Introduction:Antibodies to the extracellular domain of the astrocytic aquaporin-1 (AQP-1) have been reported in patients with neuromyelitis optica spectrum disorder (NMOSD) and a few multiple sclerosis (MS) patients with predominant spinal cord involvement. Our aim was to identify the prevalence and clinical correlates of antibodies against AQP1 (AQP1-Abs) in a broader spectrum of autoimmune inflammatory demyelinating central nervous system (CNS) disorders. Methods:Sera from patients with NMOSD (n=30), recurrent inflammatory optic neuropathy (RION) (n=15), relapsing remitting MS (RRMS) (n=69), of which 10 had optic neuritis and/or short myelitis, and healthy controls (n=36) were screened for the presence of AQP1-Abs by ELISA and for antibodies against aquaporin-4 (AQP4-Abs) and myelin oligodendrocyte glycoprotein (MOG)-Abs by cell-based assays. Results:AQP1-Abs were found in 11% of patients with optic neuritis and/or myelitis [6.7% of NMOSD, 13.3% of RION and 20% of RRMS with optic neuritis and/or short myelitis]. None of the RRMS patients without optic neuritis and/or short myelitis and none of the healthy controls had AQP1-Abs. The two AQP1-Abs-positive RRMS patients, who fulfilled Barkhof criteria by virtue of MRI lesion distribution, had experienced ≥4 short myelitis and/or optic neuritis attacks. Conclusion:AQP1-Abs are occasionally detected in autoimmune inflammatory demyelinating CNS disorders highlighting optic nerve and spinal cord involvement.

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a critical role in immune regulation, host defense, and tissue repair. Within the central nervous system (CNS), IL-6 contributes to both neuroprotection and neuroinflammation, depending on the signaling pathway involved; classic signaling, trans-signaling, or trans-presentation. Dysregulation of IL-6, particularly through sustained overexpression, disrupts the blood-brain barrier (BBB) integrity, promotes glial activation, and amplifies chronic inflammation, thereby contributing to the pathophysiology of numerous neurological disorders. This review aims to evaluate the role of IL-6 in neuroinflammatory processes and its clinical implications across a spectrum of neurological diseases. It focuses on the therapeutic potential and safety profile of IL-6 inhibitors, particularly tocilizumab and satralizumab. Key conditions discussed include neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein-associated disease (MOGAD), autoimmune encephalitis (AE), neuro-Behçet's disease (NBD), myasthenia gravis (MG), epilepsy, multiple sclerosis (MS), and Alzheimer's disease (AD). Clinical trials have demonstrated the efficacy of IL-6 receptor blockade in reducing relapse rates in NMOSD, leading to regulatory approvals. Promising off-label results have also been reported in treatment-resistant cases of MOGAD, epilepsy, and autoimmune conditions. However, IL-6 inhibition carries risks such as serious infections and paradoxical inflammatory reactions. Targeting the IL-6 pathway represents a significant advancement in neuroimmunology, offering new therapeutic opportunities for otherwise refractory conditions. Future research should focus on large-scale randomized controlled trials and the development of IL-6 inhibitors capable of crossing the BBB to enhance CNS-specific efficacy. Cost-related accessibility also remains a major challenge for broader clinical application.

To evaluate the real-world effectiveness and safety of eculizumab in patients with AQP4-IgG–positive neuromyelitis optica spectrum disorder (NMOSD) and to identify predictors of disability outcomes. This multinational, retrospective cohort study analyzed data from 46 patients across 26 centers. The outcomes included the annualized relapse rate (ARR), relapse-free status, change in expanded disability status scale (EDSS) scores, and adverse events. To identify predictors of EDSS improvement or worsening, patients were stratified into subgroups (improved vs. stable/worsened) at each follow-up time point and compared based on demographic, clinical, and radiological variables. This retrospective cohort study included 46 patients with AQP4-IgG-positive NMOSD from 26 centers, followed for a mean of 27.3 months. The mean ARR significantly decreased from 1.1 in the 2 years pre-treatment to 0.1 during eculizumab therapy. The relapse-free rate increased from 6.5

