High-Risk Headaches

High-risk headaches, sometimes also referred to as red-flag headaches, encompass secondary causes of headache that can result in irreversible end-organ damage, neurologic deficits, loss of vision, and even death. Entities such as subarachnoid hemorrhage, meningitis/encephalitis, and intracranial tumors carry high morbidity and mortality risks if not recognized and treated immediately. Diagnosis of a high-risk headache requires a high degree of clinical suspicion and is made by conducting a thorough clinical evaluation followed by a targeted workup for the most likely etiology. Management depends on the etiology but consists of prompt treatment of the underlying cause and stabilization of accompanying organ dysfunction.

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A high-risk headache is any new and sudden onset, typically severe, headache with the potential to cause damage to cerebral or precerebral structures or functions.


There are many etiologies of high-risk headache that the clinician should be aware of and work to rule out when a severe headache is encountered. The most common etiologies are presented here, separated into vascular, infectious, neoplastic, and miscellaneous causes.

Table: Vascular etiologies of high risk headaches
Clinical entityHistorical clues/risk factorsClinical features
Subarachnoid hemorrhage (SAH)
  • Sudden onset
  • Severe intensity at onset
  • Syncope/near syncope
  • Neck pain/stiffness
  • Diplopia
  • Meningeal signs
  • Nausea and vomiting
Reversible cerebral vasoconstriction syndrome (RCVS)
  • Sudden onset
  • Severe intensity at onset
  • Short duration
  • Recurrent
  • Associated with triggers
  • Transient neurologic deficits from vasospasm
  • Neurologic deficits may persist (if vasospasm persists)
Cervical artery dissection/vertebral artery dissection
  • Associated with head and/or neck trauma
  • Prominent neck pain
  • New-onset dizziness
  • New-onset tinnitus
  • Cranial nerve palsy:
    • Nystagmus
    • Horner syndrome
  • Cervical artery bruit
  • Presents with cerebrovascular accident/transient ischemic attack (TIA)
Cerebral vein thrombosis/dural sinus thrombosis
  • Hypercoagulable state/risk factors
  • Pregnancy
  • Postpartum
  • Neurologic deficits inconsistent with arterial ischemia
  • Associated with seizure
  • Papilledema on fundoscopy
  • Encephalopathy
Subdural hematoma/epidural hematoma
  • Associated with head trauma
  • Anticoagulant therapy
  • Gradual progression of neurologic deficit and/or mental status
  • Posterior fossa hematoma →
    • Nausea/vomiting
    • Visual changes
    • Ataxia
    • Dysphagia
    • Anisocoria
    • Nuchal rigidity
Intraparenchymal hemorrhage (IPH)
  • Sudden onset
  • Associated with severe hypertension
  • Anticoagulant therapy
Variable presentation depending on site of bleed (much like cerebrovascular accident/TIA)
Idiopathic intracranial hypertension
  • Overweight/obese female
  • Childbearing age
  • Transient/intermittent visual symptoms
  • Papilledema on fundoscopy
  • Abducens nerve palsy
  • Other cranial nerve palsies
  • Visual deficit
  • Tinnitus
Spontaneous intracranial hypotension
  • Severe headache in upright position
  • Headache improves with caffeine and while lying flat
  • Headache worsens with Valsalva maneuver
  • Common after dural puncture
  • Neurologic findings may be absent or widely variable
  • Tinnitus
  • Cervical pain
  • Nausea and vomiting
Giant-cell arteritis
  • Age > 50 years
  • Sudden-onset visual disturbances (often monocular)
  • Jaw claudication
  • Palpable or nodular temporal arteries
  • Fever
  • Elevated acute-phase reactants:
    • CRP
    • Erythrocyte sedimentation rate (ESR)
Hypertensive encephalopathy
  • Gradual-onset headache in the setting of severe hypertension
  • Seizures
  • Altered mental status
  • Severe hypertension
  • Papilledema and retinal hemorrhage on fundoscopy
  • Hematuria and proteinuria on urinalysis
  • Encephalopathy
Posterior reversible encephalopathy syndrome
  • Gradual-onset headache inconsistently associated with severe hypertension
  • Seizures
  • Nausea and vomiting
  • Visual changes
  • Pregnancy or postpartum period
  • Hypertension may or may not be present
  • Papilledema and retinal hemorrhage on fundoscopy
  • Hematuria and proteinuria on urinalysis
  • Encephalopathy
Table: Infectious etiologies of high-risk headaches
Clinical entityHistorical clues/risk factorsClinical features
Meningitis and/or encephalitis
  • Toxic-appearing
  • Fever
  • Neck pain/stiffness
  • Altered mental status/level of consciousness
  • Fever
  • Meningism
  • Altered mental status/level of consciousness
  • Seizure
  • Cranial nerve palsies
  • Petechiae or purpura
Brain abscess
  • Onset of headache may be sudden or gradual
  • Recent history of infection:
    • Direct spread (sinusitis, otitis)
    • Distant spread (endocarditis, bacteremia)
  • Fever may be variable
  • Neck pain/stiffness may be variable
  • Papilledema on fundoscopy
  • Insidious onset of focal neurologic deficits or cranial nerve palsies
Table: Neoplastic etiologies of high-risk headaches
Clinical entityHistorical clues/risk factorsClinical features
Brain tumor
  • Cancer
  • Headache worsens with cough, Valsalva maneuver
  • Insidious headache onset, but may be sudden if tumor bleeds
  • Nausea and vomiting
  • Papilledema on fundoscopy
  • Seizure
  • Altered mental status/level of consciousness
  • Neurologic deficits corresponding to tumor location
Colloid cyst of 3rd ventricle
  • Headache worsens in upright position, improves with lying flat
  • Altered mental status
  • Symptoms may fluctuate
  • Altered mental status
  • Diplopia
  • Memory issues
  • Vertigo
Pituitary apoplexy
  • Associated with pituitary tumors (most often benign)
  • Sudden-onset headache associated with infarction/bleeding into tumor
  • Nausea and vomiting
  • Altered mental status
  • Visual/oculomotor defect
  • Endocrine dysfunction
Table: Other etiologies of high-risk headaches
Clinical entityHistorical clues/risk factorsClinical features
Acute narrow-angle glaucoma
  • Ocular pain
  • Ocular injection
  • Loss of vision
  • Nausea and vomiting
  • Conjunctival injection
  • Corneal clouding; fixed
  • Pupillary dilation with lack of constriction
  • Elevated intraocular pressure
CO toxicity
  • Acute CO exposure
  • Headache improves with separation from CO
  • Nausea/vomiting
  • Light-headedness/dizziness
  • Fatigue/malaise
  • Seizure
  • Coma
  • Red macula on fundoscopy
  • Pregnant woman at > 20 weeks
  • Sudden-onset headache associated with blood pressure > 140/90 mm Hg
  • Tinnitus
  • Visual disturbance
  • Seizure
  • Proteinuria
  • Brisk deep tendon reflexes (DTRs)
  • Placental abruption
  • Symptoms abate on delivery of the fetus

