulation. No significant effect was detected for cognitive fatigue. In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on the quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups. In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

Fatigue, Depression, and Anxiety in Patients with COPD, Asthma and Asthma-COPD Overlap.

Asthma and COPD are extremely common respiratory diseases that have a serious impact on people's lives around the world. A disease characterized by symptoms characteristic for asthma and COPD is called asthma-COPD overlap (ACO). Fatigue and certain psychological disorders such as anxiety and depression are important comorbidities in these diseases. The purpose of this study was to assess the prevalence of fatigue, anxiety, and depression in patients with asthma, COPD, and ACO and to also consider their mutual correlations. A total of 325 patients were enrolled in the study. There were 159 women and 166 men and their mean age was 63. Two standardized questionnaires were used: the Modified Fatigue Impact Scale (MFIS) and the Hospital Anxiety and Depression Scale (HADS). The mean total MFIS score for all patients was 33.03. Patients with asthma generally scored lower than patients with COPD and ACO. There were no statistical differences in the HADS for anxiety between the groups, although around half of the patients registered a score indicating some level of disorder. Patients with COPD and ACO were proven to suffer more from depression than patients with asthma. The HADS and MFIS scores were found to correlate significantly and positively. Our study showed that patients with COPD, asthma, and ACO generally suffered from an increased level of fatigue and depression. Anxiety was high in all groups, but it was at a similar level for patients suffering from each of the three diseases under consideration. It is important to treat the physical symptoms as well as the psychological disorders since they greatly impact on the patient outcomes.

Frequency, entity and determinants of fatigue inCharcot-Marie-Tooth disease.

Fatigue, a disabling symptom in many neuromuscular disorders, has been reported also in Charcot-Marie-Tooth disease (CMT). The presence of fatigue and its correlations in CMT was investigated. The Modified Fatigue Impact Scale (MFIS) was administered to CMT patients from the Italian Registry and a control group. An MFIS score >38 indicated abnormal fatigue. The correlation with disease severity and clinical characteristics, the Hospital Anxiety and Depression Scale and Epworth Sleepiness Scale scores, and drug use was analysed. Data were collected from 251 CMT patients (136 women) and 57 controls. MFIS total (mean ± standard deviation 32 ± 18.3, median 33), physical (18.9 ± 9.7, 20) and psychosocial (2.9 ± 2.4, 3) scores in CMT patients were significantly higher than controls. Abnormal fatigue occurred in 36% of the patients who, compared to patients with normal scores, had more severe disease (median CMT Examination Score 9 vs. 7), more frequent use of foot orthotics (22% vs. 11%), need of support for walking (21% vs. 8%), hand disability (70% vs. 52%) and positive sensory symptoms (56% vs. 36%). Patients with abnormal fatigue had significantly increased frequency of anxiety/depression/general distress (Hospital Anxiety and Depression Scale), somnolence (Epworth Sleepiness Scale), obesity (body mass index ≥ 30) and use of anxiolytic/antidepressant or anti-inflammatory/analgesic drugs. Fatigue is a relevant symptom in CMT as 36% of our series had scores indicating abnormal fatigue. It correlated with disease severity but also with anxiety, depression, sleepiness and obesity, indicating different components in the generation of fatigue. CMT patients' management must include treatment of fatigue and of its different generators, including general distress, sleepiness and obesity.

Prevalence of fatigue and its explicative variables among people with multiple sclerosis.

Fatigue is the most prevalent symptom among people with multiple sclerosis (PwMS). Although exercise effectively reduces fatigue, the relationship between daily physical activity and fatigue has only recently been demonstrated. The aim of this study was to evaluate the prevalence of fatigue and to understand the relationship with several variables in French PwMS. Data were collected from 191 PwMS using Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) for fatigue, and the Godin Leisure-Time Exercise Questionnaire (GLTEQ) for physical activity. 110 PwMS (57%), 35 PwMS (18%) and 46 PwMS (24%) were considered as fatigued, non-fatigued and in the grey zone, respectively. Greater physical activity was observed in non-fatigued PwMS (20.2±19.8) compared to fatigued PwMS (12.5±14.1). FSS and MFIS scores were associated with physical activity (r = -0.28 and r = -0.25, respectively, p < 0.05). Using multivariate analysis, disability, physical activity and being unemployed explained 21% of the variance of the MFIS. The present study confirms that physical activity and fatigue are associated. Disability and unemployment status should also to be consider when assessing fatigue. Activity-oriented health policies should be redesigned to improve fatigue among PwMS.

Patient's perspective in clinical practice to assess and predict disability in multiple sclerosis

The information provided by a person with multiple sclerosis (MS) may anticipate changes in the course of the disease. To explore the role of a set of standardized patient-reported outcomes (PRO) in predicting disability progression in MS an observational study was conducted in two cohorts of 30 and 86 persons with progressive MS (pwPMS) and relapsing MS (pwRMS), respectively. The associations between baseline clinical, biochemical variables and results on MS quality of life scale (MusiQol), Modified Fatigue Impact Scale (MFIS) and Beck Depression Inventory II (BDI-II) were analyzed. The progression of disability after 2 years of follow-up in pwRMS was investigated. We show that PRO differentiated pwRMS and pwPMS cohorts with lower MusiQoL and higher MFIS and BDI-II scores in the latter. Only MFIS was correlated with disability in pwRMS and high scores in the physical MFIS domain associated with worse performance in 9HPT, and a trend in T25FW and SDMT. Instead, the cognitive MFIS domain was correlated with CHI3L1 in cerebrospinal fluid, a biomarker of progression. At the end of the study, global MFIS and BDI-II were found to be independent risk factors for disability independent of relapse. Although all PRO measures explored were altered in pwPMS, baseline MFIS discriminated current and prospective disability in pwRMS, identifying patients at risk of progression.

Fatigue and cognitive impairment in neuroborreliosis patients posttreatment-A neuropsychological retrospective cohort study.

BackgroundThe aim of this study was to determine the prevalence of fatigue and cognitive impairment in patients with neuroborreliosis (NB) posttreatment and to determine whether delayed treatment initiation led to higher levels of fatigue and cognitive impairment.MethodsThe study population consisted of 88 patients with NB included between October 10, 2014, and August 21, 2020, at the Clinical Center for Emerging and Vector‐borne Infections at Odense University Hospital, Denmark. The Symbol Digit Modalities Test (SDMT) was used as a cognitive screening test, and the Modified Fatigue Impact Scale (MFIS) was used to assess the patients’ level of fatigue over the course of a year.ResultsOverall, 14.3% of patients had an SDMT score indicative of cognitive impairment, and 38.8% of patients reported experiencing fatigue 12 months posttreatment. We found no statistically significant differences in fatigue or cognitive impairment when comparing the patients who had a treatment delay of ≤14 days and those with a treatment delay of >14 days (p > .05) 12 months posttreatment. A random effects regression model showed a significant positive correlation between longer treatment delay and higher MFIS scores, indicating higher levels of fatigue.ConclusionsThe results of this study show that both the early and late treatment groups improved significantly over a 12‐month period in terms of both cognitive symptoms and fatigue. However, it also showed that a substantial subgroup of patients with NB still suffer from fatigue and cognitive impairment 12 months posttreatment.