While cognitive functioning in multiple sclerosis has been extensively studied, the presence of social cognition deficits in persons affected by relapsing-remitting multiple sclerosis (RRMS) remains comparatively less explored. This study recruited 30 Turkish patients with RRMS and 30 healthy controls (HCs) matched for demographic characteristics and cognitive status. We tested their social cognition abilities within two main subdomains, namely, theory of mind (ToM) and emotion recognition. The combination of tests we used was novel and rather broad as ToM was evaluated in both its affective and cognitive components while emotion recognition was evaluated in two tasks requiring either naming or discriminating facial expressions. All tests required verbal responses and were scored in terms of accuracy. The results indicated that patients with RRMS exhibited significantly lower accuracy compared to the HC group across all social cognition tasks. Correlation analyses revealed a significant negative relationship between emotion discrimination performance and both level of disability and disease duration. Additionally, RRMS patients showed significant deficits in recognizing negative emotions, while no differences with the HC group were observed for positive emotion recognition. The presence of a domain-specific, selective deficit for social cognition was also confirmed after further controlling for overall cognitive functioning. Our findings capitalize on previous evidence demonstrating that social cognition impairments in RRMS have domain-specific characteristics and can be reliably detected in a new cultural context.

INTRODUCTION:This study aimed to characterize demographic features, clinical presentations, and long-term outcomes of pediatric-onset multiple sclerosis (POMS) patients in a Turkish tertiary MS center. METHODS:We retrospectively analyzed 143 patients diagnosed with multiple sclerosis (MS) before age 16, based on the 2017 McDonald criteria, and clinically monitored between 1981 and 2018. Demographic and clinical data, including age at onset, initial symptoms, relapse history, and Expanded Disability Status Scale (EDSS) scores, were collected. Disability milestones (EDSS 4 and 6) and conversion to secondary progressive MS (SPMS) were examined using Kaplan-Meier survival analysis and Cox regression. RESULTS:We followed 143 POMS patients for a median of 11 years (69.2% female; median onset age: 14.6 years). By study completion, 22.4% reached EDSS 4 and 16.8% converted to SPMS. Onset before age 14 was associated with a longer time to EDSS 4 (p < 0.001) and SPMS-free survival (p = 0.03). In multivariate analysis, male sex, onset after age 14, higher baseline EDSS, and incomplete recovery from the first attack independently predicted disability progression. Delayed disease modifying therapy initiation (≥12 months) was also associated with increased risk of reaching EDSS 4. SPMS conversion was predicted by onset after age 14, higher baseline EDSS, brainstem onset, and incomplete recovery from the first attack. CONCLUSION:In this large Turkish POMS cohort, onset after age 14, brainstem involvement, and poor recovery from the first attack were associated with earlier disability milestones. These findings highlight the prognostic role of early disease characteristics and emphasize the importance of optimizing treatment strategies in pediatric MS.

Multiple sclerosis (MS) frequently co-occurs with systemic autoimmune diseases (AID). However, the impact of these comorbidities on the long-term clinical course of MS remains controversial, with conflicting reports regarding their effect on disability accumulation. This study aimed to investigate whether the presence of a comorbid AID influences disability progression in a large, single-center cohort of patients with MS. We conducted a retrospective cohort study involving patients recruited from a tertiary referral center. Participants were stratified into two groups: those with a comorbid autoimmune disease (MSpwAID) and those without (MSpwoAID). Conditions affecting the central nervous system were excluded to prevent confounding. The primary outcomes were time to confirmed Expanded Disability Status Scale (EDSS) scores of 3.0 and 6.0. Kaplan-Meier survival curves, multivariate Cox proportional hazards and ANCOVA models were utilized to assess disability progression. The study included 1,230 MS patients, of whom 95 had a comorbid autoimmune disease and 1,135 did not. The MSpwAID group had a significantly higher proportion of female patients and longer disease duration compared to MSpwoAID. Kaplan-Meier analysis revealed no significant difference between the groups regarding the time to reach EDSS 3.0 or EDSS 6.0. The presence of a comorbid AID was not associated with an increased risk of disability progression in adjusted models. Our findings suggest that concurrent AIDs do not independently accelerate long-term disability progression in MS. Nevertheless, screening for these comorbidities remains essential for individualized treatment strategies and minimizing therapeutic risks.

