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Objective There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. Methods From the multicentre retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. Results Two hundred patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (odds ratio [OR] 2.90; 95% CI: 1.25, 7.10; P  = 0.01) and more often presented with seizures (OR 8.31; 95% CI: 2.77, 33.04; P  < 0.001) or cognitive impairment (OR 2.58; 95% CI: 1.11, 6.10; P  = 0.03). On imaging, biopsy positive patients more often had non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80; 95% CI: 15.72, 233.06; P  < 0.001) or ≥1 cerebral microbleed (OR 8.08; 95% CI: 3.03, 25.13; P  < 0.001), and less often had ≥1 acute brain infarct (OR 0.02; 95% CI: 0.004, 0.08; P  < 0.001). In the multivariable model, non-ischaemic parenchymal or leptomeningeal gadolinium enhancement (adjusted OR 8.27; 95% CI: 1.78, 38.46; P  < 0.01) and absence of ≥1 acute brain infarct (adjusted OR 0.13; 95% CI: 0.03, 0.65; P  = 0.01) were significantly associated with a positive biopsy. Conclusion Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS. [ABSTRACT FROM AUTHOR]

Background: Nonreversible hearing loss (HL) is the main sequelae of Susac syndrome (SuS). We aimed to identify risk factors for HL in SuS. Methods: The CARESS study is a prospective national cohort study that started in December 2011, including all consecutive patients with SuS referred to the French reference center. The CARESS study was designed with a follow‐up including fundoscopy, audiometry, and brain magnetic resonance imaging at 1, 3, 6, and 12 months after diagnosis and then annually for 5 years. The primary outcome was the occurrence at last follow‐up of severe HL defined as the loss of 70 dB in at least one ear on audiometry or the need for hearing aids. Results: Thirty‐six patients (female 66.7%, median age 37.5 [range 24.5–42.5] years) included in the clinical study were analyzed for the primary outcome. Thirty‐three patients (91.7%) had cochleovestibular involvement at SuS diagnosis including HL >20 dB in at least one ear in 25 cases. At diagnosis, 32 (88.9%), 11 (30.6%), and 7 (19.4%) patients had received steroids, intravenous immunoglobulin, and/or immunosuppressive (IS) drugs, respectively. After a median follow‐up of 51.8 [range 29.2–77.6] months, 19 patients (52.8%) experienced severe HL that occurred a median of 13 [range 1.5–29.5] months after diagnosis. Multivariable analysis showed that the odds of severe HL were lower in patients who received IS drugs at diagnosis (OR 0.15, 95% CI 0.01–1.07, p = 0.058). Conclusions: Severe HL in SuS is associated with the absence of IS drugs given at diagnosis. Our findings support the systematic use of IS drugs in SuS. [ABSTRACT FROM AUTHOR]

