Tohyama Sarasa, Datko Michael, Brusaferri Ludovica, Kinder Lillian D, Schnieders Jack H, Hyman Mackenzie, Goldstein Alison M, Gilbert Melaina D, Housman Hope, Le Vi, Round Kassandra, Marin Frances, Heffernan Megan R, Garcia Ronald G, Gollub Randy L, Edwards Robert R, Rosen Bruce R, Hadjikhani Nouchine, Cheng Hsinlin T, Schuman-Olivier Zev, Loggia Marco L, Napadow Vitaly
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA 02129, USA.
Brain. 2025 Jan 28. doi: 10.1093/brain/awaf029.
Although the pathophysiology of migraine involves a complex ensemble of peripheral and central nervous system changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system is believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean age ± SD: 36.28 ± 11.95 years) and 20 age-/sex-matched healthy controls (19 females, mean age ± SD: 35.45 ± 13.30 years) using ultra-high field 7 Tesla diffusion tensor imaging and functional MRI, as well as PET with the translocator protein ligand [11C]-PBR28. We evaluated MRI diffusivity measures and PET signal at the trigeminal nerve root, as well as brainstem functional MRI response to innocuous, ophthalmic trigeminal nerve territory stimulation. Patients with migraine demonstrated altered white matter microstructure at the trigeminal nerve root (n=53), including reduced fractional anisotropy, compared to healthy controls (n=18). Furthermore, in patients, lower fractional anisotropy was accompanied by 1) higher neuroinflammation (i.e. elevated [11C]-PBR28 PET signal) at the nerve root (n=36) and 2) lower functional MRI activation in an ipsilateral pontine cluster consistent with spinal trigeminal nucleus (n=51). These findings were more robust on the right side, which was consistent with the observation that right headache dominant patients demonstrated higher migraine severity compared to left headache dominant patients in our cohort. Multimodal imaging of the integrated neural mechanisms that characterize migraine underscores the importance of trigeminal system remodeling as both a key aspect of the dynamics underlying migraine pathophysiology and a target for therapeutic interventions.
尽管偏头痛的病理生理学涉及外周和中枢神经系统的一系列复杂变化，目前仍未完全了解，但三叉神经血管系统的激活和敏化被认为起主要作用。然而，研究人类偏头痛患者三叉神经系统异常潜在神经机制的非侵入性体内神经影像学研究有限。在此，我们使用超高场7特斯拉扩散张量成像、功能磁共振成像以及使用转位蛋白配体[11C]-PBR28的正电子发射断层扫描（PET），对60例偏头痛患者（55例女性，平均年龄±标准差：36.28±11.95岁）和20例年龄及性别匹配的健康对照者（19例女性，平均年龄±标准差：35.45±13.30岁）进行了研究。我们评估了三叉神经根处的磁共振扩散率测量值和PET信号，以及脑干功能磁共振成像对无害的眼支三叉神经区域刺激的反应。与健康对照者（n = 18）相比，偏头痛患者在三叉神经根处（n = 53）表现出白质微结构改变，包括分数各向异性降低。此外，在患者中，分数各向异性较低伴随着1）神经根处较高的神经炎症（即[11C]-PBR28 PET信号升高，n = 36）以及2）与三叉神经脊束核一致的同侧脑桥簇中功能磁共振成像激活降低（n = 51）。这些发现在右侧更为明显，这与我们队列中右侧头痛为主的患者比左侧头痛为主的患者偏头痛严重程度更高的观察结果一致。对偏头痛特征性综合神经机制的多模态成像强调了三叉神经系统重塑作为偏头痛病理生理学潜在动态变化的关键方面和治疗干预靶点的重要性。
