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Accurate grading of IDH-mutant gliomas defines patient prognosis and guides the treatment path. Histological grading is challenging, and aside from CDKN2A/B homozygous deletions in IDH-mutant astrocytomas, there are no other objective molecular markers used for grading. RNA-sequencing was conducted on primary IDH-mutant astrocytomas (n = 138) included in the prospective CATNON trial, which was performed to assess the prognostic effect of adjuvant and concurrent temozolomide. We integrated the RNA-sequencing data with matched DNA-methylation and NGS data. We also used multi-omics data from IDH-mutant astrocytomas included in the TCGA dataset and validated results on matched primary and recurrent samples from the GLASS-NL study. Since discrete classes do not adequately capture grading of these tumours, we utilised DNA-methylation profiles to generate a Continuous Grading Coefficient (CGC) based on classification scores from a CNS-tumour classifier. CGC was an independent predictor of survival outperforming current WHO-CNS5 and methylation-based classification. Our RNA-sequencing analysis revealed four distinct transcription clusters that were associated with (i) upregulation of cell cycling genes; (ii) downregulation of glial differentiation genes; (iii) upregulation of embryonic development genes (e.g. HOX, PAX, and TBX) and (iv) upregulation of extracellular matrix genes. The upregulation of embryonic development genes was associated with a specific increase of CpG island methylation near these genes. Higher grade IDH-mutant astrocytomas have DNA-methylation signatures that, on the RNA level, are associated with increased cell cycling, tumour cell de-differentiation and extracellular matrix remodelling. These combined molecular signatures can serve as an objective marker for grading of IDH-mutant astrocytomas., (© 2024. The Author(s).)

Purpose: To characterize vestibulocochlear involvement in patients with Susac syndrome (SuS), a rare immune-mediated endotheliopathy of cerebral, retinal and inner ear microvasculature causing a triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss., Methods: The electronic patient files of 21 patients with SuS are reviewed for data on demography, clinical presentation, disease course and audiovestibular testing., Results: All 21 patients experienced some form of audiovestibular complaints during the disease course, with vertigo and instability being most frequently reported, followed by hearing loss, tinnitus and aural fullness. These audiovestibular symptoms did not always coincide. Fifteen patients had objectified predominant low- to midfrequency sensorineural hearing loss and 8 out of 18 patients showed abnormalities on vestibular testing, most frequently vestibular evoked myogenic potential-abnormalities, indicating otolith dysfunction. Treatment protocols consisted of uniformly extensive immunosuppressive therapy and hearing loss remained mostly mild., Conclusion: Audiovestibular involvement is very common in patients with SuS. Characteristic findings include a "reverse-slope" configuration on audiological testing and otolith dysfunction on vestibular testing. Aggressive immunosuppression may prevent severe audiovestibular dysfunction. Symptoms as aural fullness and otolith dysfunction may indicate an underlying hydrops. Further investigations are necessary to elucidate the histopathological mechanisms underlying these preferentially involved cochleovestibular areas. Early recognition and treatment of SuS are important to stabilize or decrease disease activity and might also have beneficial effects on inner ear outcome. THE SUBMITTED MANUSCRIPT REPORTS DATA DERIVED FROM CLINICAL OBSERVATIONS IN HUMANS: Consent for the research was provided by the Ethics Committee of Ghent University hospital (application number 2019/1443, registration date 31/12/2021, principal investigator Guy Laureys)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives METHODS: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed RESULTS: The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p=.015), spasticity (p=.042) and gait treatment (p=.035), but also more physiotherapy (p=.004), driver's license adjustment (p<.001) and a higher employment rate (p=.004). MDT access was associated with more frequent symptomatic bladder treatment (p=.047), higher physiotherapy rate (p<.001), higher work- (p=.002), insurance- (p<.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p<.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level CONCLUSION: MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate., Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods., Methods: Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite ® -Optilite (Sint-Jan Bruges hospital) and N Latex ® -BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis., Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite ® -Optilite: 7.7; N Latex ® -BNII: 4.71), κIgG index (Freelite ® -Optilite: 14.15, N Latex ® -BNII: 12.19), and CSF κFLC/IgG ratio (Freelite ® -Optilite: 2.27; N Latex ® -BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite ® -Optilite) versus 94.6% (N Latex ® -BNII) for the κFLC index, 91% (Freelite ® -Optilite) versus 92.2% (N Latex ® -BNII) for the κIgG index, and 81.3% (Freelite ® -Optilite) versus 91.4% (N Latex ® -BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite ® -Optilite and 90.5% for N Latex ® -BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite ® -Optilite: 0.924; N Latex ® -BNII: 0.962] and κIgG index (AUC Freelite ® -Optilite: 0.929; N Latex ® -BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%)., Conclusions: The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dekeyser, De Kesel, Cambron, Vanopdenbosch, Van Hijfte, Vercammen and Laureys.)

Background and Purpose: Susac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long-term neuropsychological outcomes of patients with SuS., Methods: Thirteen patients with SuS (mean [SD] age 39.5 [11.1] years) were enrolled at the Ghent University Hospital by their treating neurologist. The cognitive functioning and emotional well-being of each patient was evaluated by means of a thorough neuropsychological test battery at baseline and after 2 years. Follow-up testing after 2 years was performed in 11 patients (mean [SD] age 42.2 [11.5] years)., Results: Patients showed normal neuropsychological test results at a group level, both at baseline and follow-up testing. Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency. Individual test results showed interindividual variability at baseline, with most impairments being in attention, executive functioning and language, which improved after a 2-year period. In addition, patients reported significantly lower mental and physical well-being, both at baseline and follow-up testing., Conclusions: Our results suggest that neuropsychological dysfunction in SuS is limited at a group level and improves over time. Nonetheless, individual test results reveal interindividual variability, making cognitive screening essential. Furthermore, a high psycho-emotional burden of the disease was reported, for which screening and follow-up are necessary., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)