Does Harlequin Syndrome and Migraine Overlap? Here's What the Science Says

You’re in the middle of a migraine attack, or maybe just finishing a workout, and you notice something odd in the mirror. One side of your face has turned bright red and is sweating normally. The other side? Completely pale. Dry. Like the two halves of your face are operating on completely different systems.

That is Harlequin syndrome in a nutshell. And if you’ve ever experienced it during or around a migraine, you’re probably wondering: Are these two things connected? Is this the same problem showing up in different costumes? Or just a strange coincidence?

The short answer is: While these conditions sometimes appear at the same time, we’re not yet sure whether that’s just coincidental.

What Is Harlequin Syndrome?

Harlequin syndrome is a rare disorder of the autonomic nervous system — the part of your nervous system that runs things without you thinking about them: heart rate, digestion, blood pressure, sweating, flushing. It’s characterized by unilateral (one-sided) decreased sweating and flushing of the face, neck, and chest in response to heat, exercise, or emotional factors, with the opposite side showing a compensatory overreaction to maintain overall normal temperature regulation.

The name comes from the Italian theatrical character Harlequin, whose iconic costume is split into two dramatically different halves — exactly what the face looks like when this condition strikes.

What’s actually happening under the surface is a disruption of the sympathetic nervous system — specifically the nerve fibers that control blood vessel dilation and sweat gland activation in the skin. Harlequin syndrome results from dysfunction of vasodilatory and sudomotor sympathetic fibers originating from the stellate ganglion or the superior cervical ganglion. When those signals go wrong on one side, you get the split-face effect.

Is Harlequin Syndrome Rare?

Yes, genuinely rare. A 2025 retrospective review at Mayo Clinic, one of the largest clinical series ever published, identified just 51 patients with a diagnosis of Harlequin syndrome over a 26-year period. Of those, 76% were women, with a median age of onset of 52 years — though cases have been documented in children as young as 8.

In most cases, no underlying cause can be identified — meaning the majority of cases are considered idiopathic, or “origin unknown”. In others, the syndrome is secondary to something more findable: carotid artery dissection, a tumor pressing on sympathetic fibers, surgical procedures, trauma, small fiber neuropathy, or autoimmune conditions.

The causes and risk factors, a 2022 mini-review in Medicina concluded, are not fully understood, which is part of why the connection to migraine is so intriguing. Both conditions involve the autonomic nervous system in complicated ways. Both can be hard to diagnose. And they’ve been found together in patients more often than chance alone might suggest.

Where Migraine and the Autonomic Nervous System Meet

Migraine is a complex neurological condition that reaches deep into the autonomic nervous system across all four of its phases — and the autonomic dysfunction doesn’t just tag along for the ride. It’s woven into the mechanism.

Migraine attacks can present with up to four phases — premonitory, aura, headache, and postdrome — each with distinguishable autonomic signs and symptoms, and altered autonomic tone can be found from the very beginning of an attack through to its end.

Those autonomic symptoms are things you might recognize: nausea, vomiting, cold hands, pallor, excessive yawning, heart palpitations, and light-headedness. These aren’t random. They’re the result of a nervous system that simultaneously activates pain pathways and scrambles normal autonomic regulation.

The key mechanism involves something called the trigeminovascular system — the network of nerve fibers and blood vessels at the heart of migraine. The activation of trigeminal sensory fibers triggers the release of neuropeptides, including CGRP (calcitonin gene-related peptide) and PACAP, which in turn activate both parasympathetic and sympathetic fibers. The result is a cascade of autonomic dysregulation that affects blood vessels, sweat glands, tear ducts, nasal passages, and more.

This is why some people with migraine experience cranial autonomic symptoms — drooping eyelid, red eye, nasal congestion, tearing, or changes in facial sweating on the side of the head where the migraine pain is occurring. Out of 136 migraine patients in one real-world study, 88 (65%) reported cranial autonomic symptoms during their attacks. These patients also had higher CGRP levels in the blood during attacks — suggesting the autonomic component is directly tied to the core biological process of migraine, not a coincidental add-on.

