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Hemicrania Continua
Hemicrania continua (HC) is a continuous, strictly unilateral headache of fluctuating intensity with superimposed exacerbations accompanied by ipsilateral autonomic features and/or restlessness. Like paroxysmal hemicrania, HC has an absolute response to indomethacin, which is required for diagnosis. Despite being classified as a TAC in the ICHD-3, HC has features that overlap with both migraine (migrainous features during exacerbations) and other TACs (autonomic features), making it a diagnostic challenge that is frequently misdiagnosed as chronic migraine or chronic TTH.
Bottom Line
Continuous unilateral headache that never shifts sides, present for >3 months, with fluctuating intensity
Exacerbations are accompanied by at least one ipsilateral autonomic feature (lacrimation, conjunctival injection, nasal congestion, ptosis) AND/OR restlessness/agitation
Migrainous features (photophobia, phonophobia, nausea) often present during exacerbations — a major source of misdiagnosis as chronic migraine
Absolute indomethacin response is diagnostic (ICHD-3 criterion). Complete resolution at therapeutic doses.
Key clue: Continuous strictly side-locked headache that never switches sides. Migraine and TTH typically alternate sides over months/years.
Estimated to be present in 1-2% of chronic daily headache patients — underdiagnosed because indomethacin trials are not routinely performed
ICHD-3 Criteria
A. Unilateral headache fulfilling B-D
B. Present for >3 months, with exacerbations of moderate or greater intensity
C. Either or both:
At least one ipsilateral autonomic feature with exacerbations: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead sweating, miosis, ptosis, eyelid edema
Restlessness or agitation, OR worsening with movement
D. Responds absolutely to therapeutic doses of indomethacin
E. Not better accounted for by another ICHD-3 diagnosis
Subtypes
Subtype
Pattern
HC with remissions (3.4.1)
Headache is not daily; there are pain-free periods of ≥24 hours without treatment
HC without remissions (3.4.2)
Headache is daily and continuous for ≥1 year without pain-free periods of ≥24 hours. More common form.
Clinical Features
Baseline Pain
Continuous mild-to-moderate unilateral head pain. Patients describe it as an ever-present "awareness" or dull ache on one side.
Strictly side-locked: The headache never switches sides. This is a critical diagnostic feature. In clinical series, side-locking is the single most distinguishing characteristic from chronic migraine.
Location: Periorbital, temporal, or frontotemporal most common. Can extend to occipital region ipsilaterally.
Exacerbations
Moderate to severe intensity flares superimposed on the continuous baseline. Frequency varies from multiple per day to a few per week.
Duration: Minutes to days
Autonomic features appear during exacerbations: ipsilateral lacrimation, conjunctival injection, ptosis, miosis, nasal congestion, rhinorrhea, facial flushing/sweating
Migrainous features are common during exacerbations: nausea (in ~50%), photophobia, phonophobia. This frequently leads to misdiagnosis as chronic migraine.
Jabs and jolts: Brief ice-pick-like stabs superimposed on the continuous pain are reported in ~40% of HC patients
Diagnostic Approach
When to Suspect Hemicrania Continua
Continuous unilateral headache that has never switched sides, even over months or years
Diagnosed as "refractory chronic migraine" but has not responded to typical migraine preventives (beta-blockers, topiramate, CGRP mAbs, Botox)
Mild autonomic features during exacerbations (even subtle — mild tearing, slight nasal stuffiness, or barely noticeable ptosis)
Patient describes a constant background headache with superimposed flares, rather than discrete migraine attacks with pain-free intervals
Rule of thumb: Any strictly side-locked continuous headache deserves an indomethacin trial before concluding it is chronic migraine
The Indomethacin Trial
Protocol: Same as for paroxysmal hemicrania — 25 mg TID × 3 days → 50 mg TID × 3 days → 75 mg TID × 7 days
Expected response: Complete resolution of both baseline pain and exacerbations. The response is typically dramatic and occurs within 24-48 hours of reaching the effective dose.
Partial response is not sufficient for diagnosis. HC patients should become pain-free on indomethacin.
IM indomethacin test: 50-100 mg IM; response within 30-60 minutes (useful for rapid diagnosis in uncertain cases)
Indo-negative HC-like headache: If the clinical features are classic but indomethacin response is absent or partial, the patient does not meet ICHD-3 criteria. Consider: chronic migraine (more likely), cervicogenic headache, new daily persistent headache, or undifferentiated continuous headache.
Differentiating HC from Chronic Migraine
Feature
Hemicrania Continua
Chronic Migraine
Laterality
Strictly side-locked (never changes sides)
May alternate sides or be bilateral
Temporal pattern
Continuous with exacerbations
Discrete attacks (though can feel near-daily in CM)
Pain-free intervals
None (in chronic form) or brief
Usually present between attacks
Autonomic features
Present during exacerbations (defining feature)
May occur but not defining
Indomethacin
Absolute response
No specific response
Triptan response
None or minimal
Yes (acute attacks respond)
Botox / CGRP mAb response
No
Yes (chronic migraine-specific preventives)
Jabs and jolts
Common (~40%)
Less common
Treatment
Indomethacin (First-Line)
Maintenance: After complete response, titrate down to the lowest effective dose (typically 25-75 mg/day). Some patients need as little as 25 mg/day; others require 150 mg/day or more.
Long-term use: Most HC patients (especially chronic form) require indefinite treatment. Periodic reassessment by brief dose reduction.
GI protection: Mandatory PPI co-prescription (omeprazole 20 mg or equivalent) for all patients on maintenance therapy.
Monitoring: Renal function (Cr) and blood pressure every 6-12 months. CBC annually.
When Indomethacin Is Not Tolerated
The following have been reported as partial alternatives (none are as reliable as indomethacin):
Alternative
Evidence
Notes
Celecoxib 200-400 mg/day
Case series; partial responses
COX-2 selective; better GI profile. Not as complete as indomethacin.
Melatonin 3-15 mg
Case reports; occasional complete responses
Very safe; worth trying. Mechanism may relate to COX-2 inhibition.
Topiramate 100-200 mg/day
Case series; partial benefit
Third-line option
Verapamil 240-480 mg/day
Rare case reports of partial response
May help exacerbation frequency
GON block with steroid
Case series; temporary benefit
Can provide weeks of relief; useful as bridge
OnabotulinumtoxinA
Occasional case reports of partial benefit
Not consistently effective; trial may be reasonable in indomethacin-intolerant patients
Occipital nerve stimulation
Small case series; positive results in refractory HC
Reserved for patients who cannot tolerate indomethacin and have failed alternatives
Important Considerations
MRI brain is mandatory to exclude secondary causes. Symptomatic HC has been reported with posterior fossa tumors, pituitary lesions, cavernous sinus pathology, and HIV
HC may be underdiagnosed in chronic daily headache clinics. Series suggest 1-2% of chronic daily headache patients have HC when systematically tested with indomethacin.
If a patient with "refractory chronic migraine" has strictly side-locked pain and has never had an indomethacin trial, this should be done before declaring the patient refractory
HC can coexist with migraine — indomethacin will resolve the HC component but not migraine attacks, which may need separate treatment
References
Cittadini E, Goadsby PJ. Hemicrania continua: a clinical study of 39 patients with diagnostic implications. Brain. 2010;133(7):1973-1986.
Peres MF, et al. Hemicrania continua is not that rare. Neurology. 2001;57(6):948-951.
Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
Prakash S, Patel P. Hemicrania continua: clinical review, diagnosis, and management. J Pain Res. 2017;10:1493-1509.
Matharu MS, et al. Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study. Brain. 2004;127(1):220-230.
