神经领域-神经系统自身免疫性疾病方向

METHODS:AIMS:Dendritic cells (DCs) actively participate in the pathogenesis of multiple sclerosis (MS), an autoimmune disease. Astragaloside IV (ASI), an active monomer isolated from the Chinese medicine Astragalus membranaceus, has a wide range of pharmacological effects. We aimed to elucidate the effects of ASI on the development of DCs in the early stage of MS/EAE. MAIN METHODS:The mice were administered with ASI (20 mg/kg) daily 3 days in advance of EAE induction and continuously until day 7 post-immunization. The effect of ASI on CD11c+ DC cells from bone marrow (BMDCs) or the spleen of EAE mice at day 7 post-immunization were investigated respectively by flow cytometry, ELISA, western blot, real-time PCR and immunofluorescence. KEY FINDINGS:ASI administration in the early stage of EAE was demonstrated to delay the onset and alleviate the severity of the disease. ASI inhibited the maturation and the antigen presentation of DCs in spleen of EAE mice and LPS-stimulated BMDCs, as evidenced by decreased expressions of CD11c, CD86, CD40 and MHC II. Accordingly, DCs treated by ASI secreted less IL-6 and IL-12, and prevented the differentiation of CD4+ T cells into Th1 and Th17 cells, which was probably through inhibiting the activation of NFκB and MAPKs signaling pathways. SIGNIFICANCE:Our results implicated the alleviative effect of early ASI administration on EAE might be mediated by suppressing the maturation and function of DCs. The novel findings may add to our knowledge of ASI in the potentially clinical treatment of MS.

METHODS:BACKGROUND:Cryptosporidium sp. are common intracellular parasites responsible of severe diarrhea in T-cell-immunocompromised patients. We report the first case of a woman who contracted cryptosporidiosis after treatment with fingolimod, a drug labeled for multiple sclerosis and responsible for marked lymphopenia. CASE PRESENTATION:A 60-year-old woman was admitted for abdominal pain diarrhea and fever. The patient suffered from multiple sclerosis and had been treated with fingolimod from august 2017 to september 2018 time of occurrence of the first digestive symptoms. Stool culture was negative but parasitological examination was positive for Cryptosporidium sp. Blood biological examination profound lymphopenia of 240/mm3 [17 CD4/mm3 (7%) and 32 CD8/mm3 (14%)]. Fingolimod was stopped, and the patient was put on nitazoxanide 500 mg bid for 7 days. The diarrhea resolved and no relapse was observed. Six other cases were found in the Pharmacovigilance database. CONCLUSION:Physicians should be aware of this association and screen for Cryptosporidium in cases of diarrhea in patients treated with fingolimod. Patients should be aware of this risk and advise to take appropriate measures to avoid such contamination.

METHODS:AIMS:Multiple sclerosis (MS) whose pathogenesis is still unclear is a chronic progressive disease in the central nervous system. Gut microbiota can directly or indirectly affect the immune system through the brain gut axis to engage in the occurrence and development of the disease. MATERIALS AND METHODS:C57BL/6 mice which were immunized by MOG35-55 to prepare experimental autoimmune encephalomyelitis (EAE) animal models were treated with rapamycin and MCC950 (CP-456773) in combination or separately. After sequencing the 16S rRNA V4 region of gut microbiota, the species, abundance and composition of gut microbiota were analyzed by Alpha diversity, Bata diversity and LEfSe analysis. The pathological changes and the expression of CD4 and CD8 of brain, large intestine and spleen were detected. KEY FINDINGS:The results showed that rapamycin and MCC950 could alleviate the progression of the disease by inducing autophagy and inhibiting the immune response. The Alpha diversity of EAE model group was no significant difference compering to control group while the number of OTUs was decreased. After the treatment by rapamycin and MCC950, the abundance and composition of gut microbiota was relatively recovered, which was close to that of normal mice. SIGNIFICANCE:Inhibiting immune cell-mediated inflammation and restoring the composition of gut microbiota may help to alleviate the clinical symptoms of multiple sclerosis. Furthermore, to research the regulatory effect between immune response and gut microbiota may be a new strategy for the prevention and treatment of multiple sclerosis.

METHODS::Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F = .84, d = .65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p < .001), bilateral frontal (both p < .001), and right insula (F = 21.8, p = .002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = -.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS.

