What is the best course of action for a 27-year-old female with a history of migraines, currently being treated for a sinus infection, presenting with headaches, anisocoria (unequal pupil size), and normal neuro exam results?

Management of Headache with Anisocoria in a Young Woman with Migraines and Sinus Infection

This patient requires urgent evaluation with neuroimaging to rule out serious intracranial pathology, despite the normal neurologic examination, because anisocoria combined with increasing head pressure represents a red flag that cannot be dismissed based on office findings alone. 1, 2

Immediate Assessment Priorities

The combination of increasing head pressure and anisocoria demands immediate attention to exclude life-threatening causes before attributing symptoms to benign conditions:

• Obtain urgent neuroimaging (MRI or CT) because anisocoria with progressive headache can indicate intracranial complications of sinusitis, including epidural empyema, subdural empyema, meningitis, or cavernous sinus thrombosis, even when the neurologic exam appears normal in the office 1, 2
• Specifically evaluate for orbital and intracranial complications of ethmoid or sphenoid sinusitis, which can present with pupillary abnormalities, ophthalmoplegia, or visual changes before other neurologic signs become apparent 1
• Consider sphenoid sinusitis as a diagnostic possibility because it presents with vague symptoms, severe headache, and ocular signs including oculomotor palsy, and is frequently missed with high morbidity if diagnosis is delayed 1

Critical Red Flags Present in This Case

This patient demonstrates multiple concerning features that elevate risk beyond simple migraine or uncomplicated sinusitis:

• Anisocoria represents a focal neurologic sign that warrants neuroimaging according to established guidelines, regardless of whether other examination findings are normal 1, 2
• Progressive worsening pattern (increasing pressure sensation) is a red flag requiring imaging to exclude mass lesion, abscess, or increased intracranial pressure 1, 2
• Active sinus infection increases risk for intracranial extension through septic thrombi via valveless diploic veins or direct extension through the lamina papyracea separating the orbit from ethmoid sinuses 1

Differential Diagnosis to Consider

While awaiting imaging, consider these potential etiologies in order of clinical urgency:

• Intracranial complications of sinusitis including cavernous sinus thrombosis (from sphenoid/ethmoid infection), orbital apex syndrome, or epidural/subdural empyema 1
• Third nerve palsy from compression or inflammation, which can present with pupillary dilation and must be differentiated from pharmacologic causes 1
• Pharmacologic anisocoria from inadvertent exposure to anticholinergic medications (nebulized ipratropium if used for concurrent respiratory symptoms, or other topical agents), which can be confirmed with pilocarpine testing 3
• Migraine-related pupillary changes are possible but remain a diagnosis of exclusion after dangerous causes are ruled out 1

Diagnostic Approach Algorithm

Follow this structured evaluation pathway:

1. Perform focused examination looking specifically for papilledema, extraocular movement abnormalities, proptosis, periorbital edema/erythema, visual field defects, and any subtle motor or sensory deficits that may have been missed 1

2. Obtain detailed medication history including any nebulized treatments, nasal sprays, eye drops, or topical preparations that could cause pharmacologic mydriasis 3

3. Order urgent neuroimaging (MRI with contrast preferred over CT for better visualization of orbital and intracranial complications; CT acceptable if MRI unavailable) 1, 2

4. If imaging is negative and pharmacologic exposure suspected, perform pilocarpine test (one drop of 1% pilocarpine in each eye; pharmacologic mydriasis will not constrict, while neurologic causes typically will) 3

Management Based on Imaging Results

The treatment pathway diverges based on imaging findings:

If intracranial complication identified:

• Immediate neurosurgical and infectious disease consultation for management of abscess, empyema, or cavernous sinus thrombosis 1
• Broad-spectrum IV antibiotics covering typical sinus pathogens and anaerobes 1
• Consider antifungal coverage if immunocompromised or if imaging suggests fungal sinusitis 1

If imaging negative and pharmacologic cause confirmed:

• Reassure patient that pupil will return to normal within 24 hours 3
• Prevent future exposure by ensuring proper mask fit during nebulizer treatments or using protective eyewear 3

If imaging negative and no pharmacologic cause identified:

• Treat as migraine with appropriate acute therapy (NSAIDs or triptans depending on severity) 1, 4
• Optimize sinus infection treatment with appropriate antibiotics (amoxicillin or high-dose amoxicillin-clavulanate for 10-14 days) 1
• Consider preventive migraine therapy if attacks occur more than twice monthly with significant disability 1, 5

Common Pitfalls to Avoid

• Do not dismiss anisocoria simply because the rest of the neurologic exam is normal—serious intracranial pathology can present with isolated pupillary findings before other signs develop 1, 2
• Do not attribute all facial pressure and headache to sinus infection—migraine is frequently misdiagnosed as "sinus headache," and the two conditions can coexist 1, 6, 7, 8
• Do not delay imaging while treating empirically—intracranial complications of sinusitis require urgent diagnosis and have high morbidity/mortality if treatment is delayed 1
• Do not assume self-reported intermittent anisocoria at home is benign physiologic anisocoria—this requires objective documentation and evaluation, especially in the context of new headache symptoms 2