Migraine is a primary headache disorder characterized by severe headache. It is accompanied by nausea, photophobia, phonophobia, and visual aura, lasting 4 to 72 hours. It is classified into episodic (less than 15 days per month) and chronic (15 or more days per month).
The main subtypes of migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) are shown below.
Cortical spreading depression (CSD) and trigeminovascular system involvement are the main causes. CSD is a wave of neuronal depolarization starting from the visual cortex in the occipital lobe, causing scintillating scotoma. Activation of the trigeminovascular system releases inflammatory substances such as CGRP and substance P, leading to vasodilation and neurogenic inflammation, which cause photophobia and headache.
The main differences are the nature of the visual symptoms, laterality, and duration. Scintillating scotoma is a positive symptom (zigzag lights) that is binocular and lasts 20–30 minutes (up to 60 minutes). Transient monocular blindness is a negative symptom (darkening or graying) that is monocular and resolves within 1–5 minutes (up to 10 minutes). Transient monocular blindness can be caused by embolism of the carotid or ophthalmic artery and should not be overlooked.
The clinical findings for each subtype presenting with ophthalmic signs are shown below.
Retinal Migraine
Monocular vision loss: Reversible monocular visual impairment or loss.
Scotoma: C-shaped, colored, scintillating, expanding scotoma. Diagnosis requires at least two episodes.
Exclusion of TMVL: Always differentiate from serious causes (arteritis, embolism).
Hemiplegic Migraine
Motor weakness: Unilateral reversible motor paralysis appears as an aura.
Various auras: Accompanied by visual, sensory, and speech symptoms. Each symptom lasts 5–60 minutes.
ICHD-3 criteria: Develops over ≥5 minutes, with headache following the aura or within 60 minutes2).
Ophthalmoplegic Neuropathy
Third cranial nerve involvement: The third cranial nerve is involved in 80% of cases. Ptosis, eye movement disorder, and pupillary dilation.
MRI findings: Characteristic focal thickening and contrast enhancement of cranial nerves.
Definitive diagnosis: Requires two or more attacks. In children, irritability and vomiting may be the main symptoms3).
Basilar-type migraine
Brainstem symptoms: Accompanied by vertigo, dysarthria, ataxia, tinnitus, and hearing loss.
Diplopia: May be accompanied by bilateral sensory abnormalities or altered consciousness as a typical aura.
Syncope: In severe cases, transient loss of consciousness may occur.
In typical migraine, ophthalmic examinations (including visual field tests) are usually normal. During a migraine attack, OCTA (optical coherence tomography angiography) shows a marked decrease in choroidal vascular density and enlargement of the foveal avascular zone (FAZ).
Food triggers include red wine, beer, chocolate, aged cheese, MSG (monosodium glutamate), and aspartame. Medications such as oral contraceptives, estrogen therapy, nasal decongestants, opioids, and SSRIs can trigger or worsen migraines. Since triggers vary greatly among individuals, self-monitoring with a headache diary is important.
Migraine diagnosis is based on medical history, physical examination, and ICHD-3 criteria. Imaging is not necessary for typical symptoms. Diagnostic tools include ID-Migraine, VARS, MIDAS questionnaire, and MSQ 2.11).
Indications for imaging (brain MRI/CT) are limited to the following cases:
Perform a complete ophthalmic examination (visual acuity, visual field, eye movement, pupillary light reflex, fundus examination, slit-lamp examination). In recurrent painful ophthalmoplegic neuropathy (RPON), MRI shows characteristic findings of focal thickening and contrast enhancement of cranial nerves3).
The following three points can be compared to differentiate between the two.
| Item | Scintillating scotoma | Amaurosis fugax |
|---|---|---|
| Nature of visual symptoms | Positive (zigzag light) | Negative (darkening/graying) |
| Unilateral (one eye) | Bilateral, homonymous | Often unilateral |
| Duration | 20–30 minutes (within 60 minutes) | 1–5 minutes (within 10 minutes) |
For mild attacks, NSAIDs, dihydroergotamine mesylate, or oral triptans are used. For severe attacks, oral triptans are used.