BACKGROUND:Multiple sclerosis (MS) exhibits remarkable heterogeneity in its clinical course, yet the determinants of long-term disability progression remain incompletely understood. Identifying demographic and clinical predictors of unfavorable trajectories is essential for individualized management. OBJECTIVE:To investigate demographic, clinical, and laboratory factors influencing disability progression and relapse dynamics in a large Turkish MS cohort with over two decades of follow-up. METHODS:This retrospective study included 1580 patients diagnosed with MS according to the 2017 McDonald criteria and followed between 1980 and 2020. Data on demographic, clinical, and laboratory parameters were analyzed. Survival analyses assessed time to expanded disability status scale (EDSS) 3 and 6 milestones, and logistic regression identified predictors of progressive disease. RESULTS:The cohort comprised 1092 females and 488 males (mean follow-up: 7.5 ± 5.7 years). Male sex and lower educational attainment were associated with faster disability accumulation (log-rank, p < 0.005 and p < 0.001, respectively). Motor, cerebellar, and spinal onset were significant predictors of a progressive phenotype, while optic neuritis, sensory, and brainstem onset indicated a relapsing-remitting course. Neither smoking, family history, nor oligoclonal band (OCB) positivity influenced disability progression. Inter-relapse intervals shortened until the fifth relapse, thereafter stabilizing, marking a potential inflection point in inflammatory activity. CONCLUSION:This long-term cohort highlights distinct demographic and clinical predictors of MS progression. Early disability accumulation, particularly before reaching EDSS 3, appears critical in determining long-term outcomes. These findings emphasize the importance of early, aggressive therapeutic intervention within the initial disease phase to alter the trajectory of MS progression.

OBJECTIVES:Somatosensory evoked potentials (SEP) reflect functional integrity of sensory pathways and may predict disability progression in multiple sclerosis (MS). Cervical spinal cord atrophy is thought to reflect neurodegenerative processes and may contribute to disability in MS. This study aimed to investigate the association between SEP abnormalities, cervical spinal cord atrophy, and disability progression in MS. METHODS:In this retrospective cohort study, MS patients who underwent SEP examination and had at least two cervical spinal MRI scans acquired more than one year apart were included. Cervical spinal cord cross-sectional areas (C2-3, C3-4) were automatically quantified using a validated deep learning segmentation model. SEP and visual evoked potentials (VEPs) were dichotomized as normal or pathological based on institutional normative values. Disability progression was assessed by time to Expanded Disability Status Scale (EDSS) scores of 3 and 6 using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS:A total of 47 patients were included. SEP abnormalities were observed in 46.8% of patients. Pathological SEP was associated with higher annual cervical spinal cord atrophy rates and a significantly shorter time to EDSS 3, but not EDSS 6. Pathological SEP was associated with earlier attainment of EDSS 3 (HR 3.4). DISCUSSION:SEP abnormalities are associated with increased cervical spinal cord atrophy and early disability progression in MS, supporting SEP as an electrophysiological biomarker of spinal cord involvement.

Multiple sclerosis (MS) is becoming more prevalent. Physical impairments and sleep issues, particularly fatigue, diminish these patients’ quality of life. One of the most successful and long-lasting strategies for managing symptoms is patient education. The aim of this study was to evaluate effect of a nurse-led online support program on fatigue, sleep, and quality of life in patients with multiple sclerosis (PwMS). This quasi-experimental study was conducted in the MS outpatient clinic of a university hospital in Istanbul. Patients participated in a five-week nurse-led online support program and were assessed using the Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), and EQ-5D Quality of Life Scale before, after, and at 3 and 6 months. Patients’ step counts were also recorded. Thirty patients who completed the program were included in the study. Compared to baseline, FSS scores and number of steps improved (p = 0.008, p = 0.008). PSQI scores also improved (p = 0.026). Although there was no difference in EQ-5D symptom scores, the EQ-5D visual analogue scale scores tended to improve (p = 0.085). A nurse-led online support program may be a feasible and resource-efficient approach to managing fatigue and sleep disturbances in PwMS, especially in settings with limited access to care. Larger controlled studies are needed to confirm these findings. This study was registered on ClinicalTrials.gov on August 24, 2023 (NCT06166043).

