A case of SUNCT syndrome responsive to zonisamide

Abstract

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare headache syndrome that represents a subtype of trigeminal autonomic cephalalgia thought to be highly refractory to treatment. More recently, numerous anticonvulsant agents including lamotrigine, topiramate, gabapentin, and carbamazepine have been reported to be partially or completely effective for treating SUNCT. We report the case of a patient with SUNCT in whom symptoms were completely relieved with carbamazepine at 600 mg/day. However, carbamazepine had to be discontinued due to severe rash. Zonisamide was selected for continued treatment, as a Na-channel blocker like carbamazepine but with lower risk of producing skin rashes as caused by carbamazepine. Attacks ceased completely with 300 mg/day of zonisamide achieving a blood serum level of 19 µg/ml. This is the first case report to describe zonisamide alone completely eliminating SUNCT symptoms. Zonisamide should be considered a viable candidate drug for the treatment of SUNCT.

Introduction

Short-lasting, unilateral, neuralgiform, headache attacks with conjunctival injection and tearing (SUNCT) is characterized by severe, strictly unilateral, brief (between 5–240 s) episodes of pain localized to the orbital, supra-orbital, and temporal areas, accompanied by ipsilateral conjunctival injection and lacrimation (1). SUNCT is traditionally thought to be highly refractory to treatment, but recent studies have reported the efficacy of newer anti-epileptic drugs (2–6). Among these, lamotrigine is recognized as the treatment of choice, while gabapentin and topiramate are considered second-line agents (4). Zonisamide is a novel anticonvulsant drug with multiple mechanisms of action, and is usually used in treatment of refractory epilepsy, very often as an add-on therapy (7). To the best of our knowledge, no previous reports have described the use of zonisamide to treat SUNCT. We successfully treated a patient with SUNCT using zonisamide, with few occurrences of dysesthesia in the oral cavity or long-term side-effects.

Case history

The patient was a 43-year-old man who presented to our orofacial pain clinic in September 2006 with a 3-year history of excruciating pain attacks in the left orbital and supra-orbital region, accompanied by obvious ipsilateral conjunctival injection and lacrimation. He had seen several specialists, including neurosurgeons and neurologists, and had undergone repeated examinations, but no organic cause had been identified. He was treated with sumatriptans (50 mg as-needed), clonazepam (1.5 mg/day, duration unknown), non-protein extract from inflamed rabbit skin inoculated with vaccinia virus (4 units/day, duration unknown), lomerizine hydrochloride (dose and duration unknown) and indomethacin (50 mg/day for 1 week) without improvement of symptoms. Carbamazepine at 600 mg/day achieved complete resolution of SUNCT symptoms, but a severe rash appeared on the skin and mucosa after 2 weeks on carbamazepine; therefore, this drug was discontinued. The patient remained untreated for approximately 1 year before visiting our orofacial pain clinic.

Pain intensity was 100/100 on the visual analogue scale. The pain was so severe that the patient was incapacitated during attacks. He reported having caused a motor vehicle accident due to onset of severe pain while driving. Duration of each attack was approximately 15 s. The frequency was approximately 10 times/day on average, but attacks occasionally occurred as many as 20–50 times during a 2–3-h period, at intervals no shorter than 5 min. Attacks were spontaneous, but could be evoked by rapid temperature changes such as steam from hot food. The patient did not report ever being woken from sleep by attacks. No family or previous history of neurovascular headaches was apparent. No period of remission had been experienced during the preceding 3 years.

Diagnosis

Diagnosis of SUNCT was based on the clinical features of the attacks, which fulfilled the ICHD-II diagnostic criteria (1). Secondary SUNCT was ruled out based on the results of cranial magnetic resonance imaging, magnetic resonance angiography and laboratory blood testing. No abnormalities were found in images of the pituitary, posterior fossa or carotid arteries, and endocrine results (growth hormone, prolactin, thyrotropin and cortisol) were normal.

Treatment

As carbamazepine prescribed by a previous physician had been effective, zonisamide was selected for continued treatment, since this agent is a Na-channel blocker like carbamazepine, but with a lower risk of producing skin rashes as caused by carbamazepine (8). Zonisamide was started at a dosage of 100 mg at bed time following his first visit in September 2006, and titrated upward.

On day 7 after initiating treatment (day 3 at 300 mg), the blood serum level of zonisamide was 19 µg/ml (reference range for treatment, 10–30 µg/ml). At this dosage, the attacks ceased completely.

The dose of 300 mg/day was maintained until December 2007, then zonisamide was titrated downward and discontinued to assess whether the patient had entered a period of remission. However, 3 days after discontinuation of zonisamide, the attacks resumed at 6 times/day. Zonisamide was, therefore, resumed and the patient has been maintained on this medication at the same dosage for 3 years without tachyphylaxis. Occasional trials of reduced dosage or when the patient has inadvertently forgotten to take his medication have caused recurrence of mild attacks.

Discussion

SUNCT was previously thought to be highly refractory to treatment (9). However, based on open-label trials, recently several agents appear to have been partially or completely effective for treatment of SUNCT. According to several reports, lamotrigine is recognized as the treatment of choice, while gabapentin and topiramate are second-line agents (4,10). However, these agents were unavailable in Japan at the time this case was diagnosed.

Carbamazepine alone is usually insufficient to suppress SUNCT symptoms effectively, with only three of 42 patients experiencing complete or nearly complete relief (11). Two previous studies reported that carbamazepine was effective in only 39% of SUNCT patients, and thus was prescribed less frequently than other alternatives (12,13). However, our patient responded dramatically to carbamazepine.

Zonisamide was prescribed to this patient because of the similar mechanisms of action compared to carbamazepine and phenytoin, inhibiting Na⁺ currents (zonisamide also inhibits T-type Ca²⁺ currents) and a different chemical structure (14), suggesting that it may be effective in controlling neuropathic pain syndromes (15). Zonisamide reportedly offers 77.1% efficacy in controlling trigeminal neuralgia, with a period of onset of 5.1 ± 3.1 days (16).

As the structural formula of zonisamide is completely different from that of carbamazepine while maintaining similar mechanisms of action, zonisamide represents a reasonable replacement drug for carbamazepine in patients who must discontinue carbamazepine due to severe rash. In our experience, zonisamide has proven to be an effective replacement for carbamazepine in the treatment of paroxysmal neuralgia, and appears effective in suppressing symptoms with minimal unfavourable side effects.

SUNCT is a rare headache syndrome associated with brief periods of excruciating pain, and is thought to be resistant to many treatments. This is the first case report in which zonisamide alone completely eliminated SUNCT symptoms. Zonisamide is a viable drug option for the treatment of SUNCT with fewer side effects and better outcomes than other medications with similar mechanisms of action.