Abstract
Introduction
SUNCT syndrome is a rare unilateral headache characterized by brief neuralgiform painful episodes recurring many times per day (1, 2). The temporal pattern is typically variable, with symptomatic periods alternating with periods of pain-free remission, in an unpredictable fashion (1, 3).
SUNCT syndrome is refractory to various drugs and anaesthetic blockades that have proved effective in other trigemino-autonomic neuralgias and short-lasting headache syndromes (3). Anecdotal reports have claimed that anti-epileptic drugs (e.g. carbamazepine, lamotrigine and gabapentin), corticosteroids or surgical procedures may be of some benefit (3–10). Recently, Matharu et al. (11) reported a SUNCT patient who responded to topiramate.
We report on two new SUNCT patients who were successfully treated with this drug.
Case reports
Case 1
A 51-year-old man consulted our Headache Clinic in June 2001 with a 1-year history of unilateral headache. The pain was described as severe, burning and located in the right forehead and periorbital area. Associated symptoms included tearing, conjunctival injection and rhinorrhoea. The patient experienced between 14 and 25 episodes a day, five to six times a week, each episode lasting 30–60 s. No remission period longer than 4 days was reported.
Attacks were precipitated by mastication and touching the forehead ipsilaterally. The patient's previous medical history was unremarkable. His general physical and neurological examination was normal, with the exception of hyperalgesia and hyperaesthesia in the headache area. A brain magnetic resonance imaging (MRI) including a study of the cerebello-pontine angle was normal.
Previous treatments with indomethacin (50 mg tid for 1 month), amitriptyline (80 mg/day for 3 months), oral prednisone (initial dose 60 mg tapered off in 1 month), carbamazepine (400 mg tid for 3 months) and verapamil (120 mg tid for 4 months) had reportedly had no effect on the pain frequency and severity. We administered lamotrigine 50 mg/day (25 mg bid), but the drug was withdrawn after a few days due to the appearance of Stevens–Johnson syndrome.
Due to the absence of reports about cutaneous hypersensitivity syndrome, topiramate was prescribed and titrated by 25 mg each week. At a daily dosage of 50 mg/day the patient experienced a dramatic reduction of the painful attacks, to one to four per day. At 75 mg/day the patient was headache free. The drug was well tolerated and the patient reported only mild diurnal somnolence. After 4 months of therapy, and with the patient's agreement, topiramate was tapered down over 2 weeks, but the painful attacks recurred at the usual attack frequency. Topiramate was re-introduced and the pain disappeared. At a follow-up examination 3 months later, the therapeutic effect was still present.
Case 2
A 32-year-old woman was referred to us by her general practitioner in March 2002 with a 6-month history of intense, brief (10–80 s), stabbing, unilateral headache attacks. The pain was located in the left orbital region and accompanied by lacrimation, prominent conjunctival injection and rhinorrhoea. No phono/photophobia or nausea was reported. No precipitating mechanism had been identified. The frequency of the attacks was 25–35 episodes per day.
The patient's family and medical history was unremarkable. The results of general physical and neurological examination were normal, as were those of a brain MRI.
Various drugs – indomethacin (50 mg tid for 1 month), non-steroidal anti-inflammatory drugs (Naproxen sodium 550 mg bid for 1 month), steroids (prednisone per os, initial dose 60 mg/day, tapered off in 3 weeks) and carbamazepine (400 mg tid for 3 months) – had failed to produce any therapeutic effect.
On the basis of previous experience we administered topiramate at 25 mg/day and increased the dose by 25 mg each week up to 75 mg. During the first week the attack frequency was reduced by an average of 50%. At a daily dosage of 50 mg the patient reported none to three attacks per day. At 75 mg/day the patient was completely pain free. The drug was well tolerated and the patient complained only of mild sleepiness. At her last follow-up examination, after 5 months of therapy (August 2002), the patient was still taking topiramate and reported only sporadic and well-tolerated pain episodes (three to six per month).
Discussion
The two new SUNCT cases presented here showed a dramatic long-term response to topiramate. Both cases were characterized by a chronic, unremitting temporal pattern and unresponsiveness to various attempted prophylactic drug treatments. As in the case described by Matharu et al. (11), topiramate was highly effective in reducing the frequency and intensity of attacks at doses (50–75 mg/day) lower than those needed in epilepsy treatment (12).
In case 1 the treatment was stopped and the attacks reappeared at the usual frequency. Topiramate was re-introduced and the symptoms disappeared, suggesting that the improvement was not due to a spontaneous remission.
Even taking into account the limitations of an open-label administration, our experience, together with that of Matharu et al. (11), suggests that topiramate might represent an effective and well-tolerated drug for the prophylactic treatment of SUNCT.
Topiramate has recently been investigated for potential use in pain therapy. Clinical experience, for the moment limited to single reports and a few controlled and uncontrolled trials, has shown that this drug may be effective in chronic pain syndromes such as refractory intercostal neuralgia, trigeminal neuralgia and cluster headache (13–17).
As the pathophysiology of SUNCT syndrome is still unclear, the mechanism of action of topiramate as a prophylactic treatment may be only speculative. Recent clinical (18) and functional MRI (19) findings suggest that SUNCT may originate and be maintained at the CNS level, but a peripheral neuropathological pain mechanism cannot be ruled out. Topiramate has several recognized mechanisms of action that may be relevant in pain therapy. It blocks AMPA species of glutamate receptors and the voltage-sensitive sodium channels, acts on the GABA system and potentiates brain GABA concentrations (20–23). These pharmacodynamic properties may account for a modulatory action reducing neuronal hyperexcitability at a central and/or peripheral site.
In conclusion, although the effectiveness of topiramate remains to be confirmed in larger series, this drug would appear to be a reasonable alternative treatment for chronic forms of SUNCT syndrome.