Objective Multiple sclerosis (MS) may present with predominant involvement of the spinal cord and optic nerve (MS/w-SCON) and mimic other autoimmune inflammatory demyelinating disorders (AIDD) such as neuromyelitis optica spectrum disorder (NMOSD), and relapsing inflammatory optic neuritis (RION). Thus, biomarkers are required for effective differential diagnosis of AIDD. Methods Patients with MS/w-SCON (n=20), MS without involvement of SCON (MS/wo-SCON) (n=22), NMOSD (n=16), RION (n=15) and healthy individuals (n=21) were included. Peripheral blood cell immunophenotypes were analyzed by flow cytometry and gene expression levels of isolated B cells were assessed by microarray analysis and quantitative real-time PCR. Results Significantly increased Breg, plasmablast, and plasma cell ratios distinguished MS/w-SCON from other groups. Most differentially expressed B cell genes were subjected to protein-protein interaction yielding a network of 13 immune mediators (IL18, IL18R1, P2RY12, CSF3R, TNFSF4, TNFRSF13C, TNFRSF1A, CCL20, CCL5, CCR4, CCL4L2, CXCL5, CXCL10). CCL4L2 and CCR4 expression levels distinguished MS/w-SCON. IL18/IL18R1 and CCL5 were distinguishing factors for NMOSD and RION, respectively. Conclusion Peripheral blood B cell expression levels of CCL4L2, CCR4, IL18, IL18R1 and CCL5 are candidate biomarkers for differential diagnosis of AIDD of CNS. Our results substantiate the significance of B cells in the pathogenesis of these disorders.

Introduction: While tissue sampling through brain biopsy is rarely required throughout the Multiple sclerosis (MS) disease course, it remains essential in cases with atypical clinical or radiological findings where other diagnostic methods are inconclusive. This study aims to present brain biopsy findings in patients diagnosed with MS. Methods: MS patients were screened from the national database. Brain MRI scans of all MS patients who underwent brain biopsywere reviewed to confirm the compliance of MAGNIMS criteria. Data on MS diagnosis, biopsy date, disease-modifying therapy (DMT) use, and the duration of DMT exposure prior to biopsy were also collected. Pathology reports of brain biopsies were reviewed with these parameters. Results: Among 87,640 MS patients, 21 patients had brain biopsies after MS diagnosis, highlighting the rarity (0.02%) of this invasive procedure, with a median age at biopsy of 43 (IQR: 13) years. Pathological findings revealed 12 malignant diagnoses, including lymphoma, glioblastoma, metastasis, and nine non-malignant conditions, such as vasculitis, demyelination, and benign masses. Conclusion: Brain biopsy is rarely required in patients with MS; however, it should be considered in cases of atypical lesion development, underscoring the need for meticulous clinical monitoring.

Background: Both the presence of multiple sclerosis (MS) and the use of immunomodulatory therapy for this disease can change the vaccine response in individuals with MS. In this study, due to the lack of guidelines for vaccination of MS patients in our country, the aim was to create a Delphi consensus on vaccination practices and vaccine types in MS patients. Methods: The Real-time Delphi technique, a more structured and predefined version of the traditional Delphi study was used to ensure a comprehensive research process. The stages of the structured online Delphi application process, which includes repeated rounds, (three rounds) are applied. Fifteen participants are sufficient to achieve homogeneous outcomes according to expertise criteria and in this study, the group comprised 31 experts who met these criteria and participated in all stages. Results: The assessment of the level of consensus among panelists revealed that there was "almost perfect consensus" on 16 items and "significant consensus" on 12 items. When examining the items in which the panelists did not reach a consensus, it was found that there was "minor consensus (slight-1)" on 1 item, and there was "no consensus (indicate poor-0)" on 2 items. Conclusion: We wanted to share a "country" practice and our current recommendations on vaccination strategies, by making use of articles containing country-based recommendations and working-group recommendations, as well as our national experiences.

Tumefactive demyelinating lesions (TDLs) are tumor-like inflammatory demyelinating lesions that may occur within the spectrum of multiple sclerosis (MS) or other neuroinflammatory conditions. TDLs account for 1.4–8.2