What are the potential secondary causes of headaches in a 30-year-old female with a history of progressively worsening migraines and normal head computed tomography (CT) scan and laboratory results?

Secondary Causes of Headache in a 30-Year-Old Female with Progressively Worsening Migraines

In a 30-year-old female with progressively worsening migraines and normal CT/labs, you must systematically evaluate for red flag features that indicate secondary causes, though the normal imaging significantly reduces the likelihood of dangerous pathology. 1

Critical Red Flags Requiring Immediate Investigation

The following features mandate urgent evaluation for secondary causes, even with normal initial imaging 1, 2:

• Thunderclap headache (sudden, severe onset) - suggests subarachnoid hemorrhage 1
• Progressive worsening pattern - indicates possible intracranial space-occupying lesion 1, 3
• Headache awakening patient from sleep - raises concern for increased intracranial pressure 1, 3
• Worsening with Valsalva maneuver, coughing, sneezing, or exercise - suggests intracranial hypertension or space-occupying lesion 1, 3
• Atypical aura - may indicate transient ischemic attack, stroke, epilepsy, or arteriovenous malformations 1
• Associated weight loss and/or change in memory or personality - strongly suggests secondary headache 1

Physical Examination Findings That Indicate Secondary Causes

During examination, specifically assess for 1:

• Focal neurological symptoms or signs - suggests secondary headache requiring neuroimaging 1, 3
• Papilledema - indicates increased intracranial pressure 1
• Neck stiffness - suggests meningitis or subarachnoid hemorrhage 1
• Unexplained fever - indicates possible meningitis 1
• Impaired memory, altered consciousness, or personality changes - suggests secondary headache 1

Specific Secondary Causes to Consider in This Patient

Medication Overuse Headache (MOH)

This is the most common secondary cause in patients with progressively worsening migraines 1, 2. Evaluate for:

• Frequent use of acute medications (NSAIDs, triptans, opioids, or barbiturates) more than 2 days per week 2
• Pattern of increasing headache frequency correlating with medication use 1

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

Consider this diagnosis particularly if the patient has 1:

• Obesity or recent weight gain 1
• Visual disturbances or papilledema on examination 1
• Headache worsened by postural changes 1

Note: CT may be normal in pseudotumor cerebri; MRI with MRV and lumbar puncture with opening pressure measurement are required for diagnosis 1

Cervicogenic Headache

Evaluate for 1:

• History of neck trauma or cervical spine pathology 3
• Headache provoked by neck movements or sustained postures 3

Giant Cell Arteritis

Though less common at age 30, if the patient is approaching or over age 50, obtain 2:

• ESR and CRP levels 2
• Temporal artery examination for tenderness or decreased pulse 1

Obstructive Sleep Apnea

This modifiable risk factor can worsen migraine frequency 2:

• Screen for snoring, witnessed apneas, daytime somnolence 2
• Consider polysomnography if suspected 2

When Normal CT is Insufficient

A normal head CT does not exclude all secondary causes. 1 Consider MRI brain with and without contrast if 1, 3:

• Progressive worsening continues despite treatment 1
• Any focal neurological findings develop 1, 3
• Atypical features emerge that don't fit primary migraine pattern 1
• Suspicion for posterior fossa lesion, venous sinus thrombosis, or pituitary pathology 1

MRI is more sensitive than CT for detecting white matter lesions, developmental venous anomalies, and small structural abnormalities, though the clinical significance of these findings may be uncertain 1

Additional Laboratory Evaluation

Beyond routine labs, consider 2, 3:

• ESR and CRP if age >50 or temporal arteritis suspected 2
• Thyroid function tests for metabolic causes 3
• Pregnancy test in women of childbearing age, as pregnancy alters headache patterns and treatment options 3

Common Pitfalls to Avoid

• Assuming primary migraine without investigating progressive worsening - this pattern demands explanation 2
• Missing medication overuse headache - directly ask about all acute medication use patterns 2, 4
• Relying solely on patient recall of headache frequency - implement a headache diary for accurate assessment 2, 4
• Failing to perform a complete neurological examination - most secondary causes have accompanying neurological signs 1
• Ordering neuroimaging without red flags - this increases false positive findings and unnecessary interventions 1

Algorithmic Approach

1. Perform meticulous neurological and physical examination looking specifically for red flags listed above 1, 3
2. Obtain detailed medication history to identify medication overuse 2
3. Implement headache diary to accurately characterize frequency and pattern 2, 4
4. If any red flags present: proceed with MRI brain with and without contrast 1
5. If examination normal but progressive worsening continues: consider MRI to exclude structural lesions 1, 3
6. If obesity and visual symptoms present: evaluate for pseudotumor cerebri with MRI/MRV and lumbar puncture 1
7. If frequent acute medication use identified: diagnose and treat medication overuse headache 2