What are the red flags to consider when evaluating a patient with a headache, particularly in those with a history of cancer, immunocompromised status, or recent trauma?

Headache Red Flags

When evaluating a patient with headache, immediately assess for life-threatening secondary causes by screening for specific red flags in the history and physical examination—these warning signs mandate urgent neuroimaging and further investigation to rule out conditions like subarachnoid hemorrhage, meningitis, intracranial mass, or temporal arteritis.

Critical Historical Red Flags

Immediate Life-Threatening Presentations

• Thunderclap headache (sudden onset reaching maximum intensity within seconds to minutes) suggests subarachnoid hemorrhage and requires immediate CT imaging 1, 2, 3
• "Worst headache of life" with abrupt onset indicates serious vascular pathology requiring emergent evaluation 1, 2, 3
• Headache awakening patient from sleep may indicate increased intracranial pressure from mass lesion or other space-occupying pathology 4, 1, 2

High-Risk Clinical Scenarios

• New headache onset after age 50 suggests secondary headache and consideration of temporal arteritis, particularly with associated visual symptoms or jaw claudication 1, 2
• Progressive headache worsening over time could indicate an intracranial space-occupying lesion such as tumor or abscess 1, 2
• Marked change in headache pattern (significant change in previously stable headache characteristics) is a red flag for secondary headache 4, 1, 2
• Persistent headache following head trauma may indicate subdural hematoma, epidural hematoma, or other intracranial injury 4, 1, 2
• Atypical aura may indicate transient ischemic attack, stroke, epilepsy, or arteriovenous malformations rather than typical migraine 1, 2

Positional and Exertional Features

• Headache aggravated by postures or maneuvers that raise intracranial pressure (coughing, sneezing, Valsalva) suggests intracranial hypertension or space-occupying lesion 4, 1, 2
• Headache brought on by exercise may indicate vascular pathology or increased intracranial pressure 1, 2

Associated Systemic Symptoms

• Constitutional symptoms including fever, weight loss, or night sweats suggest infection, malignancy, or systemic inflammatory disease 4, 1, 2
• Change in memory or personality suggests secondary headache from mass lesion, infection, or other intracranial pathology 1, 2

Critical Physical Examination Red Flags

Neurological Findings

• Focal neurological symptoms or signs (weakness, sensory loss, visual field defects, cranial nerve palsies) suggest secondary headache requiring urgent evaluation 4, 1, 2, 3
• Papilledema indicates increased intracranial pressure from mass, hydrocephalus, or idiopathic intracranial hypertension 3
• Uncoordination or ataxia may indicate cerebellar pathology from stroke, tumor, or other structural lesion 4, 1, 2, 3
• Impaired memory and/or altered consciousness suggests serious secondary headache 4, 1, 2

Meningeal Signs

• Neck stiffness is a possible indicator of meningitis or subarachnoid hemorrhage requiring immediate evaluation 4, 1, 2
• Unexplained fever may indicate meningitis, encephalitis, or other CNS infection 4, 1, 2
• Limited neck flexion on examination is part of the Ottawa SAH Rule for subarachnoid hemorrhage screening 1

Special Populations at Higher Risk

Immunocompromised Patients

• History of cancer, HIV/AIDS, or immunosuppressive therapy increases risk for CNS infection (toxoplasmosis, cryptococcal meningitis, progressive multifocal leukoencephalopathy), metastatic disease, or opportunistic infections 4, 5
• These patients require lower threshold for neuroimaging even with less dramatic presentations 4

Post-Traumatic Presentations

• Any headache following recent head trauma (even minor trauma in elderly or anticoagulated patients) requires evaluation for subdural or epidural hematoma 4, 1, 2
• Elderly patients and those on anticoagulation are at particularly high risk for delayed intracranial hemorrhage 4

Ottawa SAH Rule for Subarachnoid Hemorrhage

For alert patients >15 years with new severe nontraumatic headache reaching maximum intensity within 1 hour, investigate for subarachnoid hemorrhage if ANY of the following are present: 1

• Age ≥40 years
• Neck pain or stiffness
• Witnessed loss of consciousness
• Onset during exertion
• Thunderclap headache (instantly peaking pain)
• Limited neck flexion on examination

Diagnostic Approach When Red Flags Are Present

Imaging Selection Algorithm

• When acute intracranial hemorrhage is suspected (thunderclap headache, trauma, anticoagulation): Obtain noncontrast head CT immediately as first-line imaging 1, 3, 5
• For most other secondary headache evaluations: MRI is preferred over CT due to higher resolution and absence of radiation exposure, particularly for detecting posterior fossa lesions, venous sinus thrombosis, arterial dissection, encephalitis, and early infarction 4, 1, 2, 3
• Neuroimaging is mandatory when red flags are present to rule out secondary causes—relying solely on clinical assessment without imaging when red flags exist is a critical error 4, 1, 2, 3

Specific Protocol for Suspected Subarachnoid Hemorrhage

• Patients presenting >6 hours from symptom onset OR with new neurological deficit: Perform noncontrast head CT and, if negative for subarachnoid hemorrhage, proceed to lumbar puncture to evaluate for xanthochromia 1, 3
• Patients presenting <6 hours from symptom onset WITHOUT new neurological deficit: Noncontrast head CT on a high-quality scanner interpreted by a board-certified neuroradiologist may be sufficient if negative 1, 3

Additional Testing Considerations

• Lumbar puncture is indicated when meningitis, encephalitis, or subarachnoid hemorrhage (with negative CT) is suspected 4, 5
• MRA or CTA should be obtained when vascular pathology (aneurysm, dissection, vasculitis) is suspected 4
• MRV or CTV is indicated when venous sinus thrombosis is suspected, particularly in patients with risk factors (hypercoagulable state, pregnancy, oral contraceptives, mastoiditis) 4
• Inflammatory markers (ESR, CRP) should be obtained when temporal arteritis is suspected in patients >50 years with new headache 4

Common Pitfalls to Avoid

• Overlooking the need for neuroimaging when red flags are present is the most dangerous error—always image when warning signs exist 4, 1, 2
• Assuming all severe headaches are migraines without screening for red flags can miss life-threatening secondary causes 6, 5
• Relying solely on neuroimaging without considering the complete clinical picture—some serious conditions (arterial dissection, encephalitis, cerebral venous thrombosis) may not be obvious on routine CT and require MRI or lumbar puncture 4, 6
• Failing to obtain adequate history in the emergency setting—structured documentation of red flags and headache characteristics is essential for proper diagnostic categorization 7
• Dismissing headache in immunocompromised or cancer patients as benign without thorough evaluation for CNS infection or metastatic disease 4, 5