Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5–195.2 vs. median 37.2, range 2.3–396.9, < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans.

中文翻译：

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多发性硬化症中的鞘内 B 细胞激活和记忆障碍

认知障碍 (CI) 是多发性硬化症 (pwMS) 患者的常见且致残的特征，但其潜在机制各异且尚未完全了解。已经假设了浸润性免疫细胞在脑膜和脑实质中的作用。本研究旨在探讨鞘内 B 细胞可能影响 pwMS 认知表现的假设。对 39 名新诊断的 pwMS 进行了回顾性研究，这些患者接受了脑脊液 (CSF) 分析。 Kappa (κ) 指数作为鞘内 B 细胞激活的生物标志物进行测量。使用简短可重复神经心理学测试（BRBN）评估认知表现。计算脑 T2 病变数量 (T2LN) 和体积 (T2LV) 以及脑、皮质灰质、丘脑和海马体积，以解释 MRI 可见损伤。伴有言语记忆障碍的 pwMS 患者的 κ 指数较高（中位数 99.6，范围 58.5–195.2 对比中位数 37.2，范围 2.3–396.9，< 0.001），并且与探索言语记忆和信息处理速度的 BRBN 测试呈负相关。在多变量模型中，较高的 κ 指数被证实与探索言语记忆的 BRBN 测试得分较差以及言语记忆障碍的可能性较高独立相关。鞘内 B 细胞可能会导致 pwMS 中的记忆损伤，与 MRI 扫描中可见的脑损伤无关。