Differential Diagnosis for Unilateral Headache

Primary Headache Disorders

The American Academy of Neurology recommends suspecting migraine without aura when unilateral headache is pulsating, moderate-to-severe in intensity, lasts 4-72 hours, and is accompanied by nausea/vomiting and/or photophobia and phonophobia 1, 2
The International Headache Society suggests that cluster headache is characterized by severe unilateral orbital/periorbital pain lasting 15-180 minutes with ipsilateral autonomic symptoms and restlessness during attacks 3, 4, 5
The American Family Physician states that tension-type headache typically presents bilaterally but can be unilateral, with pressing/tightening quality, mild-to-moderate intensity, and absence of autonomic features 5

The American College of Rheumatology recommends urgently excluding giant cell arteritis in patients over 50 years old with new-onset unilateral temporal headache, characterized by continuous dull aching pain, jaw claudication, and systemic symptoms 6, 4
The American Heart Association suggests that carotid dissection presents with continuous unilateral pain and focal neurological deficits, incompatible with episodic attack patterns 4

The American Academy of Neurology recommends obtaining neuroimaging (MRI brain preferred) when any of the following red flags are present: focal neurological deficits, atypical headache pattern, progressive worsening, or abrupt-onset headache 3

The International Headache Society suggests characterizing the headache by duration, quality, location, and intensity to differentiate between migraine, cluster, and tension-type headaches 1, 3, 5
The American Family Physician recommends identifying associated symptoms such as autonomic symptoms, nausea/vomiting, photophobia, and phonophobia to aid in diagnosis 1, 3, 5

The American Academy of Neurology advises against assuming all unilateral headaches are migraines and overlooking cluster headache, which requires different acute and preventive treatment strategies 3
The American Headache Society warns against missing medication-overuse headache in patients with frequent headache days, as this perpetuates the headache cycle and requires medication withdrawal 1, 2
The American College of Rheumatology emphasizes the importance of not missing giant cell arteritis in patients over 50 with new-onset temporal headache, as delayed diagnosis risks permanent vision loss 6, 4

The American Academy of Neurology recommends propranolol, topiramate, CGRP monoclonal antibodies, or onabotulinumtoxinA as options for preventive therapy in migraine, with topiramate being the only agent with evidence in chronic migraine, according to the Mayo Clinic Proceedings 7