What is the relationship between Mast Cell Activation Syndrome (MCAS) and Hemiplegic Migraine?

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Last updated: March 26, 2025View editorial policy

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From the Guidelines

Mast Cell Activation Syndrome (MCAS) and hemiplegic migraines are potentially related, with research suggesting that mast cell mediators may trigger neurogenic inflammation and cortical spreading depression, which are implicated in migraine pathophysiology. The relationship between MCAS and hemiplegic migraines is complex and not fully understood, but it is thought that the release of inflammatory mediators from mast cells may contribute to the development of migraine symptoms, including headaches and temporary motor weakness resembling stroke symptoms 1. For patients experiencing both conditions, a comprehensive treatment approach is recommended, including:

  • Medications targeting both conditions, such as H1 antihistamines (e.g., cetirizine 10mg daily or fexofenadine 180mg daily), H2 antihistamines (e.g., famotidine 20mg twice daily), mast cell stabilizers (e.g., ketotifen 1-2mg twice daily or cromolyn sodium 200mg 3-4 times daily), and migraine preventatives (e.g., topiramate starting at 25mg daily, increasing to 50-100mg twice daily, or amitriptyline 10-25mg at bedtime) 1.
  • Lifestyle modifications, including identifying and avoiding triggers for both conditions (certain foods, stress, environmental factors), maintaining regular sleep patterns, staying hydrated, and following an anti-inflammatory diet. It is also important to note that triptans should be used cautiously in hemiplegic migraine, and other treatment options, such as amitriptyline, sodium valproate, cyproheptadine, or a combination of short-acting verapamil hydrochloride or other calcium channel antagonists and aspirin, may be considered 1. Overall, a comprehensive treatment approach that takes into account the potential relationship between MCAS and hemiplegic migraines is essential for managing these conditions and improving patient outcomes.

From the Research

Relationship Between Mast Cell Activation Syndrome (MCAS) and Hemiplegic Migraine

  • There is evidence to suggest a potential link between MCAS and migraines, including hemiplegic migraine, due to the role of mast cells in inflammatory diseases and their presence in the brain and meninges 2.
  • Mast cells can be activated by neuropeptides, leading to the secretion of vasoactive, pro-inflammatory, and neurosensitizing mediators, which may contribute to migraine pathogenesis, including hemiplegic migraine 2.
  • A case series study found that patients with neuropsychiatric disorders, including those with symptoms similar to hemiplegic migraine, experienced significant improvements after mast-cell-directed therapy, suggesting a potential connection between MCAS and hemiplegic migraine 3.
  • Hemiplegic migraine is a rare subtype of migraine with aura associated with transient hemiplegia, and its pathophysiology is similar to that of typical migraine with aura, but with a lower threshold and more severity 4.
  • While there is no direct evidence linking MCAS and hemiplegic migraine, the studies suggest that mast cell activation may play a role in the pathogenesis of migraines, including hemiplegic migraine, and that mast-cell-directed therapy may be beneficial in treating patients with MCAS and neuropsychiatric disorders, including those with symptoms similar to hemiplegic migraine 3, 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The role of mast cells in migraine pathophysiology.

Brain research. Brain research reviews, 2005

Research

Diagnostic and therapeutic aspects of hemiplegic migraine.

Journal of neurology, neurosurgery, and psychiatry, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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