BACKGROUND AND OBJECTIVES:Five to 10 percent of patients with sarcoidosis show involvement of the nervous system. Given the serious nature of neurosarcoidosis and the high risk of irreversible neurologic damage, rapid diagnosis, accurate prognostication, and individualized treatment are crucial. The aim of this study was to identify factors associated with relapses in neurosarcoidosis. METHODS:In this multicenter retrospective cohort study, patients diagnosed with possible, probable, or definite neurosarcoidosis between January 1, 2010, and June 30, 2024, at 6 tertiary neuroimmunology centers across Europe were included. Patients were identified from the respective hospital-based databases by the participating centers. Clinical presentation, imaging results, CSF analysis, and immunosuppressive therapies were evaluated. Predictors of relapse, defined as clinical relapse or progression, or new MRI lesions on follow-up ≥2 months after initial manifestation, were analyzed with log-rank tests and Cox regression models, and therapeutic strategies in clinical practice were assessed. The association between identified risk factors (RFs) and therapeutic strategies was explored. RESULTS:A total of 174 patients with neurosarcoidosis were included with a median follow-up of 24 months (interquartile range 12-48.8). The mean age was 48.1 years, and 57.5% were female. CNS parenchymal lesions including encephalitis, myelitis, and optic neuritis (hazard ratio [HR] 2.3, 95% CI 1.3-4.2); CSF-specific oligoclonal bands (OCBs) (HR 2.1, 95% CI 1.3-3.6); CSF glucose <40 mg/dL (HR 2, 95% CI 1.1-3.4); and CSF protein ≥1,000 mg/dL (HR 2.1, 95% CI 1.3-3.5) were identified as RFs of relapse. Patients with 3-4 RFs had a median relapse-free survival of 12 months (95% CI 4.3-19.7), compared with 36 months (95% CI 24.3-47.7) in patients with 1-2 RFs and 120 months (95% CI 2.1-237.9) in patients without RFs (p < 0.01). The likelihood of treatment escalation increased with the number of RFs, from 14.3% in patients without RFs to 28.2% and 50% in patients with 1-2 or 3-4 RFs, respectively (p < 0.01). DISCUSSION:The identification of specific RFs, including parenchymal lesions, OCBs, CSF glucose <40 mg/dL, and CSF protein ≥1,000 mg/dL, enables better prognostication and might inform individualized treatment approaches. Patients with multiple RFs are at greater risk of relapse, possibly suggesting the need for more aggressive therapies.

This study investigates the thickness of retinal structures in patients with neurosarcoidosis (NS) and ocular sarcoidosis (OS). We compared the central macular thickness (CMT), retinal thickness (RT), central nerve fiber layer (RNFL) thickness, and ganglion cell layer (GCL) thickness using optical coherence tomography. In a cross-sectional study, we categorized 97 sarcoidosis patients (185 eyes) into four groups: patients without ocular or central nervous system sarcoidosis (Non-Ocular/Non-CNS, n = 53), patients with OS (Ocular, n = 13), patients with NS (CNS, n = 16), and patients with combined OS and NS (Ocular/CNS, n = 15). The mean age was 51 (14) years. We found no overall difference between the groups in the CMT (p = 0.3), RT (p = 0.9), RNFL (p = 0.3), and GCL measurements (p = 0.9). Only in patients with a disease duration of more than five years, the CMT was significantly thicker in the Ocular group (278 μm, p < 0.001), the CNS group (267 μm, p = 0.04), and the Ocular/CNS group (268 μm, p = 0.04), compared to the Non-Ocular/Non-CNS group (249 μm). The RT was significantly thicker in the Ocular group (296 μm, p = 0.008) and the Ocular/CNS group (291 μm, p = 0.03) compared to the Non-Ocular/Non-CNS group (283 μm). In the RNFL measurements, the Ocular group (33.7 μm, p = 0.002) was thicker than the Non-ocular/Non-CNS group (29.1 μm). We found an increased retinal thickness in patients with ocular sarcoidosis and long disease duration.

This case report describes a 40-year-old male patient with severe cardiac failure due to eosinophilic granulomatosis with polyangiitis (EGPA) and myocarditis. The fast diagnostic approach with cardiac MRI (CMR) and immunosuppressive treatment with glucocorticoid and cyclophosphamide near-normalized the patient’s cardiac function. Myocarditis due to EGPA is rare, however life-threatening, so a systematic approach and early CMR should be considered in patients with known asthma presenting with eosinophilia and cardiac involvement.

Background This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection.Methods Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests.Results The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response.Discussion Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.

