Irreversible Physical Disability Research Articles

Bartonella henselae DNA detection in patients with type 1 leprosy reactions for more than six months

Leprosy reactions are among the main causes of physical disability resulting from an infectious disease and can culminate in irreversible physical disabilities, therefore they should be considered a clinical emergency, as well as the elucidation of its cause. Co-infections are considered one of the main triggering causes of leprosy reactions, aggravating and maintaining these reactions for longer in these patients. After reporting a high rate of Bartonella henselae infection in patients with chronic type 2 leprosy reaction, 19/47 (40.4 %) compared to the control group, 9/50 (18.0 %), p = 0.0149, we conducted this study to observe the rate of infection by Bartonella sp. in a group of patients with chronic type 1 leprosy reactions. Blood samples from 14 patients with chronic type 1 leprosy reactions were analyzed by molecular and microbiological tests and compared. The results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has a high proportion of B. henselae infection 6/14 (42.9 %), p = 0.88. We conclude that these bacteria can trigger chronic leprosy reactions and should be investigated in all chronic leprosy reactions patients.Summary Line: Our results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has the same proportion of B. henselae DNA detection 6/14 (42.9 %), p = 0.88.

Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments.

Rheumatoid arthritis (RA) is an inflammatory disease characterized by a variety of symptoms and pathologies often presenting with polyarthritis. The primary symptom in the initial stage is joint swelling due to synovitis. With disease progression, cartilage and bone are affected to cause joint deformities. Advanced osteoarticular destruction and deformation can cause irreversible physical disabilities. Physical disabilities not only deteriorate patients’ quality of life but also have substantial medical economic effects on society. Therefore, prevention of the progression of osteoarticular destruction and deformation is an important task. Recent studies have progressively improved our understanding of the molecular mechanism by which synovitis caused by immune disorders results in activation of osteoclasts; activated osteoclasts in turn cause bone destruction and para-articular osteoporosis. In this paper, we review the mechanisms of bone metabolism under physiological and RA conditions, and we describe the effects of therapeutic intervention against RA on bone.

Editorial introductions.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Massimo FilippiMassimo FilippiMassimo Filippi is currently Full Professor of Neurology at Vita-Salute San Raffaele University, Milan, Italy; Director of the Residency School in Neurology, and President of the Bacherlor's Degree in Physiotherapy at the same University. He is also Chair of the Neurology and Neurorehabilitation Units, Director of the MS Center, Director of the Neurophysiology Service, and Director of the Neuroimaging Research Unit at the IRCCS Scientific Institute San Raffaele, Milan. His research activity has always focused on the definition of the mechanisms leading to progressive accumulation of irreversible physical disability and cognitive impairment in various neurological conditions. He is member of various national and international Scientific Societies and Boards where he covered or is covering institutional roles. He is author of over 1200 papers, Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, and member of the Editorial Boards of many international scientific journals. He is very often requested as speaker and/or chairman in national and international neurological congresses. In 2001, Prof. Filippi was awarded the Rita Levi Montalcini Prize for his outstanding contributions to the study of MS. Per SvenningssonPer SvenningssonPer Svenningsson is Professor in Neurology at the Karolinska Institutet, Sweden. He received his MD and PhD from Karolinska Institutet in 1998. He then did his postdoctoral training in the laboratory of the Nobel laureate Paul Greengard at the Rockefeller University, USA, between 1999 and 2003. His studies concerned GPCR neuropharmacology and signal transduction and included the discovery of p11 as an important modulator of serotonin neurotransmission. He performed his residency in Neurology at Karolinska University Hospital and became Professor in 2012 and senior consultant in 2016. Since 2018, he is also part time Professor of Neurodegeneration at King's College London, UK. His research interests include GPCR pharmacology, Parkinson's disease both its motor and non-motor aspects and atypical parkinsonism. Studies are conducted both in preclinical models and in specimens from patients. The goal is to identify novel targets for improved diagnostics and pharmacological receptor-based treatments. Biochemical, histological, pharmacological, molecular biological and behavioral techniques are used. In the clinics, he is conducting clinical trials with therapies aiming to slow down progression of Parkinson's disease or to treat debilitating symptoms of the disease. He has published more than 300 articles. Since 2014, he is member of the Nobel Assembly annually awarding the Nobel Prize in Physiology or Medicine. He delivered the Eurolife Distinguished Medal Lecture in Barcelona in 2017 and was awarded the Arvid Carlsson Prize in 2020.

