The most important delineation to make is whether a headache needs imaging or not. When a patient presents with a headache, the first step is to always assess for “Danger Signs”. These may indicate a more life-threatening etiology such as neoplasm or infectious process that requires a more urgent assessment.

  • Systemic symptoms (Fever, chills, night sweats, etc.)
  • Neurologic deficits (vision changes, cranial nerve deficits, weakness, paresthesias, sensory loss)
  • Awakens the patient from sleep or is worse in the morning
  • New-onset daily headache or CHANGE in headache characteristics
  • Recent trauma

Differential Diagnosis

Tension Headache

  • Tightness, pain in the forehead with lateral radiation to the occiput
  • Diagnosis: Clinical
  • Treatment: Acetaminophen, aspirin, or NSAIDs as well as stress reduction


  • Intense, unilateral, pounding headache associated with nausea and vomiting, photophobia, and phonophobia lasting anywhere from a few hours to a few days. May or may not be preceded by an “aura” in which the patient has visual/sensory disturbances
  • Diagnosis: Clinical criteria
    • 2 of the 4 following characteristics:
      • Unilateral
      • Throbbing/Pulsating
      • Moderate-to-severe intensity
      • Aggravated by (or causing inhibition of) routine physical activity
    • in addition to 1 of the 2 following characteristics:
      • Associated with nausea and/or vomiting
      • Associated with photophobia and phonophobia
  • Treatment
    • Abortives
      • Initial: Tylenol/NSAIDs
      • Refractory: Serotonin-agonist/Triptans (i.e. sumatriptan)
    • Prophylaxis indicated if 3 ore more migraine headaches per month, or if at least 8 days with headache in one month (1)
      • β-Blockers (i.e. propranolol)
      • Calcium Channel Blockers (i.e. verapamil)
      • Anti-convulsants (i.e. topiramate, valproate)
      • Tricyclic antidepressants (i.e. amitryptyline)
      • CGRP antagonists (i.e. erenumab)

Cluster Headache

  • Unilateral, retro-orbital pain associated with conjunctival injection, ptosis, miosis, otorrhea, and rhinorrhea that lasts anywhere from a few days to a few hours. May have multiple episodes within a day.
  • Diagnosis: Clinical
  • Treatment:
    • Abortive:
      • High-flow 100% FiO2 supplementation
      • Triptans
    • Prophylactic (2)
      • Transitional
        • Prednisone (discontinue when symptoms are gone)
      • Maintenance (continued through expected duration of cluster)
        • Calcium Channel Blocker (Verapamil) preferred
        • Lithium, topiramate, valproate, gabapentin may be used if refractory


  • Generally associated with confusion, neurological deficits, systemic symptoms (weight loss, night sweats), and symptoms of intracranial hypertension (headache worse with bending over, papilledema on fundoscopy)
  • Typically a new-onset headache, worse in the mornings, may awaken the patient from sleep
  • Diagnosis: MRI with biopsy
  • Treatment: Depends on the type of neoplasm, but typically some combination of surgical resection, chemotherapy, and/or radiation therapy


  • Generally associated with fever and altered mental status. Physical exam may elicit meningitic signs such as neck stiffness, pain with neck manipulation, or Kernig/Brudzinski signs.
  • Diagnosis: Lumbar puncture
  • Treatment: Antimicrobials based on age and suspected etiology

Giant Cell Arteritis (“Temporal Arteritis”)

  • Typically in patients with ages ≥ 50 years. Associated with transient unilateral visual loss, jaw claudication (pain with mastication), fevers, or scalp/temporal artery tenderness to palpation
  • Associated with Polymyalgia Rheumatica
  • Diagnosis: ESR/CRP (non-specific), gold standard is a temporal artery biopsy showing lymphocytic and/or granulomatous inflammation within the arterial media (3)
  • Treatment: Glucocorticoids, to be tapered after resolution of symptoms and ESR/CRP (4)

Idiopathic Intracranial Hypertension (“Pseudotumor Cerebri”)

  • Generally presents in obese females in the setting of oral contraceptive, tetracycline, or oral retinoid use. Blurry vision and pain worse with bending over (indicative of intracranial hypertension).
  • Diagnosis: Lumbar puncture with elevated opening pressure, normal cell counts. Ventricles normal on imaging.
  • Treatment: Stop offending agent, advise weight loss, and acetazolamide for refractory cases

Acute Angle-Closure Glaucoma

  • Associated with visual halos, conjunctival irritation, mid-dilated pupils, and corneal cloudiness
  • Diagnosis: Gonioscopy
  • Treatment (5)
    • STAT Ophthalmology consult
      • IV acetazolamide (blocks production of aqueous humor)
      • IV mannitol (reduces volume of aqueous humor)
      • α-agonist and β-blocker eye drops (blocks production of aqueous humor)
      • Muscarinic-agonist eye-drops (increases outflow of aqueous humor)

Temporomandibular Joint (TMJ) Dysfunction

  • Unilateral headache/pain typically in TMJ region, pain worsened with mastication, joint may become stiff or “pop” with use.
  • Diagnosis: Clinical
  • Treatment: Acetaminophen, NSAIDs, muscle relaxers, or oral surgery if refractory

Rebound Headache/Medication Overuse Headache

  • Chronic headaches in the setting of chronic analgesic usage
  • Diagnosis: Clinical
  • Treatment: Discontinue analgesic use


  • A wide variety of infectious etiologies aside from meningitis may cause headache, including diseases such as toxoplasmosis and progressive multifocal leukoencephalopathy. Patients with these infections will likely have “danger signs” elicited during the history and physical exam, leading to an MRI.


  1. Kumar, A. (2020, October 27). Migraine Prophylaxis. Retrieved January 16, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK507873/
  2. T;, A. (n.d.). Cluster headache–acute and prophylactic therapy. Retrieved January 16, 2021, from https://pubmed.ncbi.nlm.nih.gov/21284609/
  3. Maleszewski, J., Younge, B., Fritzlen, J., Hunder, G., Goronzy, J., Warrington, K., & Weyand, C. (2017, March 03). Clinical and pathological evolution of giant cell arteritis: A prospective study of follow-up temporal artery biopsies in 40 treated patients. Retrieved January 16, 2021, from https://www.nature.com/articles/modpathol201710
  4. Fraser, J., Weyand, C., Newman, N., & Biousse, V. (2008). The treatment of giant cell arteritis. Retrieved January 16, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014829/
  5. Khazaeni, B. (2020, September 15). Acute Closed Angle Glaucoma. Retrieved January 16, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK430857/

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