Clinical Presentation

Historical clues

  • Sudden onset (variable onset among causes):
    • Peaks to maximum intensity in > 1 minute (thunderclap headache)
    • Generally lasts > 5 minutes; may persist or wax and wane
  • Severe intensity
  • No history of similar headaches:
    • “1st headache of my life”
    • “Worst headache of my life”
  • Active or recent source of infection:
    • Direct spread from cranial/extracranial structures (e.g., ears, eyes, mouth)
    • Bacteremic spread (e.g., endocarditis)
  • Altered mental status:
    • Altered level of consciousness
    • Personality change
    • Confusion
  • Syncope or seizure
  • Visual disturbance:
    • Visual loss
    • Visual-field deficit
    • Diplopia
  • Associated with exertion:
    • Walking
    • Climbing stairs
    • Sexual intercourse
    • Jaw claudication
  • Associated with trauma:
    • Motor vehicle accident
    • Fall
    • Cervical manipulation (chiropractic or osteopathic)
  • Age > 50 years
  • Immunosuppression (↑ risk of infection, lymphoma, and leukemia):
    • Autoimmune disease
    • HIV/AIDS
    • Chronic steroids
  • Pregnancy/postpartum
  • Hypercoagulable state
  • Bleeding diathesis 
  • Medications/illicit drugs:
    • Anticoagulants
    • Sympathomimetics 
  • Toxin exposure:
    • CO
    • Sodium hypochlorite (bleach)
    • Formaldehyde
  • Insect vector exposure (or travel to endemic areas):
    • Ticks
    • Mosquitos

Physical examination findings

  • Vital sign abnormalities:
    • Severe hypertension/hypotension
    • Severe tachycardia/bradycardia
    • Fever/hypothermia
    • Hypoxia 
  • Neurologic findings:
    • Cranial nerve palsy
    • Focal neurologic deficits
    • Mental status changes
  • Altered level of consciousness
  • Meningeal signs: neck stiffness
  • Ophthalmologic findings:
    • Papilledema
    • Retinal hemorrhage
    • Visual deficit
    • Elevated intraocular pressure (acute glaucoma)
    • Corneal clouding (acute glaucoma)
  • Palpatory temporal artery findings (temporal arteritis):
    • Diminished pulses
    • Firmness/edema
    • Nodularity
  • Rash:
    • Erythema migrans (Lyme meningitis)
    • Petechiae/purpura (bacterial meningitis) 
  • Evidence of active purulent infection:
    • Sinusitis
    • Otitis
    • Facial/orbital cellulitis
    • Gingivitis