Is There an Overlap? What the Research Has Found

Published case literature — which is where Harlequin syndrome research lives, given how rare it is — may have identified a recurring pattern of people with Harlequin syndrome who also have primary headache disorders, particularly migraine. By 2024, only 11 published cases of Harlequin syndrome occurring alongside a primary headache disorder had been documented in the medical literature. Of those 11:

• 8 patients had migraine (with or without aura)
• 2 had cluster headache
• 1 had post-traumatic headache

Four of those 11 patients also had primary exertional headache — a type of headache triggered by physical activity — which is far more prevalent in this patient group than in the general population, where it affects only 1–12% of people. This clustering suggests that the autonomic systems involved in regulating exercise response and blood flow may be specifically compromised in people who have both conditions.

A 2024 Case That Pushed the Question Forward

In 2024, researchers at University Hospital Zurich published a case study describing a 42-year-old woman who presented with persistent unilateral headache with trigeminal autonomic symptoms — including tearing, nasal congestion, and Horner’s syndrome — who was found to have both Harlequin syndrome and a headache resembling hemicrania continua.

Hemicrania continua is itself a trigeminal autonomic headache — a category of headache disorders characterized by one-sided head pain accompanied by autonomic symptoms on the same side. The researchers noted that cranial autonomic dysfunction is an integral feature of trigeminal autonomic headaches, and therefore an overlap in their pathophysiology seems plausible — though they also acknowledged that this was the first reported case of Harlequin syndrome and hemicrania continua occurring together.

This does not prove a causal relationship, but a growing body of evidence suggests that the shared machinery — specifically, the sympathetic nervous system pathways running through the cervical region, the superior cervical ganglion, and the trigeminal nerve — could create conditions in which both disorders arise in the same person.

A 2023 Case: Is Migraine With Autonomic Dysfunction Actually Harlequin Syndrome?

A 2023 case report published in Neurological Sciences added another layer. A patient with idiopathic left Horner’s syndrome was found to experience migraines with autonomic dysfunction that would present with unilateral flushing on the opposite side from the Horner’s — a pattern the authors identified as Harlequin syndrome triggered by or coinciding with migraine attacks.

In some people, the Harlequin presentation doesn’t exist as a separate condition; it may be part of the migraine’s autonomic expression — the same dysregulated sympathetic signaling that drives the headache and its surrounding symptoms also produces the split-face flushing pattern.

Horner’s syndrome — which involves drooping eyelid, constricted pupil, and sometimes anhidrosis on one side of the face — is itself caused by disruption of the same cervical sympathetic pathway implicated in Harlequin syndrome. The fact that all three (Harlequin syndrome, Horner’s syndrome, and migraine with autonomic features) can occur in the same patient may point to a shared vulnerability in this neural circuit.

What Does All This Mean?

Before you conclude that Harlequin syndrome is just a migraine symptom in disguise, it’s worth being precise about what the evidence does and doesn’t say.

A 2020 paper in Headache examined the relationship directly and found that between migraine and Harlequin syndrome, a pathological association does not seem likely in all cases. In several reported cases, the patients had been free of migraine attacks for years when the Harlequin symptoms were present, and the Harlequin symptoms were not simultaneous with the migraine attack.

The same paper pointed to pharmacological evidence. Sumatriptan and dihydroergotamine — medications that effectively treat migraine by constricting blood vessels and blocking CGRP release — had no effect on the Harlequin symptoms. And nitroglycerin, which is used in research settings to reliably trigger migraine attacks, provoked a migraine but not the Harlequin flushing.

This suggests the two syndromes are pathogenetically independent — meaning they can coexist in the same person without one causing the other. They may share vulnerability in the same neural architecture — the cervical sympathetic fibers, the superior cervical ganglion, the autonomic-trigeminal interface — without being the same disorder.

Think of it this way: two people can both have problems in the same neighborhood without those problems having the same cause.

What Harlequin Syndrome Actually Looks Like Day-to-Day

The most common trigger of Harlequin syndrome is heat or exercise. You finish a run, step into a sauna, or sit in a hot car — and one side of your face goes bright red while the other stays pale. The red side sweats. The pale side doesn’t. The line of demarcation usually runs right down the midline of the face.

