Abstract
Aim of investigation
Hemicrania continua (HC) is an uncommon primary headache and little is known of the characteristics of such patients managed in an orofacial pain setting. This study provides clinical features of HC, its association with other disorders, and treatment outcomes of patients managed in the TMD and Orofacial Pain Clinic at the University of Minnesota.
Methods
A retrospective review of patient records was undertaken. Inclusion criteria were a diagnosis of HC and confirmation at follow-up.
Results
Six of the 1617 new patients seen between 2015 and 2017 met the selection criteria. Four patients presented with “facial pain”, one with “toothache” and one with “jaw pain”. All were female with mean age 55 ± 10.5 years (range = 41–69). Headache characteristics included unilateral (R:L = 1:1) pain of moderate intensity with severe exacerbations in the distribution of V1 (1/6), V1 + V2 (3/6) and V1 + V2 + V3 (2/6). Lacrimation and photophobia were the most common associated symptoms. Patient presentations were complicated by multiple medical and comorbid diagnoses. All were diagnosed with temporomandibular disorder (TMD). Indomethacin alone was sufficient for adequate headache control in 2/6 patients with several add-on medications providing sustained pain relief.
Conclusions
Comorbid pain conditions can be expected in patients with HC presenting to orofacial pain clinics. Symptom presentation varies, and multimodal treatment approach is necessary for success.
Keywords
Introduction
Hemicrania continua (HC) is an uncommon trigeminal autonomic cephalalgia encountered in 1.3–2.3% of patients attending neurology or headache clinics (1,2). In orofacial pain clinics, chronic headache is a common complaint, but the vast majority of the published data on HC presents data of patients from medical settings (2). Consequently, it is unknown how frequently HC patients present to orofacial pain clinics. Furthermore, HC patients presenting to orofacial pain specialists may differ from those presenting to neurology or other headache clinics due to comorbid dental and other orofacial pathologies, referral patterns, chief complaint, as well as patient’s beliefs.
A third of patients consult a dentist for their HC pain (3), and 20% of patients with HC have been reported to receive inappropriate dental treatment (3). In addition, two cases of HC masquerading as temporomandibular pain have been reported in the literature (4). Furthermore, a few HC patients undergo unnecessary TMJ surgeries to address their HC pain (3). Confusion related to diagnosis of HC is not restricted to dentistry. The literature suggests that patients consult four or more physicians, including neurologists (3,5), over an average time of 8 years (range 1.3–21 years) to derive a diagnosis of HC (2). Misdiagnosis and inappropriate treatment have been attributed to the rarity of HC, as well as paucity of autonomic symptoms, medication overuse, clinical similarities with migraine, half-sided tension-type and cluster headaches, and dental or atypical facial pain (3,5–10). Moreover, HC may co-exist with other primary headache disorders (2), trigeminal neuralgia (11), or temporomandibular disorder (TMD) (12,13).
Recognizing the challenges involved in the differential diagnosis related to painful conditions presenting in the trigeminal nerve distribution (i.e. the head/face), it is important that both medical and dental professionals are familiar with prevalence of HC, patient characteristics, symptom overlap and association with other craniofacial conditions. Therefore, the aims of our case series were to provide patient characteristics and clinical features of HC pain, comorbid conditions, and treatment outcomes in patients presenting to an orofacial pain clinic.
Methods
We performed a retrospective record review of all patients seen in the TMD & Orofacial Pain Clinic at the University of Minnesota School of Dentistry from 1 October 2015 until 25 August 2017. Approval to conduct this study, #1612E02041, was provided by the Human Subjects Committee of the University of Minnesota Institutional Review Board.
Inclusion criteria were diagnosis of HC coded using ICD-10 at the initial visit, and diagnosis confirmation during at least one following visit. Patients were evaluated and diagnosed by either or both board-certified orofacial pain practitioners or neurologists. HC diagnostic criteria proposed by ICHD-3 beta version of International Headache Society (IHS) classification (14) were used to guide the diagnostic work-up. Clinical records were examined to extract a documented comprehensive history, physical examinations, additional investigations, as well as follow-up to monitor patients’ symptoms and response to treatment. Descriptive statistics were used to summarize the data.