Objective: To investigate the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of MS patients who were treated with ocrelizumab before first, second, and third BNT162b2 mRNA vaccinations. Background: The study included participants from three MS clinics in Denmark and the University of California, San Francisco in the United States when omicron BA.1 and BA.2 were the dominating subtypes of SARS-CoV-2. Reduced humoral response is associated with ocrelizumab treatment of multiple sclerosis (MS). Design/Methods: The study was a prospective nonrandomized controlled observational multicenter trial. Participants were diagnosed with MS and received ocrelizumab treatment for >12 months prior to the three BNT162b2 mRNA vaccinations. The follow-up period was from January 2021 to May 2022. Clinical outcomes were evaluated using WHO progression scale. The humoral and cellular immunogenicity in participants were correlated with PCR confirmed breakthrough infection. Results: Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infections were observed in all infected participants. After the third vaccination, the non-infected participants had higher mean antibody levels compared to the infected participants (54.3 vs. 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T-lymphocytes in the two groups were non-significant. Additional results regarding levels of ocrelizumab, anti-ocrelizumab antibodies and SARS-CoV-2 nucleocapsid protein, together with the immunological effects of fourth vaccination will be presented at the conference. Conclusions: Our results demonstrate high rates of breakthrough infections, along with mild disease courses after 3rd SARS-CoV-2 mRNA vaccination in ocrelizumab treated MS participants. This suggests that vaccination of B-cell depleted patients provides low protection against breakthrough infection. The study findings point to the need for better prophylactic options or more specific vaccines to allow for better clinical protection. Disclosure: Dr. Novak has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi A/S. Mr. Bajwa has nothing to disclose. The institution of Prof. Coia has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tillotts. The institution of Prof. Coia has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tillotts. The institution of Prof. Coia has received research support from Tillotts. Dr. Nilsson has received publishing royalties from a publication relating to health care. Dr. Nielsen has nothing to disclose. Mrs. Holm has nothing to disclose. Dr. Ostergaard has nothing to disclose. Miss Hvidt has nothing to disclose. Mr. BYG has nothing to disclose. Prof. Johansen has nothing to disclose. Ms. Mittl has nothing to disclose. William Rowles has nothing to disclose. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis. Dr. Sabatino has received research support from Novartis. Dr. Sabatino has received research support from Roche/Genentech. Dr. Sabatino has received personal compensation in the range of $500-$4,999 for serving as a CME course instructor with eMultiple Sclerosis Review. Dr. Sabatino has received personal compensation in the range of $500-$4,999 for serving as a CME course instructor with Physician Education Resource. Tobias Sejbaek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Merck, Novartis, Roche. Tobias Sejbaek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen, Merck, Novartis, Teva. The institution of Tobias Sejbaek has received research support from Biogen, Merck, Novartis, Roche.