Grassland represents more than half of the agricultural land. Numerous metrics (biomass, functional trait, species composition) can be used to describe grassland vegetation and its multiple functions. The measures of these metrics are generally destructive and laborious. Indirect measurements using optical tools are a possible alternative. Some tools have high spatial resolutions (digital camera), and others have high spectral resolutions (Near Infrared Spectrometry NIRS). A plenoptic camera is a multifocal camera that produces clear images at different depths in an image. The objective of this study was to test the interest of combining plenoptic images and NIRS data to characterize different descriptors of two Mediterranean legumes mixtures. On these mixtures, we measured biomass, species biomass, and functional trait diversity. NIRS and plenoptic images were acquired just before the field measurements. The plenoptic images were analyzed using Trainable Weka Segmentation ImageJ to evaluate the percentage of each species in the image. We calculated the average and standard deviation of the different colors (red, green, blue reflectance) in the image. We assessed the percentage of explanation of outputs of the images and NIRS analyses using variance partition and partial least squares. The biomass Trifolium michelianum and Vicia sativa were predicted with more than 50% variability explained. For the other descriptors, the variability explained was lower but nevertheless significant. The percentage variance explained was nevertheless quite low, and further work is required to produce a useable tool, but this work already demonstrates the interest in combining image analysis and NIRS. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of tumour necrosis factor-α (TNF-α) inhibitors used as steroid-sparing monotherapy in central nervous system (CNS) parenchymal sarcoidosis.Methods: The French Multiple Sclerosis and Neuroinflammation Centers retrospectively identified patients with definite or probable CNS sarcoidosis treated with TNF-α inhibitors as steroid-sparing monotherapy. Only patients with CNS parenchymal involvement demonstrated by MRI and imaging follow-up were included. The primary outcome was the minimum dose of steroids reached that was not associated with clinical or imaging worsening during a minimum of 3 months after dosing change.Results: Of the identified 38 patients with CNS sarcoidosis treated with TNF-α inhibitors, 23 fulfilled all criteria (13 females). Treatments were infliximab (n=22) or adalimumab (n=1) for a median (IQR) of 24 (17-40) months. At treatment initiation, the mean (SD) age was 41.5 (10.5) years and median (IQR) disease duration 22 (14-49.5) months. Overall, 60% of patients received other immunosuppressive agents before a TNF-α inhibitor. The mean (SD) minimum dose of steroids was 31.5 (33) mg before TNF-α inhibitor initiation and 6.5 (5.5) mg after (p=0.001). In all, 65% of patients achieved steroids dosing <6 mg/day; 61% showed clinical improvement, 30% stability and 9% disease worsening. Imaging revealed improvement in 74% of patients and stability in 26%.Conclusion: TNF-α inhibitors can greatly reduce steroids dosing in patients with CNS parenchymal sarcoidosis, even refractory.Classification Of Evidence: This study provides Class IV evidence that TNF-α inhibitor used as steroid-sparing monotherapy is effective for patients with CNS parenchymal sarcoidosis. [ABSTRACT FROM AUTHOR]

Objective RA is a progressive, chronic autoimmune disease. We summarize the impact of disease activity as measured by the DAS in 28 joints (DAS28-CRP scores) and pain on productivity and ability to work using the Work Productivity and Activity Impairment questionnaire (WPAI) scores, in addition to the impact of disease duration on the ability to work. Methods Data were drawn from the Burden of RA across Europe: a Socioeconomic Survey (BRASS), a European cross-sectional study in RA. Analyses explored associations between DAS28-CRP score and disease duration with stopping work because of RA, and regression analyses assessed impacts of pain and DAS28-CRP on early retirement and WPAI. Results Four hundred and seventy-six RA specialist clinicians provided information on 4079 adults with RA, of whom 2087 completed the patient survey. Severe disease activity was associated with higher rates of stopping work or early retirement attributable to RA (21%) vs moderate/mild disease (7%) or remission (8%). Work impairment was higher in severe (67%) or moderate RA (45%) compared with low disease activity [LDA (37%)] or remission (28%). Moreover, patients with severe (60%) or moderate pain (48%) experienced increased work impairment [mild (34%) or no pain (19%)]. Moderate to severe pain is significant in patients with LDA (35%) or remission (22%). A statistically significant association was found between severity, duration and pain vs work impairment, and between disease duration vs early retirement. Conclusion Results demonstrate the high burden of RA. Furthermore, subjective domains, such as pain, could be as important as objective measures of RA activity in affecting the ability to work. [ABSTRACT FROM AUTHOR]