METHODS:AIM:To evaluate fatigue, depression, and quality of life (QoL) of children with multiple sclerosis and compare to other acute demyelinating syndromes (ADS). METHOD:Children followed in the National Referral Centre of rare inflammatory brain and spinal diseases were included in this study. The Expanded Disability Status Scale, the fatigue severity scale, the Multiscore Depression Inventory for Children, and the Pediatric Quality of Life Inventory were used for evaluation. RESULTS:Thirty-seven children (23 females, 14 males) were included in this study. Multiple sclerosis was diagnosed in 26 children and ADS in 11 children. Although not significant, severe fatigue was less frequently reported by patients with multiple sclerosis than children with ADS (44% vs 63%, p=0.2). Depression was reported more often in the multiple sclerosis group compared to the ADS group (24% vs 18%, p=0.6). Concerning the QoL in patients with multiple sclerosis, both parents and children reported poor emotional and school functioning. Physical and social functioning were rated as being good in both groups, and was significantly higher in the children's group (p=0.007). INTERPRETATION:This study highlights the importance of fatigue and depression in children with ADS and particularly in paediatric onset multiple sclerosis. Moreover, difficulties in school and emotional functioning were the main concerns for parents and children in the multiple sclerosis group which need to be taken in account during their care and treatment proposal. WHAT THIS PAPER ADDS:Invisible signs such as fatigue and depression affect all forms of acute demyelinating syndromes (ADS) in children. Depression seems to be higher in children with multiple sclerosis than with other forms of ADS. Fatigue seems to be lower in children with multiple sclerosis than with other forms of ADS. Children with multiple sclerosis and their parents are most concerned with emotional and academic functioning. :FATIGA, DEPRESIÓN Y CALIDAD DE VIDA EN NIÑOS CON ESCLEROSIS MÚLTIPLE: UN ESTUDIO COMPARATIVO CON OTRAS ENFERMEDADES DESMIELINIZANTES: OBJETIVO: evaluar fatiga, depresión y calidad de vida (CDV) de niños con esclerosis múltiple y comparar con otros síndromes desmielinizantes agudos (SDA). METODO: Se incluyeron en el estudio los niños seguidos en el centro de referencia de enfermedades espinales y cerebrales inflamatorias raras. Se usaron para la evaluación la Escala de Estado de Discapacidad Expandida, la escala de severidad de fatiga, el inventario de puntaje múltiple de depresión para niños, y el inventario de calidad de vida pediátrico. RESULTADOS: Se incluyeron en este estudio 37 niños (23 niñas, 14 niños). Se diagnosticó esclerosis múltiple en 26 niños y SDA en 11 niños. Aunque no fue significativo, la fatiga se reportó en menor frecuencia en pacientes con esclerosis múltiple que en niños con SDA (44% vs 63%, p=0,2). Se reporto con más frecuencia depresión en el grupo de esclerosis múltiple en comparación con el grupo de SDA (24% vs 18%, p=0,6). En lo que concierne a la calidad de vida en pacientes con esclerosis múltiple, tanto los padres como los niños reportaron funciones emocionales y escolares disminuidas. Las funciones físicas y sociales fueron puntuadas como buenas en ambos grupos, y fue significativamente más alta en el grupo de los niños. (p=0,007). INTERPRETACION: este estudio resalta la importancia de la fatiga y la depresión en niños con SDA y particularmente con el inicio infantil de esclerosis múltiple. Además, las dificultades en la escuela y el funcionamiento emocional fueron las principales preocupaciones de los padres y los niños en el grupo de esclerosis múltiple que deben tenerse en cuenta durante el planeamiento de atención de la salud y tratamiento. :FADIGA, DEPRESSÃO E QUALIDADE DE VIDA EM CRIANÇAS COM ESCLEROSE MÚLTIPLA: UM ESTUDO COMPARATIVO COM OUTRAS DOENÇAS DESMIELINIZANTES: OBJETIVO: Avaliar fadiga, depressão e qualidade de vida (QV) de crianças com esclerose múltipla, e comparar com outras síndromes desmielinizantes agudas (SDA). MÉTODO: Crianças acompanhadas em um centro de referência nacional de doenças inflamatórias cerebrais e espinhais raras foram incluídas no estudo. A Escala Expandidade de Estado da Deficiência, a escala de severidade da fadiga, o Inventário multiescore de depressão para crianças, e o Inventário Pediátrico de Qualidade de Vida foram usados na avaliação. RESULTADOS: Trinta e sete crianças (23 do sexo feminino, 14 do sexo masculino) foram incluídas neste estudo. A esclerose múltipla foi diagnosticada em 26 crianças e SDA em 11 crianças. Embora não significativa, a fadiga severa foi menos frequentemente reportada por pacientes com esclerose múltipla do que em crianças com SDA (44% vs 63%, p=0,2). A depressão foi reportada mais frequentemente no grupo com esclerose múltipla comparado ao grupo com SDA. (24% vs 18%, p=0,6). Com relação à QV em pacientes com esclerose múltipla, pais e crianças reportaram pobre funcionamento emocional e escolar. O funcionamento físico e social foram pontuados como bons em ambos os grupos, sendo significativamente maior no grupo de crianças (p=0,007). INTERPRETAÇÃO: Este estudo destaca a importância da fadiga e depressão em crianças com SDA e particularmente nos casos de esclerose múltipla de início pediátrico. Além disso, dificuldades no funcionamento escolar e emocional foram as principais preocupações dos pais e crianças no grupo com esclerose múltipla, o que deve ser levado em conta durante a proposta de cuidado e tratamento.

