Distinct regional brain atrophy pattern in multiple sclerosis and neuropsychiatric systemic lupus erythematosus patients.

Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients.

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation.

The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-ß1, IFN-γ and TLR3 genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-ß1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-ß1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.

Lung impairment in scleroderma.

Scleroderma typically manifests as fibrosis of the skin, but may also involve other organs, particularly the lungs. Interstitial lung disease and functional abnormalities are observed in the majority of patients. The aim of this study was to evaluate radiological changes in the lungs and their correlation with functional disorders in scleroderma patients. The study was conducted in 37 scleroderma patients (F/M-31/6). High resolution computed tomography (HRCT), Warrick score system and spirometry, body plethysmography, and lung diffusion examinations (DLco) were performed. The HRCT showed septal and subpleural lines in 70%, ground-glass opacities in 51%, and honeycomb lungs in 30% of the cases. The DLco values were decreased in 92% of the patients. Total lung capacity (TLC) showed a restrictive pattern in 24% of the patients, and only in 11% of them obstruction predominated. The Warrick score correlated inversely with both DLco (r=0.36; p>0.05). Interstitial lung disease often coexists with scleroderma and is accompanied by functional lung abnormalities.

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

A review on irisin, a new protagonist that mediates muscle-adipose-bone-neuron connectivity.

Physical activity improves the quality of life and decreases the risk of several diseases (i.e. stroke, hypertension, myocardial infarction, obesity, and malignancies). Skeletal muscles are considered as an endocrine organ that produces myokines characterized by a paracrine or endocrine activity. Irisin is a circulating hormone-like myokine and is secreted as a product of fibronectin type III domain-containing protein 5 from skeletal muscle in response to exercise. This molecule regulates the energy metabolism and acts in adipose tissue, bones, and nervous system. As both animal and clinical studies confirmed the action of irisin in muscle and adipocytes, this protein is considered as adipomyokine. In adipose tissue, irisin stimulates the process of browning of beige precursor fat cells, which are present in white fat cells, and promotes energy expenditure. It affects bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation. In the nervous system, irisin influences hippocampal neurogenesis and neural differentiation of embryonic stem cells in mice and is considered as a messenger between exercise and brain function. However, the existence of this protein and its role in humans is a matter of debate. This study presents irisin as a new champion of the molecule, which could be considered as the messenger in the muscle-fat-bone-brain axis.

Neurological, otolaryngological and ophthalmological implications of Susac syndrome - a case report.

Susac syndrome is an endotheliopathy affecting the arterioles of the brain, retina, and inner ear. Many cases of Susac syndrome are underdiagnosed, mainly at the early stages of the disease, while prompt diagnosis enables a speedy recovery. Immediate treatment can halt disease progression and even prevent future disability. We report a case of Susac syndrome, describe the difficulties in the diagnosis of this case, and include a detailed history of a 35-year-old man via the presentation of extensive laboratory work-up and imaging studies. Audiometry showed sensorineural hearing loss of about 75 dB in the left ear. Ovoid lesions of the corpus callosum in magnetic resonance (MR) were present as were advanced binocular ophthalmological changes in fluorescent angiography. Methylprednisolone with acetylsalicylic acid and intravenous immunoglobulin (IVIG) were implemented with a positive outcome (clinical and audiometric improvement).

The efficacy of submucosal corticosteroid injection and dilatation in subglottic stenosis of different aetiology.

OBJECTIVE: To determine the long-term efficacy of submucosal corticosteroid injection plus dilatation for subglottic stenosis as a single modality treatment in granulomatosis with polyangiitis and relapsing polychondritis, as compared with idiopathic subglottic stenosis and traumatic subglottic stenosis. METHOD: Patients who underwent dilatation for autoimmune causes were identified. Corticosteroid injection into the submucosa of a stenotic segment was followed by serial dilatation. Definitive improvement was defined as good airway patency for more than 24 months with no further procedures needed. Clinical, demographic and procedural data were recorded. RESULTS: Patients (n = 45) were divided into three subglottic stenosis groups: traumatic (n = 24), idiopathic (n = 9) and autoimmune (n = 12). Patients were treated with dilatations, with a median follow-up time of 76 months. Six patients were tracheostomy-dependent. There were no statistical differences in the number of final improvements between autoimmune, idiopathic and traumatic groups, with values of 75, 56 and 71 per cent, respectively. There was no statistical difference between granulomatosis with polyangiitis plus relapsing polychondritis and idiopathic subglottic stenosis in terms of decannulation rates. CONCLUSION: Granulomatosis with polyangiitis and relapsing polychondritis patients have better improvement rates than patients with other subglottic stenosis types.

Granulomatosis with polyangiitis in pregnancy - clinical implications and treatment possibilities.

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which has a variable clinical presentation and usually progresses from a localized to a generalized form over the course of weeks to years. Histopathologically, it is a necrotizing systematic vasculitis that can cause sino-nasal, pulmonary, renal, ocular, and cutaneous manifestations. Diagnostic workup should include serologic, radiologic, endoscopic and histopathological examination. Autoantibody c-ANCA may be used as a marker of disease activity and individual follow-up. An appropriate local and systemic treatment should be implemented, which is particularly important in pregnancy. Comprehensive management should be planned, including the needs of both mother and fetus (particularly if vasculitis is diagnosed de novo during pregnancy). Pregnancy in patients with GPA is burdened with the risk of possible complications and increased mortality and the conception should be delayed until remission of the disease. A flare-up of GPA may be life threatening for both mother and fetus. The immunosuppressants, which are used during pregnancy include glucocorticosteroids (GCS) and azathioprine. Studies of GPA in pregnancy are scarce, and this calls for individualized management. Thus, the approach to care for pregnant women with GPA is interdisciplinary, and firmly places the rheumatologist, gynecologist, pulmonologist, otorhinolaryngologist and nephrologist on the management team.

Susac syndrome--clinical insight and strategies of therapy.

Susac syndrome is an uncommon autoimmune microangiopathy characterized mainly by neurological disorders and, to date, 304 clinical cases have been described. The background of this syndrome is an immune-mediated endotheliopathy that affects the microvasculature of the brain, retina, and inner ear resulting in encephalopathy, hearing loss, and branch retinal artery occlusions. However, the cause and the pathogenesis of this microangiopathy remain unclear. Magnetic resonance imaging, retinal fluorescein angiography, and audiography findings enable the diagnosis of this syndrome. In this review, we have demonstrated the epidemiology and pathology of Susac syndrome with detailed description of clinical signs, diagnostic procedures and therapeutic possibilities.