Trigeminal autonomic cephalalgias presenting in a multidisciplinary tertiary orofacial pain clinic

Trigeminal autonomic cephalalgias (TACs) are characterized by unilateral intense pain involving predominantly the orbito-temporal region and associated with presence of ipsilateral cranial autonomic symptoms [1]. At least one or more should be present among conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, eyelid oedema, forehead and facial sweating, miosis and/or ptosis [2].

The distinction between the four different TAC conditions is based on headache duration, frequency and treatment response. Namely, cluster headache (CH) attacks last 15–180 min when untreated, with a frequency of up to 8 attacks a day. Paroxysmal hemicrania (PH) attacks are shorter in duration (2–30 min) and usually more frequent reaching a maximum of 40 attacks per day. Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT), and Short-lasting Unilateral Neuralgiform headache Attacks with cranial autonomic features (SUNA) are the shortest type of TAC (1 s-10 min) [2] and may occur up to 100 times daily. Hemicrania continua (HC) patients have a background of continuous unilateral pain with attacks of worsenings. PH and HC, respond specifically to therapeutic treatment with indomethacin [2, 3].

The incidence of TACs is low, with CH being the most common with a prevalence of approximately 0.1% of the population [4].

The pathophysiology of these entities is thought to involve the hypothalamus in its posterior, lateral and paraventricular nucleus, the trigeminovascular complex and the parasympathetic fibres with a crucial role of the sphenopalatine ganglion via the trigeminal autonomic reflex [5].

From neuroimaging studies, the acute phase of pain involves the ipsilateral hypothalamus in CH [6], the contralateral in PH [7] and HC [8], and the ipsilateral [9] and bilateral in SUNCT [10].

The pain CH patients experience can be easily and often misdiagnosed as dental pulp pain. Interestingly, Peñarrocha and colleagues explored the possible relationship between oral surgery, endodontic procedures and CH. The authors described a series of 54 patients who underwent oral surgery and endodontic procedures [11]. Among them, 58% had a dental procedure ipsilateral to the side where CH developed and in 24 out of 54 (44%) oral surgery was performed afterwards in order to resolve this pain. Although the authors hypothesized a possible relation between nerve damage and subsequent development of CH, they also admitted that dental extraction and endodontics could have been performed in response to CH-related pain. However, the authors did not include information about the presence of paraesthesia, dysesthesia, or allodynia which has been described in patients suffering from neuropathic pain after invasive dental procedures [12].

With regards to patients with CH, Bahra and Goadsby documented that dentists and ear, nose and throat (ENT) surgeons were most commonly consulted prior to neurologists (45% of 511 subjects) and that 52% had an invasive procedure performed for pain [13]. The authors found the mean time to diagnosis of CH in the 1990s was 2.6 years compared to in the 1950s which was 22.3 years [14].

The application of the ICHD-II criteria to 502 patients who presented with Temporo-Mandibular Dysfunction (TMD) and orofacial pain in a Temporo-Mandibular Joint and Orofacial Pain Clinic found, surprisingly, one single case of CH with no other TACs reported, and being tension-type headache the most frequent entity, diagnosed in 246 patients [14].

From a neurologist’s perspective, a prospective study of all surgical referrals to one consultant neurologist in the UK over a 42-month period found 12 patients from oral and maxillofacial surgery clinics being 5 diagnosed of trigeminal neuralgia and 3 of atypical facial pain [15]. Most recently, a systematic review of diagnostic and therapeutic errors in TACs performed by Viana and colleagues [16] showed that patients with CH were found to be the largest category of mismanaged patients. Few case series included mismanagement of HC [17, 18]. Rossi and colleagues described 25 patients fulfilling the ICHD-II criteria for HC among 1612 subjects attending an Italian Headache Centre over a three-year period [18]. Among these patients, 52% had previously been misdiagnosed with migraine. Only two published cases of misdiagnosed SUNCT appeared in the review, both were incorrectly classified as Trigeminal Neuralgia (TN) [16].

This study aims to evaluate the headache disorder diagnoses seen at a tertiary Multidisciplinary Orofacial Pain (OFP) clinic and more specifically the diagnoses and management of TACs. The work has been presented in preliminary form at the Congress of the International Headache Society (Vancouver, Canada, 7–10 September, 2017) [19].

