When headache meets visual disturbance: An evidence-based review of common and critical entities

Abstract

Concurrent headache and visual symptoms pose a diagnostic challenge across specialties, ranging from benign to life-threatening etiologies. Overlapping manifestations and terminological confusion often lead to misdiagnosis and delayed care. This narrative review searched eight databases from inception to May 5th, 2026, for articles on headache and visual symptoms. Extracted data were synthesized into a structured diagnostic framework. Key benchmarks were clarified across seven categories. Retinal migraine and migraine with aura are distinguished by monocular/binocular involvement, duration, and stroke risk. Visual snow syndrome is confirmed as a persistent disorder distinct from migraine aura. Life-threatening vascular emergencies—including giant cell arteritis, posterior reversible encephalopathy syndrome, subarachnoid hemorrhage, cerebral venous sinus thrombosis, and arterial dissection—exhibit unique red-flag patterns and imaging features. Intracranial pressure disorders present with pressure-dependent headaches. Optic neuritis subtypes (MS-associated, MOGAD, NMOSD) differ significantly in visual impairment, imaging lesions, treatment response, and prognosis. Occipital lobe epilepsy is differentiated by ultra-short visual hallucinations with ictal activity. Additional ophthalmic, structural, and infectious etiologies further broaden the differential spectrum. This evidence-based framework standardizes clinical differentiation of headache with visual symptoms. Emphasizing key historical features, red-flag signs, advanced imaging biomarkers, and antibody testing enables accurate classification, timely intervention, prevents irreversible vision loss and fatal complications, and optimizes long-term prognosis.

Introduction

The co-occurrence of headache and visual symptoms is a common clinical presentation across neurology, ophthalmology, and emergency medicine. While migraine with aura represents the most frequently encountered etiology, the differential diagnosis encompasses a wide spectrum of conditions—from benign visual snow syndrome to life-threatening vascular emergencies such as subarachnoid hemorrhage, giant cell arteritis, and acute arterial dissection. The diagnostic challenge is compounded by overlapping phenomenology: monocular vision loss may arise from retinal migraine or carotid artery dissection; transient visual phenomena may reflect cortical spreading depression or occipital lobe seizures; and papilledema with headache may indicate idiopathic intracranial hypertension or cerebral venous sinus thrombosis. Recent advances—including the 2025 systematic review differentiating retinal migraine from migraine with aura, ¹ the recognition of visual snow syndrome as a distinct clinical entity, ² and the emergence of antibody-based subclassification of optic neuritis (myelin oligodendrocyte glycoprotein antibody-associated disease, MOGAD; aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, NMOSD; multiple sclerosis, MS)—have substantially refined our understanding of these conditions. ³ However, terminological confusion persists, and misdiagnosis remains common. This narrative review provides a practical, evidence-based framework for differentiating disorders that present with combined headache and visual symptoms. We systematically examine key clinical features—headache characteristics, visual symptoms, accompanying manifestations, diagnostic differentiators, and prognostic implications—across seven domains: retinal migraine versus migraine with aura, visual snow syndrome, vascular emergencies, intracranial pressure disorders, optic neuritis subtypes, occipital lobe epilepsy, and a broad differential of other ophthalmic, structural, infectious, and inflammatory causes. Emphasis is placed on red flag features that mandate urgent intervention, with the goal of equipping clinicians with a structured approach to accurate diagnosis and timely management.

Methods

This narrative review synthesizes clinical evidence on disorders presenting with combined headache and visual symptoms. Eligibility criteria included original articles, reviews, systematic reviews and meta-analyses, case reports, case series, editorials, and clinical practice guidelines published in English or Chinese, with full text available. Studies focusing on basic animal research without clinical translation were excluded. Search strategy and information sources: a comprehensive literature search was conducted across multiple electronic databases, including PubMed (publicly available), SinoMed (Chinese Biomedical Literature Database, covering domestic Chinese-language journals), China National Knowledge Infrastructure (CNKI), and Wanfang Data. Additionally, Embase, Cochrane Library, and Web of Science were searched via institutional subscription (Bethune International Peace Hospital library access). ScienceDirect was searched for open-access and subscription-based Elsevier content. Where full text was unavailable, interlibrary loan or direct author contact was attempted. The search spanned from database inception to May 5th, 2026. Search terms were developed around three thematic blocks: (1) headache and visual symptoms (“headache”, “visual”, “retinal migraine”, “migraine with aura”, “visual snow syndrome”, “occipital lobe epilepsy”, “optic neuritis”, “myelin oligodendrocyte glycoprotein antibody-associated disease”, “MOGAD”, “multiple sclerosis”, “MS”, “aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder”, “NMOSD”, “idiopathic intracranial hypertension”, “spontaneous intracranial hypotension”, “giant cell arteritis”, “posterior reversible encephalopathy syndrome”, “subarachnoid hemorrhage”, “cerebral venous sinus thrombosis”, “cervical artery dissection”, “acute angle-closure glaucoma”); (2) diagnostic modalities (“optical coherence tomography angiography”, “MRI”, “MR venography”, “CSF opening pressure”, “antibody testing”); and (3) red flag features (“thunderclap headache”, “amaurosis fugax”, “papilledema”, “Horner syndrome”). Boolean operators (AND, OR) were used to combine terms. Key clinical features—headache characteristics, visual symptoms, accompanying manifestations, key differentiators, and prognostic implications—were extracted and synthesized across those disorders presenting with combined headache and visual symptoms. We have consulted the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines ⁴ during the preparation of our manuscript.

