Is it possible for a patient with a history of rare migraines with aura to develop 4 brain lesions?

Brain Lesions in Rare Migraine with Aura: Clinical Plausibility

Yes, this patient's presentation of 4 brain lesions with only 5 lifetime auras is entirely consistent with established migraine-related brain pathology, though the pattern warrants careful exclusion of alternative diagnoses.

Evidence Supporting Migraine-Related Lesions

The American Heart Association/American Stroke Association guidelines establish that women with migraine with aura develop infarct-like brain lesions at significantly elevated rates, even with infrequent attacks 1:

• Baseline risk elevation: Migraine with aura increases late-life infarct-like lesions (OR 1.4; 95% CI 1.1-1.8) regardless of attack frequency 1
• Subclinical posterior circulation infarcts: The CAMERA study found migraineurs with aura have dramatically higher prevalence of subclinical posterior circulation infarcts (OR 13.7; 95% CI 1.7-112) 1
• White matter lesions in women: Female migraineurs face independently increased risk of white matter lesions (OR 2.1; 95% CI 1.0-4.1) 1
• Cerebellar predilection: Women with migraine with aura show particular association with cerebellar lesions (OR 1.9; 95% CI 1.4-2.6) 1

The described lesion locations (subcortical, periventricular, subventricular) match the typical distribution pattern documented in migraine populations 1.

Critical Distinction: Attack Frequency Does Not Predict Lesion Burden

This is the key clinical pitfall: The guidelines demonstrate that lesion development occurs even with infrequent auras 1. While high attack frequency (>weekly) increases ischemic stroke risk (HR 4.25; 95% CI 1.36-13.29) 1, the presence of subclinical lesions does not correlate linearly with attack frequency 1.

The mechanism remains unclear but involves complex interactions beyond simple attack accumulation: cortical spreading depression, meningeal inflammation, trigeminovascular activation, and possible hypercoagulable states 1.

Mandatory Differential Diagnosis Workup

Despite plausibility, new lesion appearance between 2023-2025 requires systematic exclusion of alternative etiologies 2, 3, 4:

Multiple Sclerosis Evaluation

• McDonald criteria assessment: The appearance of 2 new lesions over 2 years with periventricular distribution raises MS concern 2
• Required testing: Lumbar puncture for oligoclonal bands, comprehensive autoimmunity panel 4
• Red flags for MS: Worsening migraine pattern, poor response to migraine treatment (though this patient responds to Sumatriptan), any focal neurological deficits beyond aura 2
• Lesion characteristics: Look for corpus callosum involvement, infratentorial lesions, gadolinium enhancement suggesting active demyelination 2, 3

Patent Foramen Ovale Assessment

• Cardiological evaluation with bubble study: PFO is present in 45% of migraine patients with white matter lesions 4
• Specific association: PFO strongly correlates with visual aura (p<0.001) and occipital lesion distribution (p<0.001) 4
• Prognostic significance: PFO-related lesions show stationary burden on follow-up, never develop enhancement or corpus callosum involvement 4

Vascular Risk Factor Assessment

• Hypercoagulable workup: Migraine with aura associates with hypercoagulable states (OR 6.81; 95% CI 1.01-45.79 in patients <50 years with infarcts) 1
• Screen for: Antiphospholipid antibodies, protein C/S deficiency, Factor V Leiden, prothrombin mutation 1
• Cardiovascular evaluation: Hypertension, diabetes, hyperlipidemia screening 5

Lesion Progression Monitoring Algorithm

The appearance of 2 new lesions over 2 years (2023-2025) is the concerning element requiring active surveillance:

1. Repeat MRI at 6-12 months to assess for further progression 2, 4
2. If stable: Consistent with migraine-related lesions; continue annual monitoring 4
3. If progressive: Strongly suggests alternative diagnosis (MS, vasculitis, PFO with recurrent emboli) 2, 4
4. Gadolinium enhancement: Active enhancement indicates active demyelination or inflammation, not typical migraine pathology 2, 3

Stroke Risk Mitigation Strategy

Even with infrequent auras, this patient faces elevated stroke risk requiring aggressive prevention 1:

• Absolute contraindication to estrogen: Never prescribe estrogen-containing contraceptives (RR 7.02; 95% CI 1.51-32.68) 1, 5
• Smoking prohibition: Catastrophic risk amplification (RR 9.03; 95% CI 4.22-19.34) 1, 5
• Consider migraine prophylaxis: Propranolol 80-160 mg daily or topiramate 50-100 mg daily may reduce future lesion accumulation, though evidence is indirect 5
• Aspirin consideration: Low-dose aspirin for primary stroke prevention in women with migraine with aura remains controversial but reasonable given lesion burden 1

Clinical Significance and Prognosis

The presence of these lesions does not predict clinical stroke or cognitive decline in most patients 1, 6. The mechanism and long-term relevance remain unclear 1. However, their presence confirms the patient's migraine with aura diagnosis carries real vascular consequences requiring ongoing risk factor management 1.

The documented response to sumatriptan supports primary migraine rather than secondary headache from structural lesions 2.