Abdorreza Naser Moghadasi

Background: Quantitative susceptibility mapping (QSM) characterizes multiple sclerosis (MS) lesions through susceptibility changes related to iron and myelin. However, the prevalence, regional distribution, and relationship of QSM‐defined lesion subtypes with choroid plexus alterations remain unclear. Purpose: To characterize MS lesion subtypes using QSM and evaluate their prevalence, regional distribution, and associations with choroid plexus volume changes. Study Type: Prospective longitudinal study. Population: Forty‐six patients with MS (44 relapsing–remitting, 2 primary progressive; mean age, 37 ± 8 years). QSM data were available for lesion classification in 32 participants. Field Strength/Sequence: 1.5T MRI with 3D T2‐FLAIR, 3D T1‐MPRAGE, and multi‐echo gradient‐echo sequences for QSM. Assessment: Following whole‐brain segmentation, white matter was parcellated into periventricular, juxtacortical, and deep regions. White matter lesions were segmented using the SAMSEG algorithm and classified on QSM as isointense, hypointense, hyperintense, or paramagnetic rim lesions. Lesion counts, lesion volumes, regional distribution, and associations with choroid plexus volume changes were evaluated. Statistical Tests: Normality was assessed using the Kolmogorov–Smirnov test. Spearman correlation and Mann–Whitney U tests were used. Bonferroni correction was applied for multiple comparisons. Results: Eight hundred ninety lesions were identified: 512 isointense (57.1%), 65 hypointense (7.2%), 291 hyperintense (32.4%), and 29 paramagnetic rim lesions (3.2%). Isointense and hypointense lesions, potentially reflecting different stages of tissue repair, accounted for 64.3% of all lesions. Juxtacortical white matter was most frequently affected (43.4%), followed by subcortical (40.4%) and periventricular (16.2%) regions. Hyperintense lesion volume correlated significantly with baseline lesion volume ( r = 0.71), follow‐up lesion volume ( r = 0.81), and total lesion volume ( r = 0.87). Total lesion volume was significantly associated with bilateral choroid plexus volume changes ( r = 0.515–0.595). Data Conclusion: QSM has the potential to characterize MS lesion heterogeneity by identifying distinct lesion susceptibility patterns. Total lesion volume was associated with choroid plexus volume changes. Evidence Level: 2. Technical Efficacy: Stage 2.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, immune‐mediated astrocytopathy disorder that predominantly affects adults. Postoperative cases are scarcely reported. A 75‐year‐old woman underwent uncomplicated endoscopic resection of a nonfunctional pituitary macro‐adenoma. Seven days postoperatively, she developed encephalopathy without focal deficits. Magnetic resonance imaging (MRI) revealed extensive confluent T ₂ and fluid attenuated inversion recovery (FLAIR) hyperintensities in the corpus callosum, periventricular white matter, and cervical spinal cord, absent preoperatively. Metabolic, infectious, and structural etiologies were excluded. Despite high‐dose corticosteroids and intravenous immunoglobulin (IVIG) administration, she deteriorated with brainstem involvement, respiratory failure, and fatal arrhythmias. This exceptionally rare case emphasizes NMOSD as a critical differential in postoperative neurological decline, particularly after CNS procedures. Clinicians must prioritize early recognition to guide timely intervention. Future studies should investigate surgical stress, pituitary dysfunction, and immune activation in demyelination pathogenesis.