The sonographic identification of cortical bone interruptions in rheumatoid arthritis: a morphological approach.

Bone erosions are the hallmark of structural damage in rheumatoid arthritis (RA). Among imaging techniques, ultrasonography (US) has emerged as an accurate, reliable, repeatable, low-cost and non-invasive imaging modality to detect erosive changes in RA. However, small interruptions of the cortical bone detectable by last generation US equipment do not necessarily represent bone erosions. According to the available data, in addition to cortical bone interruption itself, only a few morphological US findings have been proposed to define RA bone erosions. However, other additional features may be considered to facilitate the interpretation of US cortical bone interruptions in RA. These could be summarised using the following four domains: size, site, shape and scenery. This hypothesis article provides a critical literature review of US features characteristic of RA bone erosions and pictorial evidence supporting the potential role of a morphological analysis in the US identification of bone erosions in RA patients.Plain language summary The ultrasonographic morphology of cortical interruptions is helpful for the identification of bone erosions in rheumatoid arthritis: the “four Ss” approach Bone erosions are characteristic features of rheumatoid arthritis. They are associated with a more aggressive disease and with irreversible physical disability. In recent years, ultrasonography has emerged as an accurate and reliable technique for the detection of bone erosions, that appear as interruptions of the cortical bone with variable size. However, cortical bone interruptions do not necessarily represent bone erosions. Since bone erosions represent the earliest evidence of the destructive behaviour of RA, their identification is crucial.Besides the cortical interruption itself, only a few morphological ultrasonographic features were proposed to characterise bone erosions in rheumatoid arthritis.We believe that a morphological approach, including size, site, shape and scenery, may be considered to facilitate the interpretation of ultrasonographic cortical bone interruptions in rheumatoid arthritis.In this hypothesis article we carried out a critical review of the scientific literature and provided extensive pictorial evidence of the ultrasonographic spectrum of cortical interruptions supporting the potential role of considering the “four Ss” for the ultrasonographic identification of bone erosions in rheumatoid arthritis.

Best Practices for Long-Term Monitoring and Follow-Up of Alemtuzumab-Treated MS Patients in Real-World Clinical Settings.

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in the absence of continuous treatment and with a consistent safety profile. There is an increased incidence of autoimmune events in patients treated with alemtuzumab (mainly thyroid events, but also immune thrombocytopenia and nephropathy), which imparts a need for mandatory safety monitoring for 4 years following the last treatment. The risk management strategy for alemtuzumab-treated patients includes laboratory monitoring and a comprehensive patient education and support program that enables early detection and effective management of autoimmune events, yielding optimal outcomes for MS patients. Here we provide an overview of tools and techniques that have been implemented in real-world clinical settings to reduce the burden of monitoring for both patients and healthcare providers, including customized educational materials, the use of social media, and interactive online databases for managing healthcare data. Many practices are also enhancing patient outreach efforts through coordination with specialized nursing services and ancillary caregivers. The best practice recommendations for safety monitoring described in this article, based on experiences in real-world clinical settings, may enable early detection and management of autoimmune events, and help with implementation of monitoring requirements while maximizing the benefits of alemtuzumab treatment for MS patients.

The effects of laser acupuncture on the modulation of cartilage extracellular matrix macromolecules in rats with adjuvant-induced arthritis.

