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Indomethacin testing in suspected paroxysmal hemicrania and hemicrania continua: Clinical phenotypes and response
Antoine Bender1,2, Mirela Muresan3, Lauriane Joganah3
1Centre d'Evaluation Et de Traitement de La Douleur, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. antoine.bender@chru-strasbourg.fr.
Background:
Indomethacin responsiveness is considered the defining diagnostic feature of hemicrania continua and paroxysmal hemicrania. However, the clinical presentation of indomethacin-responsive headaches is often heterogeneous, and practical guidance regarding which patients should undergo an indomethacin trial, the optimal duration of treatment, and the interpretation of partial responses remains limited.
Cases:
Eighteen patients underwent an indomethacin trial in our pain centre over the last year, of whom eleven (61%) achieved a positive response. Positive responders included patients ultimately diagnosed with probable or definite hemicrania continua (n = 6); and probable or definite paroxysmal hemicrania (n = 5), including secondary forms. Clinical presentations frequently departed from ICHD-3 criteria. Trigeminal autonomic symptoms were absent in several responders, while migrainous features were common. Attack duration in patients with paroxysmal hemicrania frequently exceeded the 30-min upper limit defined by ICHD-3, and some patients presented with pain characteristics suggestive of neuropathic disorders. The median time to a clinically meaningful response was 13 days for hemicrania continua (range 3-35 days) and 11 days for paroxysmal hemicrania (range 4-23 days). Most patients responded to 150 mg/day, although escalation to 225 mg/day or prolonged treatment exceeding four weeks was occasionally required. Seven patients had negative trials, leading to alternative diagnoses including migraine, cluster headache, SUNA, post-traumatic headache, and idiopathic mandibular neuropathy.
Conclusions:
This case series illustrates the broad clinical spectrum of indomethacin-responsive headaches and highlights the limitations of relying exclusively on ICHD-3 criteria when selecting patients for an indomethacin trial. Clinical suspicion should remain broad, particularly in patients with strictly unilateral headaches, atypical trigeminal autonomic cephalalgias, or refractory unilateral primary headaches.