Clinical differentiation of retinal migraine and migraine with aura: Challenges and advances

Retinal migraine (RM) and migraine with aura (MA) present a persistent diagnostic challenge, yet they likely represent fundamentally different disorders rather than two variants of the same condition. The core difficulty lies in terminological confusion—“ocular migraine” is frequently misapplied to both conditions, ⁵ while patients often misattribute binocular homonymous phenomena to monocular involvement. ¹ Importantly, RM is a rarely diagnosed and disputed entity; the classic review by Hill et al. concluded that most cases labeled as “retinal migraine” do not meet diagnostic criteria and likely represent other etiologies, including retinal vasospasm or embolic phenomena. ⁶ Unlike MA—which is common, clinically well-characterized, and strongly linked to cortical spreading depression (CSD)—RM probably reflects a disorder of the retinal circulation without convincing evidence for a shared pathophysiology. The distinction between these disorders is therefore not merely a matter of monocular versus binocular involvement, but likely reflects fundamentally different underlying mechanisms.

A 2025 systematic review of 65 studies (1985–2025) provides the most definitive comparative framework to date. ¹ Headache characteristics in both conditions fulfill migraine criteria, though RM headaches are strictly ipsilateral to the affected eye. ⁷ Visual symptoms represent the key differentiator: RM is characterized by monocular involvement in 90% of attacks, with negative phenomena predominating (scotoma 84%, transient complete vision loss up to 100%). Conversely, MA demonstrates binocular/homonymous patterns in 75% of cases, with positive symptoms dominating (scintillating scotoma 77%, zigzag/fortification patterns 53%). Temporal profiles offer additional discrimination: MA follows a stereotyped 5–60 minute duration (79% of attacks), while RM shows greater variability—89% resolve within 60 minutes, but prolonged episodes occur. ⁸ Accompanying features differ substantially: MA frequently involves sensory or language disturbances reflecting cortical spreading depression, ⁹ whereas RM lacks such extra-visual neurological symptoms. ¹⁰ The prognostic implications are clinically significant: MA confers an approximately two-fold increased stroke risk, while RM carries rare but reported risks of permanent retinal ischemia including central retinal artery occlusion and retinal infarction. ⁷

Emerging imaging biomarkers have been explored for their potential in differential diagnosis, though their clinical utility remains to be established. Optical coherence tomography angiography (OCTA) reveals that MA patients exhibit significantly larger foveal avascular zones compared to both migraine without aura and healthy controls, with reduced vessel and perfusion densities.^11,12 Furthermore, children with MA demonstrate selective thinning of temporal and inferotemporal retinal nerve fiber layers. ¹³ To date, no similar results have been published on OCTA studies in RM. However, these findings have not yet been consistently reproduced, and their pathophysiological relationship to MA—a disorder originating in the cerebral cortex—remains uncertain. These measures should therefore be considered exploratory rather than established clinical biomarkers. In the context of RM, OCTA may have more direct utility in demonstrating retinal vasospasm, though no such studies have been published to date.

Accurate differentiation requires systematic history-taking with emphasis on monocularity confirmed by alternate eye covering. RM warrants aggressive vascular risk factor management given the potential for permanent visual sequelae, while MA necessitates stroke risk counseling.

Visual snow syndrome and migraine: A complex relationship

Visual snow syndrome (VSS) is a neurological condition characterized by the continuous perception of tiny, dynamic dots across the entire visual field, resembling analog television static. ¹⁴ While VSS shows strong comorbidity with migraine—affecting approximately 60–70% of VSS patients—emerging evidence establishes it as a distinct clinical entity rather than a migraine variant. ²

Headache features: Pre-existing migraine is present in 57–70% of VSS patients, yet the visual snow itself is not temporally linked to headache episodes. Unlike MA, VSS symptoms are persistent (≥3 months) and continuous, without the stereotyped 5–60 minute duration of typical aura. ¹⁵ Visual symptoms: VSS diagnostic criteria require continuous visual snow plus at least two of four additional symptoms: palinopsia (visual trailing), enhanced entoptic phenomena (e.g., floaters, blue field entoptic phenomenon), photophobia, and nyctalopia (impaired night vision). ¹⁴ These phenomena are qualitatively distinct from migraine aura—VSS lacks the scintillating scotoma or fortification spectra characteristic of aura, and its symptoms are static rather than migrating. ¹⁶ Accompanying features: Non-visual symptoms frequently accompany VSS, including tinnitus (up to 65%), anxiety (43–45%), depression (40%), depersonalization, and vestibular disturbances. ¹⁷ These reflect widespread sensory network hyperexcitability rather than isolated visual pathway dysfunction. While migraine also involves multimodal sensory disturbances—such as phonophobia, osmophobia, and allodynia—the non-visual symptoms in VSS are typically continuous rather than episode-locked, and more prominently feature depersonalization and vestibular dysfunction. This distinction suggests that although both conditions share cortical hyperexcitability, VSS manifests as a persistent perceptual network disorder, whereas migraine is characterized by paroxysmal network disruptions. Key differentiators from magraine: The fundamental distinction lies in temporal profile and response to treatment. MA is episodic, resolves completely between attacks, and may respond to standard migraine preventives. VSS is continuous, persists unchanged for years, and shows minimal response to typical migraine medications (e.g., beta-blockers, topiramate) while lamotrigine offers benefit in only 10–20% of cases. ¹⁷

Prognostic insights: VSS is a benign albeit often distressing condition. Neuroimaging reveals functional connectivity dysregulation in visual networks (particularly lingual gyrus hypermetabolism) and salience networks, without structural pathology. ¹⁵ Mindfulness-based cognitive therapy has demonstrated sustained improvements in symptom severity and daily functioning, with associated normalization of visual network connectivity. Chromatic tints (blue-yellow spectral filters) and oculomotor training show 80–90% symptomatic benefit in preliminary studies. ¹⁷ However, the optimal filter color is not invariably on the yellow-blue axis, and individual precision spectral filters may offer more effective treatment, particularly given that VSS intensity may vary depending on the visual scene on which it is superimposed. ¹⁸

