Department of Neurosurgery, Bonn, Germany; University Hospital Bonn, Rheinische Friedrich-Wilhelms-University of Bonn, Germany.
Department of Neurosurgery, Bonn, Germany; Helsinki University Hospital, Helsinki, Finland.
Brain Stimul. 2019 May-Jun;12(3):643-651. doi: 10.1016/j.brs.2019.01.008. Epub 2019 Jan 19.
To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.
This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.
No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p < 0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p > 0.05]. No severe device-/stimulation-related adverse events occurred.
2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics].
检测偏头痛患者外周发作间期细胞因子的血清水平，并探讨其与非侵入性迷走神经刺激（nVNS）反应性的关系。
本双盲、假刺激对照研究纳入了 48 名受试者，在基线时和 nVNS 辅助治疗 2 个月后（与假刺激和适当匹配的对照组相比），通过酶联免疫吸附试验测量头痛严重程度、频率[每月头痛天数、每月总头痛发作次数和轻度/中度/重度头痛发作次数]、功能状态[睡眠、情绪、体重、偏头痛相关残疾]和炎症标志物的血清水平[发作间期]。
在基线和 2 个月时，与假刺激 nVNS 相比，真刺激 nVNS 组的头痛严重程度、每月总头痛发作次数、每月头痛天数和功能结局[睡眠、情绪、残疾]无显著差异。然而，每月重度头痛发作次数在真刺激 nVNS 组中显著减少，而在假刺激组中循环促炎细胞因子 IL-1β水平显著升高。与健康对照组相比，两组在基线时的抗炎细胞因子 IL-10 水平均显著升高，但在 2 个月随访时则无差异[P<0.05]。高迁移率族蛋白 1（HMGB-1）、IL-6、肿瘤坏死因子-α（TNF-α）、瘦素、脂联素、胃饥饿素的浓度无变化[P>0.05]。未发生严重的设备/刺激相关不良事件。
2 个月的辅助性颈部 nVNS 可显著减少每月重度头痛发作次数。与真刺激 nVNS 相比，假刺激治疗的偏头痛患者的发作间期促炎细胞因子 IL-1β 血浆水平更高。然而，促炎[IL-6、HMGB-1、TNF-α、瘦素]和抗炎[IL-10、脂联素、胃饥饿素]介质的水平无统计学差异。偏头痛神经炎症回路的分析以预测 nVNS 反应性仍然是一种实验方法，可能受到预分析变量的影响，需要基于生物样本库的大规模系统研究[组学]。