Clinic letters from the initial consultation and subsequent follow up reviews of the 142 patients, who were seen in the tertiary Multidisciplinary Orofacial Pain clinic between January 2015 until January 2018 were reviewed as a clinical audit. In this clinic, all patients are first reviewed by an experienced Orofacial Surgeon (TR) to exclude a dental cause for their facial pain. The Multidisciplinary Orofacial Pain clinic has approximately 300 new patients a year, approximately 12% of patients present with a dental cause for primary complaint, of which the most common is painful post-traumatic trigeminal neuropathic (48%) and TMD is second most common (23%). Patients are then seen by Headache fellows under the supervision of a Headache Specialist (PJG). For these patients, their demographics, the presence of dental work, time until diagnosis and diagnosis were recorded. Of the patients with a possible TAC diagnosis, the pain localisation, cranial autonomic symptoms and result of the indomethacin test (if applicable) were recorded. The diagnoses were made according to ICHD-III beta [20].

Of the one hundred and forty-two patients reviewed; there were 100 women (70%) and 42 men (30%). The mean age was 51 ± 3 (52 ± 4 for men, 50 ± 3 for women, mean ± SD). Among all consultations, 109 (77%) were new patients and 33 (23%) were follow ups. A TAC was suspected in 62 patients (44%) based on the history of unilateral pain in the trigeminal distribution and the presence of ipsilateral cranial autonomic symptoms, as per ICHD-III beta criteria. Of the remaining patients, the most common diagnoses were chronic and episodic migraine, painful post-traumatic trigeminal neuropathy and trigeminal neuralgia (Fig. 1 and Table 1). There was one patient that was initially diagnosed as intermedius nerve neuralgia following the first consultation, however, with subsequent review was diagnosed with SUNA and is included into the TAC cohort. One patient was referred with dystonia and therefore excluded from the cohort. Interestingly, 18 patients were diagnosed with more than one headache type (Table 2), the most common presentation being the presence of painful post-traumatic trigeminal neuropathy and migraine.

TACs often present to other specialities given the distribution and location of the pain. Patients often see dentists and orofacial specialists to find the root of the pain. Therefore, a multi-disciplinary team approach involving dental, oral surgery team and headache specialists is important to optimise patient outcomes. The patients presenting to our Multidisciplinary Orofacial Pain clinic are often complex and have had dental causes excluded as the reason for the pain. Within our cohort, the most common initial diagnosis was possible TAC, this was more common than migraine. Most patients with possible TAC, localised their pain to the second and/or third trigeminal nerve distribution, this should be considered with some care and can be explained by selection bias as most patients presented to a dentist for the pain initially.

The delay to diagnosis for patients with a TAC (HC, PH, CH and SUNCT/SUNA) was 7 years, in particular the delay until diagnosis for CH was 6 years for an episodic CH patient and 17 years for a chronic CH patient; this is higher than the average delays reported in a systemic review [16] and case series, where the range was 2.6 years to 11 years [13]. Although the delay to diagnosis for CH in this study is longer, it is not a true representation of the time to CH diagnosis, as there were only two cases in this cohort and it is likely that with the education of many dentists, CH cases are diagnosed earlier and therefore not presenting in a tertiary Orofacial Pain clinic. There was only one case of PH, and the delay until diagnosis was 12 years, this is within the range reported in the systemic review (range 10 months-12 years) [16]. The average delay till diagnosis was 5 years. The pooled mean delay of diagnosis in HC has been reported to be 8 ± 7.2 years [16], this is similar to what we have found, a delay of 8.7 years. TACs are generally not recognised and therefore diagnosis is often delayed, furthermore there is a large group of TAC patients that present to the orofacial services.

Traditionally, HC has been considered a rare condition and a recent study by Hryvenko and colleagues reviewed 1617 new patients seen in their TMD and Orofacial Pain Clinic, and only found 6 (0.4%) patients with HC, with 5 patients with nearly complete response with oral indomethacin (150-225 mg/day) and one patient had to remain on 75 mg/day due to intolerable side effects, and therefore had partial pain relief [21]. In a pooled analysis of published HC case series, HC represents 1.7% (range 1.3–2.3%) of neurology or headache clinics patients [22]. We have found a higher prevalence of HC in our cohort of 142 patients from our tertiary Multidisciplinary Orofacial Pain clinic. There were 13 patients (9%) with confirmed HC on either placebo-controlled intramuscular indomethacin or oral indomethacin titrating trial. Our findings suggest HC patients present to orofacial pain services due to the distribution and characteristics of the pain, and we encourage orofacial pain services to consider this diagnosis perhaps more often than may have been the case. SUNCT/SUNA was the second most common TAC diagnosis made in our cohort, 6 patients (10%).

TACs are an important group of primary headache disorders dentists and oral surgeons should be aware of as many patients with unilateral side-locked primary headaches present to the dental services. Neurologists should be cognisant of this presentation pattern when seeing patients from these pathways. HC is underdiagnosed and this may be due to the presentation to other specialities rather than to neurology and headache services. We have found the most effective way to ensure patients are diagnosed correctly and managed optimally is a multidisciplinary service with dentists, oral surgeons and headache specialists.