Skip to main content

Trigeminal autonomic cephalalgias presenting in a multidisciplinary tertiary orofacial pain clinic


Orofacial pain may have a variety of causes and offers a significant clinical challenge for its diagnosis and management.


To assess the headache disorders presenting in a tertiary multidisciplinary orofacial pain clinic, after dental causes have been excluded.


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.


The most common diagnoses were possible trigeminal autonomic cephalalgia (n = 62, 44%), migraine (n = 38, 27%) and painful post-traumatic trigeminal neuropathy (n = 17, 12%). The most common trigeminal autonomic cephalalgia diagnosis was hemicrania continua (n = 13, 9%), which is higher than the reported prevalence in neurology and headache clinics.


This study demonstrates the importance of a multidisciplinary approach to diagnosing complex orofacial pain patients and the importance of awareness of primary headache disorders, in particular trigeminal autonomic cephalalgias, thereby reducing unnecessary diagnostic delays or procedures.


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].

Indomethacin response

Indomethacin response was determined either by intramuscular indomethacin placebo-controlled testing with 150 mg indomethacin or by course of oral indomethacin, with a titrating regime starting at 25 mg three times a day in the first week, increased to 50 mg three times a day for a week and finally 75 mg three times a day. A positive test was deemed to be at least a 50% reduction in pain intensity and/or 50% in frequency or duration of the worsenings present with the indomethacin and not with the placebo.


Data were collected in Excel, where quantitative analysis was performed, and STATA (SE 15.1 for Mac) was used for chi square and Fischer’s exact testing..


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.

Fig. 1

Initial diagnosis following consultation

Table 1 Initial diagnosis of patients in the cohort, taking into account that some of them had more than one headache type (Table 2); CSF: Cerebrospinal fluid; aOne patient excluded, was diagnosed with dystonia
Table 2 Patients with two headache diagnoses: Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT), and Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic features (SUNA)

Diagnosis prior to clinic

A previous suspected diagnosis was only reported in 17 patients, including trigeminal neuralgia (n = 6), migraine (n = 8), SUNCT (n = 1) and painful trigeminal neuropathy (n = 2). However, only 7 had a correct previous diagnosis and, interestingly, trigeminal neuralgia was the most commonly misdiagnosed (5/6 patients). As a previous comorbidity, temporo-mandibular dysfunction, was present in 10 (7%) patients. Neuroimaging (either MRI or CT) had been performed in 72 patients (51%) by the time they attended the consultation.

Delay to diagnosis

Time to diagnosis for the whole cohort was 5.6 years, in patients with a confirmed TAC (HC, PH, CH and SUNCT/SUNA) was 7 years. Time to diagnosis in patients with HC, the most common diagnosis among TACs, was 8.7 years. In the two CH patients the delay was 6 and 17 years, in the one case with chronic PH the delay was 12 years and in SUNCT/SUNA patients (n = 6) the average delay was 5 years.

TAC patients

TAC was suspected in 62 patients. This group included 40 women (65%) and 22 men (31%). The mean age was 53 ± 4 years (54 ± 6 for men, 53 ± 4 for women).

This group comprised of 13 confirmed HC, 1 confirmed PH, 6 SUNCT/SUNA, 2 CH, 17 negative indomethacin (chronic migraine), 21 possible HC and 2 possible PH (not confirmed) patients (Table 3). In the group with possible HC and possible PH, the clinical phenotype fits the ICHD-III beta, however had equivocal indomethacin response or from patient’s personal choice did not proceed with the indomethacin test.

Table 3 TAC diagnosis

Pain location and description

As expected from a population of patients undergoing OFP assessment, most patients referred their pain to the second and/or third trigeminal branches (60/62), being only two cases of strictly V1 pain. Pain located in V2 (18/62) as well as V2 and V3 (17/62) were the most commonly reported followed by pain in V1 and V2 (9/62), hemifacial pain involving all three branches (13/62) and pain exclusively on V3 (3/62).

Description of the pain varied widely among patients. However, the pain was described, at least at times, as throbbing by 25 out of 62 patients. This type of pain, was present in migraineurs and non-migraineurs, although it was significantly associated with a migrainous background (Chi square: p − 0.001) but not with a negative indomethacin test (Fisher’s exact, p = 0.157). Pain was also described as pressure-like, stabbing, sharp, shooting, dull, burning or shooting/electrical, with no noteworthy differences among patients. Pain was rated as moderate to severe in all cases.