Emotional stress can also trigger it. Some people notice it when they’re embarrassed, anxious, or in a heated conversation — the body’s normal stress response, which involves sympathetic activation, becomes visibly asymmetric.

Additional symptoms may include cluster headaches, tearing, nasal discharge, abnormal pupil constriction, neck muscle weakness, and drooping of one upper eyelid — all signs of cranial autonomic dysregulation in the same circuit.

The Mayo Clinic series confirmed that idiopathic Harlequin syndrome — the most common type — is typically not a sign of a dangerous underlying condition. But when it appears for the first time, it warrants medical evaluation to rule out secondary causes, particularly carotid artery dissection, tumors, and multiple sclerosis.

Getting a Diagnosis

Harlequin syndrome is diagnosed clinically — meaning a doctor familiar with it can often identify it from the description and a witnessed episode. But autonomic function testing, including thermoregulatory sweat test (TST) and autonomic reflex screening (ARS), can objectively confirm the distribution and severity of sympathetic dysfunction.

The Mayo Clinic series found that pupil abnormalities were present in 25.5% of patients with Harlequin syndrome, and abnormal muscle stretch reflexes in 33.3% — suggesting that a neurological examination can reveal supporting signs even when the patient isn’t actively flushing at the time of the appointment.

If you have migraine and have noticed asymmetric facial flushing — especially during or after exercise, or during an attack — it’s worth specifically mentioning this to your neurologist. It may be dismissed as a curious coincidence. But given the case literature, it may also be a meaningful part of your clinical picture, particularly if you have other autonomic symptoms, such as POTS-like symptoms, Horner’s sign (drooping eyelid on one side), cold extremities, or intolerance to heat and exercise.

The Autonomic Migraine Nobody Talks About

The autonomic chaos that surrounds a migraine is frequently where the strangest and most disabling symptoms live.

Nausea that makes eating impossible for two days. Heart rate swings that feel like panic attacks. Temperature dysregulation. A face that betrays exactly which side of your nervous system is fighting itself.

A 2024 systematic review and meta-analysis of autonomic function testing in migraine patients confirmed that multiple measures of autonomic nervous system function are significantly altered in migraineurs compared to healthy controls — and this dysregulation is present not just during attacks but between them, suggesting a persistent baseline state of autonomic imbalance in people with chronic migraine.

What This Means if You Have Both

If you have migraine and you’ve also been told — or noticed yourself — that your face flushes asymmetrically, there are a few practical takeaways:

• Get it on the record. Tell your neurologist specifically. It matters for the overall picture of your autonomic function, and it may be relevant to treatment decisions.
• Rule out secondary causes. First-time Harlequin syndrome warrants at least a basic neurological workup to exclude carotid artery dissection or other structural causes. This is especially important if the onset was sudden or accompanied by neck pain.
• Consider autonomic testing. If you have a broader constellation of autonomic symptoms — POTS features, exercise intolerance, temperature sensitivity, unusual sweating patterns — dedicated autonomic function testing may help characterize what’s happening in your nervous system more precisely.
• Know that you’re not imagining it. Asymmetric flushing, half-face sweating, and autonomic weirdness during migraine attacks are documented, published, and real phenomena.

The Bottom Line

Harlequin syndrome and migraine share fundamental infrastructure in the cervical sympathetic nervous system. Migraine involves significant, persistent autonomic dysregulation. And the small but growing body of case literature consistently shows that when Harlequin syndrome co-occurs with a primary headache disorder, that headache disorder is often a migraine.

Are they the same condition? No. The pharmacological evidence suggests they’re independent — migraine treatments don’t fix the Harlequin symptoms, and migraine triggers don’t reliably trigger Harlequin episodes. They’re more like neighbors than twins: living close together, sharing some of the same walls, occasionally making noise at the same time.

The science is still building. There are only 11 published cases of the overlap. For a condition as common as migraine and a condition as rare as Harlequin syndrome, that means we’re early in the story.