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Abstract Acute transverse myelitis (ATM) is a disease characterized by inflammation of the spinal cord and may have various causes. In the context of this work, the distinction between isolated ATM and initial manifestation of autoimmune-mediated diseases of the central nervous system such as multiple sclerosis (MS) is crucial. Hence, the aim of this work was to identify predictive factors associated with the conversion to definite MS in a collective of individuals after their initial episode of isolated ATM (no initial identified cause). In this retrospective data analysis from the Vienna MS Database, all patients from Jan. 1, 1999, to Dec. 31, 2019, with a diagnosis of isolated ATM (according to the criteria of the Transverse Myelitis Consortium Working Group) who underwent lumbar puncture were extracted. Electronic medical records were reviewed on the availability of clinical data including therapy and follow-up, laboratory results including cerebrospinal fluid (CSF) analysis, evoked potentials (EP) as well as magnetic resonance imaging data. Among 42 patients with the diagnosis of isolated ATM, 12 (29%) were subsequently diagnosed with MS over a median follow-up period of 7.7 years. Univariately, MS converters were younger (32 years [25–39] vs. 42 years [31–50], p = 0.032), had a lower CSF/serum albumin ratio (29 [24–35] vs 37 [27–52], p = 0.037), lower CSF total protein (4.5 [2.8–4.8] vs. 5.5 [3.4–8.5], p = 0.023) and a higher proportion of CSF-specific oligoclonal bands (OCB; 83% vs. 30%, p = 0.002). In the multivariate regression analysis, the presence of CSF-specific OCB emerged as the sole predictive factor of subsequent MS diagnosis (OR: 14.42, 95% CI 1.39 to 149.48, p = 0.03). In a collective of 42 patients with isolated ATM and an MS conversion rate of nearly 30%, the only but highly predictive factor were CSF-specific OCB. This emphasizes the significance of conducting timely CSF analysis in such patients and underscores the need for tailored monitoring and follow-up strategies in this specific group.

Brown tumors, resulting from elevated osteoclast activity, are uncommon skeletal symptoms of hyperparathyroidism. Because of their similar characteristics, it is challenging to differentiate these tumors from multiple myeloma or osteolytic metastases. A 24-year-old female with a painful lump in her left thigh and arm in the past 10 months. The patient reported a history of left femoral bone fracture over a year ago due to low-impact trauma. Plain radiograph images and chest MSCT showed osteolytic lesions at the skull, ribs, and extremities, followed by increased Tc99 bone scan image uptake. Thyroid ultrasound and cervical MSCT showed parathyroid mass. Biochemical and pathologic examination supported the diagnosis of brown tumor. A multidisciplinary approach, including clinical evaluation, biochemical assessment, pathological examination, and advanced imaging modalities such as CT scan, MRI, and bone scintigraphy, is necessary for the differential diagnosis of brown tumors from bone metastasis. Medical history, PTH, calcium levels in the blood, and additional systemic symptoms can all be used to help distinguish between the 2 disorders. The clinical presentation and imaging findings of brown tumors may mimic bone metastasis, necessitating comprehensive evaluation. Multidisciplinary collaboration plays a vital role in reaching an accurate diagnosis. Increased awareness of brown tumors as a potential mimic of bone metastasis may help prevent misdiagnosis and ensure optimal care for patients presenting with osteolytic bone lesions associated with hyperparathyroidism.

Introduction Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 (cluster of differentiation) monoclonal antibodies (mAbs) such as ocrelizumab (OCR) and ofatumumab (OFA) show a reduction mainly of B-lymphocytes, but also other lymphocyte subsets can be affected by these treatments. There is limited data on differences between lymphocyte subset counts of pwMS after treatment initiation with OCR or OFA. Objective To compare lymphocyte subset counts after treatment initiation in pwMS treated with OCR and OFA. Methods We analyzed 22 pwMS initiated on OFA and 56 sex-, age- and MS course matched pwMS initiated on OCR from 2 prospectively collected observational MS databases (Bern [n: OFA 14, OCR 44] and Vienna [n: OFA 8, OCR 12]) statistically comparing lymphocyte subset counts (Mann Whitney Test). Results We found that pwMS treated with OCR showed a stronger reduction of CD20 B-lymphocytes ( P = .001), and a trend towards lower counts of CD8 + T cells ( P = .056) compared to pwMS treated with OFA, whereas reduction of total lymphocyte, CD4 + lymphocyte and NK cell count was equally distributed between both treatments. Conclusion Different effects on lymphocyte subpopulations appear to be present in pwMS after treatment initiation with different anti-CD20 mAbs. Further studies are needed to determine potential effects on anti-CD20 treatment efficacy as well as treatment associated risks such as failed vaccinations and infections.

