Abstract
Introduction
The International Headache Society recognizes several headache syndromes that are characterized by a trigeminal distribution of pain and accompanying ipsilateral autonomic symptoms (1). These disorders include cluster headache, chronic paroxysmal hemicrania, and others not yet included in the classification criteria such as episodic paroxysmal hemicrania, hemicrania continua, and SUNCT syndrome. Because of the highly consistent location of the pain and the coexistent autonomic signs, Goadsby and Lipton (2) referred to these syndromes as ‘trigeminal-autonomic cephalgias’ (Table 1). Diagnosis depends on the presence of par-oxysmal unilateral trigeminal region headaches that follow a unique and characteristic temporal profile and autonomic features (e.g. tearing, rhinorrhoea, conjunctival injection) ipsilateral to the pain.
Primary short-lasting headache
From Goadsby and Lipton (2). By permission of Oxford University Press.
We report on a patient with an unusual medically refractory syndrome characterized by paroxysms of pharyngeal pain associated with ipsilateral autonomic features.
Case report
A 41-year-old right-handed woman had a history of childhood migraine with aura that abated spontaneously 3 years previously. In the summer of 1996, a new pain syndrome developed with stereotypic clinical features. Without identifiable triggers, a sudden unilateral right- or left-sided throat pain would develop, beginning behind the glossopharyngeal arch and radiating down the posterior portion of the oesophagus. The pain was sharp, lancinating, and moderately severe. The pain did not radiate to other cranial or cervical regions. Simultaneously, she experienced ipsilateral conjunctival injection, lid oedema, tearing, rhinorrhoea, and salivation. The symptoms lasted an average of 45 s, with a range from 20 s to 90 s. The pain was moderately severe, and she would stop her activities and clench her teeth during its gradual resolution. She estimated that 70% of the attacks occurred on the left and 30% on the right, but individual attacks were always unilateral. Every attack included both pain and autonomic features; neither occurred in isolation. The frequency of attacks ranged from 4 to 40 per day, and many would wake her from sleep. During an attack, her voice was hoarse and she would occasionally cough at the resolution. She denied dizziness, dysphagia, diplopia, dysarthria, ataxia, or syncope. She was completely free from paroxysms for 2 weeks in October 1996, but otherwise she had daily attacks for 12 months. She was asymptomatic between attacks. The patient attempted to treat her symptoms with ibuprofen, which had no effect.
Results of a general physical and neurologic examination were normal. Examination during a typical attack revealed ipsilateral conjunctival injection, lacrimation, lid oedema, rhinorrhoea, slight lid ptosis, and hoarseness during a paroxysm which lasted approximately 45 s.
Computed tomographic (CT) and magnetic resonance imaging of the brain revealed a 2-cm enhancing mass in the region of the cribriform plate, somewhat more prominent on the right. This was thought to have the imaging characteristics of a meningioma and thought to be incidental to her presenting complaint. Follow-up CT imaging at 10 months showed no change in the presumed meningioma, and results of the neurologic examination remained normal. CT scan of the neck was normal.
Treatment with carbamazepine was initiated at a dose of 200 mg twice daily and the dose was gradually escalated to 400 mg three times a day. The initial response was a slight increase in attack frequency for about 3 days, with no subsequent benefit. Carbamazepine therapy was tapered and discontinued. There was no clinical response to indomethacin up to a divided daily dosage of 225 mg. Subsequent trials of gabapentin (900 mg three times a day) and prednisone (60 mg with taper) also failed.
Discussion
This patient presented with severe, short-lasting, unilateral neuralgiform pain with conjunctival injection and tearing and an attack frequency of up to 40 per day. However, the pain was confined to the pharynx, associated with hoarseness, and terminated with a cough, thus resembling glossopharyngeal neuralgia. However, there were no triggers and the pain was refractory to carbamazepine and gabapentin. This pattern has not been described and illustrates two major concepts (i): anatomic descriptions and criteria for these syndromes do not address underlying pathophysiologic mechanisms; and (ii) there are important intrinsic brain-stem connections linking the cranial parasympathetic pathway with other brain-stem centres, including the glossopharyngeal nerve. Therefore, pain may be referred to the somatic and visceral areas supplied by individual cranial nerves.