Purpose The DAWN trial (Diffusion weighted imaging or CT perfusion assessment with clinical mismatch in the triage of Wake-up and late presenting strokes undergoing neurointervention with Trevo) has demonstrated the benefits of thrombectomy in patients with unknown or late onset strokes, using automated software (RAPID) for measurement of infarct volume. Because RAPID is not available in all centers, we aimed to assess the accuracy and repeatability of visual infarct volume estimation by clinicians and the consequences for thrombectomy decisions based on the DAWN criteria. Materials and Methods 18 physicians, who routinely depend on MRI for acute stroke imaging, assessed 32 Mr scans selected from a prospective databaseover two independent sessions. Raters were asked to visually estimate the diffusion weighted imaging (DWI) infarct volume for each case. Sensitivity, specificity, and accuracy of the estimated volumes were compared with the available RAPID measurements for various volume cut-off points. Thrombectomy decisions based on DAWN criteria with RAPID measurements and raters' visual estimates were compared. Inter-rater and intra-rater agreement was measured using kappa statistics. Results The mean accuracy of raters was <90% for all volume cut-points. Inter-rater agreement was below substantial for each DWI infarct volume cut-off points. intra-rater agreement was substantial for 55--83% of raters, depending on the selected cut-off points. Applying DAWN criteria with visual estimates instead of RAPID measurements led to 19% erroneous thrombectomy decisions, and showed a lack of reproducibility. Conclusion The visual assessment of DWI infarct volume lacks accuracy and repeatability, and could lead to a significant number of erroneous decisions when applying the DAWN criteria. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) corresponds to the deposition of amyloid material in the cerebral vasculature, leading to structural modifications of blood vessel walls. The most frequent form of sporadic CAA involves fibrillar β-amyloid peptide (Aβ) deposits, mainly the 40 amino acid form (Aβ1−40), which are commonly found in the elderly with or without Alzheimer's disease. Sporadic CAA usually remains clinically silent. However, in some cases, acute complications either hemorrhagic or inflammatory can occur. Similar complications occurred after active or passive immunization against Aβ in experimental animal models exhibiting CAA, and in subjects with Alzheimer's disease during clinical trials. The triggering of these adverse events by active immunization and monoclonal antibody administration in CAA-bearing individuals suggests that analogous mechanisms could be involved during spontaneous CAA complications, drawing particular attention to the role of anti-Aβ antibodies. However, antibodies that react with several monomeric and aggregated forms of Aβ spontaneously occur in virtually all human individuals, hence being part of the "natural antibody" repertoire. Natural antibodies are usually described as having low-affinity and high cross-reactivity toward microbial components and autoantigens. Although frequently of the IgM class, they also belong to IgG and IgA isotypes. They likely display homeostatic functions and protective roles in aging. Until recently, the peculiar properties of these natural antibodies have hindered proper analysis of the Aβ-reactive antibody repertoire and the study of their implication in CAA complications. Herein, we review and comment the evidences of an auto-immune nature of spontaneous CAA complications, and discuss implications for forthcoming research and clinical practice. [ABSTRACT FROM AUTHOR]

This French multicenter retrospective cohort study aimed to describe the autoimmune manifestations (AIMs) associated with lymphoma among patients hospitalized between 2005 and 2016 in three French University Hospitals. Among 2503 patients with lymphoma, 108 (4.3%) had AIMs, mostly autoimmune cytopenias (71.3%), neurological diseases (10.2%), kidney diseases (6.5%), systemic vasculitis (5.6%) and others. As compared with the 2395 lymphoma patients without AIMs, those with AIMs were older (p = .01), more frequently had B-cell chronic lymphocytic leukemia (p < .01) and less frequently diffuse large B-cell lymphomas (p = .01) and Hodgkin lymphoma (p = .01). The 5-year overall survival with lymphoma was 65% and 79% (p = .03) with and without AIMs. This large cohort study shows that various types of AIMs, mostly cytopenias, could be associated with lymphoma and affect the overall outcome with lymphoma, in particular for B-cell non-Hodgkin lymphoma (p = .01) and T-cell non-Hodgkin lymphoma (p = .01), with no survival difference noted for other types of lymphoma (p = .2). [ABSTRACT FROM AUTHOR]

Objectives: A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia).Research Design and Methods: Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up.Main Outcome Measures: Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications.Results: A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support.Conclusions: The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA.Limitation: The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and diseases difficult. [ABSTRACT FROM AUTHOR]