Serum biomarkers such as soluble triggering receptor expressed on myeloid cells-2 (sTREM-2) and glial fibrillary acidic protein (GFAP) can indicate astrocyte and microglial activity in Multiple sclerosis (MS) patients. GFAP has been linked to disability progression, but the role of serum sTREM-2 in MS disability remains unclear. To assess the relationship between serum levels of GFAP and sTREM-2, the Expanded Disability Status Scale (EDSS), and clinical characteristics in MS patients. This cross-sectional study involved 120 MS patients who were diagnosed using the updated 2017 McDonald criteria at Sina Hospital in Tehran, Iran. Following the collection of demographic data and EDSS scores, patient blood samples were obtained, and serum levels of GFAP and sTREM-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. After determining normality, the connection between serum GFAP and sTREM-2 levels and clinical variables was examined using appropriate tests. The squared correlation coefficient was calculated for significant biomarker-EDSS correlations to estimate the percentage of explained/shared variance. The significance level was set at p < 0.05. The mean ± standard deviation (SD) age of participants was 38.72 ± 8.86 years. The majority were female, comprising 79.2% of the sample (95 out of 120). Most patients had relapsing-remitting MS (RRMS, 79.2%). The median EDSS score was 2.50 (IQR 1.0-4.0). The median serum levels of GFAP and sTREM-2 were 1.13 (0.85-1.38) ng/mL and 0.60 (0.39-0.86) ng/mL, respectively. Both GFAP and sTREM-2 showed statistically significant but modest-to-weak positive correlations with EDSS. GFAP was correlated with EDSS (r = 0.279, p = 0.002), corresponding to approximately 7.8% explained/shared variance, while sTREM-2 was correlated with EDSS (r = 0.199, p = 0.030), corresponding to approximately 4.0% explained/shared variance. In multivariable linear regression models adjusting for age, sex, disease duration, MS subtype, DMT efficacy, and relapse rate, both GFAP (p = 0.020) and sTREM-2 (p = 0.035) remained independently associated with EDSS. There was no significant correlation found between age, disease duration, annual relapse rate, MS subtypes, treatment groups, and the biomarkers studied. Our results show statistically significant but modest-to-weak positive correlations between EDSS and serum levels of sTREM-2 and GFAP, suggesting these biomarkers could help evaluate current disability and further our knowledge of MS pathophysiology.

Background Ocrelizumab, a CD20-targeting monoclonal antibody, is a novel disease-modifying therapy for relapsing-remitting multiple sclerosis (MS) and primary progressive multiple sclerosis. Despite established efficacy in reducing relapse rates and disease progression, its impact on patient-reported outcomes (PROs) such as health-related quality of life (HRQOL), depression, and fatigue remains understudied. Methods This single-arm observational study included 30 MS patients receiving ocrelizumab at a tertiary center in Tehran, Iran. Selected PROs were assessed at 0-, 6-, and 12-month time points using the Medical Outcomes Study Short Form-36 for HRQOL, the Beck Depression Inventory-II for depression severity, and the Fatigue Severity Scale for fatigue. Longitudinal changes were analyzed using linear mixed models. Linear regression models were used to explore associations between patient demographics, clinical characteristics, and PRO scores at baseline. Results At baseline, participants had impaired HRQOL across multiple domains. Over 12 months, significant improvements were observed in general health (P < .001), vitality (P = .032), and role-emotional (P = .012), along with increases in the mental (P = .026) and physical (P = .020) component summary scores. Depression severity decreased significantly (P = .029), but no significant changes were detected in fatigue levels (P = .818). Higher baseline EDSS was associated with lower physical functioning (P < .001) and general health (P = .023). Conclusion Ocrelizumab treatment was associated with improved physical and mental HRQOL and reduced depression severity in MS patients.