Results
HC prevalence and diagnostic work-up
Over the 23-month period, 1617 new patients were seen in our clinic, and eight were given a diagnosis of HC. Six patients met the selection criteria, with one patient lost to follow-up after the initial evaluation and one not fulfilling the IHS indomethacin-related diagnostic criteria at follow-up, and thus excluded from this review (Figure 1). Neurological, otorhinolaryngological, and dental evaluations were non-contributory in all patients except for hyperesthesia and allodynia in the region of perceived pain. All patients, except for one patient (Table 1, patient #3), had records of having a brain magnetic resonance imaging (MRI) with no significant findings.
Flow chart describing the dispositon of consecutive eligible patients. Hemicrania continua patient- and pain-related characteristics, comorbid conditions, and treatment outcomes. * ø: “no” or “none”; D/C: discontinued due to intolerable adverse effects. SPG: sphenopalatine ganglion; TMD: temporomandibular disorder; TN: trigeminal neuralgia; CVD: cardiovascular disease; RA: rheumatoid arthritis; PTSD: post-traumatic stress disorder.
Referral source and diagnostic delay
Patients were referred from a general dentist (1), endodontist (1), primary care physician (1), and neurosurgeon (3). Patients consulted at least one, and up to six, health care provider(s) (average = 3.7 ± 2.1; median = 3.5). Our clinical notes described previous evaluations and treatments by a general dentist (1), endodontist (1), orofacial pain specialist (1), primary care physician (1), nurse practitioners (2), otolaryngologist (1) neurotologist (1), ENT surgeon (1), neurologists (2), neurosurgeons (3), immunologist (1), physical therapists (3), health psychologist (1), as well as a team management in a pain center (1) and an emergency room admission (1). Average time to diagnosis of HC was 3 ± 3.5 years (median = 2 years, range = 0.5–10 years).
Age, gender, pain complaint
Four patients (4/6) presented to our clinic with the chief complaint of “facial pain”, while one of the patients (1/6) presented with “toothache” and one (1/6) with “jaw pain”. All of them were Caucasian females with mean age of 55 ± 10.5 years (median = 58; range = 41–69).
Pain characteristics
The pain characteristics included mostly continuous (unremitting to remitting ratio 2:1), strictly unilateral (right to left ratio 1:1), with one patient experiencing pain within only the V1 distribution (ophthalmic), three patients within the V1 + V2 distributions (ophthalmic and maxillary), and two patients within the V1 + V2 + V3 distributions (ophthalmic, maxillary, and mandibular) (Figure 2). The pain was perceived in periorbital and temporal regions by 4/6 and 5/6 patients respectively and 3/6 described ipsilateral intraoral pain (2/6 in the mucosa and 2/6 in the teeth). On average, the patients rated the intensity of their baseline pain as moderate (mean = 5 ± 3/10, median = 5/10; range = 1–9.85/10) and exacerbations as severe (mean = 9 ± 1/10, median = 8.5/10, range = 5–10/10). The duration of the latter ranged from seconds to days. Frequency data was not recorded consistently, resulting in data on five patients having exacerbations more than once daily. Jaw function was an aggravating factor for four out of six patients. Three patients reported that the pain disrupted their sleep. All of the patients described a combination of painful sensations. Pain quality features for the background pain included predominantly pressure (3/6) and dull pain (2/6). Burning was used to describe either the baseline pain or pain exacerbations by two patients, while “throbbing” was the most frequent (4/6) pain description for the attacks. One patient who reported shooting baseline pain was given the diagnosis of HC at the Mayo Clinic (Rochester, MN), presenting to our clinic with the chief complaint of a flare up of the dull and achy TMD-related pain. Other less common pain quality characteristics included “stinging”, “twitching” pain, and “numb” sensations as well as “jabs and jolts”. Lacrimation was the most common autonomic symptom (6/6), followed by rhinorrhea (3/6). Other common associated symptoms included: Photophobia (4/6), nausea/vomiting (3/6), sensation of facial warmth or swelling without their visible manifestations (3/6), allodynia on the ipsilateral side of the face (2/6), blurry vision (2/6), and a sensation of a foreign body in the eye (2/6) (Table 1).