Background Steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is characterized by encephalopathy and the presence of antithyroid antibodies. We describe the clinical presentation, outcome and treatments for SREAT by a systematic review of the literature. Methods MEDLINE via PubMed, Web of Science and the Cochrane Library were searched for articles published until 2015. Inclusion criteria were unexplained encephalopathy with antithyroid antibodies. Results We found reports of 251 patients (median age 52 years [range 18–86], 73% females, 80 [32%] with preexisting thyroiditis). Patients presented encephalitis signs with convulsions (n = 117; 47%), confusion (n = 115, 46%), speech disorder (n = 91, 37%), memory impairment (n = 107, 43%), gait disturbance (n = 67, 27%) and persecutory delusions (n = 61, 25%). Twenty-eight patients (11%) presented progressive memory impairment and 26 (10%) isolated psychiatric disorders. In serum, 34% of patients were positive for anti-thyroid peroxidase (TPO) antibodies, 7% for anti-thyroglobulin (TG) antibodies, and 69% both. Thyroid-stimulating hormone levels were usually normal, at 2 UI/ml [0.001–205]. Cerebrospinal fluid from 10/53 patients (19%) was positive for anti-TPO antibodies, 2/53 (4%) anti-TG antibodies and 28 (53%) both. Electroencephalography findings were abnormal for 82% of patients, showing diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%). The first-line treatment was steroids in 193 patients and other immunosuppressive drugs in 10 cases. At a median follow-up of 12 months [ range 0.2 – 110], 91% of patients showed complete or partial neurological response, with anti-TPO and -TG antibody titers at 347 UI/ml [0–825,000] and 110 UI/ml [0–50,892], respectively. During follow-up, 40 patients (16%) experienced at least one relapse. Relapse was more frequent in patients with initial coma (26% vs 13%, p = 0.08). Conclusion The diagnosis of SREAT should be suspected in case of encephalopathy without obvious cause, to quickly start corticosteroid treatment. The exact modalities of treatment must be defined. [ABSTRACT FROM AUTHOR]

• MEFV heterozygosity is not associated with multiple sclerosis (MS). • MS is more frequent in familial Mediterranean fever (FMF) patients. • MS is more likely to lack oligoclonal bands when associated with FMF. • MS should be suspected upon neurological manifestations in FMF. • The association between FMF and MS is plausible but remains to be confirmed. Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system; and its development seems to be partly correlated with IL-1β levels. It is hypothesized that FMF could be associated with MS. We aim to describe the features of patients displaying both diseases and to investigate the MEFV mutation rate in MS patients. Patients with definite MS were retrieved from the cohort of FMF patients in the Reference Center for Rare Auto-inflammatory Diseases and Amyloidosis (CEREMAIA). We also performed a systematic literature review of articles from PubMed that were published from 1990 to 2020. Twenty-four patients were included in the case series: five patients (1.3%) from our cohort of 364 and 19 patients from the literature. The sex ratio was 2:1. The mean age at diagnosis of FMF was 19 years old; and that for MS was 29 years old. Seven studies investigating the MEFV mutation rate in MS patients were included. Three studies found a higher mutation rate in MS patients than in the control group. FMF and MS features were comparable to those of patients with unrelated diseases; and MEFV mutation carriage was not positively correlated with MS. However; MS prevalence in FMF patients was higher than was expected in a healthy population. To a lesser extent; FMF prevalence in MS patients was higher than expected in a healthy population and the difference might not be significant. These data suggest that FMF could be associated with MS; and further studies are needed to investigate a potential causal association. [ABSTRACT FROM AUTHOR]

ABSTRACT- We describe two patients with myeloid metaplasia in whom portal hypertension resulted, not from infiltration of the liver sinusoids by myeloid cells, but from perisinusoidal fibrosis and nodular regenerative hyperplasia of the liver. We hypothesize that myeloid metaplasia induced the development of perisinusoidal fibrosis, which resulted in heterogeneous hepatic tissue blood perfusion, with atrophy of the liver cells in the underperfused areas and nodular regenerative hyperplasia in the normally perfused areas. [ABSTRACT FROM AUTHOR]