Cranial autonomic symptoms

Of the patients with a possible TAC diagnosis, the average number of cranial autonomic symptoms per patient was 3. Patients with a confirmed TAC diagnosis (n = 22) reported on average 2.5 cranial autonomic symptoms per patient. The most common cranial autonomic symptom, within the whole group with possible TAC, was lacrimation (n = 35), followed by nasal congestion (n = 27) and conjunctival injection (n = 23).

Oral procedures in the possible-TAC-population

Specifically, among patients with possible TAC (including all patients with suspected HC who underwent the indomethacin test), different dental procedures were recorded. Overall, dental extraction was the most common (15/62; 24%), followed by root canal treatment (8/62; 13%) and dental filling (4/62; 6%). Dental implant, minor trauma in the gum, mucosal biopsy and parotid surgery were performed in single cases (Table 4).

Table 4 Dental procedures in possible TAC patients

A significant association (χ2 = 26.2; p = 0.000) was found between the variables “previous oral work” (25/62) and the variable “pain within 1 week after the procedure” (16/62), however this test does not show causation and there is a potential selection bias as all the patients have been referred from dentists and oral surgeons. Additionally, 10 patients underwent dental work afterwards to treat their pain, with only one patient getting some pain relief. A single patient underwent 3 procedures (tooth extractions) with no benefit. Only one procedure to treat the pain was performed in the remaining patients.

History of headache and pain syndromes

Twenty-six out of 62 patients (42%) had a previous pain background, migraine being the most common. Namely, 16 patients had been previously diagnosed with episodic migraine without aura, 5 with episodic migraine with aura and 2 with chronic migraine. Two patients had fibromyalgia and one patient had temporomandibular joint dysfunction and bruxism.

Indomethacin test

An indomethacin test was performed in 31 patients (26 intramuscular and 5 oral).

After the administration of the drug, pain relief was observed in 14 (positive) patients, with no benefit in the remaining 17 subjects (negative).


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%).


This is a retrospective study of clinic letters to identify patients who attended the Multidisciplinary Orofacial Pain clinic, therefore we cannot assess any predictive or causative factors. The clinical documentation is, however, structured and systematic since a priori we have seen patients referred from such services before our new service was initiated. A strength of the study is the certainty of the diagnosis, as we followed the patients carefully through the years. Importantly, the patients with HC were confirmed with placebo-controlled intramuscular indomethacin testing.


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.

Availability of data and materials

All data generated or analysed during this study are included in this published article.



Cluster headache


Paroxysmal hemicrania


Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic features


Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing


Trigeminal autonomic cephalalgia


Trigeminal neuralgia


  1. 1.

    Goadsby PJ, Lipton RB (1997) A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain 120:193–209

    Article  Google Scholar 

  2. 2.

    Headache Classification Committee of the International Headache Society (2018) (IHS) the international classification of headache disorders, 3rd edition. Cephalalgia 38:1–211

    Google Scholar 

  3. 3.

    Newman LC. Trigeminal Autonomic Cephalalgias Continuum (Minneapolis, Minn) 2015;21:1041–57

  4. 4.

    Russell MB (2004) Epidemiology and genetics of cluster headache. Lancet Neurol 3:279–283

    Article  Google Scholar 

  5. 5.

    Hoffmann J, May A (2018) Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol 17:75–83

    Article  Google Scholar 

  6. 6.

    May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ (1998) Hypothalamic activation in cluster headache attacks. Lancet 352:275–278

    CAS  Article  Google Scholar 

  7. 7.

    Matharu MS, Cohen AS, Frackowiak RS, Goadsby PJ (2006) Posterior hypothalamic activation in paroxysmal hemicrania. Ann Neurol 59:535–545

    Article  Google Scholar 

  8. 8.

    Matharu MS, Cohen AS, McGonigle DJ, Ward N, Frackowiak RS, Goadsby PJ (2004) Posterior hypothalamic and brainstem activation in hemicrania continua. Headache 44:747–761

    Article  Google Scholar 

  9. 9.

    May A, Bahra A, Buchel C, Turner R, Goadsby PJ (1999) Functional magnetic resonance imaging in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 46:791–794

    CAS  Article  Google Scholar 

  10. 10.

    Sprenger T, Valet M, Platzer S, Pfaffenrath V, Steude U, Tolle TR (2005) SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression. Pain 113:422–426

    Article  Google Scholar 

  11. 11.