The SUNCT syndrome is characterized by neuralgic pain that is associated with autonomic manifestations. Like cluster headache, there is a clear male predominance, with an approximately 8:1 male-to-female ratio. The pain is short-lasting, frequent, and stereotypic. Each attack is exclusively unilateral, with the epicentre of pain usually located in the orbital or periorbital area. The painful paroxysms usually last 10–60 s but may last up to 300 s. The frequency of attacks during symptomatic periods ranges from less than one per day to more than 30 per hour. The syndrome is usually recalcitrant to medical therapy, including drugs conventionally used to treat migraine, cluster, and trigeminal neuralgia (3–5). The syndrome was first reported in 1989 by Sjaastad et al. (3), but since that time several case reports have expanded the clinical spectrum of the disorder. Although the majority of patients have normal results of neurologic examinations and neuroimaging studies, two patients were documented to have a symptomatic form of SUNCT: one with a cavernous malformation in the brain stem (6) and the other with a vascular malformation in the cerebellopontine angle (7). In addition, first-division trigeminal neuralgia has been reported to transform into a SUNCT-like syndrome with severe vasomotor phenomena (8).
Glossopharyngeal neuralgia is a syndrome characterized by severe paroxysms of neuralgic pain, usually in the pharynx or tonsillar fossa, which are triggered by minimal sensory stimuli in the distribution of the glossopharyngeal nerve. Glossopharyngeal neuralgia was reported to occur with trigeminal neuralgia in 12% of a large case series reported from the Mayo Clinic (9). It too is associated with evidence of autonomic and specifically parasympathetic (vagal) involvement, such as cardiac syncope (9–11). Although this patient had neuralgic pain in the distribution of the glossopharyngeal nerve, the underlying pathophysiology may be more similar to SUNCT syndrome, given the temporal profile of the pain, intense cranial autonomic symptoms, lack of response to anti-convulsants, and the lack of triggers for the pain.
Because the sensory innervation to the ear, pharynx, tonsil, tongue, neck, and jaw may overlap (cranial nerves V, VII, IX, and X; C1–2 afferents) and converge within the brain stem (nucleus of the solitary tract, spinal nucleus of V, caudal trigeminal nucleus), activation within this system can lead to pain that is referred to the somatic distribution of one or more of these cranial nerves (12). Indeed, this anatomic overlap may account for the extratrigeminal location of pain in the occiput in patients with cluster headache (13) and episodic paroxysmal hemicrania (14) and in the ear in patients with chronic paroxysmal hemicrania (15).
The presence of ipsilateral cranial autonomic symptoms reflects activation of the cranial parasympathetic pathway. The preganglionic neurones of this pathway reside in the superior salivatory nucleus. The efferent fibres of this pathway travel with the facial nerve and synapse in the sphenopalatine ganglion. Postganglionic fibres containing nitric oxide and vasoactive intestinal polypeptide provide vasomotor innervation to large cerebral blood vessels and secretomotor innervation to the lacrimal and nasal mucosal glands. Therefore, because sensory information from various cranial nerves and cervical afferents undergoes convergent processing with the potential for reflexive activation of the cranial parasympathetic pathway, ipsilateral autonomic signs can occur in paroxysmal pain syndromes, which involve various somatic distributions. Functional neuroimaging, particularly positron emission tomography, holds great promise in furthering our understanding of the basic mechanisms and anatomical underpinnings of primary headache disorders. Unfortunately, this imaging modality was not available at the time of this patient's evaluation.
We propose that this case illustrates an example of SUNCT syndrome with extratrigeminal pain. Given the degree of anatomic overlap between the cranial nerves which provide somatic innervation to head and neck structures and the convergent processing which occurs within the cranial and visceral autonomic brain-stem centres, perhaps the term ‘cranial-autonomic cephalgias’ would represent a more inclusive characterization of the group of disorders that have been referred to as trigeminal-autonomic cephalgias.