Diagnosis and Management


It is important to take a focused, thorough history: 

  • Headache descriptors:
    • Onset
    • Location
    • Duration
    • Intensity
    • Similarity to previous headaches
  • To narrow etiology, ask about:
    • Recent trauma
    • Pregnancy/postpartum
    • Recent/current infection
    • Vascular risk factors/comorbidities
    • Cancer history 
    • Immunocompromised states

Physical examination

It is important to do a focused, thorough examination:

  • Vital signs, especially:
    • Temperature
    • Blood pressure
  • Neurologic exam:
    • Level of consciousness
    • Mental status/orientation/cognition
    • Cranial nerves
    • Screen limbs for motor/sensory deficit
    • Gait/coordination
  • Extracranial exam:
    • Carotid bruit
    • Meningismus
    • Ear infection
    • Sinus tenderness
    • Facial/orbital cellulitis
    • Visual-field testing
    • Fundoscopic exam: papilledema, hemorrhage
    • Intraocular pressure testing
    • Temporal artery palpation
  • Other pertinent exam findings:
    • Heart murmur
    • Abnormal heart rhythm
    • Splinter hemorrhages
    • Osler nodes
    • Janeway lesions
    • Homan’s sign
    • Rash
    • Evidence of distant infection

Laboratory evaluation

Suspected infectious etiology:

  • WBC count with differential
  • Cultures:
    • Blood
    • CSF
    • Purulent nasal/otic/optic/skin discharge
    • Wound, urine, sputum, etc., of distant spread is suspected
  • CSF studies (obtained via lumbar puncture (LP)):
    • Opening pressure
    • Protein 
    • Glucose 
    • Cell counts
    • Gram stain

Suspected hematologic/vascular etiology:

  • Temporal arteritis:
    • ESR
    • CRP
  • Venous sinus/cerebral vein thrombosis:
    • D-dimer
    • Hypercoagulation workup 
  • Intracerebral/intracranial hemorrhage:
    • PT/PTT for evaluate for bleeding diathesis (native or iatrogenic)
    • CSF for the presence of erythrocytes (obtained via LP)
      • Performed after initial CT if negative for bleeding in suspected SAH
      • Beware misinterpretation of a traumatic tap
      • If traumatic tap is suspected, opening pressure > 20 mm Hg indicates a pathologic intracranial process

Suspected neoplastic etiology:

  • CSF examination for presence of malignant cells
  • May consider liquid biopsy for metastatic markers (approximately 1-week turnaround time)
  • May consider measuring pituitary hormone levels if suspected pituitary involvement


  • CT of the head without contrast:
    • Rapidly available in most emergency triage settings
    • Often the 1st test performed regardless of suspected etiology 
    • Test of choice for thunderclap headaches to rule out SAH
    • Perform before LP if the following restrictions exist:
      • Papilledema on fundoscopy
      • Altered level of consciousness
      • Presence of new-onset neurologic deficit
      • Immunocompromised state
      • Known or suspected intracranial mass effect
      • Headache presents with new-onset seizure
    • 2nd-line method for head imaging in pregnancy:
      • Radiation is generally avoided in pregnancy
      • Radiation scatter for head CT is distant from the fetus
  • CT of the head/brain with contrast
  • CTA
  • MRI of the head with and without contrast
  • MRA

Evaluation and management of specific high-risk headaches

Thunderclap headache: 

  • CT without contrast: initial test of choice
  • LP should be performed if CT negative:
    • Evaluate for presence of erythrocytes
    • Measure opening pressure
  • If CT or LP suggests hemorrhage, further imaging is warranted to evaluate for source:
    • CTA
    • MRA
    • Traditional fluoroscopic angiography 
  • If any of the above suggest hemorrhage/vasospasm → immediate consultation with a neurosurgeon or vascular interventionist 

Meningitis or encephalitis:

  • On initial suspicion, obtain blood cultures 
  • Begin antibiotics:
    • Antibacterials for common bacterial entities
    • Antivirals, antifungals, antiprotozoals, antirickettsials as guided by clinical suspicion
  • Prior to performing LP, CT without contrast to evaluate for contraindications to LP:
    • Mass lesion
    • Hydrocephalus
  • LP if no contraindications to obtain CSF and evaluate for:
    • Opening pressure
    • Protein 
    • Glucose 
    • Cell counts
    • Gram stain
  • Consider neurology and/or infectious disease consultation