ObjectivesArticular cartilage damage related to irreversible physical disability affects most patients with chronic rheumatoid arthritis (RA). Strategies targeting the preservation of cartilage function are needed. Laser acupuncture (LA) can be an emerging alternative therapy for RA; however, its molecular mechanism underlying the beneficial effect on cartilage has not been elucidated. This study aimed to examine the potential chondroprotective effects of LA on extracellular matrix (ECM) macromolecules and proinflammatory cytokines in the articular cartilage of adjuvant-induced arthritis (AIA) rats and explore its related mechanisms.DesignMonoarthritis was induced in adult male Sprague–Dawley rats (250–300 g) via intraarticular injection of complete Freund’s adjuvant (CFA) into the tibiotarsal joint. Animals were treated with LA at BL60 and KI3 acupoints three days after CFA administration with a 780 nm GaAlAs laser at 15 J/cm2 daily for ten days. The main outcome measures including paw circumference, paw withdrawal threshold, histopathology and immunoassays of tumor necrosis factor-α (TNF-α), collagen type II (CoII), cartilage oligomeric matrix protein (COMP) were analyzed.ResultsLA significantly reduced ankle edema and inflammation-induced hyperalgesia in AIA rats (P < 0.05). Moreover, the TNF-α levels were significantly decreased while CoII, COMP and proteoglycans proteins were significantly enhanced following LA stimulation of the AIA cartilage compared to those treated with sham-LA (P < 0.05).ConclusionsLA attenuates cartilage degradation in AIA rat by suppressing TNF-α activation and up-regulating ECM macromolecules, suggesting LA might be of potential clinical interest in RA treatment.

Ciąża, poród i połóg u kobiety po przebytym w dzieciństwie rozległym urazie miednicy oraz obustronnej wysokiej amputacji kończyn dolnych – opis przypadku

Wstęp: Celem pracy było przedstawienie przebiegu ciąż, porodów i połogu u 42-letniej pacjentki, która w dzieciństwie przebyła obustronną wysoką amputację kończyn dolnych, złamanie kości miednicy oraz uszkodzenie układu moczowo-płciowego.Opis przypadku: Pacjentka w 4. r.ż. uległa wypadkowi tramwajowemu, doznając zmiażdżenia obu kończyn dolnych oraz rozległego urazu krocza. Dokonano wówczas obustronnej amputacji ud w stawach biodrowych. Rozerwaną pochwę i odbytnicę zaopatrzono chirurgiczne, wytworzono sztuczny odbyt naokrężnicy esowatej. Po licznych operacjach rekonstrukcyjnych pacjentka mogła samoistnie oddawać mocz i stolec, kontrolując potrzeby fizjologiczne.Pierwsza ciąża powikłana była nadczynnością tarczycy. Ciążę ukończono drogą cięcia cesarskiego w 31. tyg. z powodu przedwczesnego pęknięcia błon płodowych po przeprowadzeniu sterydoterapii. Kolejna ciąża pacjentki powikłana była także nadczynnością tarczycy, okresową tachykardią oraz cukrzycą ciężarnych. W 32. tyg. zastosowano sterydoterapię. Ciążę zakończono w 36. tyg. drogą cięcia cesarskiego z powodu rozpoczynającego się porodu.U pacjentki nie stwierdzano zaburzeń neurologicznych, była w stanie prawidłowo ocenić aktywność ruchową płodu i ewentualną czynność skurczową macicy, co pozwoliło na ambulatoryjne prowadzenie obu ciąż. Przebyte operacje naprawcze w obrębie układu moczowego oraz dolnego odcinka przewodu pokarmowego stanowiły nie tylko istotny czynnik ryzyka powikłań porodu operacyjnego drogą cięcia cesarskiego, ale również, z uwagi na zmienioną anatomię i możliwą obecność rozległych zrostów, mogły wpłynąć na przebieg ciąży.

Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae

Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed.

THU0229 Association of Radiographic Damage with Physical Function in Patients with Rheumatoid Arthritis – Results from the RAPID1 Trial

BackgroundIn patients with rheumatoid arthritis (RA), joint damage can determine irreversible physical disability. The different types of joint structures affected can be evaluated separately on radiographs as erosions (E), joint...

