Abstract
Hemicrania continua (HC) is an indomethacin-responsive headache characterized by a chronic, strictly unilateral, side-locked without side-shifting, persistent headache. We report three cases of HC with atypical features in which an acute administration of indomethacin 50 mg IM (INDOTEST) was performed. In all three cases INDOTEST predicted chronic responsiveness to indomethacin. Thus, in cases of HC with atypical features, INDOTEST could help for a correct diagnosis and therapy.
Introduction
Hemicrania continua (HC) is an indomethacin-responsive headache characterized by a chronic, strictly unilateral, side-locked without side-shifting, persistent headache. The pain is typically of moderate intensity with exacerbations of severe intensity that are accompanied by at least one ipsilateral cranial autonomic feature (1). HC has a range of onset 5–67 years (2) and it exists with or without spontaneous remission (2).
We report three cases of HC with atypical features in which an acute administration of indomethacin 50 mg IM (INDOTEST) (3) was performed in a double-blind fashion.
Case reports
Patient 1
A 33-year-old woman referred with a history of headache which had started 3 years previously. Her mother had suffered from headaches with similar features. The patient described a continuous strictly unilateral pain on the right side, over the frontal region with radiation to the orbit. The intensity of headache fluctuated from mild to severe. The pain had a stabbing quality with ipsilateral lacrimation and palpebral ptosis during exacerbations. Exacerbations were daily lasting 2–4 h, rarely during the night. Since their onset headaches had occurred in a seasonal pattern, starting in May and ending in September. Subcutaneous sumatriptan during exacerbations did not show any benefit. Neurological examination was unremarkable. Brain magnetic resonance imaging (MRI) was normal as well as routine blood examination. We administered a single dose of intramuscular (i.m.) placebo that was ineffective, whereas INDOTEST was able to lessen pain within 45 min. Further chronic treatment with indomethacin 75 mg/day brought about complete and stable pain relief. The medication was stopped after 6 months without pain recurrence after 1 year's follow-up.
Patient 2
A 44-year-old woman complained of 7 months of persistent headache. The pain was unilateral, over the temporal-parietal regions with radiation to forehead and orbit.
Although it was strictly unilateral, headache was side-shifting with an unpredictable pattern. The intensity of pain fluctuated between mild to moderate with daily exacerbations lasting 3–5 h, rarely at night. These exacerbations were associated with ipsilateral lacrimation, palpebral ptosis and nausea. The quality of pain was throbbing. She had tried naproxen, paracetamol, and amytriptiline (50 mg/day), which were ineffective. Neurological examination was normal, as was haematological screening. Brain MRI was negative. We tried a single dose of i.m. placebo that did not produce any variation of the clinical picture, but there was a prompt response to INDOTEST within 50 min and chronic treatment with indomethacin 75 mg/day maintained complete pain relief in the following 6 months.
Patient 3
A 77-year-old woman presented to us for a persistent headache, which had started 4 months before, strictly unilateral without side-shifting, over the right fronto-orbital region. The intensity of pain fluctuated between mild to moderate with daily exacerbations lasting 5–6 h, often during the night. Exacerbations were associated with ipsilateral lacrimation, rhinorrhoea and photophobia. The quality of pain was throbbing. She had tried ibuprophene and diclofenac with partial benefit for only 2–3 h. Neurological examination, routine haematological and biochemical screening were normal. Brain MRI showed mild leucoencephalopathy of white matter. A trial with topiramate 100 mg/day for a month and a cycle of dexamethasone 8 mg/day for a week did not modify symptomatology. We administered a single dose of i.m. placebo that did not produce any benefit, whereas INDOTEST gave complete pain relief after 45 min and a trial with indomethacin 75 mg/day maintained the patient pain free after the first dose, for 4 months.
Discussion
In the literature atypical features of HC have been previously reported (2, 4).
In patients 1 and 3 clinical features of the headache fulfil the 2nd International Classification of Headache Disorders (ICHD-II) diagnostic criteria for HC (1). Case 1 is a remitting type of HC with a particular circannual periodicity that has been described in only one other previous case (5). Case 3 is an HC with continuous feature and represents, to the best of our knowledge, the oldest patient with HC described (2). Considering the age of onset of the disease in this case, we can speculate that HC can start at any age; thus, a possible diagnosis of HC should be considered also in the elderly. Case 2 respects the ICHD-II diagnostic criteria for HC, in its persistent form, except for the unilateral side-locked without side-shifting headache (1). However, some cases presenting as HC with a side-shifting feature have been previously described (2, 4, 6).
In all the three cases INDOTEST predicted chronic responsiveness to indomethacin therapy, as previously reported by Antonaci et al. in 12 patients with HC (3). Clinically, HC might be heterogeneous because its clinical phenotype overlaps with that of migraine and trigeminal autonomic cephalalgias. On the other hand, also pathophysiologically, HC seems to share characteristics of cluster headache and migraine, as demonstrated in a recent study with positron emission tomography for regional cerebral blood flow (7); in this study, seven patients with HC showed an activation of the contralateral posterior hypothalamus and ipsilateral rostral pons that corresponded to those active in cluster headache and migraine, respectively (7). Thus, given the variable phenotypic expression of HC, we suggest INDOTEST as a useful diagnostic tool in every unilateral headache during the diagnostic work of HC, as it can provide a straightforward answer.