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Background: Fatigue is a complex and disabling symptom of Multiple Sclerosis (MS); however, there is conflicting evidence of the relationship between fatigue and clinical features of MS. Furthermore, few studies have considered these relationships specifically in a progressive MS population. Aims:(1) estimate the prevalence of self-reported fatigue in people with MS; (2) evaluate the relationship between fatigue severity/impact and clinical features of MS; (3) compare the prevalence of fatigue, and the strength of relationship between fatigue severity/impact and clinical features of MS in progressive and non-progressive forms of MS.Methods: An online survey was conducted to measure the severity (Fatigue Severity Scale (FSS)) and impact of self-reported fatigue (Modified Fatigue Impact Scale) in people with MS. The survey also contained questionnaires related to disability, quality of life, MS impact, anxiety and depression, cognition, and sleep quality.Results: 412 people responded to the survey, of which 68.7% reported having fatigue (FSS≥5). The prevalence of fatigue was significantly higher in participants with progressive MS (81%) in comparison to those with non-progressive forms of MS (64%, p=0.01). Fatigue severity and impact were associated with quality of life, MS impact, anxiety, depression, cognition, and sleep quality in both progressive and non-progressive MS populations (p<0.05). However, fatigue severity (r = 0.335) and impact (r = 0.391) were correlated with disability only in participants with non-progressive MS. Conclusion:Fatigue was more prevalent amongst participants with progressive MS. In addition, higher fatigue severity and impact were associated with greater physical, cognitive, and psychological impairment, although the strength of association between these outcomes was generally similar regardless of the type of MS.

Summary Background Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. Objectives To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression. Methods We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort. Results Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)‐17A, IL‐17F, IL‐21 and IL‐23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL‐17F, IL‐17E and IL‐23. We hypothesized that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. Our assessment of psychiatric comorbidity in AA using HADS scores showed that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL‐22 and IL‐17E are positively and significantly associated with depression. Conclusions Our data highlight changes in both type 17 and type 2 cytokines among people with AA, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression. What's already known about this topic? NKG2D+CD8+ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood. AA is associated with changes in levels of interleukin (IL)‐6, tumour necrosis factor‐α, IL‐1β and type 17 cytokines. Psychiatric comorbidity is common among people with AA. What does this study add? People with AA have increased plasma levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25), in addition to the type 17 cytokines IL‐17A, IL‐21, IL‐23 and IL‐17F. Levels of IL‐17E and IL‐22 positively predict depression score. What is the translational message? AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17‐ and type 2 immune pathways. Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17‐ and type 2 immune dysregulation, rather than focusing narrowly on the CD8+ T‐cell response. An immunological mechanism might contribute directly to the depression observed in people with AA.

Background: Fatigue is a common and debilitating symptom of Multiple Sclerosis (MS); however, it is unknown what constitutes a clinically significant change in fatigue. Establishing the minimally important difference (MID) of fatigue outcome measures can inform the interpretation of changes in fatigue by estimating the level of change that is considered clinically relevant. Aim: Determine the MID for the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) in people with MS. Methods: This cross-sectional study collected information on self-reported fatigue (FSS and MFIS) and quality of life (EQ-5D and MS Impact Scale 29) through an online survey. Anchor-based methods were used to estimate MID, and ordinal logistic regression models were used to determine the difference in fatigue that would predict a significant effect on quality of life. Results: 365 people with MS (81.9% female, 69.3% relapsing-remitting MS, mean age 46.2±11.6 years, mean time since diagnosis 9.6±8.7 years) responded to the survey. MID estimates for the FSS and MFIS ranged from 0.45-0.88 and 3.86-8.11 respectively, accounting for 6.4-12.6% of maximum FSS score and 4.6-9.7% of maximum MFIS score. Conclusions: MID estimates derived from this study indicate that a difference of at least 0.45 points on the FSS or 4 points on the MFIS constitutes a clinically significant difference in fatigue. Therefore, these estimates represent a threshold value which can be used to interpret changes in the FSS and MFIS over time or in response to an intervention.

CME/CNE Information Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Delaware Media Group. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physician Credit The CMSC designates this journal-based activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Credit The CMSC designates this enduring material for 1.0 contact hour (none in the area of pharmacology). Disclosures: Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has disclosed relationships with Springer Publishing (royalty), Biogen (speakers' bureau), and Adamas Pharmaceuticals (contracted research).Francois Bethoux, MD, has served as reviewer for this activity. She has disclosed no relevant financial relationships.Laurie Scudder, DNP, NP, has disclosed no relevant financial relationships.Scott Rooney, BSc (Hons), has disclosed no relevant financial relationships.Fiona Moffat, PhD, has disclosed no relevant financial relationships.Les Wood, PhD, has disclosed no relevant financial relationships.Lorna Paul, PhD, The peer reviewers for IJMSC have disclosed no relevant financial relationships. The staff at IJMSC, CMSC, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Financial relationships for some authors may have changed in the interval between listing these disclosures and publication of the article. Method of Participation: Release Date: February 1, 2019 Valid for Credit Through: February 1, 2020 In order to receive CME/CNE credit, participants must: Statements of Credit are awarded upon successful completion of the post-test with a passing score of &gt;70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.