The migraine-VSS relationship likely reflects shared cortical hyperexcitability as a common risk factor rather than direct causation. Future research priorities include identifying specific biomarkers and developing targeted therapies for this increasingly recognized disorder. Worth noting, visual stress phenomena—including pattern glare, characterized by anomalous visual effects elicited by viewing striped patterns—are more prevalent in individuals with frequent headache and are thought to reflect the cortical hyperexcitability that is prominent in migraine.^19–21 Building on this association, the Pattern Glare Test may offer a non-invasive window into the shared and distinct pathophysiological mechanisms underlying migraine and VSS. Beyond its mechanistic value, the test also holds promise as a predictive and stratification tool for personalized interventions, particularly in identifying patients who may benefit from precision spectral filtering. To translate these potentials into clinical practice, however, the temporal dynamics of the neural response to pattern-glare stimuli—specifically the interplay between short-term sensitization and long-term habituation—merit systematic investigation in well-phenotyped cohorts.

Vascular emergencies presenting with headache and visual disturbance: Red flag conditions

Prompt recognition of vascular emergencies presenting with combined headache and visual disturbance is essential to prevent permanent vision loss or death. Recent evidence has refined understanding of five critical entities.

Giant Cell Arteritis (GCA) remains the most urgent vasculitic emergency in patients over 50. Headache features: New-onset temporal headache with scalp tenderness is classic, though atypical presentations are increasingly recognized—including isolated recurrent binocular diplopia without headache, and occipital neuralgia-like symptoms with bilateral optic nerve sheath enhancement on MRI.^22,23 Visual symptoms: Afferent manifestations dominate, with arteritic anterior ischemic optic neuropathy (AAION) accounting for 85% of GCA-related vision loss, characterized by chalky-white pallid disc edema. Central retinal artery occlusion occurs in 5% of arteritic cases, showing cherry-red spot fundoscopy. ²⁴ Efferent manifestations include cranial neuropathies (CN III, IV, VI) and extraocular muscle ischemia, with isolated diplopia as a rare sentinel sign. ²² Accompanying features: Jaw claudication, polymyalgia rheumatica, and markedly elevated ESR/CRP. Key differentiators from non-arteritic optic neuropathy: AAION shows cupping on resolution (92% of cases) versus diffuse pallor without cupping in NAION. Prognosis: High-dose corticosteroids must be initiated immediately when suspected, as vision loss is irreversible once established. Tocilizumab shows promising adjunctive efficacy. ²⁴

Posterior Reversible Encephalopathy Syndrome (PRES) presents with acute neurological symptoms driven by endothelial dysfunction and blood-brain barrier disruption. Headache features: Acute or subacute onset, often progressive; thunderclap pattern suggests alternative diagnosis of reversible cerebral vasoconstriction syndrome. ²⁵ Visual symptoms: Range from blurred vision to complete cortical blindness with preserved pupillary reflexes—a key clinical clue. Positive visual phenomena (shapes, figures) may occur. ²⁶ Accompanying features: Encephalopathy (hallmark), seizures, nausea/vomiting. MRI demonstrates bilateral parieto-occipital FLAIR hyperintensities indicating vasogenic edema. Key differentiators: Unlike ischemic stroke, PRES typically shows no diffusion restriction (except in malignant transformation). Prognosis: Usually favorable with prompt trigger removal (blood pressure control, discontinuation of offending agents). However, severe cases can result in persistent deficits,^27,28 and recurrent PRES occurs.^29,30 Novel triggers include tyrosine kinase inhibitors, CAR-T cell therapy, and essential thrombocythemia (platelet counts >700 × 10⁹/L) even with normal blood pressure. ²⁶

Subarachnoid Hemorrhage (SAH) demands immediate recognition. Headache features: Sentinel or “warning” headache preceding aneurysmal rupture by days may be thunderclap in quality—described as the “worst headache of life”—but atypical headaches can delay diagnosis. ³¹ Visual symptoms and ocular signs: Afferent visual symptoms include blurred vision and visual field defects. Ocular motor signs—including oculomotor nerve palsy (ptosis, dilated non-reactive pupil, eye in down-and-out position)—are classic sentinel signs, particularly in posterior communicating artery aneurysms. Importantly, isolated third nerve palsy can precede radiographic hemorrhage by days, as documented in nonaneurysmal SAH cases. ³¹ Accompanying features: Neck stiffness, nausea, vomiting, altered consciousness. Key differentiators: CT alone has 95% sensitivity; lumbar puncture is nearly 100% sensitive for detecting SAH when CT is negative but suspicion remains. Prognosis: Mortality approaches 50% without intervention. ³² Early detection of sentinel headaches and isolated cranial neuropathies enables life-saving aneurysm securing. Genetic evidence supports cerebrospinal fluid haptoglobin as a potential therapeutic target to improve outcomes after aneurysmal SAH.^33,34