METHODS:PURPOSE:The aim of the study was to assess dual-task cost to spatio-temporal gait parameters in people with multiple sclerosis and a matched control group. METHOD:The multiple sclerosis group was composed of 17 participants with a diagnosis of multiple sclerosis and an Expanded Disability Status Scale score of less than 6. A total of 17 healthy participants were allocated to the control group by stratification. Controls were matched on the basis of age, sex, sociocultural habits, and body structure. Dual-task cost was determined by within-group repeated-measures analysis of variance. Participants were instructed to ambulate under normal conditions and perform a discrimination and decision-making task concurrently. Then, between-group analysis of variance was used to assess differences in mean dual-task cost between groups and determine dual-task cost differential. Testing was performed using three-dimensional photogrammetry and an electronic walkway. RESULTS:Based on dual-task cost differential, gait cycle time increase (-5.8%) and gait speed decrease (6.3%) because of multiple sclerosis-induced impairment. CONCLUSIONS:During single- and dual-task conditions, gait speed was lower in multiple sclerosis participants, because of a shorter step length and increased swing time. Increased gait time might be the result of compensatory mechanisms adopted to maintain stability while walking specially during the double-support phases.

METHODS:OBJECTIVE:The aims of the study were to compare mobility in multiple sclerosis, Parkinson disease, and stroke, and to quantify the relationship between mobility and participation restrictions. DESIGN:This is a multicenter cross-sectional study. Included were compliant subjects with Parkinson disease, multiple sclerosis, and stroke seen for rehabilitation, with no comorbidities interfering with mobility. Functional scales were applied to each subject to investigate gait speed (10-meter walking test), balance while maintaining body position (Berg Balance Scale), dynamic balance and mobility (Timed Up and Go and Dynamic Gait Index), and participation (Community Integration Questionnaire). RESULTS:Two hundred ninety-nine patients (111 multiple sclerosis, 94 Parkinson disease, and 94 stroke) were enrolled. Stroke had the slowest gait speed (mean gait speed = 0.9 m/sec) compared with Parkinson disease (1.1 m/sec), and multiple sclerosis (1.2 m/sec) (P < 0.001). Multiple sclerosis was more limited than Parkinson disease and stroke in dynamic balance both in the Timed Up and Go Test (multiple sclerosis = 16.7 secs, Parkinson disease = 11.4 secs, stroke = 14.0 secs; P < 0.001) and Dynamic Gait Index (multiple sclerosis = 11.6 points, Parkinson disease = 12.9 points, stroke = 13.6 points; P = 0.03); ability to maintain balance and body position (Berg Balance Scale) was more affected in stroke and Parkinson disease than multiple sclerosis (multiple sclerosis = 42.6 points, Parkinson disease = 39.4 points, stroke = 39.7 points; P = 0.03). Balance disorders were associated with participation restrictions but not gait speed. CONCLUSIONS:Neurological conditions have differing impacts on gait and balance, leading to different levels of participation restriction.

METHODS::Checkpoint inhibition has become an important target in the management of malignant melanoma. As anti-CTLA4 inhibitors and anti-PD1 antibodies are increasingly utilized, reports of immune-related adverse events (IRAEs) are becoming more frequent. Common noted cutaneous IRAEs are morbilliform, lichenoid, bullous, granulomatous, psoriasiform, and eczematous eruptions. We report a case of interstitial granulomatous dermatitis and granulomatous arteritis in the setting of nivolumab (anti-PD1) monotherapy for metastatic melanoma. There are many different causes for granulomatous vasculitis, such as herpes virus infection, lymphoproliferative disorders, systemic vasculitis, and inflammatory bowel disease. This report adds to the growing literature on granulomatous IRAEs due to checkpoint inhibition.

METHODS::Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413-420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77-84, 2019. © 2019 Wiley Periodicals, Inc.

METHODS:BACKGROUND:Although nursing intervention studies typically focus on testing hypothesized differences between intervention and control groups, moderator variables can reveal for whom or under what circumstances an intervention may be most effective. OBJECTIVES:The aim of the study was to explain and illustrate moderator effects using data from a nursing intervention study to improve cognitive abilities in those with a chronic health condition. METHODS:The sample consisted of 178 individuals with multiple sclerosis participating in an experimental study of a cognitive intervention. General linear models were used for analyses. Interaction terms were created to represent moderator effects on three outcomes: self-reported cognitive abilities, use of memory strategies, and verbal memory performance. RESULTS:The Charlson comorbidity index significantly moderated the intervention effect on self-perceived cognitive abilities. Years of education significantly moderated the intervention effect on use of memory strategies. Scores on a general self-efficacy measure significantly moderated the intervention effect on the Controlled Verbal Learning Test-Second Edition. DISCUSSION:These analyses highlight the key role that moderator effects can play in nursing research. Although random assignment to groups can control potentially biasing effects of extraneous differences among individuals in intervention and control groups, those very differences may suggest fruitful avenues for hypothesis generating research about what works best for whom in intervention studies.