Anti-CGRP Migraine Drugs May Also Prevent Migraine Aura — Two Case Reports | Research

The takeaway

Two patients with migraine with aura reported complete disappearance or significant reduction of aura symptoms while taking anti-CGRP antibodies, suggesting these peptide-targeting drugs may affect both headache and aura.

Complete aura disappearance
One patient on galcanezumab experienced complete resolution of migraine aura — an unexpected benefit from a drug designed to prevent headache, suggesting CGRP is involved in aura generation.

What the researchers found

Two patients with migraine with aura reported striking improvements in their aura symptoms while taking anti-CGRP antibodies. One patient on galcanezumab experienced complete disappearance of aura, while another on erenumab had reduced aura duration and intensity. This is notable because anti-CGRP antibodies are primarily expected to work peripherally (they can't easily cross the blood-brain barrier), yet migraine aura is believed to originate from cortical spreading depression — a brain phenomenon.

Why it matters

Migraine aura — visual disturbances, numbness, or speech difficulties before headache — has no specific treatment. Anti-CGRP antibodies were developed to prevent headache, not aura. These cases suggest CGRP may be involved in aura generation, potentially through a peripheral-central connection, and that anti-CGRP drugs might benefit both components of migraine with aura. This raises fundamental questions about how CGRP signaling relates to brain events.

The numbers in context

n=2 case reports · patient 1: galcanezumab → complete aura disappearance · patient 2: erenumab → reduced aura duration and intensity · 4 anti-CGRP mAbs reviewed (eptinezumab, fremanezumab, galcanezumab, erenumab)

How the study worked

Two case reports of migraine with aura patients treated with anti-CGRP monoclonal antibodies (galcanezumab and erenumab), combined with a literature review examining the relationship between cortical spreading depression (CSD) and CGRP, and the potential central mechanisms of peripherally-acting antibodies.

Who was studied

Two patients with migraine with and without aura treated with anti-CGRP monoclonal antibodies

What this study cannot tell us

Based on only two case reports, the findings are anecdotal and cannot establish efficacy. Placebo effect cannot be ruled out. The mechanism by which peripheral anti-CGRP antibodies might affect central cortical events (aura) remains speculative. Systematic studies of anti-CGRP effects on aura are needed.

How to read the evidence

These are two anecdotal case reports, the lowest level of clinical evidence. While intriguing, they cannot establish efficacy or mechanism. Prospective studies specifically designed to measure aura outcomes with anti-CGRP therapy are needed.

When this study was published

Published in 2022, these case reports contribute to an emerging discussion about anti-CGRP drug effects beyond headache prevention. Larger datasets have since begun to explore aura outcomes.

The bigger picture

These case reports challenge the assumption that anti-CGRP antibodies only work on the peripheral pain component of migraine. If confirmed in larger studies, the finding that they also affect aura would have two major implications: expanding their clinical utility to a symptom currently without treatment, and fundamentally changing our understanding of how peripheral CGRP signaling interacts with central brain events in migraine.

Questions still open

Do anti-CGRP antibodies consistently reduce aura in larger patient populations, or are these isolated cases?
Through what mechanism could peripheral anti-CGRP antibodies influence cortical spreading depression in the brain?
Would gepants (small molecule CGRP antagonists that cross the blood-brain barrier) be even more effective against aura than the antibodies?

Common questions

What is migraine aura and why is it hard to treat?

Migraine aura is a neurological disturbance — usually visual (flashing lights, zigzag lines, blind spots) but sometimes sensory or speech-related — that occurs before or during a migraine. It's caused by a wave of electrical activity spreading across the brain's surface (cortical spreading depression). Unlike the headache phase, which responds to many medications, aura has no approved specific treatment, making these observations about anti-CGRP drugs particularly interesting.

If anti-CGRP antibodies can't easily cross the blood-brain barrier, how could they affect aura?

This is the central puzzle. Possible explanations include: (1) small amounts of antibody may cross at areas where the barrier is weakest; (2) peripheral CGRP blockade may prevent signals from reaching the brain that would trigger cortical spreading depression; (3) the relationship between peripheral and central CGRP signaling in migraine may be more connected than previously thought. The exact mechanism remains unknown.

Read the original research

Could the New Anti-CGRP Monoclonal Antibodies Be Effective in Migraine Aura? Case Reports and Literature Review.

Journal of clinical medicine, 11(5)

View on PubMed ↗Publisher’s paper ↗

Citation

Albanese, Maria; Mercuri, Nicola Biagio. (2022). Could the New Anti-CGRP Monoclonal Antibodies Be Effective in Migraine Aura? Case Reports and Literature Review.. Journal of clinical medicine, 11(5). https://doi.org/10.3390/jcm11051228