BackgroundRecent studies proposed cellular immunoprofiling as a surrogate for predicting treatment response and/or stratifying the occurrence of adverse events (AEs) in persons with multiple sclerosis (pwMS). However, applicability in real-world circumstances is not sufficiently addressed.ObjectiveWe aimed to explore whether standard routine clinical leukocyte phenotyping before treatment initiation could help stratify patients according to treatment response or AEs in a real-world MS cohort.MethodsIn this retrospective study, 150 pwMS were included, who had been newly initiated on a disease-modifying drug (DMD) and had been assessed for standard immunophenotyping before DMD initiation (baseline) and at least once during the following year. Multivariate models were used to assess an association of immune subsets and the association between immune cell profiles regarding treatment response and AEs.ResultsWe found that the composition of T cell subsets was associated with relapse activity, as an increased proportion of CD8+ lymphocytes at baseline indicated a higher likelihood of subsequent relapse (about 9% per 1% increase in CD8+ proportion of all CD3+ cells). This was particularly driven by patients receiving anti-CD20 therapy, where also EDSS worsening was associated with a higher number of CD8+ cells at baseline (3% increase per 10 cells). In the overall cohort, an increase in the proportion of NK cells was associated with a higher risk of EDSS worsening (5% per 1% increase). Occurrence of AEs was associated with a higher percentage of T cells and a lower number of percentual NKT cells at baseline.ConclusionImmune cell profiles are associated with treatment response and the occurrence of AEs in pwMS. Hence, immunophenotyping may serve as a valuable biomarker to enable individually tailored treatment strategies in pwMS.

Thematic learning is an integrated learning that focuses on student involvement in the learning of each sub-theme. The research in this paper is to uncover and explain the teacher's skills in managing the class for the fifth-grade students' thematic learning at SD Khatolik St. Vincentius Noongan. The researchers used qualitative research methods with data collection methods in the form of observation, interviews, and documentation. Data analyses were data reduction, data presentation, and conclusion drawing. The research result indicates that there are two types of class management in theme learning, non-physical and physical class management. Caring, firmness, change, and high standards comprise non-physical classroom management. Meanwhile, physical classroom management entails rearranging the blackboard's position, seating adjustment, bulletin boards, and window rearrangement in the classroom. Thematic learning is unusual in that it takes a teacher's inventiveness to manage the class. Of course, this management is dependent on the qualities and requirements of the pupils. Because each student's demands are unique, we must make the class as appealing as feasible while managing it.

Abstract Critical illness polyneuropathy (CIP) is a frequent and underdiagnosed phenomenon among intensive care unit patients. The lipophilic nature of neuronal synapses may result in the association of low serum cholesterol levels with a higher rate of CIP development. We aimed to investigate this issue in critically ill patients. All cases diagnosed with CIP in our tertiary care hospital between 2013 and 2017 were 1:1 matched with controls without the condition by age, sex, and ICD diagnoses. The main risk factors examined were the differences in change between initial and minimum serum total cholesterol levels, and minimum serum total cholesterol levels between matched pairs. Other predictors were serum markers of acute inflammation. We included 67 cases and 67 controls (134 critically ill patients, 49% female, 46% medical). Serum total cholesterol levels decreased more profoundly in cases than controls (median: −74 (IQR −115 to −24) vs. −39 (IQR −82 to −4), median difference: −28, 95% CI [−51, −5]), mg/dl). Minimum serum total cholesterol levels were lower in the cases (median difference: −24, 95% CI [−39, −9], mg/dl). We found significant median differences across matched pairs in maximum serum C-reactive protein (8.9, 95% CI [4.6, 13.2], mg/dl), minimum albumin (−4.2, 95% CI [−6.7, −1.7], g/l), decrease in albumin (−3.9, 95% CI [−7.6, −0.2], g/l), and lowest cholinesterase levels (−0.72, 95% CI [−1.05, −0.39], U/l). Subsequently, more pronounced decreases in serum total cholesterol levels and lower minimum total cholesterol levels during critical care unit hospitalizations may be a risk factor for CIP.