Background: Anti-CD20 are among the high-efficacy DMTs commonly used in treating multiple sclerosis (MS). Long-term safety data on anti-CD20s are limited. There is convincing evidence of hypogammaglobulinemia in the long-term use of anti-CD20s, raising the likelihood of infection. Accordingly, there is an unmet need for de-escalation therapy in stable patients to reduce adverse events. Herein we aimed to describe our experience with ten relapse-remitting MS (RRMS) patients who were switched from anti-CD20s to the low-moderate efficacy DMTs. Methods: This cohort study was conducted between January 2020 and February 2023 at the MS Research Center of Sina Hospital, Tehran, Iran, to identify the characteristics of RRMS patients who were switched from anti-CD20s to low-moderate efficacy DMTs within 12 months of the last anti-CD20 infusion. Patients were then followed up to 18 months after de-escalation. Results: All patients were females, with a mean age of 39.3 +/- 2.53-year-old and a mean disease duration of 9.7 +/- 1.39 years. After a mean of 2.95 +/- 0.44 years of treatment with anti-CD20s, patients were de-escalated to INF-beta 1a (n=5), dimethyl fumarate (DMF) (n=3), fingolimod (n=1), and teriflunomide (n=1). The main reason for anti-CD20 discontinuation was an infectious concern. Within 18 months of follow-up, no patient developed clinical or MRI activity. Additionally, we did not find evidence of disability progression in any patients (P=0.13). Conclusion: The present study is a real-world experience of de-escalating anti-CD20s to low-moderate efficacy DMTs, which suggests that at short-term follow-up, deescalating anti-CD20s appeared to be effective and safe in RRMS patients.

We aim to discuss the importance of accurately diagnosing atypical inflammatory demyelinating diseases (IDD), particularly neuromyelitis optica spectrum disorders (NMOSD), which exhibit similar pathological characteristics to multiple sclerosis (MS). An accurate diagnosis is crucial as the disease‐modifying treatments (DMTs) used for MS can be ineffective or even exacerbate NMOSD. Our case was a 20‐year‐old man who presented with acute quadriparesis and hyperreflexia. Brain and cervical MRI revealed several T2‐weighted hyperintensities in the periventricular and corticomedullary junction areas. The CSF analysis showed six oligoclonal bands restricted to the CSF, and the serum AQP4‐IgG was negative. The patient was diagnosed with an atypical relapsing and remitting MS based on the 2017 revised McDonald criteria and was treated with intravenous methylprednisolone and therapeutic plasma exchange. Eventually, his EDSS score improved from 8.5 to 3 after treatment with rituximab. Accurate diagnosis of atypical cases of IDD is not only to prevent potential harm associated with misdirected therapies but also to promptly initiate the most effective treatment. Vigilance for diagnostic red flags in MS is particularly important given its clinical and radiographic overlap with NMOSD.

Mesenchymal stem cell (MSC) has attracted significant attention in clinical research due to their immunomodulatory properties and potential to reduce inflammation in autoimmune disorders, such as multiple sclerosis (MS). This study evaluates the safety and feasibility of placenta-derived MSCs (PLMSCs) in five participants with secondary-progressive multiple sclerosis (SPMS). The primary outcomes focused on safety and tolerability, assessed through adverse event monitoring over six months. Secondary exploratory outcomes included clinical, imaging, and immunological measures. Patients underwent baseline evaluations and follow-up assessments comprising cognitive and psychological assessments, expanded disability status scale (EDSS), clinical signs, diffusion tensor imaging (DTI), functional MRI (fMRI), cytokine levels (IL-10, IL-6, IL-17, TNFα), and CD20/CD19 B cell marker analysis. No serious complications were noted, except for temporary headache in two patients, which was resolved with tablet. Results demonstrated sustained improvements in clinical outcomes, as indicated by significant reductions in EDSS scores (P < 0.0001), cognitive and psychological assessments, and radial diffusivity (RD) indices (P = 0.0186) in DTI metrics over six months. Furthermore, fMRI analysis showed significant enhancements in brain connectivity and cognitive function. Immunologically, CD20/CD19 B cell markers decreased significantly (P = 0.0077), and anti-inflammatory cytokine IL-10 increased alongside reductions in pro-inflammatory TNFα, IL-6, and IL-17 (P < 0.0001) three months post-therapy. These findings suggest PLMSC transplantation is safe and feasible in SPMS patients. While exploratory outcomes indicate potential clinical and immunological benefits, this phase 1 trial was not designed to assess efficacy. Larger, controlled phase II trials are warranted to validate these preliminary observations and investigate PLMSCs’ therapeutic potential in MS.