Paroxysmal hemicrania - 2010
By Dr Elizabetta Cittadini, Clinical Researcher at the Institute of Neurology, Queen Square, London
Paroxysmal hemicrania (PH) is a rare primary headache disorder exquisitely responsive to indometacin. PH was first described by Sjaastad and Dale (Sjaastad and Dale 1974) and named ‘chronic paroxysmal hemicrania’ two years later (Sjaastad and Dale 1976). In the first edition of the classification (Headache Classification Committee of The International Headache Society 1988) all cases were referred to as chronic paroxysmal hemicrania. However, with validation of the episodic variant over the years (Kudrow et al, 1987; Newman et al, 1992; Goadsby and Lipton 1997), the second edition of the classification recognised both an episodic and a chronic form (Headache Classification Committee of The International Headache Society 2004).
Case series of PH have been presented with 84 cases reviewed in the research literature for the largest one (Antonaci and Sjaastad 1989). Russell (1984) described 105 attacks, although samples were taken from only five patients with chronic paroxysmal hemicrania to assess severity, duration and circadian pattern. In 2002 (Boes and Dodick 2002) 74 cases from the Mayo Clinic were retrospectively reviewed in an attempt to refine further the clinical spectrum of this condition.
Further to this, in 2005 (Zidverc- Trajkovic et al, 2005), there were described prospectively eight patients affected by PH and 54 affected by cluster headache in order to identify any clinical difference between these two disorders. In 2008, a large case series of 31 patients (Cittadini et al, 2008) were prospectively described in detail and more recently the first prospective study of children has been reported (Blankenburg et al, 2009).
Patients with PH have been described in several countries (Joubert et al, 1987; Antonaci and Sjaastad 1989; Sjaastad 1992). The incidence and prevalence of paroxysmal hemicrania has been estimated to be about 1-3 per cent that of cluster headache (Antonaci and Sjaastad 1989), or about 1 in 50,000 (Matharu et al. 2003), although it may be even rarer (Sjaastad and Bakketeig 2007). PH can begin at any age (Kudrow and Kudrow 1989; Broeske et al, 1993; Gladstein et al. 1994; de Almeida et al, 2004; Talvik et al, 2006) , but the mean age at onset is in the thirties (Antonaci and Sjaastad 1989). The Vaga study suggests that the prevalence of PH is no more than 1 in 1838 (Sjaastad and Bakketeig 2007). PH has been considered to be predominantly a problem of females. Initially the reported female: male ratio was 7:1 (Sjaastad and Dale 1974), and in a subsequent review of 84 patients (Antonaci and Sjaastad 1989) the female: male ratio was 2.36:1. However, the recent study of 31 patients with PH (Cittadini et al, 2008) did not show a clear female preponderance and this is different from cluster headache where there is a clear male preponderance (Bahra et al, 2002).
According to the International Headache Society (Headache Classification Committee of The International Headache Society 2004) PH is defined by at least twenty attacks of severe unilateral orbital, supraorbital (in or around the eye) or temporal pain, lasting 2-30 minutes, accompanied by ipsilateral (on the same side) cranial autonomic features such as eye-redness, eyewatering, nasal blocking, nasal-running, eye-swelling, forehead and facial sweating, small pupil of the eye and eye-dropping. Attacks usually have a frequency of above five a day, and respond completely to indometacin. In addition, migrainous symptoms such as photophobia (sensitivity to lights), phonophobia (sensitivity to sounds), nausea and vomiting can also occur during the pain (Cittadini et al, 2008).
Most attacks are spontaneous, while identified triggers included stress, relaxation after stress, alcohol, exercise and neck movement (Antonaci and Sjaastad 1989; Cittadini et al, 2008).
Two temporal patterns are described in PH: an episodic form characterised by attacks lasting seven days to one year separated by a pain-free period lasting one month or longer and a chronic form in which the headache occurs for more than one year without remission or with remissions lasting less than one month.
In PH the attacks occur regularly throughout the day, without a nocturnal preponderance (Russell 1984; Antonaci and Sjaastad 1989; Boes and Dodick 2002; Zidverc-Trajkovic et al, 2005; Cittadini et al, 2008) as typically occurs in cluster headache (Bahra et al, 2002).
The differential diagnosis frequently is between PH and cluster headache. When patients with PH have constant background pain between attacks, there is a considerable overlap in the clinical phenotype of paroxysmal hemicrania and cluster headache: both are strictly unilateral, relatively brief but frequent headaches that occur in association with ipsilateral cranial autonomic features. At present the absolute response to indometacin is the only crucial factor that permits a distinction between these two conditions. Nevertheless, there are useful clinical characteristics that help during the differential diagnosis between these two conditions. In contrast to cluster headache, typically paroxysmal hemicrania is characterised by i) shorter duration and ii) high frequency of the attacks. In contrast to paroxysmal hemicrania, cluster headache is characterised by the presence of i) often strictly circadian and circannual periodicity and ii) alcohol as typical precipitating factor within one hour in 90 per cent of patients during their cluster bout (Bahra et al, 2002).
Furthermore, the differential diagnosis between paroxysmal hemicrania with interictal (between attacks) pain and hemicrania continua can be difficult and certainly a headache diary is very useful during the diagnostic work-up. In fact, it can provide important information regarding temporal aspects of the pain. Some clinical features can help. First, the background pain in HC is typically moderate, although severe and very severe pain can also occur, whereas interictal pain in PH is generally less severe. Secondly, painful exacerbations in HC are long lasting, usually several hours, whereas those in PH are short lasting, typically a few minutes to one hour. Thirdly, the severity of pain during exacerbations is often moderate or severe in HC, whereas in PH it is excruciating (Matharu et al, 2003; Cittadini et al, 2008). In general, a careful history supplemented with a headache diary does allow these two headache types to be differentiated one from the other.
A good clinical history with the employment of a headache diary, a detailed neurological examination and therapeutic trial of indometacin are necessary to make a diagnosis of paroxysmal hemicrania. A brain MRI scan is a sensible screening investigation to rule out secondary underlying causes.
The treatment of PH is prophylactic and it has a rapid and consistent response to indometacin. The mean daily dosage is 100mg with a range of 25-300 mg. However, some patients needed only 12.5 mg per day (Antonaci and Sjaastad 1989). Dosage adjustment may be necessary to address the clinical fluctuation seen in paroxysmal hemicrania. During active headache cycles, skipping or even delaying doses may result in the prompt reoccurrence of the headache. During the indometacin trial a gastricmucosa protective agent should be added in order to reduce the possible gastric problem, especially if patients require long term treatment (Matharu et al, 2003).
Daily dosing of indometacin for a long period may be troublesome. There are no controlled trial options for the management of PH when indometacin cannot be tolerated. There has been limited success reported with the use cyclooxygenase-2 (COX-2) inhibitors, rofecoxib (Lisotto et al, 2003; Siow 2004) and celecoxib (Mathew et al, 2000). However, prolonged use of both these agents has recently been linked to an increased risk of myocardial infarction and strokes that led to the withdrawal of rofecoxib from the market worldwide (Lenzer 2005). For that reason, the available COX-2 inhibitors should be prescribed with caution in this condition. Topiramate (Cohen and Goadsby 2007; Camarda et al. 2008) and greater occipital nerve injection with lidocaine and methylprednisolone are helpful in some patients (Afridi et al, 2006).
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