Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2024 Dec;271(12):7547-7556. doi: 10.1007/s00415-024-12689-3. Epub 2024 Sep 19.
Fatigue is commonly observed in pediatric multiple sclerosis (pedMS) patients, but its underlying mechanisms remain largely unexplored. We evaluated whether resting-state (RS) functional connectivity (FC) abnormalities in monoaminergic networks contributed to explain fatigue in pedMS.
Fifty-five pedMS and twenty-three matched healthy controls (HC) underwent clinical and RS functional MRI assessment. Patients with Fatigue Severity Scale (FSS) score ≥ 4 were classified as fatigued (F). Patterns of dopamine-, noradrenaline- and serotonin-related RS FC were derived by constrained independent component analysis, using PET atlases for dopamine, noradrenaline, and serotonin transporters obtained in HCs' brain.
Compared to non-fatigued (NF)-pedMS patients and HC, F-pedMS patients (15/55, 27.3%) showed decreased dopamine-related RS FC in the right postcentral gyrus. They also showed decreased dopamine-related RS FC in the left insula vs. HC and increased dopamine-related RS FC in the left middle temporal gyrus and cerebellum (lobule VI) vs. NF patients. In the noradrenaline-related network, F-pedMS patients showed decreased RS FC in the left superior parietal lobule and increased RS FC in the right thalamus vs. HC and NF-pedMS. Compared to HC, F-pedMS patients also showed decreased RS FC in the right calcarine cortex and increased RS FC in the right middle frontal gyrus. In the serotonin-related network, F-pedMS patients showed decreased RS FC in the right angular gyrus and increased RS FC in the right postcentral gyrus vs. NF-pedMS patients.
In pedMS, fatigue is associated with specific monoaminergic network abnormalities, providing pathological markers for this bothersome symptom and putative targets for its treatment.
疲劳是小儿多发性硬化症（pedMS）患者常见的症状，但疲劳的潜在机制仍未得到充分探索。我们评估了单胺能网络的静息态（RS）功能连接（FC）异常是否有助于解释 pedMS 患者的疲劳。
55 例 pedMS 患者和 23 例匹配的健康对照（HC）接受了临床和 RS 功能磁共振成像评估。疲劳严重程度量表（FSS）评分≥4 的患者被归类为疲劳（F）患者。使用在 HC 大脑中获得的多巴胺、去甲肾上腺素和 5-羟色胺转运体的 PET 图谱，通过约束独立成分分析得出与多巴胺、去甲肾上腺素和 5-羟色胺相关的 RS FC 模式。
与非疲劳（NF）-pedMS 患者和 HC 相比，F-pedMS 患者（15/55，27.3%）右侧中央后回的多巴胺相关 RS FC 降低。与 HC 相比，他们的左侧岛叶和与 NF 患者相比，左侧颞中回和小脑（VI 叶）的多巴胺相关 RS FC 也降低。在去甲肾上腺素相关网络中，F-pedMS 患者的左侧顶上回的 RS FC 降低，右侧丘脑的 RS FC 增加，与 HC 和 NF-pedMS 相比。与 HC 相比，F-pedMS 患者的右侧楔前回的 RS FC 降低，右侧额中回的 RS FC 增加。在 5-羟色胺相关网络中，F-pedMS 患者的右侧角回和与 NF-pedMS 患者相比，右侧中央后回的 RS FC 降低，RS FC 增加。
在 pedMS 中，疲劳与特定的单胺能网络异常相关，为这种烦人的症状提供了病理标志物和潜在的治疗靶点。
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