Background Sarcoidosis is a disease characterized by non-caseating granulomatous inflammation, which can affect the eyes as ocular sarcoidosis (OS) and the central nervous system (CNS) as neurosarcoidosis (NS). Neurofilament light chain (NFL) is a structural neuronal cytoskeletal protein, and glial fibrillary acidic protein (GFAP) is part of the cytoskeleton in astrocytes and retinal Müller glial cells. Inflammation would cause leakage of NFL and GFAP. It has been demonstrated that plasma NFL is highly elevated in newly diagnosed NS patients with levels over 11.4 ng/L. Objectives The objectives were to compare the level of NFL and GFAP in sarcoidosis patients with or without OS and NS. Methods This cross-sectional study included 106 biopsy-verified chronic sarcoidosis patients examined between May and November 2019. After excluding 18 patients due to systemic comorbidity, the patients were divided according to their organ involvement over time: sarcoidosis without ocular or CNS affection (non-OS/non-NS, n=44), OS (n=14), NS (n=15), and combined OS and NS (n=15).EDTA plasma was stored at -80 ◦C until analysis. NFL and GFAP were measured blinded to clinical data by single molecule array technology (Simoa, HD-1 Analyser, Quanterix©, Billerica, MA, USA), using the commercially available 2-Plex assay.Kruskal–Wallis test, Dunn test, and Fisher's exact test were used for statistical analysis. Results We included 88 patients with an age median (IQR) of 52 years (41 - 60). The non-OS/non-NS group was younger than the other groups (p = 0.02) but did not differ with respect to disease duration (p=0.5). Between 67-100% of the patients received immunosuppressive treatment, most frequently in the OS group (93%) and the NS group (100%) (p = 0.02).Median NFL was 5.1, 8.4, 7.0, and 7.0 ng/L in patients with non-OS/non-NS, OS, NS, and combined OS and NS, respectively (p = 0.003), although this was only statistically significant in patients with a disease duration < 5 years (p = 0.005).The frequency of patients with an NFL level >11.4 ng/L was lower in non-OS/non-NS group compared to the three other groups (2% vs. 14% vs. 33% vs. 20%, p = 0.004).There was a trend (p = 0.06) towards a lower median GFAP in patients with non-OS/non-NS as compared to the other groups (52 vs. 72 vs. 71 vs. 69 ng/L), which became statistically significant in patients with a disease duration < 5 years (48 vs. 67 vs. 127 vs. 52 ng/L, p = 0.02). Conclusion In this cross-sectional study of chronic sarcoidosis patients, we generally found a low median NFL level, including in OS and NS patients. Our results suggest that neuroaxonal damage and, thereby, active inflammation decreases in treated sarcoidosis patients. However, the median NFL levels were significantly lowest in the non-OS/non-NS group, and between 14-33% of patients in OS, NS, and combined OS and NS groups had an NFL level above 11.4 ng/l, which could indicate active CNS inflammation leading to ongoing silent neuroaxonal damage. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Baseline characteristics and clinical findings in sarcoidosis patientsNon-OS/non-NS(n=44)OS(n=14)NS(n=15)OS and NS(n=15)p-valueAge, years45 (41-55)56 (38-66)*60 (51-65)**52 (32-60)0.02Age <40, %2329740Age 40-59, %66294033Age ≥60, %11435327Sex, % male455073600.3Duration of sarcoidosis,years5 (3-9)6 (3-9)9 (4-10)5 (3-9)0.5<5 years, %503627400.4Immunosuppres., %6893100670.02NFL, ng/L5.1(4.1-6.2)8.4**(6.6-10.3)7.0**(5.7-14.1)7.0a(4.5-10.8)0.003Duration <5 years4.4(3.2-5.5)10.3**(8.6-10.9)12.5**(8.1-14.6)8.8*(3.5-10.0)0.005≥ 5 years5.7(5.0-6.9)8.0(6.6-8.5)6.6(5.2-11.8)4.7(4.5-10.8)0.4NFL > 11.4 ng/L, %21433200.004GFAP, ng/L52 (39-71)72(45-107)a71 (43-132)*69 (49-102)*0.06Duration <5 years48 (39-60)67 (45-107)a127 (88-171)**52 (48-58)0.02≥ 5 years62 (39-93)73 (46-83)69 (41-120)83 (69-110)a0.4Values are median and interquartile range (IQR), or count and percentage. * Compared to non-ocular/non-CNS group p < 0.05. ** Compared to non-ocular/non-CNS group p < 0.01. a Compared to non-ocular/non-CNS group p = 0.06.

Objective The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients. Method We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function. Results MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05). Conclusion Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS.

BACKGROUND:Our study investigated the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of multiple sclerosis (MS) patients who were treated with the anti-CD20 monoclonal antibody (Ab), ocrelizumab, before first, second and third BNT162b2 mRNA vaccinations. To correlate clinical outcomes with the humoral and cellular response.METHODS:The study was a prospective non-randomised controlled multicentre trial observational study. Participants with a diagnosis of MS who were treated for at least 12 months with ocrelizumab prior to the first BNT162b2 mRNA vaccination were prospectively followed up from January 2021 to June 2022.RESULTS:Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infection was observed in all infected participants. After the third vaccination, the non-infected participants had higher mean Ab levels compared to the infected participants (54.3 binding antibody unit (BAU)/mL vs 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T lymphocytes in the two groups was not significant.CONCLUSION AND RELEVANCE:The study results demonstrate rates of 59% in breakthrough infections after the third SARS-CoV-2 mRNA vaccination in ocrelizumab-treated patients with MS, without resulting in critical disease courses. These findings suggest the need for continuous development of prophylactic treatments when proved important in the protection of severe breakthrough infection.