Number of patients presenting pain within each nerve distribution. Pain 100% unilateral R:L ratio 1:1.
Comorbid diagnoses
Five out of six patients’ presentations were complicated by multiple (>2) medical and comorbid diagnoses. All of the patients were diagnosed with painful TMD (i.e. myofascial pain with or without TMJ arthralgia). One patient reported successful TMD treatment by an orofacial pain practitioner prior to onset of HC, which was subsequently diagnosed by a neurologist at Mayo Clinic (as mentioned above). Three patients described neck pain, two reported preceding diagnosis and treatment for trigeminal neuralgia, two had a history of craniotomy, and two reported history of trauma to the head or neck, two had fibromyalgia, two described medication overuse, two had depression, anxiety and/or PTSD, and one was diagnosed with chronic migraine in addition to HC. Of the three patients who complained of an intraoral pain, one had a comorbid herpes zoster infection and one an odontogenic/periodontal pathology. A complete list of accompanying conditions is presented in Table 1.
Treatment outcomes
Most (3/6) patients responded to indomethacin dose of 150 mg/day. Adverse effects were uncommon (2/6) and included diarrhea and vomiting, managed with long-term misoprostol 200–800 mcg/day. Due to intolerable side effects, one patient had to remain at 75 mg/day of indomethacin and experienced partial pain relief. One patient reported complete pain relief at 225 mg/day, with the effective maintenance dose of 175 mg/day. Even though indomethacin was effective in all patients, four of them needed add-on treatment options to provide absolute and protracted headache control at a tolerable indomethacin dose (Table 1). In addition, management of the comorbid pain conditions was provided. Overall, taking into consideration all care provided, patient’s perceived pain reduction was 90 ± 8% (median = 92.5%, range = 80–100%).
Discussion
To the best of our knowledge, besides three individual case reports (7,13,15), this is the first case series providing group-wise data on HC patients seen in an orofacial pain setting. Our data suggests that such patients present to orofacial pain practitioners having HC and seeking care for pain that they describe in terms other than “headache”, with the most common complaint being “facial pain”. While HC is described as being a rare disorder, it is not a clinically insignificant condition in our orofacial pain clinic population with a prevalence of about four HC patients per 1000 new patients evaluated. Our HC patient population was female, rather than a more even distribution of 1:2 typically described (2), with a diagnosis occurring in their fifth decade of life as opposed to the third or fourth decade (2). The differences we observed in gender and age characteristics seem to be small, and could be explained by our case series being small in number.
The pain characteristics reported by our patients were similar to those described in previous reports in terms of the pain frequency, intensity, duration of exacerbations, laterality, associated and autonomic symptoms, nocturnal exacerbations, and peculiar ocular irritation. Although autonomic symptoms are expected to be absent in about 25% of cases, all of our patients reported noticeable parasympathetic activation, also witnessed by their family members, work colleagues, or their physician/dentist. While articles do not often report on pain quality, and it is not a criterion within the IHS classification, we found commonality with several patients describing their pain as dull pressure on the background and throbbing during the pain attacks. Interestingly, our patients also used additional descriptors to communicate the blend of sensations they experience, ranging from the feelings of numbness and discomfort to stinging, twitching, and shooting pain. There have been no previous records of HC presenting as a burning pain, which was a common complaint across the patients in our case series. Although HC may affect any part of the head and neck (16), V3 involvement has not been well documented in the literature (4) (possibly with the exception of the auriculotemporal branch supplying innervation to the temple). However, a third of our patients reported HC pain in all three branches of CN V, including the lower third of the face, during both the continuous background pain and its exacerbations. One patient complained of pain primarily in the maxillary teeth, spreading to the V1 distribution only during the exacerbation phases. Jaw function has not been reported to exacerbate the HC pain, but in our sample various functions of the jaw explicitly aggravated the patients’ HC headache even when care was taken to distinguish TMD pain from HC headache. Therefore, besides being a rare disorder, the inconsistent reporting of pain characteristics can easily confuse an inexperienced clinician.