Increased ICP:

  • MRI without and with contrast preferred to evaluate for intracranial mass/pathology:
    • Neoplasm
    • Metastasis
    • Abscess
    • Hematoma
    • Hydrocephalus
    • Cerebral edema from ischemia/infarction
  • CT with and without contrast if MRI is contraindicated/unavailable
  • LP for opening pressure and to evaluate for underlying infection if imaging negative

CO toxicity:

  • Administer high-flow supplemental oxygen
  • Obtain arterial blood gas (ABG) sample 
  • Symptoms generally improve as CO levels diminish

Headache with neck pain:

  • Stabilize any instability related to head/neck trauma
  • Neurologic exam for Horner syndrome/cranial nerve palsies
  • CT without contrast is the initial test of choice to evaluate for intracranial pathology
  • CT and CTA of head and neck with contrast if initial CT negative to evaluate for:
    • Carotid artery dissection
    • Vertebral artery dissection

Headache in adults > 50 years of age:

  • Examine for temporal artery abnormalities
  • MRI with and without contrast to evaluate for:
    • Mass
    • Hemorrhage
    • Elevated intracranial pressure (ICP) 
  • CT with and without contrast, if MRI contraindicated/unavailable 
  • Start corticosteroids and obtain immediate ophthalmology consultation if temporal arteritis suspected
  • Further management/consultation depending on findings

Headache in immunosuppressed individuals:

  • CT without contrast to evaluate for:
    • Infection
    • Lymphoma
    • Leukemia 
  • MRI with and without contrast to evaluate for:
    • Abscess 
    • Encephalitis
    • Causes of elevated ICP: 
      • Hydrocephalus
      • Hemorrhage
      • Mass effect
    • LP if imaging is negative to evaluate for:
      • Opening pressure
      • Infection
      • Malignant cells
    • Consider infectious disease, neurosurgery, neurology consultation depending in findings

Headache in individuals with cancer:

  • MRI with and without contrast to evaluate for metastases and infection 
  • CT with and without contrast if MRI contraindicated or unavailable 
  • Consider oncology, neurosurgery, neurology consultation depending in findings

Headache during pregnancy/postpartum:

  • Evaluate for preeclampsia/eclampsia 
  • Blood pressure management/seizure stabilization as indicated
  • Immediate obstetrics/maternal-fetal medicine consultation
  • MRI without contrast is preferred method of neuroimaging to evaluate for:
    • Cerebral vein or venous sinus thrombosis
    • Causes of elevated ICP: 
      • Hydrocephalus
      • Hemorrhage
      • Mass effect
  • LP if neuroimaging negative and increased ICP or if infection suspected

Headache with visual impairment, periorbital pain, ophthalmoplegia: 

  • MRI of the head and orbits to evaluate for:
    • Glaucoma
    • Infection
    • Inflammation
    • Tumor 
  • Measure intraocular pressure
  • Start corticosteroids and obtain immediate ophthalmology consultation if temporal arteritis is suspected.
  • Immediate ophthalmology consultation if glaucoma suspected
  • Outpatient ENT consultation if sinus involvement suspected
  • Outpatient dental consultation if temporomandibular joint (TMJ), gingival, or dental disorder suspected 
  • Outpatient neurology or pain management consultation if trigeminal neuralgia suspected

Clinical Relevance

  • Cluster headache: may be of sudden onset and may be severe, but sufferers are generally very aware that frequent, sudden, and severe headaches are to be expected during a cluster period. Although neurologic symptoms are typical of cluster headache, they are autonomic in nature, predictable, reproducible, and transient. Thorough clinical evaluation with neuroimaging is indicated at the initial workup for cluster headache to rule out high-risk etiologies. A change in the pattern of headaches warrants emergent reevaluation. 
  • Migraine headache: Although typically gradual in onset, migraine headaches may be severe and accompanied by neurologic symptoms. These neurologic symptoms are often part of the typical migraine milieu for the individual; they are predictable, reproducible, and transient. Clinical evaluation with neuroimaging is indicated at the initial occurrence of migraine headache with neurologic symptoms to rule out high-risk etiologies. A change in the pattern of headaches warrants emergent reevaluation.
  • Cervicogenic headache: headache caused by referred pain from the upper cervical joints. Typically unilateral, of moderate to severe intensity, and increased by movement of the head, with radiation from the occipital to the frontal regions. Many high-risk headaches also present with cervical symptoms. The distinguishing feature is the absence of structural cervical disease.


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