Benign Episodic Mydriasis (BEM) is a rare condition characterized by transient, self-limiting unilateral (rarely bilateral) pupillary dilation. If anisocoria is isolated and episodic without accompanying neurological symptoms or signs, a diagnosis of BEM is made.
Unilateral cases are called benign episodic unilateral mydriasis (BEUM), and bilateral cases are called benign episodic bilateral mydriasis (BEBM). In the same patient, subsequent attacks may involve either unilateral or bilateral dilation.
Physiological anisocoria is present in up to 20% of healthy individuals. If the difference is 1 mm or less, does not change with light/dark, and the pupillary light reflex and near reflex are normal, it is considered physiological.
Epidemiology: Case reports show a strong female predominance, with reported ages ranging from 5 to 53 years. It is said to be more common in healthy young women. Literature is mainly limited to case reports and case series, and the true prevalence is unknown 1). Risk is higher in those with a history or family history of migraine.
It is very rare, and there are no comprehensive epidemiological data. Available literature is mainly limited to case reports and case series 1). It is more common in women, with reported ages ranging from 5 to 53 years.
The main symptoms that occur during an attack are as follows.
Opinions differ regarding the relationship with headache. Some reports indicate that when the pupil is dilated, headache is usually absent, while other reports suggest that headache may occur with ipsilateral ocular symptoms and does not shift to the contralateral side.
The characteristic examination findings of BEM are as follows.
The characteristics of the attacks are as follows.
| Characteristic | Description range |
|---|---|
| Duration | 10 minutes to several hours (average 12 hours), sometimes lasting weeks |
| Frequency | Several times a day to several times a year, often recurring for about 1 year |
| Laterality | Mainly unilateral. Rarely bilateral (Ahn et al., 19-year-old female: bilateral intermittent mydriasis every 2–3 days, lasting 1–2 hours) |
The most common duration is 10 minutes to several hours, with an average duration of 12 hours. Cases lasting several weeks have also been reported. Attacks often recur about once a year, with a frequency ranging from several times a day to several times a year.
The exact cause of BEM is unknown, but it is thought to involve dysregulation of autonomic innervation to the iris muscles.
Main risk factors:
Main etiological hypotheses:
The basic concept is an imbalance between the sympathetic nervous system (controlling the iris dilator muscle) and the parasympathetic nervous system (controlling the iris sphincter muscle).
A history of migraine is not essential for the diagnosis of BEM. Reports also suggest an association with anxiety, and it can occur in patients with diverse backgrounds.
BEM is a diagnosis of exclusion. It is confirmed after systematically ruling out serious causes.
Check the following findings:
The following are major diseases to be excluded.
| Disease | Key differences from BEM |
|---|---|
| Third cranial nerve palsy | Associated with ptosis and eye movement disorder |
| Adie tonic pupil | Loss of light reflex; positive denervation supersensitivity with 0.125% pilocarpine |
| Horner syndrome | Miosis + mild ptosis; anhidrosis. Differentiated by apraclonidine eye drop test |
| Drug-induced mydriasis | Most common cause of fixed dilated pupil. Unresponsive to 1% pilocarpine. |
| Intracranial aneurysm | Excluded by MRI/MRA |
| Angle-closure glaucoma | Associated with elevated intraocular pressure, severe eye pain, and corneal edema |
| Ophthalmoplegic migraine | Accompanied by ocular motor palsy |
Other differential diagnoses include stroke, intracranial hemorrhage, infection, orbital cellulitis, tumor, trauma, Pourfour du Petit syndrome, and uncal herniation1).
There is no specific treatment for BEM. Symptomatic treatment and patient explanation are the mainstays of therapy.
In the case by Darko & Basnet (2025), a 52-year-old woman with unilateral mydriasis and headache improved spontaneously during hospitalization and was discharged with usual migraine medication 1). They conclude that awareness of BEM helps avoid unnecessary invasive tests and provide appropriate reassurance.
There is no specific treatment; the mainstay is symptomatic therapy and providing explanation and reassurance to the patient. If there is a history of migraine, treat the migraine. The neurological prognosis of isolated BEM is good 1).
Normal pupil size is determined by the balance between the sympathetic and parasympathetic nervous systems.
Sympathetic Hyperactivity Hypothesis
Spasm of the dilator pupillae muscle: Peripheral, transient spasm due to sympathetic stimulation causes mydriasis.
Tadpole-shaped pupil (irregular mydriasis due to segmental spasm of the dilator muscle) is considered essentially the same.
Parasympathetic Underactivity Hypothesis
Reduced function of the iris sphincter muscle: Decreased parasympathetic activity leads to unopposed sympathetic action, resulting in mydriasis.
Some reports suggest that decreased parasympathetic nervous system function plays a significant role.
Migraine-related theory
Cortical spreading depression (CSD): CSD during migraine alters autonomic regulation and causes pupil dilation1).
Another theory proposes that dilation of the posterior cerebral artery and posterior communicating artery blocks the pupillary sphincter fibers on the third cranial nerve.
There is a theory that vasogenic edema causes internal carotid artery constriction, leading to cranial nerve compression and preganglionic parasympathetic palsy, while others argue that ischemia rather than compression is the cause. The mechanism remains unconfirmed at present.
The exact pathophysiology of BEM remains unclear, and establishing the true prevalence, elucidating the pathogenic mechanisms, and developing targeted treatment strategies are future challenges 1).
Currently, no RCTs or large-scale prospective studies exist. Related basic research is accumulating, such as studies on the association between migraine and pupil cycle time (reports that the edge-light pupil cycle test may detect early stages of trigeminal sensitization).