Cerebral Venous Sinus Thrombosis (CVST) is an uncommon cerebrovascular disorder driven by thrombotic occlusion of dural sinuses and/or cerebral veins, leading to elevated intracranial pressure, venous infarction, and potential hemorrhage. Headache features: The most consistent symptom (80–90% of cases), typically subacute in onset over days to weeks, often mimicking benign intracranial hypertension or migraine; thunderclap headache suggests alternative diagnoses such as subarachnoid hemorrhage or reversible cerebral vasoconstriction syndrome. ³⁵ Visual symptoms: Blurred vision, transient visual obscurations, diplopia (from cranial nerve VI palsy), and progressive visual field loss due to papilledema; vision loss can be irreversible if intracranial hypertension is not promptly managed. ³⁶ Accompanying features: Seizures (16–23%, focal or generalized), focal neurological deficits (30%, including hemiparesis and aphasia), altered consciousness, and fever; bilateral or extensive sinus involvement correlates with poorer outcomes. ³⁷ Key differentiators: Unlike arterial ischemic stroke, CVST predominantly affects younger adults (mean age 30–50 years) with female preponderance; MRI with MR venography demonstrates filling defects within sinuses, and D-dimer may be normal in up to 30% of confirmed cases, including those with extensive thrombus burden mimicking giant cell arteritis. ³⁸ Prognosis: Generally favorable with prompt anticoagulation—recent prospective studies report 93–94% functional independence (modified Rankin Scale <2) at 12 months; however, admission NIHSS score ≥9 independently predicts poor long-term outcomes (OR 1.21 per point), and the hyperdense sinus sign on non-contrast CT identifies a subgroup with more extensive thrombosis and poorer outcomes (71% vs 82% excellent outcome, p=0.022).^35,39

Acute Arterial Dissection (Cervical and Intracranial) is a critical vascular emergency caused by a tear in the arterial wall with intramural hematoma formation, leading to ischemic stroke, subarachnoid hemorrhage, or mass effect, predominantly affecting young and middle-aged adults without traditional vascular risk factors.^40,41 Headache features: Headache is the most common presenting symptom, occurring in 60–90% of patients, typically ipsilateral to the dissection site. In internal carotid artery dissection (ICAD), headache is often frontotemporal or periorbital, described as throbbing or constant, while vertebral artery dissection (VAD) typically presents with occipital or posterolateral neck pain.^42,43 A sentinel headache preceding ischemic events by days is common, and thunderclap headache at onset suggests subarachnoid hemorrhage from intracranial extension. ⁴⁴ Visual symptoms: Ophthalmic manifestations are hallmark features of ICAD. Partial Horner syndrome (ptosis, miosis, anhidrosis) occurs in up to 50% of patients, resulting from sympathetic plexus involvement, and may be the only presenting sign. ⁴² Transient monocular vision loss (amaurosis fugax) from retinal ischemia is another key feature, often with pain. ⁴¹ Diplopia from oculomotor (CN III), trochlear (CN IV), or abducens (CN VI) palsies can occur, particularly in VAD with brainstem involvement. ⁴⁵ In intracranial dissection, visual field defects and cortical blindness may result from posterior circulation ischemia. Accompanying features: Ischemic stroke or transient ischemic attack develops in 50–80% of patients, with hemiparesis being the most common deficit. Horner syndrome with ipsilateral headache and contralateral hemiparesis constitutes the classic “Triple H″ syndrome in ICAD. ⁴⁶ Subarachnoid hemorrhage occurs in 50–60% of intracranial dissections, more commonly in posterior circulation, presenting with sudden severe headache, nausea, vomiting, and altered consciousness. ⁴⁷ Other features include pulsatile tinnitus, dysgeusia, and neck bruit. Key differentiators: Unlike atherosclerotic disease, arterial dissection affects younger patients (mean age 40–50 years) without significant vascular risk factors. Cervical artery dissection accounts for 20% of ischemic strokes in patients aged <45 years. ⁴⁴ Neuroimaging is diagnostic: high-resolution MRI with fat-saturated T1-weighted black-blood sequences demonstrates intramural hematoma, while catheter angiography reveals the classic “pearl and string sign” (alternating stenosis and dilation), intimal flap, or pseudoaneurysm formation. Spontaneous dissections may be associated with underlying connective tissue disorders (Ehlers-Danlos, Marfan), fibromuscular dysplasia, recent mechanical triggers (trauma, chiropractic manipulation, vigorous coughing), or styloid process. ⁴⁸ Prognosis: Prognosis depends on dissection location, presence of SAH, and timely intervention. Cervical dissections without SAH have favorable outcomes with antithrombotic therapy—mortality 0–3% and 75–85% achieving good functional recovery (modified Rankin Scale 0–2) at 3–6 months. ⁴⁹ Intracranial dissections presenting with SAH carry a grave prognosis with mortality 19–83%, primarily due to high early rebleeding risk, making emergent endovascular or surgical treatment essential. ⁵⁰

Intracranial pressure disorders with headache and visual symptoms: From idiopathic hypertension to spontaneous hypotension

Intracranial pressure (ICP) disorders—both elevated (idiopathic intracranial hypertension, IIH) and reduced (spontaneous intracranial hypotension, SIH)—represent a spectrum of conditions where headache and visual symptoms frequently co-occur. Recent evidence has refined understanding of their clinical profiles, diagnostic challenges, and prognostic factors.

Idiopathic intracranial hypertension (IIH)