The objective of this pilot study was to assess the impact of a salivary gland ultrasound (SGUS) atlas for scoring parenchymal changes in Sjögren’s syndrome by assessing the reliability of the scoring system (0–3), without and with the use of the SGUS atlas. Ten participants with varying experience in SGUS contributed to the reliability exercise. Thirty SGUS images of the submandibular and parotid gland with abnormalities ranging from 0 to 3 were scored using the written definitions of the OMERACT SGUS scoring system and using the SGUS atlas based on the OMERACT scoring system. For intra-reader reliability, two rounds were performed without and with the atlas—in the 2nd round the 30 images were rearranged in random order by a physician not included in the scoring. Inter-reader reliability was also determined in both rounds. Without using the atlas, the SGUS OMERACT scoring system showed fair inter-reader reliability in round 1 (mean kappa 0.36; range 0.06–0.69) and moderate intra-reader reliability (mean kappa 0.55; range 0.28–0.81). With the atlas, inter-reader reliability improved in round 1 to moderate (mean kappa 0.52; range 0.31–0.77) and intra-reader reliability to good (mean kappa 0.69; range 0.46–0.86). Higher intra-reader reliability was noted in participants with previous SGUS experience. The SGUS atlas increased both intra- and inter-reader reliability for scoring gland pathology in participants with varying SGUS experience suggesting a possible future role in clinical practice and trials. Key Points • Ultrasonography can detect parenchymal changes in salivary glands in patients with Sjögren’s disease. • An ultrasound atlas may improve reliability of scoring parenchymal changes in salivary glands.

METHODS:Cerebrospinal fluid (CSF) and plasma levels of 38 biomarkers from 20 neurosarcoidosis (NS) patients were compared to healthy controls (HC). RESULTS:In CSF, 25 biomarkers were significantly elevated compared to HC: IFNγ, TNFα, TNFβ, IL-2, IL-6, IL-10, IL-12B, IL-15, IL-16, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26, CXCL8, CXCL10, TNFR2, VEGF-A, PIGF, SAA, VCAM1, and ICAM1. In plasma, 12 biomarkers were significantly elevated compared to HC: IFNγ, TNFα, CCL2, CCL3, CCL4, CCL17, CXCL10, VEGFR1, PIGF, SAA, VCAM1, and ICAM1. CONCLUSION:NS patients have profoundly elevated cytokines, chemokines, vascular angiogenesis, and vascular injury biomarkers in CSF and plasma.

Giant cell arteritis (GCA) is a potential sight-threatening disease. Although it is associated with polymyalgia rheumatica (PMR), visual loss is not common in PMR. A retinal oximeter can be used to conduct a direct, non-invasive, in vivo assessment of the vascular system. In a cross-sectional study, we measured the retinal oxygen saturation and retinal vessel calibers in GCA patients, PMR patients, and control participants. Twenty GCA patients (38 eyes), 19 PMR patients (33 eyes), and 12 controls (20 eyes) were investigated. Images were analyzed using Oxymap Analyzer software 2.5.0 (Oxymap ehf., Reykjavik, Iceland). Groups were compared using an age- and sex-adjusted linear mixed model regression. The median (IQR) age for GCA patients was 69.0 (66.5–76.5) years, for PMR 69.0 (67.0–72.0) years, and for the controls 75.5 (71.5–81.0) years, respectively. As compared to the controls (115.3 µm), the retinal arterioles were significantly wider in patients with GCA (124.4 µm; p = 0.023) and PMR (124.8 µm; p = 0.049). No difference was found in the retinal venular caliber or vascular oxygen saturation. These results indicate that GCA and PMR patients differ similarly in the retinal arteriolar diameter compared to controls. Further studies are needed in order to clarify the underlying inflammatory mechanisms in retinal arteriolar vessels and if these parameters can be used to predict clinical outcomes.

To examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination. Methods: A prospective longitudinal study design from first throughout third vaccination in Danish and American MS centers. All participants were treated with ocrelizumab. Antibody (Ab) levels were assessed before and after third vaccination using SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). B-and T-lymphocytes enumeration was done with BD MultitestTM6-color TBNK reagent. Spike-specific T-cell responses were measured through PBMC stimulation with spike peptide pools (JPT Peptide Technologies). Results: We found that 14.0%, 37.7%, and 33.3% were seropositive after first, second and third vaccination. The median Ab-levels were 74.2 BAU/mL (range: 8.5-2427) after second vaccination, as well as 43.7 BAU/ml (range: 7.8-366.1) and 31.3 BAU/mL (range: 7.9-507.0) before and after third vaccination, respectively. No difference was found in levels after second and third vaccination (p = 0.1475). Seropositivity dropped to 25.0% of participants before the third vaccination, a relative reduction of 33.3% (p = 0.0020). No difference was found between frequencies of spike reactive CD4(+)and CD8(+) T -cells after second (0.65 +/- 0.08% and 0.95 +/- 0.20%, respectively) and third vaccination (0.99 +/- 0.22% and 1.3 & PLUSMN; 0.34%, respectively). Conclusion: In this longitudinal cohort we found no significant increased humoral or cellular response with administration of a third SARS-CoV-2 mRNA vaccination. These findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.