Abstract Objective Assessing severity of antibody‐mediated encephalitis (AE) or paraneoplastic encephalitis (PE) requires valid and reliable scores to guide treatment decisions and predict outcome both in clinical routine and studies. We aimed to validate the prognostic value of the clinical assessment scale in autoimmune encephalitis (CASE) and the anti‐NMDAR‐encephalitis one‐year functional status (NEOS) score in patients suffering from AE and PE in a large monocentric cohort. Methods We retrospectively applied the CASE and NEOS score to patients with definite AE and PE treated at a tertiary hospital. Correlations were established between the CASE and NEOS score and the modified Rankin scale (mRs). Multivariable analyses were calculated to identify predictors of outcome. Results Thirty‐four patients (27 AE, 7 PE) were included. Correlations between mRS and CASE score were strongest in patients with AE compared to PE at all intervals, but in the subgroups (LGI1, NMDAR, GAD, miscellaneous surface antibodies, PE) the correlation was strongest in the interval after baseline. Patients with AE seemed to display better outcomes compared to PE, which was underlined by multivariable analysis. Improvement was mostly observed within 6–12 months after disease onset, after which little or no further improvement was noted with some exception for two patients with anti‐NMDARE who recovered substantially even after 12 months of treatment. The NEOS score significantly predicted the outcome at last follow‐up in patients with AE with a sensitivity of 79% at a cut‐off value of 2 points (AUC 0.79, 95% CI 0.58–0.99, p = 0.04). Interpretation The CASE and NEOS score are suitable supplementary tools in addition to the mRS for capturing diverse symptoms, for grading and monitoring symptom severity.

Summary: Background: X-linked adrenoleukodystrophy (X-ALD) is highly variable, ranging from slowly progressive adrenomyeloneuropathy to severe brain demyelination and inflammation (cerebral ALD, CALD) affecting males with childhood peak onset. Risk models integrating blood-based biomarkers to indicate CALD onset, enabling timely interventions, are lacking. Therefore, we evaluated the prognostic value of blood biomarkers in addition to current neuroimaging predictors for early detection of CALD. Methods: We measured blood biomarkers in a retrospective, male CALD risk-assessment cohort consisting of 134 X-ALD patients and 66 controls and in a phenotype-blinded validation set (25 X-ALD boys, 4–13 years) using Simoa®and Luminex® technologies. Findings: Among 25 biomarkers indicating axonal damage, astrocye/microglia activation, or immune-cell recruitment, neurofilament light chain (NfL) had the highest prognostic value for early indication of childhood/adolescent CALD. A plasma NfL cut-off level of 8.33 pg/mL, determined in the assessment cohort, correctly discriminated CALD with an accuracy of 96% [95% CI: 80–100] in the validation group. Multivariable logistic regression models revealed that combining NfL with GFAP or cytokines/chemokines (IL-15, IL-12p40, CXCL8, CCL11, CCL22, and IL-4) that were significantly elevated in CALD vs healthy controls had no additional benefit for detecting neuroinflammation. Some cytokines/chemokines were elevated only in childhood/adolescent CALD and already upregulated in asymptomatic X-ALD children (IL-15, IL-12p40, and CCL7). In adults, NfL levels distinguished CALD but were lower than in childhood/adolescent CALD patients with similar (MRI) lesion severity. Blood GFAP did not differentiate CALD from non-inflammatory X-ALD. Interpretation: Biomarker-based risk prediction with a plasma NfL cut-off value of 8.33 pg/mL, determined by ROC analysis, indicates CALD onset with high sensitivity and specificity in childhood X-ALD patients. A specific pro-inflammatory cytokine/chemokine profile in asymptomatic X-ALD boys may indicate a primed, immanent inflammatory state aligning with peak onset of CALD. Age-related differences in biomarker levels in adult vs childhood CALD patients warrants caution in predicting onset and progression of CALD in adults. Further evaluations are needed to assess clinical utility of the NfL cut-off for risk prognosis of CALD onset. Funding: Austrian Science Fund, European Leukodystrophy Association.