IIH is a condition of raised intracranial pressure in the absence of a structural brain lesion, most commonly seen in young, obese women, and characteristically manifests with headache and visual disturbances including papilledema. ⁵¹ The contribution of the glymphatic system to the pathogenesis of IIH is increasingly being recognized. ⁵² Headache features: Headache is nearly universal in IIH, reported in 84–100% of patients. The most common phenotype is migraine-type headache (58.8%), followed by tension-type and daily persistent headaches. Crucially, CSF opening pressure shows significant positive correlation with headache severity (p < 0.001). Notably, headache is more frequently reported by women than men (83% vs. 50%, p = 0.007). ⁵³ Visual symptoms: Visual disturbance affects 89% of patients. The most common presenting visual symptoms include blurred vision (97.6%) and transient visual obscurations (70.7%). ⁵⁴ Papilledema is present in 98% of cases, with Frisén grade 2 (median) at baseline. ⁵³ Visual field defects are extremely common—enlarged blind spot (66.7% of patients, 32.5% of eyes), annular scotoma (26.3%), and generalized sensitivity reduction (25.0%) represent the predominant patterns. ⁵⁴ Abducens nerve palsy occurs in 9–15.7% of patients, manifesting as horizontal diplopia. ⁵³ Accompanying features: Pulsatile tinnitus occurs in 46.3% of patients. ⁵⁴ Vertigo (45%), diplopia (39%), and nausea/vomiting are frequent accompaniments. ⁵³ Facial pain and ear fullness may mimic chronic rhinosinusitis or migraine, leading to diagnostic delays in otolaryngology settings. ⁵⁵ Key differentiators: Diagnosis requires elevated opening pressure (>25 cm H₂O) with normal CSF composition and exclusion of secondary causes. Characteristic neuroimaging findings include empty or partially empty sella (78.4%), transverse sinus stenosis (76.5%), and dilated optic nerve sheaths. ⁵⁶ Notably, CSF opening pressure does not correlate with headache frequency or severity in some studies, suggesting additional pathophysiological factors beyond absolute ICP values. ⁵⁵ The glymphatic system—a perivascular network facilitating CSF-interstitial fluid exchange—has emerged as a potential link between IIH and migraine pathophysiology, with dysfunction in aquaporin-4 channels and impaired metabolite clearance implicated in both conditions. ⁵⁷ Prognostic insights: Poor visual outcome occurs in 30% of patients. ⁵⁸ Male sex (OR 8.7, p = 0.009) and severe papilledema at baseline (OR 7.7, p = 0.02) are independent predictors of irreversible visual loss. Age, BMI, disease duration, and CSF opening pressure do not reliably predict visual outcomes. Visual acuity typically improves with treatment (p = 0.03), though visual field defects may persist. ⁵³

Spontaneous intracranial hypotension (SIH)

SIH results from spinal CSF leaks and presents with orthostatic headache—worsening within 15 minutes of upright posture and improving when recumbent. ⁵⁹ Headache features: Orthostatic headache is the hallmark, frequently accompanied by neck pain and stiffness. ⁶⁰ However, recent evidence challenges orthostatic headache as a defining characteristic—patients with CSF-venous fistulas (now accounting for ≥50% of leaks without epidural collections) may present with pressure/throbbing headache quality lacking clear postural component. ⁶¹ Visual symptoms: Visual changes include blurred vision, diplopia (from cranial nerve traction), and rarely visual field defects. ⁶² Patients may experience vestibulo-auditory distortions including tinnitus and hearing disturbances. ⁶³ Key differentiators: Brain MRI findings include subdural fluid collections, dural enhancement, engorged venous structures (venous distention sign), pituitary enlargement, and brain sagging with effacement of basal cisterns (Bern score assessment). ⁶⁴ Detection of the specific leak type—CSF-venous fistula versus dural defect—requires advanced imaging including dynamic decubitus CT myelography. ⁶⁵ Prognosis: Long diagnostic delays are common but deleterious. Rare but serious sequelae include superficial siderosis, subdural hematoma, bibrachial amyotrophy, brain sagging dementia, and even death. Epidural blood patch and surgical leak closure are definitive treatments. ⁶⁶

Optic neuritis subtypes in the antibody era: MOGAD, NMOSD, and MS-Associated phenotypes

Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve that presents with acute or subacute visual loss, often accompanied by pain. ⁶⁷ The recognition of distinct immunological subtypes— multiple sclerosis (MS)-associated ON , myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) , and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD) —has transformed diagnostic and therapeutic approaches. ³ These subtypes differ markedly in clinical presentation, imaging findings, treatment response, and prognosis.^67,68

Headache features: Headache is not a classic presenting symptom of isolated ON but may occur in the context of underlying demyelinating disease activity. In NMOSD, area postrema involvement can present with intractable hiccups, nausea, and headache. Headache prevalence varies across subtypes and often reflects concurrent CNS involvement rather than the optic nerve inflammation itself. ³

Visual symptoms: The pattern of visual impairment is the most distinguishing feature among ON subtypes. MS-associated ON typically presents with monocular vision loss (i.e., loss of vision in one eye), mild-to-moderate severity (20/40–20/200), and optic disc pallor rather than swelling.^67,69 In contrast, MOGAD-ON frequently involves bilateral optic neuritis (71–80% of cases), presents with marked optic disc edema, and may have perineural enhancement on MRI.^3,70 NMOSD-ON is characterized by severe, often bilateral vision loss that is frequently irreversible, with longitudinally extensive optic nerve involvement extending to the chiasm (present in 70% of NMOSD patients). ⁶⁷

Accompanying features: Orbital MRI findings provide critical diagnostic clues. MS-ON typically shows short-segment, anteriorly located optic nerve lesions. MOGAD-ON demonstrates long anterior optic nerve involvement with characteristic “fluffy” T2 lesions and perineural enhancement. ⁷¹ NMOSD-ON is associated with optic chiasm T2 lesions (OR 5.95), longitudinally extensive optic neuritis (LEON, OR 11.38), and hypothalamic involvement. ⁷¹ Optical coherence tomography (OCT) reveals distinct atrophy patterns: MS-ON predominantly affects the temporal retinal nerve fiber layer (RNFL) quadrant, NMOSD-ON causes diffuse RNFL loss across all quadrants (chronic pRNFL often <80 μm), while MOGAD-ON shows relatively symmetric but milder thinning. ⁷⁰

