Abstract
We report two cases of SUNCT that demonstrate the medically and surgically refractory nature of this disorder and support the hypothesis that the causative ‘lesion’ lies within the central nervous system. After both patients had failed medical therapies, the first underwent a glycerol rhizotomy, gammaknife radiosurgery and microvascular decompression of the trigeminal nerve. The second patient underwent gammaknife radiosurgery of the trigeminal root exit zone and two microvascular decompression surgeries. Neither patient benefited from these procedures. Currently, the first patient suffers from anaesthesia dolorosa and the second patient from unilateral deafness, chronic vertigo and dysequilibrium as a result of surgical trauma. These cases of SUNCT highlight the uncertainty regarding the role of surgery given the potential for significant morbidity. These cases also suggest that SUNCT originates and may be maintained from within the CNS and this central locus explains why SUNCT is not typically amenable to interventions aimed at the peripheral portion of the trigeminal nerve.
Introduction
SUNCT is a syndrome of intermittent, brief, unilateral, severe paroxysms of orbital-temporal pain recurring multiple times per day. Each painful episode is associated with multiple cranial autonomic symptoms, including conjunctival injection and tearing. Since the original description of this syndrome in 1989, less than 100 cases have been published and our knowledge of its pathophysiology has only modestly progressed (1). Surgical procedures for other short-lasting primary headache disorders, including alcohol or glycerol rhizotomy, balloon compression, gamma knife radiosurgery and microvascular decompression, have been shown to be beneficial in some peripherally driven pain disorders such as trigeminal neuralgia. Though very effective in the right clinical setting, these treatments carry some surgical morbidity and are usually reserved for cases refractory to medical therapy.
Recently there have been several reports of patients with SUNCT whose pain was alleviated by various surgical procedures. These include microvascular decompression of the trigeminal nerve root, balloon compression of the trigeminal ganglion, and local opioid blockade of the superior cervical ganglion (2–5). The long-term outcome of these patients is not known and as yet, no reports of failed surgical procedures in this syndrome have been reported. We report two patients whose symptoms met the proposed International Headache Society (IHS) criteria for SUNCT who each underwent exhaustive and unfortunately unsuccessful therapeutic attempts using invasive surgical techniques (6).
Cases
Case 1
A 39-year-old businessman presented for evaluation of a 2-year non-progressive history of a sharp, stabbing right retro-orbital pain that occurred 60–400 times a day, lasting 2–3 s, occurring singly or in repeated volleys lasting up to 30 s. The pain never migrated nor occurred on the left side. Attacks were accompanied by prominent ipsilateral tearing, rhinorrhea and conjunctival injection. After about 6–8 months of these symptoms, he also noticed a dull, continuous pain in the same distribution that persisted at a minor intensity all the time. His neurological examination and MRI scan with and without gadolinium were normal. He had been tried on carbamazepine, indomethacin (75 mg three times a day), amitriptyline (75 mg per day), phenytoin (300 mg per day), gabapentin (900 mg per day), verapamil (240 mg sustained release per day) and methylprednisolone (24 mg to 0 tapered over 7 days) without benefit. Carbamazepine at dosages between 800 and 1000 mg induced a temporary but partial response with a lessening of the frequency and intensity of the painful paroxysms. Hydrocodone/acetaminophen (10/500 mg) also helped slightly in reducing the pain intensity. He had one trigger point just within the right nostril, but this was not reliable.
After 1 year of disabling symptoms, he underwent a glycerol rhizotomy with approximately 2 weeks of significant reduction of pain but his original symptoms returned. He was left with a residual hypoesthesia involving all three divisions of the trigeminal nerve. Subsequent to this he came to the Mayo Clinic and underwent gamma knife radiosurgery, which involved a maximum of 90 Gy directed at the trigeminal nerve with a 4-mm isocentre. This resulted in near complete pain relief for about 2 months, during which time the patient was able to taper and discontinue carbamazepine and his need for opioids nearly resolved. He still suffered the stereotypic attacks but they were much less intense (5 on a 10-point visual analogue pain scale) and the continuous background headache resolved completely, although the area of hypoesthesia from the prior glycerol rhizotomy had persisted. Unfortunately, 3 months after the second procedure he developed a dull boring pain in the hypoesthetic area consistent with anaesthesia dolorosa and the brief painful paroxysms of pain and cranial autonomic symptoms gradually recurred completely. He went on to be treated with other medications including topiramate and lamotrigine without any benefit. A trigeminal root section was considered but ultimately not performed. One year later, at yet another institution, he underwent a suboccipital microvascular decompression of the trigeminal nerve. Five months later he was still suffering significant pain.
