Abstract
A 45-year-old woman, who had been diagnosed in our unit with episodic paroxysmal hemicrania, was seen 2 years later for ipsilateral hemicrania continua in remitting form. Both types of headache had a complete response to indomethacin and did not occur simultaneously. The patient had a previous history of episodic moderate headaches that met criteria for probable migraine without aura and also had a family history of headache. The clinical course in this case suggests a pathogenic relationship between both types of primary headache.
Introduction
Hemicrania continua (HC) and paroxysmal hemicrania (PH) are two different and well-characterized primary headaches. In the last classification of the International Headache Society (IHS), HC was included in the group of ‘other primary headaches’ and PH in the group of ‘cluster headache and other trigeminal autonomic cephalalgias (TAC)’ (1). Both syndromes are strictly unilateral headaches which can be accompanied by autonomic ipsilateral symptoms, more often and prominent in the case of PH, and with an absolute response to indomethacin. The main difference between the two disorders is that PH is a short-lasting and severe headache with multiple attacks per day, whereas HC is characterized by a persistent dull headache with exacerbations. Remitting and unremitting courses have been described in both syndromes (2). In the case of PH, the remitting form has been recognized as a nosological entity in the last IHS classification and is now called episodic paroxysmal hemicrania (EPH), while the classic term of chronic paroxysmal hemicrania has retained for the unremitting form (1).
We report here a case of EPH evolving to a remitting form of ipsilateral HC.
Case report
This female patient was first seen in our unit in February 2000, when she was 43 years old. She had a previous history of rare episodic bilateral headaches of moderate intensity, accompanied by photophobia and phonophobia, without nausea or other symptoms. She had a family history of headaches in her mother and paternal grandfather. In the last 8 months, she had had two bouts of right-sided severe headache attacks lasting about 5 min with a frequency of 15–25 per day, most of them occurring during the diurnal period. This headache had an abrupt onset, was more severe in the forehead and orbital area and was described as excruciating; it was accompanied by ipsilateral ptosis, watering and conjunctival injection. The patient tried to sit quietly during the attacks. She had no photo/phonophobia, nausea or vomiting and no trigger mechanisms such as head bending or rotating were recognized. The patient was asymptomatic between attacks. Each bout lasted 2 weeks, with a 3-month asymptomatic interval. No precipitating factors were identified at the onset of bouts. She had tried different treatments with no response, including ergotamin, acetaminofen and flunaricine. Funduscopy, physical and neurological examination were normal except for slight tenderness by palpation in the greater occipital nerve. Computed tomography of the brain was normal. Treatment with indomethacin 25 mg t.i.d. was recommended for this pain and resulted in a complete response in the first 12 h after administration in the following two bouts. The patient took the indomethacin for 1 week in each of these bouts. She was diagnosed with chronic paroxysmal hemicrania in its remitting form (EPH, according to the new diagnostic criteria of the IHS).
Two years later the patient returned to our unit with a recurrence of headache. She had been asymptomatic for 18 months and 6 months previously she had begun with a continuous right-sided unilateral headache, with the maximum pain in the forehead and orbit. It was of moderate intensity and boring quality, with exacerbations (two or three times per week) that resembled in some way her previous attacks of EPH, although they were less severe, had a progressive onset, lasted several hours and were sometimes accompanied by ipsilateral ptosis. There had been no other accompanying symptoms such as nausea, vomiting or photo/phonophobia during these exacerbations. The patient had been taking indomethacin 75–100 mg/day for this new type of headache, with an absolute response, but the pain had recurred every time she skipped a dose. Neurological examination and magnetic resonance imaging (MRI) of the brain were normal. In the following 2 years the disease followed a fluctuating course, with asymptomatic periods without medication of 1–3 months, similar periods of mild headache that responded to 25–50 mg/day of indomethacin and others with a more severe headache requiring a larger dose (75 mg). In the last visit, in October 2005, she reported that she had been pain free for the last 2 months without medication.
Discussion
This patient is, to our knowledge, the first documented case of an association between PH and HC. The diagnosis of each type of headache was made by the same neurologist at the time of presentation and the patient fulfilled the IHS diagnostic criteria for both entities, including a complete response to indomethacin (1). The association of HC with other primary headaches has been reported for migraine with aura (3), familial hemiplegic migraine (4) and cluster headache (5, 6). PH has also been described in association with other primary headaches, specially with cluster headache and other TAC (7–11). The relationship between PH and migraine has been postulated to occur by chance owing to the high prevalence of the latter (12).
A coincidental occurrence of two disorders can not be excluded in a single case report, but there are several reasons for a probable pathogenic relationship between PH and HC in this patient: (i) both types of headache are very infrequent in the general population, (ii) the ipsilateral location of pain with maximal intensity in the fronto-orbital area in both disorders, (iii) the similar remitting course of each type of pain, and (iv) in the HC exacerbations the only autonomic symptom that was occasionally present was ipsilateral ptosis, which was the most prominent accompanying symptom in EPH attacks. Furthermore, the patient spontaneously referred to a similarity between EPH attacks and HC exacerbations, although it can be argued that this is a subjective perception and there were clear differences in the quality and severity of pain as in the temporal pattern.
It is also remarkable that there was a prolonged asymptomatic period between the cessation of EPH and the onset of HC and that the two types of headache had not occurred during the same period until this moment. Thus, it seems that one type of headache had been replaced by the other, but they did not appear simultaneously. Another interesting fact is that our patient had a family history of headaches and that she herself had a previous history of episodic moderate headaches meeting IHS diagnostic criteria for probable migraine without aura (1). Thus, three different types of primary headaches can be recognized in this patient. Although the coexistence of migraine may be coincidental, this clinical phenotype could be considered illustrative of more recent research into the relationship between HC, TAC and migraine. There are some clinical similarities between HC and migraine, i.e. the duration of HC exacerbations is similar to migraine attacks and many patients with HC have, in addition to autonomic ocular signs, accompanying symptoms typical of migraine such as nausea, photo- and phonophobia (13). Moreover, functional neuroimaging studies with positron emission tomography and functional MRI have shown that HC has a mixed pattern of central activation which overlaps with migraine and TAC (14): in HC there is an activation in the posterior hypothalamus, which is shared with PH (15), cluster headache and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome), and also in the dorsal pons, which is shared with migraine. It is noteworthy that activation in the ventral midbrain has been described only in HC (14) and recently in PH (15). Whether this means that there is some aetiopathogenic connection between these two primary headaches is unknown, as the clinical and physiological implications of these neuroimaging findings are only partially understood.
In summary, this case report may represent further evidence in considering whether HC is a primary brain disorder with clinical characteristics that overlap with PH, other TAC and migraine. Nevertheless, further research is needed to understand the relationship between these different headache disorders.