Key differentiators: The 2023 MOGAD diagnostic criteria and refined NMOSD classification have established clear biomarker-based distinctions. MOG antibody positivity is associated with favorable visual recovery (7/8 patients with full recovery in one series, p=0.011), whereas AQP4 antibody positivity predicts poor visual outcomes (4/7 patients with no recovery). ⁷² On multivariate analysis, NMOSD (p<0.05) and LEON (p<0.05) are significantly associated with poor visual outcome, while age at onset and diagnostic delay do not reach statistical significance. The presence of disc edema favors MOGAD or idiopathic ON over MS-ON, as disc swelling was associated with a significantly lower likelihood of developing MS in the ONTT report. ³

Prognostic insights: Visual prognosis varies dramatically by subtype. MOGAD-ON demonstrates excellent recovery potential—even after severe acute vision loss, GCIPL thinning is modest (mean reduction 14 μm) and visual outcomes are favorable with high-dose corticosteroids. ⁷⁰ In contrast, NMOSD-ON has poor visual recovery; IVMP alone may be suboptimal, and early plasma exchange (PLEX) improves outcomes when initiated within 2 days of symptom onset (40–50% complete recovery vs. 0–5% after 20 days). ⁶⁷ MS-associated ON has intermediate prognosis; while high-dose corticosteroids accelerate initial recovery, long-term visual outcomes are generally good, with 81.8% of patients with severe baseline vision loss (counting fingers or worse) recovering to 20/40 or better. Intravenous methylprednisolone treatment in patients with full recovery was significantly higher than in patients with partial/no recovery (p=0.010). ⁷²

Occipital lobe epilepsy and migraine with aura: Differentiating ictal visual phenomena from cortical spreading depression

Visual symptoms and headache commonly co-occur in specific epileptic disorders, particularly occipital lobe epilepsy (OLE), creating substantial diagnostic challenges with MA.^73,74 Recent evidence has refined understanding of their clinical profiles.

Headache characteristics: Headache is a frequent postictal phenomenon in OLE, often indistinguishable from migraine. ⁷⁵ In OLE, headaches are typically global (90%), compressive (90%), and of shorter duration (median 210 minutes), whereas migraine headaches are more often unilateral or bilateral with throbbing quality (72%) and longer duration (median 720 minutes). ⁷⁴ Ictal epileptic headache—headache as the sole ictal manifestation—is a rare but recognized phenomenon. ⁷⁶

Visual symptoms: Elementary visual hallucinations are the hallmark of OLE. Ictal visual phenomena are stereotyped for each patient, typically lasting seconds (median 35 seconds, range 3–375 seconds).^74,75 They consist predominantly of multiple, brightly colored, small circular spots or balls, often appearing in the temporal hemifield and moving contralaterally. In contrast, migraine visual aura typically consists of white/golden dots or scotomas lasting minutes (83.3% of cases). ²⁴

Accompanying features: The most significant differentiator is the presence of associated seizures. In OLE, 60% of patients have associated focal or bilateral tonic-clonic seizures (p < 0.001 vs. migraine). ⁷⁴ Other accompanying features include eye version/head turning (ictal nystagmus or forced eye deviation), postictal confusion, amnesia, and Todd’s paralysis. None of the above-mentioned symptoms are observed in MA.

Key differentiators from MA: Differential diagnosis rests on integrating multiple features, with temporal evolution being the most discriminating.^73,77 The color of visual phenomena alone has limited discriminatory value, as recent systematic work by Viana et al. demonstrates that visual aura in migraine is frequently colorful. ⁷⁸ Instead, the most useful distinguishing features are: (1) duration—OLE typically produces visual symptoms lasting seconds, whereas MA involves a stereotyped 5–60 minute duration; (2) temporal evolution—OLE symptoms are abrupt in onset and offset without a migrating pattern, while MA spreads gradually across the visual field over minutes; (3) progression pattern—epilepsy visual phenomena may multiply and increase in size during the seizure and can progress to other occipital seizure symptoms, whereas MA is typically characterized by a slow, gradual spread of symptoms across the visual field, corresponding to the propagation of CSD across the occipital cortex at a rate of approximately 2–3 mm per minute ⁷⁹ ; and (4) sequential recruitment—when multiple aura symptoms occur, a subset of MA patients may exhibit a stereotyped progression of symptom modalities (visual → sensory → language), reflecting the spatiotemporal propagation of CSD across functionally distinct cortical areas. However, this sequence is subject to considerable inter- and intra-individual variability, with subsequent symptoms potentially starting simultaneously (34%), during (37%), at the end of (5%), or after (24%) the preceding symptom. ⁸⁰ In OLE, visual phenomena may also evolve during the seizure—multiplying, increasing in size, or progressing to other occipital seizure symptoms, and more rarely, to extra-occipital manifestations or generalized convulsions. Unlike the relatively predictable visual–sensory–language march in MA, the evolution in OLE reflects the spread of ictal activity from the occipital focus to neighboring cortical regions, and occurs over a much shorter timescale (seconds rather than minutes). Interictal EEG reveals occipital epileptiform activity in OLE but may be normal interictally, limiting diagnostic sensitivity. Ictal EEG recording or intracranial monitoring may be required for the definitive diagnosis of OLE. ⁸¹

Prognostic insights: Prognosis varies significantly by etiology. Idiopathic OLE (childhood occipital visual epilepsy, COVE) shows excellent prognosis with early remission within 36 months (p = 0.012). ⁸² Response to carbamazepine is excellent (90% good response at 12 months), and seizures may remit spontaneously. Symptomatic OLE due to structural lesions (space-occupying lesions, post-stroke encephalomalacia, vascular malformations) has poorer prognosis; no cases achieved remission within 36 months in pediatric series. ⁷⁴ Older age at epilepsy onset is associated with poorer outcomes. ⁸³ Surgical treatment for drug-resistant OLE with identifiable epileptogenic foci achieves good outcomes after detailed preoperative evaluation. First unprovoked seizure carries 40–50% recurrence risk, with risk factors including younger age, abnormal EEG, and structural brain abnormalities. ⁸⁴