Case 2
A 28-year-old man presented with a 10-year history of lancinating ‘piercing’ right retro-orbital pain lasting 20–30 s that occurred 100–200 times per day. During the initial 3 years of this disorder the pain had been intermittent. During each attack he developed right-sided conjunctival injection, very prominent lacrimation and rhinorrhea. However, it transformed quickly into a daily pattern of pain. His neurological examination and MRI scan with and without gadolinium were normal. Indomethacin (75 mg TID), carbamazepine (800 mg per day), verapamil (240 mg sustained release per day), lithium, verapamil with valproic acid, and verapamil with clonazepam, baclofen, gabapentin (3600 mg per day), lamotrigine (200 mg per day), topiramate (200 mg per day), clonidine, methysergide, ergotamine, dihydroergotamine and sumatriptan (6 mg subcutaneous) were all ineffective. The patient had been seen at four academic tertiary referral centres prior to consultation at the Mayo Clinic. Gamma knife radiosurgery did not produce even temporary or partial resolution of his symptoms. Five months later he underwent a microvascular decompression of cranial nerves, five, seven, eight, nine and ten without any benefit. Two months later, the same team of surgeons repeated the microvascular decompression and sectioned the nervus intermedius. Unfortunately, not only did this second procedure fail to provide relief, but he suffers from unilateral deafness, chronic vertigo, and dysequilibrium as a result of the procedure. He opted to endure the pain and attempt further medication trials rather than any other surgical procedures.
Discussion
SUNCT syndrome is one of a number of trigeminal-autonomic cephalgias characterized by first division pain and cranial autonomic symptoms (7). These syndromes differ mainly in the duration of individual painful episodes, the frequency with which they occur, and their response to medical therapy. In contrast to cluster headache, paroxysmal hemicranias and hemicrania continua, SUNCT syndrome is characterized by ultra-short paroxysms of pain that are neither responsive to indomethacin nor to medications characteristically effective for cluster headache. Although the brevity of attacks and the neuralgiform pain resembles trigeminal neuralgia, the presence of autonomic symptoms, the first division distribution of pain, and the lack of response to medications usually effective for trigeminal neuralgia, are distinguishing characteristics. These differences, and the descriptions of central lesions reported to give rise to a clinical picture indistinguishable from idiopathic SUNCT, suggest that SUNCT syndrome has a strictly central pathogenesis (8–11).
Using functional neuro-imaging, May et al. identified an area of activation in the posterior hypothalamic grey in a patient with SUNCT syndrome (12). This area is believed to be the possible site from which cluster headache originates based upon similar findings in patients with cluster headache using PET and voxel-based morphometric imaging (13, 14). The reciprocal connections between the hypothalamus and brainstem autonomic nuclei and the central antinociceptive network may explain how dysfunction in the hypothalamic pacemaker could give rise to periodic trigeminal-autonomic cephalgias. The explanation for the differences in temporal profile and response to specific treatments is as yet unclear.
SUNCT syndrome is perhaps the most refractory of all primary headache disorders to medical therapy, although rare cases responsive to gabapentin, lamotrigine and carbamazepine have been described (15–20). Thus, given the refractory nature of this disorder, the disabling severity of the pain, and the efficacy of various ablative surgical procedures directed at the trigeminal nerve complex for trigeminal neuralgia and cluster headache, it is not surprising that patients and their physicians pursue this line of treatment. Percutaneous trigeminal nerve compression was recently reported to have provided complete pain relief, except for a single brief episode, in a patient who was followed for 18 months (3).
The cases reported here illustrate the potential resistance of this syndrome to ablative procedures of the trigeminal nerve complex. If SUNCT syndrome is a primary brain disorder with pain that can be generated and maintained from within the central nervous system, the failure of destructive procedures directed towards the peripheral trigeminal nerve would not be surprising. There are certainly an ample number of patients who have undergone complete surgical trigeminal root sections for cluster headache only to have attacks continue, switch to the opposite side, or continue to express the central dysfunction in the form of cranial autonomic symptoms without pain (21, 22).
Investigations into the nature of the hypothalamic-brainstem dysfunction and the failure of central pain modulation will no doubt be fruitful in improving our understanding of this and other primary headache disorders and ultimately provide more specific targets for treatment. Recently, stereotactic implantation of a stimulating electrode into the posterior hypothalamus was shown to be effective in a patient with medically and surgically resistant cluster headache (23). Given the similar clinical features and activation pattern seen with functional imaging in the posterior hypothalamus in SUNCT and cluster headache, the possibility that a similar stereotactic approach would be effective for medically resistant SUNCT syndrome is of great interest. SUNCT is a rare disorder and achieving adequate numbers of surgical outcomes will be exceedingly difficult. Until then, physicians and patients should bear in mind that in patients with SUNCT, more so than in either cluster headache or certainly trigeminal neuralgia, the risk to benefit ratio may be unacceptably high. The lack of knowledge regarding surgical outcomes for SUNCT, combined with its dismal response to less invasive therapies, makes it paramount that candidates for such procedures receive thorough education and counselling so that they may adjust their expectations accordingly.