From the Departments of Neurology (E.A.K., A.I., E.B.H., B.L.C., G.K.A.) and Neuroscience (H.M.), Perelman School of Medicine, and Department of Psychology (D.H.B.), University of Pennsylvania, Philadelphia.
Neurology. 2021 Oct 26;97(17):e1672-e1680. doi: 10.1212/WNL.0000000000012734. Epub 2021 Sep 7.
To quantify interictal photophobia in migraine with and without aura using reflexive eye closure as an implicit measure of light sensitivity and to assess the contribution of melanopsin and cone signals to these responses.
Participants were screened to meet criteria for 1 of 3 groups: headache-free (HF) controls, migraine without aura (MO), and migraine with visual aura (MA). MO and MA participants were included if they endorsed ictal and interictal photophobia. Exclusion criteria included impaired vision, inability to collect usable pupillometry, and history of either head trauma or seizure. Participants viewed light pulses that selectively targeted melanopsin, the cones, or their combination during recording of orbicularis oculi EMG (OO-EMG) and blinking activity.
We studied 20 participants in each group. MA and MO groups reported increased visual discomfort to light stimuli (discomfort rating, 400% contrast, MA: 4.84 [95% confidence interval 0.33, 9.35]; MO: 5.23 [0.96, 9.50]) as compared to HF controls (2.71 [0, 6.47]). Time course analysis of OO-EMG and blinking activity demonstrated that reflexive eye closure was tightly coupled to the light pulses. The MA group had greater OO-EMG and blinking activity in response to these stimuli (EMG activity, 400% contrast: 42.9%Δ [28.4, 57.4]; blink activity, 400% contrast: 11.2% [8.8, 13.6]) as compared to the MO (EMG activity, 400% contrast: 9.9%Δ [5.8, 14.0]; blink activity, 400% contrast: 4.7% [3.5, 5.9]) and HF control (EMG activity, 400% contrast: 13.2%Δ [7.1, 19.3]; blink activity, 400% contrast: 4.5% [3.1, 5.9]) groups.
Our findings suggest that the intrinsically photosensitive retinal ganglion cells (ipRGCs), which integrate melanopsin and cone signals, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Moreover, we find a dissociation between implicit and explicit measures of interictal photophobia depending on a history of visual aura in migraine. This implies distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which the amplification of ipRGC signals elicits implicit and explicit signs of visual discomfort.
本研究旨在通过反射性闭眼来量化偏头痛伴或不伴先兆患者的发作间期畏光情况，以此作为衡量光敏感性的隐性指标，并评估褪黑素能和视锥信号对这些反应的贡献。
参与者需满足以下 3 个组别之一的标准进行筛选：无头痛（HF）对照组、偏头痛无先兆（MO）组和偏头痛伴视觉先兆（MA）组。若 MO 和 MA 患者出现发作期和发作间期畏光，则将其纳入研究。排除标准包括视力受损、无法收集可用的瞳孔测量数据，以及头部外伤或癫痫病史。参与者在记录眼轮匝肌肌电图（OO-EMG）和眨眼活动的同时，观看选择性靶向褪黑素能、视锥或两者组合的光脉冲。
每组纳入 20 名参与者。与 HF 对照组（2.71 [0，6.47]）相比，MA 和 MO 组报告对光刺激的视觉不适明显增加（不适评分，400%对比度，MA：4.84 [95%置信区间 0.33，9.35]；MO：5.23 [0.96，9.50]）。OO-EMG 和眨眼活动的时程分析表明，反射性闭眼与光脉冲紧密耦合。与 MO 组（OO-EMG 活动，400%对比度：9.9%Δ [5.8，14.0]；眨眼活动，400%对比度：4.7% [3.5，5.9]）和 HF 对照组（OO-EMG 活动，400%对比度：13.2%Δ [7.1，19.3]；眨眼活动，400%对比度：4.5% [3.1，5.9]）相比，MA 组对这些刺激的 OO-EMG 和眨眼活动增加（EMG 活动，400%对比度：42.9%Δ [28.4，57.4]；眨眼活动，400%对比度：11.2% [8.8，13.6]）。
我们的研究结果表明，内在光敏性视网膜神经节细胞（ipRGCs）整合褪黑素能和视锥信号，为光诱导反射性闭眼提供了在畏光状态下的传入输入。此外，我们发现偏头痛患者的发作间期畏光的隐性和显性测量之间存在差异，这取决于是否有视觉先兆的病史。这意味着偏头痛的不同形式存在不同的病理生理学机制，通过独立的神经通路相互作用，放大 ipRGC 信号引发隐性和显性视觉不适症状。
