What is the best approach to manage migraines with aura and cranial nerve dysfunction, specifically ptosis, in an adult patient?

Migraine with Ptosis: Urgent Exclusion of Secondary Causes Required

When a patient with migraine presents with ptosis or other cranial nerve dysfunction, this represents a red flag requiring immediate neuroimaging to exclude life-threatening secondary causes such as posterior communicating artery aneurysm, pituitary apoplexy, or cavernous sinus pathology before attributing symptoms to ophthalmoplegic migraine. 1, 2

Critical Diagnostic Approach

Rule Out Secondary Causes First

• Obtain urgent MRI/MRA or CT angiography to exclude:

  • Posterior communicating artery aneurysm (can present with third nerve palsy and headache mimicking migraine) 1
  • Pituitary apoplexy (presents with sudden severe headache and complete ptosis) 2
  • Cavernous sinus pathology
  • Stroke, particularly in patients with migraine with aura who have elevated baseline stroke risk 3, 4

• Key distinguishing features to assess:

  • New or atypical symptoms in a patient with known migraine history warrant investigation 1
  • Ophthalmoplegic migraine is extremely rare (0.7 per million incidence) and should be a diagnosis of exclusion 5
  • Third cranial nerve is most commonly affected in ophthalmoplegic presentations, causing mydriasis and ptosis 5

Contraindications in Migraine with Aura

• Absolutely contraindicated medications if this represents migraine with aura:
  • All combined hormonal contraceptives containing estrogen (due to compounded stroke risk) 3, 6
  • Triptans are contraindicated in patients with history of stroke, TIA, hemiplegic or basilar migraine 4

Acute Treatment Algorithm (After Exclusion of Secondary Causes)

During Aura Phase

• Initiate NSAIDs (ibuprofen, diclofenac) or aspirin immediately when aura symptoms appear to abort or diminish subsequent headache 7, 3, 6
• Do NOT use triptans during aura phase due to theoretical vasoconstriction concerns during cortical hypoperfusion 3, 6, 4

During Headache Phase

• Triptans can be used once headache begins (if no contraindications exist) 6, 4
• Separate triptan doses by at least 2 hours; maximum 200 mg sumatriptan in 24 hours 4
• If one triptan fails, others may still provide relief 7

Preventive Treatment Strategy

First-Line Options

• Propranolol 80-160 mg oral once or twice daily 7, 6
• Metoprolol 50-200 mg oral once daily 7, 6
• Topiramate 50-100 mg oral daily 7, 6

Second-Line Options

• Amitriptyline 10-100 mg oral at night (particularly useful if comorbid JME, as reported in ophthalmoplegic migraine cases) 7, 6, 5
• Candesartan 16-32 mg oral daily 7, 6
• Flunarizine 5-10 mg oral once daily 7

Third-Line Options

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) when first and second-line options fail 7

Critical Monitoring Requirements

Medication Overuse Prevention

• Limit acute medication use to <2 days per week to prevent medication overuse headache 3, 6
• Medication overuse headache develops from:
  • Non-opioid analgesics on ≥15 days/month for >3 months 3, 6
  • Triptans on ≥10 days/month for >3 months 3, 6

Follow-Up Assessment

• Evaluate treatment response within 2-3 months using headache calendars to track attack frequency, severity, and medication use 7, 3
• Monitor for residual cranial nerve deficits (complete recovery typically occurs within days to weeks in true ophthalmoplegic migraine, though minority have persistent deficits) 5

Special Considerations for Ophthalmoplegic Migraine

• If secondary causes excluded and ophthalmoplegic migraine confirmed, acute treatment with NSAIDs plus prophylaxis with propranolol or divalproex sodium has shown efficacy 5
• Intravenous steroids for 10 days may be considered in severe cases, though evidence is limited 2
• Neurosurgical consultation if imaging reveals structural lesions requiring intervention 2