AB1246 Reproducible metacarpal joint space thickness measurements using 3D analysis of images acquired with high-resolution peripheral quantitative computed tomography (HR-PQCT)

BackgroundJoint space narrowing from cartilage loss in RA is associated with irreversible physical disability (1). HR-pQCT, a novel instrument capable ofaccurately and reproducibly imaging bone microstructure at a nominal isotropic...

AB0308 Optimal timing for tocilizumab administration to patients with rheumatoid arthritis in japan based on a cost-effectiveness analysis using the iorra cohort study

BackgroundRheumatoid arthritis (RA) imposes a considerable economic burden on societies. Early, adequate control of disease activity can prevent permanent disability and decrease the overall costs of treatment. In clinical studies,...

Etanercept for the treatment of rheumatoid arthritis.

Etanercept is a soluble tumour necrosis factor alpha-receptor disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). The purpose of this review was to update the previous Cochrane systematic review published in 2003 assessing the benefits and harms of etanercept for the treatment of RA. In addition, we also evaluated the benefits and harms of etanercept plus DMARD compared with DMARD monotherapy in those people with RA who are partial responders to methotrexate (MTX) or any other traditional DMARD. Five electronic databases were searched from 1966 to February 2003 with no language restriction. The search was updated to January 2012. Attempts were made to identify other studies by contact with experts, searching reference lists and searching trial registers. All controlled trials (minimum 24 weeks' duration) comparing four possible combinations: 1) etanercept (10 mg or 25 mg twice weekly) plus a traditional DMARD (either MTX or sulphasalazine) versus a DMARD, 2) etanercept plus DMARD versus etanercept alone, 3) etanercept alone versus a DMARD or 4) etanercept versus placebo. Two review authors independently extracted data and assessed the risk of bias of the trials. Three trials were included in the original version of the review. An additional six trials, giving a total of 2842 participants, were added to the 2012 update of the review. The trials were generally of moderate to low risk of bias, the majority funded by pharmaceutical companies. Follow-up ranged from six months to 36 months.BenefitAt six to 36 months the American College of Rheumatology (ACR) 50 response rate was statistically significantly improved with etanercept plus DMARD treatment when compared with a DMARD in those people who had an inadequate response to any traditional DMARD (risk ratio (RR) 2.0; 95% confidence interval (CI) 1.3 to 2.9, absolute treatment benefit (ATB) 38%; 95% CI 13% to 59%) and in those people who were partial responders to MTX (RR 11.7; 95% CI 1.7 to 82.5, ATB 36%). Similar results were observed when pooling data from all participants (responders or not) (ACR 50 response rates at 24 months: RR 1.9; 95% CI 1.3 to 2.8, ATB 29%; 36 months: RR 1.6; 95% CI 1.3 to 1.9, ATB 24%). Statistically significant improvement in physical function and a higher proportion of disease remission were observed in combination-treated participants compared with DMARDs alone ((mean difference (MD) -0.36; 95% CI -0.43 to -0.28 in a 0-3 scale) and (RR 1.92; 95% CI 1.60 to 2.31), respectively) in those people who had an inadequate response to any traditional DMARD. All changes in radiographic scores were statistically significantly less with combination treatment (etanercept plus DMARD) compared with MTX alone for all participants (responders or not) (Total Sharp Score (TSS) (scale = 0 to 448): MD -2.2, 95% CI -3.0 to -1.4; Erosion Score (ES) (scale = 0 to 280): MD -1.6; 95% CI -2.4 to -0.9; Joint Space Narrowing Score (JSNS) (scale = 0 to 168): MD -0.7; 95% CI -1.1 to -0.2), and with combination treatment compared with etanercept alone (TSS: MD -1.1; 95% CI -1.8 to -0.5; ES: MD -0.7; 95% CI -1.1 to -0.2; JSNS: MD -0.5, 95% CI -0.7 to -0.2). The estimate of irreversible physical disability over 10 years given the radiographic findings was 0.45 out of 3.0.When etanercept monotherapy was compared with DMARD monotherapy, there was generally no evidence of a difference in ACR50 response rates when etanercept 10 mg or 25 mg was used; at six months etanercept 25 mg was significantly more likely to achieve ACR50 than DMARD monotherapy but this difference was not found at 12, 24 or 36 months. TSS and ES radiographic scores were statistically significantly improved with etanercept 25 mg monotherapy compared with DMARD (TSS: MD -0.7; 95% CI -1.4 to 0.1; ES: MD -0.7; 95% CI -1.0 to -0.3) but there was no evidence of a statistically significant difference between etanercept 10 mg monotherapy and MTX.HarmsThere was no evidence of statistically significant differences in infections or serious infections between etanercept plus DMARD and DMARD alone at any point in time. Infection rates were higher in people receiving etanercept monotherapy compared with DMARD; however, there were no differences regarding serious infections. For those participants who had an inadequate response to DMARDs, the rate of total withdrawals was lower for the etanercept plus DMARD group compared with DMARD alone (RR 0.53; 95% CI 0.36 to 0.77, ATB 18%). No other statistically significant differences were observed in any of the assessed comparisons. Etanercept 25 mg administered subcutaneously twice weekly together with MTX was more efficacious than either etanercept or MTX monotherapy for ACR50 and it slowed joint radiographic progression after up to three years of treatment for all participants (responders or not). There was no evidence of a difference in the rates of infections between groups.

Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction

BackgroundJoint destruction in rheumatoid arthritis is comprised of cartilage and bone damage, which can be evaluated radiographically separately by the joint space narrowing (JSN) and erosion (ERO) scores. It is...

Guidelines for the diagnosis and treatment of schistosomal myeloradiculopathy

Schistosomal myeloradiculopathy is the most severe and disabling ectopic form of Schistosoma mansoni infection. The prevalence of SMR in centres in Brazil and Africa that specialise in attending patients with non traumatic myelopathy is around 5%. The initial signs and symptoms of the disease include lumbar and/or lower limb pain, paraparesis, urinary and intestinal dysfunctions, and impotence in men. The cerebrospinal fluid of SMR patients shows an increase in protein concentration and in the number of mononuclear cells in 90% of cases; eosinophils have been reported in 40%. The use of magnetic resonance imaging is particularly valuable in the diagnosis of Schistosomal myeloradiculopathy. The exclusion of other myelopathies and systemic diseases remains mandatory. Early diagnosis and treatment with steroids and schistosomicides provide a cure for most patients, whilst delayed treatment can result in irreversible physical disabilities or death. To improve awareness concerning Schistosomal myeloradiculopathy amongst public health professionals, and to facilitate the control of the disease, the Brazilian Ministry of Health has launched a program of education and control of this ectopic form of schistosomiasis. The present paper reviews current methods for the diagnosis of SMR and outlines protocols for treatment of the disease.

Impact on the quality of life of patients with arteriovenous malformations during the latent interval between gamma knife radiosurgery and lesion obliteration

Object. The aim of this study was to measure the quality of life (QOL) in patients with cerebral arteriovenous malformations (AVMs) receiving gamma knife treatment before total AVM obliteration. Quality of life was assessed as it related to the knowledge of rebleeding risk during the waiting period, AVM symptoms, and previous bleeding. Methods. Thirty-nine patients age 18 years or older without other medical problems were asked to complete a questionnaire that included demographic variables, immediate effect of gamma knife radiosurgery, symptoms of AVM, previous hemorrhage, and the Duke—University of North Carolina Health Profile (63 items). Conclusions. The QOL of patients with cerebral AVM during the waiting period after undergoing gamma knife treatment was affected by irreversible physical disabilities rather than the knowledge of hemorrhage risk and bleeding experience.