Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Ophthalmology, Medical University of Innsbruck, Innsbruck, Austria.
Mult Scler. 2020 Jan;26(1):57-68. doi: 10.1177/1352458518814113. Epub 2018 Nov 22.
Peripapillary retinal nerve fiber layer (pRNFL) thickness and olfactory function are both emerging biomarkers in multiple sclerosis (MS). Impairment of odor identification and discrimination is an irreversible feature of more advanced MS suggested to be associated with neurodegeneration, while olfactory threshold is a transient feature of early, active MS possibly associated with short-term inflammatory disease activity.
The aim of this study was to validate the association of olfactory (dys)function and parameters of MS disease course in a large cohort of MS patients and to correlate olfactory function with pRNFL thickness as a surrogate biomarker of neurodegeneration.
In a cross-sectional design, olfactory function was assessed using the Sniffin' Sticks test, which quantifies three different qualities of olfactory function (threshold, discrimination, and identification). pRNFL thickness was measured by spectral-domain optical coherence tomography (OCT). Results were correlated with age, sex, disease duration, relapses, Expanded Disability Status Scale (EDSS), cognitive function, depression, smoking, and pRNFL thickness by multivariable linear regression models.
We included 260 MS patients (mean age of 35.9 years, 68.7% female). Olfactory threshold correlated significantly with number of relapses in the year prior to assessment and shorter disease duration. Odor discrimination, identification, and their sum score were significantly correlated with longer disease duration, higher EDSS, and reduced cognitive function. pRNFL thickness was associated with identification and discrimination, but not with threshold.
Olfactory threshold is a marker of short-term inflammatory relapse activity unrelated to parameters of neurodegeneration, while odor identification and discrimination are markers of neurodegeneration mostly independent of relapse activity. Assessment of olfactory function provides an opportunity to stratify MS patients with regard to inflammation and neurodegeneration.
视盘周围视网膜神经纤维层（pRNFL）厚度和嗅觉功能都是多发性硬化症（MS）的新兴生物标志物。嗅觉识别和辨别障碍是 MS 更严重阶段的不可逆特征，提示与神经退行性变有关，而嗅觉阈值是早期、活跃 MS 的短暂特征，可能与短期炎症性疾病活动有关。
本研究旨在验证嗅觉（功能）障碍与 MS 病程参数在大型 MS 患者队列中的相关性，并将嗅觉功能与 pRNFL 厚度相关联，作为神经退行性变的替代生物标志物。
采用横断面设计，使用嗅探棒测试评估嗅觉功能，该测试量化了嗅觉功能的三种不同质量（阈值、辨别和识别）。使用谱域光学相干断层扫描（OCT）测量 pRNFL 厚度。通过多元线性回归模型将结果与年龄、性别、疾病持续时间、复发、扩展残疾状况量表（EDSS）、认知功能、抑郁、吸烟和 pRNFL 厚度相关联。
我们纳入了 260 名 MS 患者（平均年龄 35.9 岁，68.7%为女性）。嗅觉阈值与评估前一年的复发次数和较短的疾病持续时间显著相关。气味辨别、识别及其总和与较长的疾病持续时间、较高的 EDSS 和认知功能下降显著相关。pRNFL 厚度与识别和辨别相关，但与阈值无关。
嗅觉阈值是与神经退行性变无关的短期炎症性复发活动的标志物，而嗅觉识别和辨别是主要与复发活动无关的神经退行性变的标志物。嗅觉功能评估为 MS 患者的炎症和神经退行性变分层提供了机会。
