Abstract
Dear Sir,
We read with great interest the article “Primary continuous unilateral headaches: A nosologic model for hemicrania continua” by Pareja et al. (1). We appreciate the authors’ contribution to expanding the understanding of hemicrania continua (HC). In the current article, the authors suggest that indomethacin-resistant HC might be entirely different from indomethacin-responsive HC and labelled it as HC-incerta. We have the following concerns about this article:
1. Why do we expect complete response in all patients with HC? Is there any disease in medical science where we get a complete response in all patients to a single drug option? A complete response to any drug in any disease seems to be an overstatement. Even in a disease with known pathophysiology, a complete response with the correction of pathophysiology could not be achieved. Segawa’s disease (dopa-responsive dystonia) is a genetically determined movement disorder with decreased dopamine levels. The rapid therapeutic response to L-dopa is a hallmark of Segawa’s disease. However, mild abnormalities may be observed even in patients who show no functional abnormalities after supplementation of L-dopa (2,3). Moreover, in the recent past, many genetically confirmed Segawa’s disease cases had shown little or no response to dopamine (4). Variability in treatment response is a well-known fact even in other primary headache disorders. It is said that chronic daily headache (CDH) with daily pain is more treatment-refractory than CDH without daily pain (5). Patients with HC have ‘daily and continuous’ headache since onset. Therefore, a possibility to become refractory to treatment is high with HC. However, labelling it as a separate disease entity will open up other areas of controversy. Are we ready for triptan-unresponsive migraine (or migraine-incerta)? Do we think that triptan-unresponsive migraine is entirely different from triptan-responsive migraine?
2. In early descriptions, HC was characterised as a headache disorder that was responsive to indomethacin, and simultaneously unresponsive to other drugs. However, a response to drugs other than indomethacin has been increasingly reported in patients with HC (6). This feature (responsive to other drugs) makes such classification (indomethacin responsive and unresponsive variants) futile. What will be the diagnosis in a patient who showed a response to a drug other than indomethacin before receiving a trial of indomethacin?
3. Anecdotal evidence suggests that indomethacin may be effective in a number of primary headache disorders, including migraine, tension-type headache, cluster headache, hypnic headache, etc. The analgesic properties of indomethacin are multifactorial: structurally similar to serotonin and triptans; central analgesic activity; abolish peripheral and central hyperalgesia; vasoconstrictive effect on cerebral vessels (reducing intracranial pressure); inhibit neurogenic inflammation; improves cerebral perfusion pressure (7,8). Therefore, a possibility exists that indomethacin may be effective in various other primary headache disorders. Therefore indomethacin may work in HC mimickers.
To the best of our knowledge, no syndrome in medicine has been classified on the basis of a response to a particular drug. The authors compared HC and HC-incerta with paroxysmal hemicrania and CH. They also compared it with the classification of bacteria (Gram+ and Gram–). However, we think this comparison is not appropriate. Both classifications have clinical and therapeutic importance. Although cases with CH responsive to indomethacin are reported in the literature, we do not give indomethacin (to see the unresponsiveness) in patients with CH. We will have to give indomethacin to see the cases of HC-incerta. Such classification is not useful in clinical practice. We suggest that current IHS criteria should be modified to accommodate the non-responsive variant of HC, as suggested by many authors in the past. We agree with the authors that distinguishing both phenotypes (HC and HC-incerta) may be useful for research purposes.