scholarly journals Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis

2018 ◽  
Vol 115 (51) ◽  
pp. E12063-E12072 ◽  
Author(s):  
Karin M. E. Andersson ◽  
Caroline Wasén ◽  
Lina Juzokaite ◽  
Lovisa Leifsdottir ◽  
Malin C. Erlandsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Functional Disability ◽  
Hippocampal Neurogenesis ◽  
Joint Disease ◽  
Neurological Sequelae ◽  
Molecular Features ◽  
Igf1r Signaling ◽  
Igf1 Receptor ◽  
The Brain

Rheumatoid arthritis (RA) is an inflammatory joint disease with a neurological component including depression, cognitive deficits, and pain, which substantially affect patients’ quality of daily life. Insulin-like growth factor 1 receptor (IGF1R) signaling is one of the factors in RA pathogenesis as well as a known regulator of adult neurogenesis. The purpose of this study was to investigate the association between IGF1R signaling and the neurological symptoms in RA. In experimental RA, we demonstrated that arthritis induced enrichment of IBA1+ microglia in the hippocampus. This coincided with inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) and up-regulation of IGF1R in the pyramidal cell layer of the cornus ammoni and in the dentate gyrus, reproducing the molecular features of the IGF1/insulin resistance. The aberrant IGF1R signaling was associated with reduced hippocampal neurogenesis, smaller hippocampus, and increased immobility of RA mice. Inhibition of IGF1R in experimental RA led to a reduction of IRS1 inhibition and partial improvement of neurogenesis. Evaluation of physical functioning and brain imaging in RA patients revealed that enhanced functional disability is linked with smaller hippocampus volume and aberrant IGF1R/IRS1 signaling. These results point to abnormal IGF1R signaling in the brain as a mediator of neurological sequelae in RA and provide support for the potentially reversible nature of hippocampal changes.

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

scholarly journals The Role of Estrogens in Rheumatoid Arthritis Physiopathology

2020 ◽  
Author(s):  
Maria Fernanda Romo-García ◽  
Martín Zapata-Zuñiga ◽  
José Antonio Enciso-Moreno ◽  
Julio Enrique Castañeda-Delgado
Keyword(s):  
Rheumatoid Arthritis ◽  
Direct Action ◽  
Hormone Replacement ◽  
Joint Disease ◽  
Dependent Manner ◽  
Sexual Hormones ◽  
Dose Dependent ◽  
Estrogen Administration

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that can lead to irreversible disability. It affects women in a higher proportion than men (3:1 cases). Several reports suggest a link between female sexual hormones (estrogens) and RA features. It’s been described that biological processes where basal estrogen levels are altered like in menstruation, pregnancy, and menopause modifies RA onset, flare, disease severity, and inflammation. Estrogens have a direct action upon the immune system though ERα and ERβ receptors, which have distinct affinity to estrogen concentrations and modifications and have effects upon RA in a dose and receptor dependent manner. The studies focused on dose dependent response at experimental settings reveal a wide (from 25 pg/L to several μg/L) and even contradictory spectrum of effects in patients and cells. This chapter summarizes the contributions and effects of estrogens in RA physiopathology, clinical features, and discusses the possible contributions of estrogen administration and concentration of hormone replacement therapy (HRT) to improve the quality of life and reduce the symptoms of RA patients based on the knowledge of the biology of these hormones.

Development and Implementation of a Brain Rest Protocol in Nonintellectually Challenged Youth With Head-Banging Behaviors

2020 ◽  
Vol 26 (3) ◽  
pp. 282-287
Author(s):  
Lori Keough ◽  
Susan Gardner ◽  
Alyssa Kirby
Keyword(s):  
Traumatic Brain Injury ◽  
Athletic Injury ◽  
Nursing Assessment ◽  
Neurological Sequelae ◽  
Self Injury ◽  
Intervention Protocol ◽  
Strength Based ◽  
The Brain

INTRODUCTION: Concussions as a result of mild traumatic brain injury (MTBI) in youth are often associated with athletic injury; however, they can also occur as a result of intentional self-injury by head banging. Despite the known neurological sequelae secondary to MTBI, assessment, interventions, and consequences of head banging in the nonintellectually disabled populations have not been well studied. AIMS: The intent of this nurse-led intervention was to develop a brain rest protocol at a residential treatment program serving youth who were between 12 and 19 years old in order to improve the quality of care and moderate negative sequelae resulting from MTBI. METHODS: A nursing assessment guided by an adaptation of the acute concussion evaluation and a strength-based intervention protocol was developed and applied to youth who engage in head banging. RESULTS: The result was a protocol that defined the process by which a youth would be assessed and treated after head banging. There are no outcome measures that would assist to measure the effectiveness of this intervention in the short or long term. CONCLUSION: This intervention filled a need for improved assessment and appropriate interventions in youth with head-banging behavior. It is feasible that the assessment and implementation of the brain rest protocol is the first step in understanding how to best evaluate and manage the sequelae of intentional head banging resulting from MTBI.

scholarly journals Fibromyalgia Is Common and Adversely Affects Pain and Fatigue Perception in North Indian Patients with Rheumatoid Arthritis

2009 ◽  
Vol 36 (11) ◽  
pp. 2443-2448 ◽  
Author(s):  
VARUN DHIR ◽  
ABLE LAWRENCE ◽  
AMITA AGGARWAL ◽  
RAMNATH MISRA
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Health Assessment ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
The North ◽  
Indian Patients