    Peñarrocha M, Bandrés A, Peñarrocha MA, Bagán JV (2001) Relationship between Oral surgical and endodontic procedures and episodic cluster headache. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:499–502

    Article  Google Scholar 

  12. 12.

    Spierings EL, Dhadwal S (2015) Orofacial pain after invasive dental procedures: neuropathic pain in perspective. Neurologist 19:56–60

    Article  Google Scholar 

  13. 13.

    Bahra A, Goadsby PJ (2004) Diagnostic delays and mis-management in cluster headache. Acta Neurol Scand 109:175–179

    CAS  Article  Google Scholar 

  14. 14.

    Kang JK, Ryu JW, Choi JH, Merrill RL, Kim ST (2010) Application of ICHD-II criteria for headaches in a TMJ and orofacial pain clinic. Cephalalgia 30:37–41

    Article  Google Scholar 

  15. 15.

    Larner AJ (2011) Referrals to the neurology clinic from oral and maxillofacial surgery clinics. Br J Oral Maxillofac Surg 49:576–577

    CAS  Article  Google Scholar 

  16. 16.

    Viana M, Tassorelli C, Allena M, Nappi G, Sjaastad O, Antonaci F (2013) Diagnostic and therapeutic errors in trigeminal autonomic cephalalgias and hemicrania continua: a systematic review. The Journal of Headache and Pain 14:14

    Article  Google Scholar 

  17. 17.

    Cortijo E, Guerrero AL, Herrero S et al (2012) Hemicrania continua in a headache clinic: referral source and diagnostic delay in a series of 22 patients. J Headache Pain 13:567–569

    Article  Google Scholar 

  18. 18.

    Rossi P, Faroni J, Tassorelli C, Nappi G (2009) Diagnostic delay and suboptimal management in a referral population with hemicrania continua. Headache 49:227–234

    Article  Google Scholar 

  19. 19.

    Wei D, Renton TF, Goadsby PJ (2017) Trigeminal autonomic Cephalalgias in tertiary multi-disciplinary orofacial pain clinic. Cephalalgia 37:213–214

    Google Scholar 

  20. 20.

    Headache Classification Committee of the International Headache Society (IHS) (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33:629–808

    Article  Google Scholar 

  21. 21.

    Hryvenko I, Cervantes-Chavarria AR, Law AS, Nixdorf DR (2018) Hemicrania continua: case series presenting in an orofacial pain clinic. Cephalalgia 38:1950–1959

    Article  Google Scholar 

  22. 22.

    Prakash S, Patel P (2017) Hemicrania continua: clinical review, diagnosis and management. J Pain Res 10:1493–1509

    Article  Google Scholar 

Download references


This paper represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.



Author information




DYW, PJG designed and conceptualised the study. DYW, DMA, TR and PJG all contributed equally to the first draft and revising for final draft. All authors read and approved the final manuscript.

Corresponding author

Correspondence to P. J. Goadsby.

Ethics declarations

Ethics approval and consent to participate

This clinical audit was registered in King’s College Hospital on 11th September 2016.

Consent for publication

Not applicable.

Competing interests

DYW, DMA, TR have nothing to disclose. PJG has no conflict of interest with the submitted work. PJG reports personal fees from Alder Biopharmaceuticals, personal fees from Allergan, grants and personal fees from Amgen, personal fees from Autonomic Technologies Inc., personal fees from Biohaven Pharmaceuticals Inc., personal fees from Dr. Reddy’s Laboratories, grants and personal fees from Eli Lilly and Company, personal fees from Electrocore LLC, personal fees from eNeura Inc., personal fees from MundiPharma, from Novartis, personal fees from Teva Pharmaceuticals, other from Trigemina, outside the submitted work; In addition, PJG has a patent Magnetic stimulation for headache licensed to eNeura without fee and Fees for publishing from Oxford University Press, Massachusetts Medical Society, Wolters Kluwer and for medicolegal work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This work was supported by the NIHR South London and the Maudsley Biomedical Research Centre.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wei, D.Y., Moreno-Ajona, D., Renton, T. et al. Trigeminal autonomic cephalalgias presenting in a multidisciplinary tertiary orofacial pain clinic. J Headache Pain 20, 69 (2019).

Download citation


  • Orofacial pain
  • Trigeminal autonomic cephalalgias
  • Hemicrania continua