Highlights 1. Lesions that are regularly diagnosed in the spine include TB of the spine and tumors that have spread throughout the body. 2. The examined papers included 35 individuals with tuberculous spondylitis and 31 patients with metastatic spinal malignancies. 3. A methodology for MRI imaging and an accurate medical history will aid in establishing an accurate diagnosis. Abstract Background: Spinal tuberculosis and metastatic tumors are commonly diagnosed lesions in the spine. Tuberculosis spondylitis, also known as Pott's Disease, is the most common extrapulmonary tuberculosis disease. MRI is the gold standard for early diagnosis because there is no significant difference in the results of clinical manifestations and histopathological examination. A biopsy will usually be used for a final exam for diagnosis. Objective: To provide information to confirm the diagnosis of TB spondylitis cases and metastatic spinal tumors. Method: A literature search was conducted via PubMed, Science Direct, and Scopus by selecting studies according to inclusion and exclusion criteria. The quality and risk of bias assessments were performed using Joanna Briggs Institute (JBI) tools. Overall, 35 spinal tuberculosis and 31 metastatic spinal tumor patients from 2 studies were reviewed. Result: Of the 35 patients with tuberculous spondylitis and 31 patients with metastatic spinal tumors from the two studies reviewed. It was found that the thorax was the most common region. The following imaging findings were of statistical significance (p

Elevated levels of saturated very long-chain fatty acids (VLCFAs) in cell membranes and secreted lipoparticles have been associated with neurotoxicity and, therefore, require tight regulation. Excessive VLCFAs are imported into peroxisomes for degradation by β-oxidation. Impaired VLCFA catabolism due to primary or secondary peroxisomal alterations is featured in neurodegenerative and neuroinflammatory disorders such as X-linked adrenoleukodystrophy and multiple sclerosis (MS). Here, we identified that healthy human macrophages upregulate the peroxisomal genes involved in β-oxidation during myelin phagocytosis and pro-inflammatory activation, and that this response is impaired in peripheral macrophages and phagocytes in brain white matter lesions in MS patients. The pharmacological targeting of VLCFA metabolism and peroxisomes in innate immune cells could be favorable in the context of neuroinflammation and neurodegeneration. We previously identified the epigenetic histone deacetylase (HDAC) inhibitors entinostat and vorinostat to enhance VLCFA degradation and pro-regenerative macrophage polarization. However, adverse side effects currently limit their use in chronic neuroinflammation. Here, we focused on tefinostat, a monocyte/macrophage-selective HDAC inhibitor that has shown reduced toxicity in clinical trials. By using a gene expression analysis, peroxisomal β-oxidation assay, and live imaging of primary human macrophages, we assessed the efficacy of tefinostat in modulating VLCFA metabolism, phagocytosis, chemotaxis, and immune function. Our results revealed the significant stimulation of VLCFA degradation with the upregulation of genes involved in peroxisomal β-oxidation and interference with immune cell recruitment; however, tefinostat was less potent than the class I HDAC-selective inhibitor entinostat in promoting a regenerative macrophage phenotype. Further research is needed to fully explore the potential of class I HDAC inhibition and downstream targets in the context of neuroinflammation.

Abstract Objective White matter lesions (WML) in multiple sclerosis (MS) differ from vascular WML caused by Fabry disease (FD). However, in atypical cases the discrimination can be difficult and may vary between individual raters. The aim of this study was to evaluate interrater reliability of WML differentiation between MS and FD patients. Materials and methods Brain MRI scans of 21 patients with genetically confirmed FD were compared to 21 matched patients with MS. Pseudonymized axial FLAIR sequences were assessed by 6 blinded raters and attributed to either the MS or the FD group to investigate interrater reliability. Additionally, localization of WML was compared between the two groups. Results The median age of patients was 46 years (IQR 35–58). Interrater reliability was moderate with a Fleiss' Kappa of 0.45 (95%CI 0.3–0.59). Overall, 85% of all ratings in the MS group and 75% in the FD group were correct. However, only 38% of patients with MS and 33% of patients with FD were correctly identified by all 6 raters. WML involving the corpus callosum (p