复发缓解型和继发进展型多发性硬化中的嗅觉功能障碍与边缘系统体积变化

文献信息

中文摘要

目的： 比较复发缓解型多发性硬化（RRMS）与继发进展型多发性硬化（SPMS）患者的嗅觉表现及嗅觉相关脑区体积，并探讨嗅觉表现与区域脑体积之间的关系。
材料与方法： 这项前瞻性横断面研究纳入65例MS患者（43例RRMS和22例SPMS）。使用Sniffin' Sticks-12气味识别测试评估嗅觉功能。通过volBrain平台可用的vol2Brain自动分析流程，从三维T1加权MRI获取海马、杏仁核、内嗅皮层和岛叶皮层的双侧体积。分析原始和经总颅内体积（TIV）标准化的区域体积。对于体积结局，多变量分析校正年龄、性别和TIV；而嗅觉表现分析校正年龄和性别。额外的敏感性分析纳入病程和EDSS。
结果： 在未校正比较中，SPMS患者的Sniffin' Sticks-12评分显著低于RRMS患者（p=0.004），且SPMS组原始海马体积显著较低（p=0.028）。然而，在校正年龄、性别和TIV后，临床亚型与海马、杏仁核、内嗅皮层或岛叶皮层体积无独立关联（所有p>0.05）。这些发现在额外考虑病程和EDSS的敏感性分析中仍无统计学意义。校正年龄和性别后，Sniffin' Sticks-12评分的组间差异也减弱（B=-1.06；95% CI，-2.15至0.04；p=0.058），并在进一步敏感性分析中仍无统计学意义。未观察到Sniffin' Sticks-12评分与区域体积测量之间存在显著相关性。
结论： 尽管SPMS患者在未校正比较中表现出较差的嗅觉表现和较低的原始海马体积，但在校正年龄、性别和TIV后，临床亚型与区域脑体积无独立关联，且校正年龄和性别后嗅觉差异未达到统计学显著性。此外，嗅觉表现与区域体积测量无直接关联，提示MS中的嗅觉功能障碍可能反映区域结构体积之外的机制。

英文摘要

OBJECTIVE: To compare olfactory performance and olfactory-related brain region volumes between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) and to examine the relationship between olfactory performance and regional brain volumes.
MATERIALS AND METHODS: This prospective cross-sectional study included 65 patients with MS (43 RRMS and 22 SPMS). Olfactory function was assessed using the Sniffin' Sticks-12 Odor Identification Test. Bilateral volumes of the hippocampus, amygdala, entorhinal cortex, and insular cortex were obtained from three-dimensional T1-weighted MRI using the vol2Brain automated analysis pipeline available through the volBrain platform. Both raw and total intracranial volume (TIV)-normalized regional volumes were analyzed. For volumetric outcomes, multivariable analyses were adjusted for age, sex, and TIV, whereas analyses of olfactory performance were adjusted for age and sex. Additional sensitivity analyses incorporated disease duration and EDSS.
RESULTS: In unadjusted comparisons, patients with SPMS had significantly lower Sniffin' Sticks-12 scores than those with RRMS (p = 0.004), and raw hippocampal volume was significantly lower in the SPMS group (p = 0.028). However, after adjustment for age, sex, and TIV, clinical subtype was not independently associated with hippocampal, amygdala, entorhinal cortex, or insular cortex volume (all p > 0.05). These findings remained non-significant in sensitivity analyses additionally accounting for disease duration and EDSS. The between-group difference in Sniffin' Sticks-12 scores was also attenuated after adjustment for age and sex (B = - 1.06; 95% CI, - 2.15 to 0.04; p = 0.058) and remained non-significant in further sensitivity analyses. No significant correlations were observed between Sniffin' Sticks-12 scores and regional volumetric measures.
CONCLUSION: Although patients with SPMS showed poorer olfactory performance and lower raw hippocampal volume in unadjusted comparisons, clinical subtype was not independently associated with regional brain volumes after adjustment for age, sex, and TIV, and the olfactory difference did not reach statistical significance after adjustment for age and sex. Furthermore, olfactory performance was not directly associated with regional volumetric measures, suggesting that olfactory dysfunction in MS may reflect mechanisms beyond regional structural volume alone.