A broad differential: Other causes of combined headache and visual symptoms

Other disorders causing combined headache and visual symptoms include ophthalmic conditions, intracranial space-occupying lesions, arterial dissection, and intracranial infections. Glaucoma , particularly acute angle-closure crisis, presents with severe ipsilateral headache, eye pain, nausea, and vomiting, with visual symptoms including blurred vision, halos around lights, and fixed mid-dilated pupil; key differentiators are elevated intraocular pressure and corneal edema on examination. ⁸⁵ Refractive errors (uncorrected hyperopia, astigmatism, presbyopia) typically cause frontal or bifrontal headache after prolonged visual tasks, accompanied by eye strain and transient blurring that clears with pinhole ⁸⁶ ; normal ophthalmologic examination and symptom relief with correct lenses distinguish them from organic pathology. Intracranial space-occupying lesions (tumors, abscesses) produce progressive headache worse in the morning or with Valsalva, with visual symptoms including papilledema, diplopia from sixth nerve palsy, and visual field defects (e.g., bitemporal hemianopia from chiasmal compression); imaging and presence of focal neurological deficits are key discriminators. Intracranial infections (meningitis, encephalitis, brain abscess) feature acute to subacute headache often with fever, neck stiffness, and altered consciousness, with visual symptoms ranging from photophobia and blurred vision to diplopia (cranial nerve palsies) and cortical blindness; CSF analysis and neuroimaging are essential for etiologic diagnosis. Tolosa-Hunt syndrome features unilateral periorbital or retro-orbital pain with ipsilateral oculomotor palsies (CN III, IV, VI), diplopia, and dramatic response to corticosteroids ⁸⁷ ; MRI shows cavernous sinus granulomatous inflammation, and exclusion of other causes is essential. In clinical practice, we also encounter many rare or very rare diseases that cause headache and visual symptoms. In all cases, careful history, targeted examination, and appropriate imaging guide accurate diagnosis.

An increasingly recognized concept relevant to the differential diagnosis of headache with visual symptoms is that cortical lesions and cortical irritation may trigger spreading depression, thereby producing transient neurological symptoms that are clinically indistinguishable from migraine with aura.^88,89 Ischemic stroke, vascular malformations, subdural hematoma, tumors, and other cortical lesions may all trigger spreading depression, resulting in typical aura-like symptoms. This phenomenon—often termed “symptomatic migraine” or “secondary spreading depression”—has direct clinical implications: patients presenting with a first episode of typical migraine aura may in fact have secondary spreading depression caused by an underlying cortical lesion. ⁸⁸ Red flags that should raise suspicion for secondary causes include: (1) age at onset >50 years; (2) side-locked aura symptoms; (3) frequent attacks consistently (>1/week); (4) non-visual onset of aura episodes; and (5) atypical aura features not fulfilling ICHD-3 criteria for migraine with typical aura. ⁸⁸ Recognition of this phenomenon is increasingly important in acute stroke and emergency neurology, where new-onset aura symptoms should not be automatically attributed to migraine without appropriate evaluation.

Structured diagnostic frameworks for headache with visual symptoms: Clinical implications

To facilitate bedside clinical reasoning, we propose a stepwise diagnostic algorithm (Figure 1) that sequentially integrates three key historical features: the duration of visual symptoms, the laterality (monocular versus binocular involvement), and red-flag accompanying features. The approach begins with temporal profiling of visual symptoms: persistent (≥3 months) suggests VSS; paroxysmal episodes lasting seconds point to OLE; 5–60 minutes indicate MA (binocular) or RM (monocular); days to weeks raise suspicion for intracranial pressure disorders, CVST, or space-occupying lesions; acute onset within minutes signals vascular emergencies including GCA, SAH, PRES, or arterial dissection. Step 2 distinguishes monocular involvement (RM, GCA, arterial dissection, acute angle-closure glaucoma) from binocular involvement (MA, OLE, PRES, ON, IIH). Step 3 identifies red-flag accompaniments: temporal tenderness with jaw claudication (GCA), thunderclap headache with neck stiffness (SAH), hypertension with seizures and cortical blindness (PRES), pulsatile tinnitus with papilledema (CVST/IIH), Horner syndrome with ipsilateral headache (arterial dissection), postictal confusion with ultra-short hallucinations (OLE), and eye pain with fixed pupil and high intraocular pressure (acute angle-closure glaucoma). To further standardize the description of visual symptoms and enhance diagnostic accuracy across specialties, a concise visual reference was constructed in Figure 2, where the core clinical features—including visual symptom profiles, headache relationships, and key distinguishers—of seven disorders presenting with combined headache and visual symptoms are systematically integrated. The coding system (①–⑫) standardizes the description of twelve core visual symptoms, facilitating consistent communication across neurology, ophthalmology, and emergency medicine while reducing terminological confusion that commonly leads to misdiagnosis. By highlighting key distinguishing features—such as the ultra-short duration with ictal seizures in occipital lobe epilepsy, the strict monocularity in retinal migraine, and the cortical blindness with preserved pupillary reflexes in PRES—the figure equips clinicians with practical bedside rules for rapid triage and appropriate referral.

Figure 1.