Comorbid orofacial pain conditions are known to be common among patients presenting for care, such as migraine headache and TMD pain (17,18). HC case reports/series often lack information about overlapping comorbid pain conditions, seemingly omitting this level of detail and focusing on the headache presentation alone. A case report on an HC patient from another orofacial pain clinic (7) did mention a physical examination finding of “some mild” pain in the ipsilateral masseter, temporalis and suboccipital muscles elicited by palpation. However, it did not elaborate on whether the patient had a history of TMD besides the non-contributory CT findings, whether the palpation duplicated the chief complaint or showed referral pattern, whether the comorbid TMD diagnosis was given, or whether it was thought to be allodynia associated with HC. In our series of HC patients, we observed multiple other orofacial pain conditions co-existing with HC but deemed to be distinct because these various pain conditions had different exacerbating factors and responded independently to treatment. Underreporting of simultaneous presence of various orofacial pain conditions, which suggests an uncomplicated clinical presentation, may be another factor in why HC is challenging to diagnose. It is important to point out that a patient reporting “shooting” pain, suggestive of trigeminal neuralgia, was not the one with a comorbid disorder of trigeminal neuralgia in our case series (see Table 1). Similar to our experience, two cases of HC with concomitant TMD have been described by a neurologist (12) and dentists (13) when initial treatment for either one of the disorders provided only incomplete remission of the pain. To achieve adequate pain control, both comorbid pain disorders need to be diagnosed and treated to avoid a situation where only partial pain control is achieved, leading to patient perception of treatment failure when only one of the pain disorders is addressed. Moreover, given that most patients reach the HC diagnosis after they have already consulted multiple care providers, it is reasonable to treat the co-existing orofacial pains simultaneously rather than sequentially. Such an approach would eliminate further diagnostic quest, minimize care-seeking behavior, and ultimately arrest pain chronification though the central facilitation of multiple nociceptive inputs in the trigeminal system.
In our case series, two patients had a history of head trauma and two patients had a history of craniotomy. Yet, none of these patients had temporal association with the time of onset of headache close enough to meet the diagnostic criteria for the secondary HC. It is important to point out that, despite the expected self-limiting nature of the post-traumatic headache (19), these patients had not experienced evident pain relief or previous treatment success prior to the diagnosis and management in our clinic. Although identifying the possible traumatic causation of HC could potentially shed some light on the pathophysiology of the condition, the existence of post-traumatic headaches is debatable (20,21), and the relevance of the diagnosis for the clinical decision-making or treatment approach seems questionable at the present time. Post-operative HC-like headache has been described (22), but there appears to be no report of HC-like headache developed post-microvascular decompression, or acoustic neuroma surgery (23).
