What are the red flag symptoms and appropriate assessment, pathophysiology, and pharmacology for a person presenting with a headache?

Red Flag Symptoms in Headache: Assessment, Pathophysiology, and Pharmacology

When evaluating a patient with headache, immediate recognition of red flag symptoms is critical as they may indicate life-threatening conditions requiring urgent intervention and neuroimaging.

Red Flag Symptoms

Sudden Onset and Character

• Thunderclap headache: Abrupt, severe headache reaching maximum intensity within seconds to minutes - strongly suggestive of subarachnoid hemorrhage 1
• "Worst headache of life": Patient-described severity that is unprecedented 2, 3
• New headache pattern: Marked change from previous headache pattern 2
• Headache worsened by Valsalva maneuver: May indicate increased intracranial pressure 2, 3

Age and Timing

• New-onset headache after age 50: Higher risk of secondary causes including temporal arteritis, malignancy 2, 3
• Headache that awakens patient from sleep: May indicate increased intracranial pressure 2, 3
• Progressive worsening over time: Suggests expanding intracranial lesion 3

Associated Neurological Symptoms

• Focal neurological deficits: Including weakness, sensory changes, visual disturbances 2, 3
• Altered mental status: Confusion, decreased consciousness 4
• Seizures: Particularly new-onset seizures with headache 3
• Papilledema: Indicates increased intracranial pressure 3
• Neck stiffness: Suggests meningeal irritation 2, 5

Patient History Factors

• Recent head/neck trauma: Risk of intracranial hemorrhage, arterial dissection 2, 3
• History of cancer or immunocompromised state: Risk of CNS metastases or opportunistic infections 3, 4
• Pregnancy or postpartum state: Risk of venous sinus thrombosis, preeclampsia 5
• Anticoagulant therapy: Increased risk of intracranial hemorrhage 5

Assessment Approach

Initial Evaluation

1. Detailed headache history:

   • Onset (sudden vs. gradual)
   • Pattern (constant vs. intermittent)
   • Location (unilateral vs. bilateral)
   • Quality (throbbing, pressure, stabbing)
   • Severity (0-10 scale)
   • Associated symptoms (nausea, photophobia, phonophobia)
   • Aggravating/alleviating factors 2

2. Focused neurological examination:

   • Mental status
   • Cranial nerves (especially fundoscopic exam for papilledema)
   • Motor and sensory function
   • Coordination
   • Reflexes
   • Meningeal signs (neck stiffness, Kernig's and Brudzinski's signs) 2

Neuroimaging Indications

• Brain MRI: Preferred for most suspected secondary headaches
• CT without contrast: When acute subarachnoid hemorrhage is suspected or MRI contraindicated
• Angiography (CTA/MRA): For suspected vascular abnormalities
• Venography (CTV/MRV): For suspected venous sinus thrombosis 3

According to the U.S. Headache Consortium guidelines, neuroimaging is indicated when:

• Patient has unexplained abnormal findings on neurological examination
• Headache worsened by Valsalva maneuver
• Headache awakens patient from sleep
• New-onset headache in older patients
• Progressively worsening headache pattern 2

Pathophysiology of Secondary Headaches

Vascular Causes (60.4% of fatal headaches) 1

• Subarachnoid hemorrhage: Rupture of cerebral aneurysm causing meningeal irritation
• Cerebral venous sinus thrombosis: Venous outflow obstruction leading to increased intracranial pressure
• Arterial dissection: Tear in arterial wall causing pain and potential stroke
• Reversible cerebral vasoconstriction syndrome: Transient segmental constriction of cerebral arteries 4

Space-Occupying Lesions (16.7% of fatal headaches) 1

• Brain tumors: Primary or metastatic lesions causing increased intracranial pressure
• Brain abscess: Focal infection with surrounding edema
• Hydrocephalus: Obstruction of CSF flow causing increased intracranial pressure 4

Infectious/Inflammatory Causes (6.25% of fatal headaches) 1

• Meningitis/Encephalitis: Infection and inflammation of meninges/brain parenchyma
• Vasculitis: Inflammation of cerebral blood vessels 4

Pharmacological Management

Approach to Treatment

1. Rule out secondary causes before initiating treatment for primary headache
2. Treat underlying cause if secondary headache is identified
3. Provide symptomatic relief while diagnostic workup is ongoing

Acute Migraine Treatment (if primary headache confirmed)

• First-line: NSAIDs (ibuprofen, naproxen, aspirin) or acetaminophen for mild-moderate attacks 2
• Second-line: Triptans (sumatriptan, rizatriptan, etc.) for moderate-severe attacks 2, 6
• Alternative options:
  • CGRP antagonists (rimegepant, ubrogepant) for those who don't respond to or can't tolerate triptans/NSAIDs 2
  • Dihydroergotamine for refractory cases 2
  • Lasmiditan for those with cardiovascular contraindications to triptans 2, 6

Important Cautions

• Avoid opioids and butalbital for headache treatment 2
• Consider non-oral routes (nasal, injectable) for patients with severe nausea/vomiting 2
• Be aware of medication overuse headache: Can occur with frequent use of acute medications (≥15 days/month for NSAIDs, ≥10 days/month for triptans) 2
• Cardiovascular risk: Triptans are contraindicated in patients with coronary artery disease, uncontrolled hypertension, or history of stroke 3, 7

Key Pitfalls to Avoid

1. Missing red flags: Failing to recognize warning signs of secondary headache
2. Premature diagnosis: Assuming primary headache without adequate exclusion of secondary causes
3. Delayed imaging: Not obtaining timely neuroimaging when red flags are present
4. Inappropriate treatment: Using migraine-specific treatments before ruling out secondary causes
5. Overlooking medication overuse: Not recognizing headache caused by frequent use of analgesics

Remember that while most headaches are benign primary disorders, the presence of red flags significantly increases the likelihood of a dangerous secondary cause requiring urgent intervention. Thorough assessment and appropriate neuroimaging can be lifesaving in these cases.