Diagnostic algorithm for patients presenting with concurrent headache and visual symptoms. The proposed three-step approach begins with temporal profiling of visual symptoms, followed by determination of monocular versus binocular involvement, and concludes with identification of key red-flag accompanying features. This algorithm is intended as a bedside clinical tool to guide differential diagnosis and prompt recognition of emergency conditions. Abbreviations: GCA, giant cell arteritis; SAH, subarachnoid hemorrhage; PRES, posterior reversible encephalopathy syndrome; CVST, cerebral venous sinus thrombosis; IIH, idiopathic intracranial hypertension.

Figure 2.

Visual symptom profiles and headache characteristics of seven disorders presenting with combined headache and visual disturbance. The figure integrates twelve core visual symptoms (① scintillating scotoma, ② zig-zag/fortification lines, ③ blurred vision, ④ multicolored circular spots, ⑤ visual flashes, ⑥ visual distortion, ⑦ impaired color vision, ⑧ fine dynamic pixelated dots, ⑨ central scotoma, ⑩ visual field defect, ⑪ amaurosis/vision loss, ⑫ tunnel vision) with disorder-specific headache relationships and key distinguishing features. This schematic aids bedside differentiation between common and critical etiologies. Abbreviations: MS, multiple sclerosis; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; NMOSD, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.

While neuroimaging plays an indispensable role in the diagnostic workup of headache with visual symptoms, the strength of evidence varies considerably across conditions. In vascular emergencies—including GCA, PRES, SAH, CVST, and arterial dissection—imaging findings are diagnostic and reproducible: temporal artery MRI (GCA), parieto-occipital FLAIR hyperintensities (PRES), non-contrast CT plus lumbar puncture (SAH), MR venography (CVST), and fat-saturated T1-weighted black-blood MRI with angiographic confirmation (dissection). In contrast, for MA and RM, imaging abnormalities remain exploratory: OCTA findings—including enlarged foveal avascular zones and reduced vessel densities—have been reported in MA but require replication, and no OCTA studies have been published for RM. In ON, orbital MRI findings (short-segment lesions in MS, long anterior lesions with perineural enhancement in MOGAD, chiasmal involvement in NMOSD) and OCT atrophy patterns are well-established subtype differentiators. In IIH, neuroimaging signs—empty sella, transverse sinus stenosis, and dilated optic nerve sheaths—are highly supportive though not diagnostic in isolation. In OLE, interictal EEG and ictal EEG recordings remain the gold standard, with structural MRI for etiology. For VSS, functional imaging (lingual gyrus hypermetabolism) and resting-state connectivity changes are promising but remain investigational. Thus, when integrating imaging into clinical decision-making, it is critical to distinguish between established diagnostic markers and exploratory observations that require further validation.

Limitations

Several limitations of this narrative review should be acknowledged. First, as a narrative synthesis rather than a systematic review, the selection and interpretation of studies may be subject to reviewer bias, despite our structured search strategy. Second, while we included studies published in English and Chinese, relevant reports in other languages may have been missed. Third, we did not conduct a formal quality assessment or meta-analysis, which limits the ability to quantify the strength of evidence across studies. Finally, some imaging biomarkers discussed remain exploratory, and their clinical utility requires further validation in larger, well-designed cohorts.

Conclusion

Headache with visual symptoms encompasses a broad diagnostic spectrum, from benign perceptual disorders to life-threatening vascular emergencies. This narrative review provides a structured framework to navigate this complexity, grounded in recent advances in biomarker-based subclassification and neuroimaging. Accurate diagnosis hinges on systematic integration of three key elements: precise characterization of visual symptom duration and laterality, recognition of red-flag features, and appropriate application of targeted investigations—including MRI, MR venography, CSF analysis, and antibody testing. Developing a standardized framework that integrates headache characteristics with visual symptom profiles is a key priority. Prospective validation of OCTA and functional MRI biomarkers, standardization of precision therapies, and integration of AI-assisted phenotyping into emergency workflows will drive progress. Multidisciplinary collaboration and prospective registries are essential to translate these innovations into improved clinical outcomes.

Appendix.

Abbreviations

AAION

Arteritic Anterior Ischemic Optic Neuropathy

COVE

Childhood Occipital Visual Epilepsy

CN

Cranial Nerve

CRP

C-Reactive Protein

CSD

Cortical Spreading Depression

CSF

Cerebrospinal Fluid

CTA

Computed Tomography Angiography

CVST

Cerebral Venous Sinus Thrombosis

EEG

Electroencephalography

ESR

Erythrocyte Sedimentation Rate

GCA

Giant Cell Arteritis

GCIPL

Ganglion Cell Inner Plexiform Layer

ICAD

Internal Carotid Artery Dissection

IIH

Idiopathic Intracranial Hypertension

IVMP

Intravenous Methylprednisolone

LEON

Longitudinally Extensive Optic Neuritis

MA

Migraine with Aura

MOGAD

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

MRA

Magnetic Resonance Angiography

MRI

Magnetic Resonance Imaging

mRS

modified Rankin Scale

MRV

Magnetic Resonance Venography

MS

Multiple Sclerosis

NAION

Non-Arteritic Anterior Ischemic Optic Neuropathy

NIHSS

National Institutes of Health Stroke Scale

NMOSD

Neuromyelitis Optica Spectrum Disorder

OCT

Optical Coherence Tomography

OCTA

Optical Coherence Tomography Angiography

OLE

Occipital Lobe Epilepsy

ON

Optic Neuritis

PLEX

Plasma Exchange

PRES

Posterior Reversible Encephalopathy Syndrome

RM

Retinal Migraine

RNFL

Retinal Nerve Fiber Layer

SAH

Subarachnoid Hemorrhage

SIH

Spontaneous Intracranial Hypotension

VAD

Vertebral Artery Dissection

VSS

Visual Snow Syndrome.

ORCID iD

Shusheng Jiao https://orcid.org/0009-0003-2524-6605