Acute treatment 1):
Preventive therapy 1):
Hemiplegic migraine 2):
No standardized treatment guidelines exist. For acute attacks, NSAIDs and non-narcotic analgesics are used. For prevention, beta-blockers, calcium channel blockers, tricyclic antidepressants, and antiepileptic drugs are used. For frequent attacks, long-acting verapamil or lamotrigine may be used.
RPON (Recurrent Painful Ophthalmoplegic Neuropathy) 3):
Corticosteroids are used in 70% of cases during the acute phase. Regimens include prednisone 2 mg/kg/day for 10 days or methylprednisolone IV 25 mg/kg for 5 days. For prevention, flunarizine (reported to reduce attack frequency) and pizotifen are used.
Topiramate is widely used as a migraine preventive, but it can cause acute angle closure (TiAAC) about two weeks after starting treatment. Ciliochoroidal effusion causes forward movement of the lens-iris diaphragm, leading to a rapid increase in intraocular pressure. If eye pain, vision loss, or blurred vision occurs, prompt ophthalmologic consultation and contact with the prescribing physician are necessary 4).
The basic mechanism of migraine is stimulation of the meninges, blood vessels, and trigeminal innervation area, and it is a vascular headache triggered by dilation of branches of the external carotid artery 1).
Triggers such as stress, food, and hormones → dysregulation of brainstem vascular control → peripheral vasodilation → stretch signals to trigeminal neurons → production of inflammatory and vasoactive substances such as CGRP and interleukins → further dilation and increased vascular permeability → tissue edema cascade 1).
The neurotransmitters involved are substance P, nitric oxide, and CGRP. The periaqueductal gray (PAG), locus coeruleus (LC), and dorsal raphe nucleus (DRN) are brain regions implicated in migraine pathophysiology.
The cause of visual aura is CSD. A wave of neuronal depolarization originating in the occipital region propagates forward. Depolarization increases potassium concentration, and the release of excitatory amino acids further enhances spreading. Scintillating scotomas appear due to transient ischemia of the occipital visual area caused by cerebral vasospasm 2).
During spontaneous migraine attacks, OCTA shows a marked decrease in choroidal vascular density and enlargement of the FAZ. This suggests that choroidal circulation is more vulnerable than retinal circulation during attacks.
Three genes are known to be associated with familial hemiplegic migraine: CACNA1A (calcium channel), ATP1A2 (Na/K pump), and SCN1A (sodium channel)2). Mutations in the TREK gene (two-pore potassium channel) are involved in resting membrane potential dysregulation and neuronal hyperexcitability1).
Fremanezumab, erenumab, and galcanezumab are FDA-approved preventive medications for chronic migraine 1).
A meta-analysis by Deng et al. (2020) of 4,402 patients across 11 RCTs showed that anti-CGRP mAbs significantly improved the 50% responder rate and reduced monthly migraine days and acute medication use. There is broad agreement that the benefit-risk profile is superior to propranolol and topiramate 1).
Galcanezumab improved headache severity, frequency, and duration with a regimen of 240 mg subcutaneous loading dose followed by 120 mg/month for 5 months. Injection site pruritus and rash have been reported as main side effects1).
Ubrogepant is an oral acute treatment approved by the FDA in 2019. It can be used regardless of the presence of aura1). Atogepant is being developed as an oral preventive medication.
Tonabersat is a novel benzopyran compound that inhibits cortical spreading depression (CSD) by blocking glial-neuronal gap junction communication. A 39-patient RCT (Goadsby et al. 2009) showed efficacy in preventing migraine with aura, but it is not yet FDA-approved1).
Mutations in two-pore potassium channels (TREK) lead to impaired regulation of resting membrane potential and neuronal hyperexcitability. Therapeutic research targeting TREK activation and inhibition is ongoing1).
