Peripherally acting anti-CGRP monoclonal antibodies alter cortical gray matter thickness in migraine patients: A prospective cohort study.
Peripherally acting anti-CGRP monoclonal antibodies alter cortical gray matter thickness in migraine patients: A prospective cohort study.
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DOI：
10.1016/j.nicl.2023.103531
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发表时间：
2023
影响因子：
4.2
通讯作者：
Burstein, Rami
中科院分区：
文献类型：
--
作者：
Szabo, Edina;Ashina, Sait;Melo-Carrillo, Agustin;Bolo, Nicolas R.;Borsook, David;Burstein, Rami
抗CGRP-mAb在3个月治疗后改变皮质厚度。在反应者的特定皮质区域观察到厚度减少。结果可反映偏头痛患者从高兴奋脑状态恢复的过程。偏头痛的基础是中枢神经系统神经可塑性改变，认为这是由大脑在头痛阶段（皮质过度兴奋）接受的重复性外周传入阻滞引起的。降钙素基因相关肽单克隆抗体（抗CGRP单克隆抗体）是高度有效的偏头痛预防治疗。它们改变治疗应答者与无应答者脑形态测量学的能力尚不清楚。我们的目的是确定抗CGRP-mAb galcanezumab对高频发作性或慢性偏头痛患者治疗3个月后皮质厚度的影响。对36例偏头痛患者在治疗前后进行高分辨率磁共振成像。在该组中，19名患者被分类为应答者（每月偏头痛天数减少≥ 50%），17名被认为是无应答者（每月偏头痛天数减少<50%）。在横截面处理以分析皮质厚度的基线差异后，进行两阶段纵向处理和对称化百分比变化以研究处理相关的脑变化。在基线时，应答者和非应答者之间没有发现显著差异。治疗3个月后，在躯体感觉皮层、前扣带皮层、内侧额叶皮层、上级额回和缘上回区域的反应者中观察到皮层厚度降低（与基线相比）。无应答者表现为左侧背内侧皮质和上级额回皮质厚度减少。我们解释在反应组中观察到的皮质变薄，表明头痛的减轻可能导致神经肿胀和树突复杂性的变化，这种变化反映了从适应不良的神经活动中恢复的过程。我们最近的研究进一步支持了这一结论，该研究表明，治疗开始后3个月，伴随头痛的先兆症状和预防的发生率降低，但先兆症状或预防本身的发生率没有降低（即，皮质变薄与反应者伤害性信号的减少有关）。我们推测，需要更长的恢复期才能让大脑恢复到更“正常”的功能状态，从而不再出现预防性和先兆性症状。
Anti-CGRP-mAbs change cortical thickness after 3-month treatment. Decreased thickness was observed in specific cortical regions in the responders. Results could reflect recovery process from the hyperexcitable brain state in migraine. Migraine is underpinned by central nervous system neuroplastic alterations thought to be caused by the repetitive peripheral afferent barrage the brain receives during the headache phase (cortical hyperexcitability). Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) are highly effective migraine preventative treatments. Their ability to alter brain morphometry in treatment-responders vs. non-responders is not well understood. Our aim was to determine the effects of the anti-CGRP-mAb galcanezumab on cortical thickness after 3-month treatment of patients with high-frequency episodic or chronic migraine. High-resolution magnetic resonance imaging was performed pre- and post-treatment in 36 migraine patients. In this group, 19 patients were classified responders (≥50 % reduction in monthly migraine days) and 17 were considered non-responders (<50 % reduction in monthly migraine days). Following cross-sectional processing to analyze the baseline differences in cortical thickness, two-stage longitudinal processing and symmetrized percent change were conducted to investigate treatment-related brain changes. At baseline, no significant differences were found between the responders and non-responders. After 3-month treatment, decreased cortical thickness (compared to baseline) was observed in the responders in regions of the somatosensory cortex, anterior cingulate cortex, medial frontal cortex, superior frontal gyrus, and supramarginal gyrus. Non-responders demonstrated decreased cortical thickness in the left dorsomedial cortex and superior frontal gyrus. We interpret the cortical thinning seen in the responder group as suggesting that reduction in head pain could lead to changes in neural swelling and dendritic complexity and that such changes reflect the recovery process from maladaptive neural activity. This conclusion is further supported by our recent study showing that 3 months after treatment initiation, the incidence of premonitory symptoms and prodromes that are followed by headache decreases but not the incidence of the premonitory symptoms or prodromes themselves (that is, cortical thinning relates to reductions in the nociceptive signals in the responders). We speculate that a much longer recovery period is required to allow the brain to return to a more ‘normal’ functioning state whereby prodromes and premonitory symptoms no longer occur.
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影响因子：
34.7
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