Abstract
Paroxysmal hemicrania (PH) is a trigeminal autonomic cephalgia, characterised by unilateral attacks responsive to indomethacin. There are no published reports of a family history in PH. We report a mother and daughter both with PH. The daughter and her sister also had migraine.
Introduction
For patients, and clinicians who care for them, one of the most fundamental questions so often asked is, why me? Thus information on possible inheritance of primary headaches is crucial in advancing our overall understanding of the conditions. Paroxysmal hemicrania (PH) is one of the rarer primary headaches for which we have no prevalence data. It belongs to the family of trigeminal autonomic cephalalgias (TACs) (1) and is characterized by attacks of severe unilateral orbital, supraorbital or temporal pain, lasting 2–30 min, accompanied by ipsilateral cranial autonomic symptoms such as ptosis, eyelid oedema, conjunctival injection, lacrimation, nasal blockage or rhinorrhoea (2). Attacks usually have a frequency of above five a day, and respond absolutely to indomethacin (3). We describe here the first cases of PH with a clear family history.
It is widely acknowledged that migraine has a strong genetic component (4, 5), although it is only relatively recently that the first genes have been identified (6, 7). For cluster headache it is less obvious clinically but the evidence of a familial basis is growing (8–13). For the other TACS there are currently no published reports of a family history in PH and only one family with familial SUNCT reported (14). We report the cases of a mother and daughter, both with PH, previously reported in preliminary form at the XIVth Migraine Trust International Symposium (15).
Clinical cases
Case 1: PH
This 52-year-old lady presented with headache for 10 years, with no precipitating cause identified. These would affect the left side, in the eye, retro-orbital region and in the temple up to the vertex of the head. The pain was a cramping, stabbing-type pain associated with ipsilateral ptosis, lacrimation, nasal congestion and eyelid oedema. There was no nausea, photophobia, phonophobia or osmophobia. There was some agitation and a feeling of needing to move her head during the attacks. Each attack lasted 3–4 min. Initially she would have one attack every 3 months, but the frequency increased to 7–14 attacks a day.
Triggers to an attack included strong smells such as cleaning fluids, stress and lack of sleep. There was no other headache history. Past medical history was significant for hypertension and stress incontinence, for which she underwent colposuspension.
She had tried carbamazepine 250 mg, propranolol 80 mg, ibuprofen and cocodamol (paracetamol/acetaminophen and codeine phosphate), all with no effect on her headaches. She underwent a blinded, placebo-controlled, modified ‘indotest’, and the 100-mg intramuscular injection of indomethacin caused complete cessation of her attacks, whereas a saline injection had no effect on the attacks, thus confirming the diagnosis of PH (Fig. 1).
Charted response of case 1 relating attack frequency to injection of saline or indomethacin over a 48-h period demonstrating abolition of attacks after injection of indomethacin. The patient was attack free for 18 h after indomethacin 100 mg. The arrows indicate the time of injection or either placebo (saline) or indomethacin.
Case 2: PH and migraine
The daughter of the patient in case 1 was a 24-year-old who had had head pains for 2 years. These affected the right side, at the vertex, and radiated to the right retro-orbital region and cheek, and down the back of the neck. The attacks were described as sharp pressure, and were associated with ipsilateral nasal congestion, ptosis and eyelid oedema. There was nausea but no photophobia, phonophobia or osmophobia. Movement would make the pain worse. Each attack usually lasted 15 min. Initially she would have four to five attacks a day for 4–5 weeks, then a few days off, before the cycle started again. Over the next 2 years the frequency of the attacks increased up to 11 attacks a day. Triggers to an attack included strong smells and stress.
She had a history of episodic migraine with aura since the age of 15, with one attack per year of throbbing pain with nausea, photophobia, phonophobia and aggravation by movement, preceded by a visual aura 1 h before the pain. In her past medical history she had hyperthyroidism which was treated twice with carbimazole.
She had taken cocodamol (paracetamol/acetaminophen and codeine phosphate), pizotifen and diclofenac tablets with no effect. Sumatriptan 6 mg subcutaneous injections had no abortive effect on the pain. A right greater occipital nerve injection was ineffective. A blinded modified ‘indotest’ was performed, and 100 mg of intramuscular indomethacin abolished her attacks, whilst the saline injection had no effect. She was started on oral indomethacin but only tolerated up to 50 mg t.d.s. before experiencing side-effects of gastric irritation.
Family history
The sister of the index patient (case 2), aged 19, also gave a history of headaches. On further questioning these were holocranial throbbing headaches with photophobia and worsening with movement, but no nausea, phonophobia or osmophobia. The headaches could last all day and occurred up to twice a week with no identifiable trigger. These are probable migraine without aura (2).
Her maternal grandmother (now deceased) had headaches in the past, although the phenotype of these was unclear. She had two siblings and two other children, all of whom were unaffected by headaches. The family tree is presented in Fig. 2.
Family history of primary headache in the reported cases.
Discussion
These cases present a family association of PH which has previously not been described. Interestingly, there is also a family history of migraine in both daughters of the patient in case 1. It would have been informative to ascertain the phenotype of her mother's headaches, as to whether they were migraine or PH, but this was not possible.
There have been no reports of a family history in PH. In a recent series of 74 patients with PH, 80% of patients had no family history of headache, 15% had family history of migraine, and the remainder had family histories of cluster headache, trigeminal neuralgia or other headaches (16). Sixteen per cent of these 74 patients had concomitant migraine.
There is a well-documented genetic basis for migraine, both in familial hemiplegic migraine (6, 7), and clinical experience (17) and epidemiological data (18) for migraine with and without aura, suggesting an important familial aggregation. Similarly, evidence for a genetic component for the TACs is growing. The evidence for familial occurrence in cluster headache is consolidating (8–13), although it is certainly not an invariate feature of the presentation. Taken with the recent report of familial occurrence of SUNCT (14), the familial occurrence of paroxysmal hemicrania is to be expected.
The fact that the familial link has been hitherto unreported may be due to the rarity of the syndrome, and possibly failure to identify the diagnosis in family members. We can only encourage to question carefully patients and their relatives for further evidence of familial occurrence in TACs and other rare primary headaches.