Issues with the diagnostic value of indomethacin response have been repeatedly raised in the literature (24). They include cases with all clinical features of HC but response to indomethacin (25); a possibility of misdiagnosis of HC that responded to other medications before administration of indomethacin (26); and therapeutic effect of indomethacin in a number of other headache disorders (26,27). Given that indomethacin belongs to the group of NSAIDs, which are commonly used for inflammatory and musculoskeletal pains, it would be expected that they would alleviate pain associated with other craniofacial disorders. Although three cases of HC presenting as or with TMD have been described by dentists (4,13), the reports lacked elaborate patient and pain characterization, comprehensive diagnostic work-up, or adequate timeline to assess TMD treatment response when ruling out TMD as the sole cause for the headache pain, and attributing it to HC based primarily on the response to indomethacin. It could potentially lead to HC over-diagnosis in cases of other chronic continuous orofacial pain, such as TMD. An issue of over- and misdiagnosis of HC may arise when a practiotioner is not trained to recognize and treat orofacial pain of different origins or in the absence of brain imaging, thorough history, and physical examination. Likewise, lack of the response to indomethacin should not indicate the absence of HC. Therefore, we believe that indomethacin response should be utilized to help separate HC from some other disorders, but it should not be the main determinant of the HC diagnosis. In the light of our outcomes treating patients with partial response to indomethacin, it is important to note that a more optimal pain control was achieved when the comorbid conditions were addressed. Therefore, it is possible that cases of indomethacin-resistance reported in the literature could be a result of potential untreated comorbidity.
Although alternative treatment options have been described in patients unable to tolerate indomethacin long term (28), efficacy of second-line treatment options for headaches that are phenotypically compatible with HC but refractory to indomethacin has not been reported. In our case series, gabapentin, topiramate, verapamil, amitriptyline, diazepam, short-term oral corticosteroids, intra- and extraoral botulinum toxin injections, and self-administered application of lidocaine to the sphenopalatine ganglion via an intranasal approach were used to successfully manage the HC symptoms in patients with incomplete response to indomethacin.
A limitation of our study is that it is a retrospective case series without explicitly standardized data collection and treatment protocols across different providers, with an inherent possibility of recall bias. In addition, how much HC-like symptoms are attributed to just HC is difficult to estimate in the presence of the long and complex medical history and a number of comorbid conditions. Combinations of medications were used in the individual patients with comorbid conditions; therefore, the effect of the association between medication response and HC might not be absolute. Treatment success is also difficult to separate from non-specific and placebo effects, as well as from the natural course of the disease and regression to the mean.
Nevertheless, the strength of our study is that we provide a detailed description of HC patients presenting to an orofacial pain clinic setting. They differ from those typically reported from headache and neurology clinics in how they present their pain complaint, as well as in their complexity from the diagnosis and treatment perspective due to the comorbid pain conditions. As orofacial pain practitioners, we have extensive experience diagnosing and treating both HC and other orofacial pain disorders, such as TMD, trigeminal neuropathic pain, and other headache disorders; and therefore feel comfortable that comorbid pain conditions were adequately addressed accordingly. Finally, we report on our multimodal treatment success and set forth a possible explanation for partial indomethacin response in HC patients reported in the literature.
Conclusions
HC is an uncommon – but not clinically insignificant – disorder presenting to our TMD and orofacial pain clinic, with the characteristics of HC patients in our clinic being similar to published characteristics. The stark difference in presenting HC symptomology in our clinic consists of the pain location in the V3 distribution of the trigeminal nerve and the burning quality of the HC pain. Symptom presentation and co-morbid pain disorders likely contribute to the difficulty in diagnosing and treating patients with HC. Lack of awareness about HC, symptom overlap and complicating comorbid diagnoses can result in a high rate of misdiagnosis and mismanagement. It is therefore necessary to recognize a possibility of such comorbidity, tease apart the symptoms presented by the patients, and identify the possible multiple sources of pain to provide the complex treatment regimen.
Clinical implications
Patients with hemicrania continua (HC) are encountered in TMD and orofacial pain clinics. They present with the chief complaint of “facial” or “jaw” pain as opposed to “headache”. Comorbid orofacial pain disorders and symptom overlap may result in misdiagnosis and mismanagement of HC. A multimodal approach to address the co-existing orofacial pain disorders is essential for treatment success to be achieved.
Footnotes
Acknowledgments
The authors would like to thank Estephan Moana-Filho for his valuable contributions during manuscript preparation.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.