MethodsTwenty patients with newly diagnosed neurosarcoidosis were examined for multiple outcomes in an observational cohort study with 12-month follow-up.ResultsThe patients' contrast-enhancing lesions on MRI scans reduced during treatment (p < 0.0001). The mean modified Rankin Score improved from 3.0 to 1.8 (p < 0.0001), and 75% of patients experienced clinically important improvement. Patients improved on the Symbol Digit Modalities Test (p < 0.0001) and on SF-36 Physical (p = 0.003) and Mental Component Summary scores (p = 0.03). Proportions of patients with substantial fatigue (75%) and high depression score (35%) were unchanged.Conclusions12-month immunosuppression improved several outcomes, and 75% of patients experienced clinically important improvement.

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

Objective. To evaluate retinal oxygen metabolism by retinal oximetry for ocular and CNS diseases in a crosssectional study of sarcoidosis. Methods. Overall 201 eyes from 103 biopsy-verified sarcoidosis patients were included and divided into four groups depending on the organ affection: (i) sarcoidosis without ocular or CNS affection, (ii) ocular sarcoidosis, (iii) CNS sarcoidosis, and (iv) combined ocular and CNS sarcoidosis. Retinal oximetry was obtained and analysed, with the mean retinal arteriolar and venular saturation as well as arteriovenous difference as principal outcomes. Comparison between groups was done in a multi linear regression model adjusted for age, sex, duration of sarcoidosis, best corrected visual acuity and retinal oximetry quality. Results. Mean (S.D.) age was 50.5 (13.4) (95% CI: 47.9, 53.1) years and 52.2% were males. Eyes of the combined Ocular/CNS group had a higher retinal arteriovenous difference than eyes of the Non-ocular/no-CNS group (42.1% vs 37.7%, P = 0.012) but did not differ between other groups. Eyes in the four groups (Non-ocular/no-CNS, Ocular, CNS and Ocular/CNS) did not differ according to retinal arterial (94.5%, 93.5%, 93.5% and 94.5%, respectively) or venular (57.5%, 56.4%, 55.0% and 52.5%, respectively) oxygen saturation. Conclusions. The results of this study suggest that eyes of sarcoidosis patients with combined ocular and CNS affection have an altered oxygen metabolism indicating a subclinical eye affection that is not recognized by conventional screening methods.

The use of non-selective tumor necrosis factor (TNF) inhibitors is well known in the treatment of inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, and psoriasis. Its use in neurological disorders is limited however, due to rare adverse events of demyelination, even in patients without preceding demyelinating disease. We review here the molecular and cellular aspects of this neuroinflammatory process in light of a case of severe monophasic demyelination caused by treatment with infliximab. Focusing on the role of TNF, we review the links between CNS inflammation, demyelination, and neurodegenerative changes leading to permanent neurological deficits in a young woman, and we discuss the growing evidence for selective soluble TNF inhibitors as a new treatment approach in inflammatory and neurological diseases.

Background The impact of a pandemic on unplanned hospital attendance has not been extensively examined. The aim of this study is to report the nationwide consequences of the COVID-19 pandemic on unplanned hospital attendances in Denmark for 7 weeks after a ‘shelter at home’ order was issued. Methods We merged data from national registries (Civil Registration System and Patient Registry) to conduct a study of unplanned (excluding outpatient visits and elective surgery) hospital-based healthcare and mortality of all Danes. Using data for 7 weeks after the ‘shelter at home’ order, the incidence rate of unplanned hospital attendances per week in 2020 was compared with corresponding weeks in 2017–2019. The main outcome was hospital attendances per week as incidence rate ratios. Secondary outcomes were general population mortality and risk of death in-hospital, reported as weekly mortality rate ratios (MRRs). Results From 2 438 286 attendances in the study period, overall unplanned attendances decreased by up to 21%; attendances excluding COVID-19 were reduced by 31%; non-psychiatric by 31% and psychiatric by 30%. Out of the five most common diagnoses expected to remain stable, only schizophrenia and myocardial infarction remained stable, while chronic obstructive pulmonary disease exacerbation, hip fracture and urinary tract infection fell significantly. The nationwide general population MRR rose in six of the recorded weeks, while MRR excluding patients who were COVID-19 positive only increased in two. Conclusion The COVID-19 pandemic and a governmental national ‘shelter at home’ order was associated with a marked reduction in unplanned hospital attendances with an increase in MRR for the general population in two of 7 weeks, despite exclusion of patients with COVID-19. The findings should be taken into consideration when planning for public information campaigns.