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While acknowledging limited evidence, the authors stress a theoretical mechanism: blocking CGRP dampens compensatory vasodilation, risking hypoperfusion, transient ischemic attacks, or stroke. They note CGRP blockade worsening strokes in animal models, discuss RCT exclusions of relevant vascular disease, and call to classify CGRP-targeting agents as contraindicated in MMA, paralleling triptans.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/letter-to-the-editor-reaffirming-caution-the-unacceptable-vasoconstrictive-risk-of-cgrp-related-therapies-in-moyamoya-angiopathy/468312/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/letter-to-the-editor-reaffirming-caution-the-unacceptable-vasoconstrictive-risk-of-cgrp-related-therapies-in-moyamoya-angiopathy/468312.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why do the authors consider headache treatment in Moyamoya angiopathy particularly challenging?","Question",{"text":112,"@type":113},"They emphasize that MMA stroke mechanisms are hemodynamic, embolic, and hemorrhagic, each carrying different treatment risks. This complexity makes both acute and prophylactic headache management difficult.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What mechanism leads to the authors’ concern about CGRP-related therapies in MMA?",{"text":117,"@type":113},"CGRP is described as a potent endogenous vasodilator that supports perfusion during ischemia. 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The stroke mechanisms in MMA are hemodynamic, embolic, and haemorrhagic, all of which carry different risks for treatment. High-dose ASA, for example, may lead to an increased risk of bleeding in this patient group with a pre-existing increased risk. NSAIDs are suboptimal due to their interaction with ASA used for ischemia prophylaxis; metamizole may lead to hypotension, and triptans, due to their vasoactive properties, are not only formally contraindicated in this context. Regarding prophylactic treatment, we find calcium channel blockers and beta blockers difficult due to hypotension and the resulting hemodynamic risks.  \nHowever, our most important addition to the Consensus Review is our stricter assessment of calcitonin gene-related peptide (CGRP) antagonists. Although the authors adopted a cautious approach to the use of CGRP-based therapies, we believe that the severity of the inherent vascular risk in MMA requires an even more definitive stance against these agents.  \nThe available evidence, while limited, points to a potential for harm that far outweighs the therapeutic benefit in this high-risk population.  \n1 | Unacceptable Risk Profile of CGRP Blockade in MMA  \nThe core pathophysiology of MMA involves progressive stenoocclusive disease of the intracranial carotid arteries and the compensatory formation of fragile collateral (Moyamoya) vessels. In this delicate, flow-compromised system, maintaining adequate cerebral blood flow (CBF) and oxygen delivery is paramount [1].  \nCGRP is one of the most potent endogenous vasodilators [2] . Its presence is particularly vital in the setting of ischemia, where it acts as a critical compensatory mechanism to maximize blood flow and perfusion pressure [3] . This appears to be of the utmost relevance when considering the pathophysiology of MMA. Blocking this compensatory mechanism carries an unacceptable theoretical risk of precipitating cerebral ischemic events. By dampening the body's intrinsic ability to induce vasodilation in areas of critical flow, CGRP-related therapies could potentially shift the delicate balance, leading to hypoperfusion, transient ischemic attacks (TIAs), or stroke, particularly in patients with borderline flow dynamics.  \nThe risk here is not just theoretical, as Mulder and colleagues were able to document very clearly and convincingly that  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2026 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.  \nEuropean Journal of Neurology, 2026; 33:e70481 1 of 2  \n[https://doi.org/10.1111/ene.70481](https://doi.org/10.1111/en","cbCaiaJI6TrXSW2J","https://ap.wps.com/l/cbCaiaJI6TrXSW2J","pdf",145154,"English","# Letter to the Editor\n## Key challenges in headache treatment for Moyamoya angiopathy\n## Unacceptable risk profile of CGRP blockade in MMA\n## Call for contraindication","[{\"question\":\"Why do the authors consider headache treatment in Moyamoya angiopathy particularly challenging?\",\"answer\":\"They emphasize that MMA stroke mechanisms are hemodynamic, embolic, and hemorrhagic, each carrying different treatment risks. This complexity makes both acute and prophylactic headache management difficult.\"},{\"question\":\"What mechanism leads to the authors’ concern about CGRP-related therapies in MMA?\",\"answer\":\"CGRP is described as a potent endogenous vasodilator that supports perfusion during ischemia. Blocking CGRP could impair compensatory vasodilation in a flow-compromised system, increasing risk of hypoperfusion and ischemic events.\"},{\"question\":\"What is the authors’ requested clinical stance on CGRP-targeting therapies for MMA patients?\",\"answer\":\"They call for CGRP-related therapies to be classified as contraindicated for MMA, similar to triptans in acute treatment, because of the impaired compensatory vasodilation and lack of safety data.\"}]","Letter to the Editor - Reaffirming Caution - The Unacceptable Vasoconstrictive Risk of CGRP-Related Therapies in Moyamoya Angiopathy | PDF",1790774031]