Objectives.Fibromyalgia (FM) has been shown to be common in patients with rheumatoid arthritis (RA), but studies on Asian patients are lacking. It remains unclear whether FM has an adverse influence on pain, fatigue, quality of life, and mood in these patients, and what its relationship is with disease activity. We studied prevalence and effects of FM in North Indian patients with RA and associations of RA with disease activity.Methods.This cross-sectional study included 200 RA patients and an equal number of controls. Presence of FM was defined using the American College of Rheumatology 1990 criteria. Pain and fatigue scores were assessed using a 10 cm visual analog scale. Quality of life and presence of depression/anxiety were determined using validated questionnaires. Disease activity and functional disability in RA patients was assessed using the Disease Activity Score 28-3 and Health Assessment Questionnaire, respectively.Results.FM was present in 15% of patients with RA compared to 2.5% of controls in the North Indian population. RA patients with FM did not differ from those without FM in terms of age, gender, current disease-modifying agents, or steroid use. RA patients with FM had higher disease activity and worse functional disability. The number of tender and swollen joints was higher in patients with FM, but correlated poorly with each other. RA patients with FM had higher pain and fatigue scores but were not different in the quality of life or mood.Conclusion.FM is more common in North Indian patients with RA compared to controls. It adversely affects the pain and fatigue felt by RA patients. Disease activity and FM influence each other.

scholarly journals Evaluation of sexual dysfunction and its predictive factors in female and male patients with rheumatoid arthritis

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Mohamed Azab ◽  
Maii Abdelraheem Abdellatif ◽  
Mai Mohamed Abdelnaby
Keyword(s):  
Rheumatoid Arthritis ◽  
Sexual Dysfunction ◽  
Disease Duration ◽  
Joint Disease ◽  
Female Patients ◽  
Number Of Children ◽  
Vas Score ◽  
Joint Deformity ◽  
Male Patients

Abstract Background Rheumatoid arthritis (RA) is a common disabling joint disease affecting both males and females. Sexual dysfunction (SD) is a common association with RA. The aim of this work was to study the prevalence and predictors of sexual dysfunction in male and female patients with rheumatoid arthritis. Results The mean age of female patients was 32.1 years and 39.7 years for males. The prevalence of sexual dysfunction was higher in RA female patients than controls, 62.1% versus 41.2% respectively (P ≤ 0.05). The prevalence of global sexual dysfunction was higher in RA male patients than controls, 63.8% versus 47.5% respectively (P ≤ 0.05). Predictors of sexual dysfunction in female RA patients were the number of children, BMI, disease duration, DAS score, HADs-D score, HAQ score, VAS score, joint deformity, and the number of drugs. Predictors of sexual dysfunction in male RA patients were age, disease duration, DAS score, HAQ score, VAS score, and the number of drugs. Conclusion SD is prevalent in RA patients. Disease activity, pain, depression, and disturbed quality of life affect nearly all domains of sexual functions in female and male patients.

scholarly journals Has the Severity of Rheumatoid Arthritis at Presentation Diminished Over Time?

2014 ◽  
Vol 41 (8) ◽  
pp. 1590-1599 ◽  
Author(s):  
Janet G. Diffin ◽  
Mark Lunt ◽  
Tarnya Marshall ◽  
Jacqueline R. Chipping ◽  
Deborah P.M. Symmons ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Drug Exposure ◽  
Functional Disability ◽  
Health Assessment ◽  
Joint Disease ◽  
Symptom Duration ◽  
Recent Onset ◽  
American College Of Rheumatology ◽  
Over Time

Objective.To examine the pattern of disease severity in patients with rheumatoid arthritis (RA) at presentation to the Norfolk Arthritis Register (NOAR) over 20 years.Methods.NOAR is a primary-care–based cohort of patients with recent-onset inflammatory polyarthritis. At baseline, subjects are assessed and examined by a research nurse. The Health Assessment Questionnaire (HAQ) is administered and the DAS28 (28-joint Disease Activity Score) is calculated. Information is collected on disease-modifying antirheumatic drug exposure. In this study, patients (symptom duration of < 2 years at baseline) were grouped into 4 cohorts (Cohort 1: 1990–1994; Cohort 2: 1995–1999; Cohort 3: 2000–2004; Cohort 4: 2005–2008). The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for RA were applied retrospectively at baseline. Regression analyses were used to examine whether calendar year of presentation to NOAR was associated with baseline HAQ and DAS28 scores. Potential confounders included age at symptom onset, sex, rheumatoid factor, and anticyclic citrullinated peptide antibody positivity.Results.A total of 1724 patients met the ACR/EULAR 2010 RA criteria at baseline. Unadjusted mean DAS28 scores decreased over time. Calendar year of presentation to NOAR was significantly associated with lower DAS28 scores over time [Y = 4.51 + (–0.56 × year) + (0.44 × year2)]. Although unadjusted median HAQ scores increased over time, calendar year of presentation to NOAR was not significantly associated with HAQ scores [Y = (1.1) + (0.023 × year) + (0.05 × year2)]. Similar results were observed in each subpopulation of patients.Conclusion.While baseline disease activity has lessened slightly over time, there has been no improvement in baseline levels of functional disability.

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