Facial epicrania fugax: A prospective series of eight new cases

Introduction

Epicrania fugax (EF) is a primary headache of recent description whose main feature is the dynamic character of the pain. It was first described in 2008 by Pareja et al as brief episodes of stabbing or electric pain with its origin in a fixed area of the posterior scalp and rapid forward radiation to reach the ipsilateral forehead, eye or nose in one or a few seconds (1). Two years later, a backward variant of EF was identified, with the pain starting in the forehead, the eye or the nose, and quickly moving in the opposite direction (2). EF pain typically migrates across the territories of different nerves in a linear or zigzag trajectory. Some patients have autonomic signs and symptoms, and some have triggers. Between attacks, a mild pain or tenderness may persist at the stemming area. The frequency of EF paroxysms ranges from a few episodes per year to numerous episodes per day (3–7).

In 2013, EF was classified as a primary headache in the Appendix of the International Classification of Headache Disorders, 3rd edition, beta version (ICHD-3 beta) (8). Two years later, a facial pain with EF features was reported in five patients. Pain paroxysms moved from the lower face up to the forehead or the scalp following a linear trajectory across different dermatomes. Three patients had ocular or nasal autonomic accompaniments, and three had triggers. Between the paroxysms, two patients had transient or continuous pain at the facial area where the pain started. This clinical picture was proposed as a facial variant of EF (9). We aim to report eight new cases having an EF-type of pain with facial location, and thus contribute to the characterization of this emerging type of pain.

Patients and methods

We considered all patients attending the Headache Unit in a tertiary hospital from January 2015 to January 2016. We identified eight cases of brief dynamic pain paroxysms with EF features, with the pain moving either upwards or downwards through different dermatomes of the face. For each patient we recorded all relevant demographic and clinical data, including sex, age, age of onset, prior history of headaches, trajectory and duration of the pain, pain quality and intensity, associated symptoms, possible triggers, as well as treatment and clinical course. All patients were asked to clearly depict the trajectory of the pain and the remaining clinical features during a symptomatic period. We accomplished a complete physical and neurological examination in all of them. Brain magnetic resonance imaging (MRI) was obtained in all cases, including fast imaging with steady state acquisition (FIESTA) sequences for the assessment of neurovascular compression of the trigeminal nerve. MRI studies were evaluated independently by two radiologists with more than 20 years of experience in neuroradiology.

Results

Of the eight reported patients, seven were women and one was a man. The mean age was 76.1 years (standard deviation (SD) 11.3; median 77; range 65–83 years), and the mean age at onset was 63.3 years (SD 17.6; median 65; range 44–73 years). Their main demographic and clinical characteristics are shown in Table 1. Only one patient suffered from another headache, which was diagnosed as episodic tension-type headache and had no temporal relationship with the paroxysms of facial pain.

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Table 1.

Demographic and clinical characteristics of this series of patients with facial epicrania fugax.

Patient no.	1	2	3**	4	5	6	7	8
Sex	F	F	F	F	F	M	F	F
Age	80	83	73	74	75	65	79	80
Age at onset	66	68	64	44	73	65	69	60
Other headaches	–	Tension-type	–	–	–	–	–	–
Side	L	R	R	R	R	R	L	R
Origin and trajectory (dermatomes)	Lower dental arch (V3) – Temple (V3) – Forehead (V1)	Lower dental arch (V3) – Cheek (V2) – Temple (V3)	Submandibular area (C2) – Jaw (V3) – Cheek (V2)	Mandibular angle (C2) – Temple (V3) – Vertex (V1)	Lower dental arch (V3) – Upper lip (V2) – Nose (V1) – Forehead (V1)	Upper dental arch (V2) – Periorbital (V1) –Forehead (V1)	Cheek (V2) – Upper lip (V2) – Lower dental arch (V3)	Forehead (V1) – Periorbital (V1) – Cheek (V2) – Chin (V3)
Duration (seconds)	7–10	3–4	2	1	1	1–2	3–5	5–10
Frequency (per day)	Uncountable	2–3	Uncountable	Uncountable	> 20	2–3	Around 20	2–3
Direction	Upwards	Upwards	Upwards	Upwards	Upwards	Upwards	Downwards	Downwards
Quality	Electric	Burning/electric	Electric	Stabbing	Stabbing	Stabbing	Stabbing	Electric
Intensity*	8	9	9	10	9	10	10	10
Autonomic signs	Lacrimation, ptosis	–	Conjunctival injection, lacrimation	–	Rhinorrhoea	–	–	Lacrimation
Triggers	Touch, cough, chew	Touch, chew	Touch, orofacial movements, extreme temperatures	Touch, speak, chew	Touch	Touch	Touch, speak, chew	Touch, chew, speak, air
Postictal pain at the stemming area	–	Moderate pain (minutes-hours)	–	–	Mild pain (minutes)	–	Severe pain (hours)	Mild pain (hours)
Neurovascular contact on the symptomatic side	Compression (SCA over V)	Contact (SCA over V)	Compression (SCA over V)	–	–	Compression (SCA over V)	–	–
Spontaneous remissions (duration)	7 years	–	3 years	10 years	–	–	–	–
Current therapy	PGB 50 mg b.i.d. +  LTG 50 mg b.i.d.	PGB 75 mg t.i.d.	ESL 1600 mg q.d. +  GBP 400 mg t.i.d.	ESL 400 mg q.d.	GBP 300 mg t.i.d.	PGB 150 mg b.i.d. +  LTG 50 mg b.i.d.	CBZ 400 mg t.i.d. +  LTG 50 mg t.i.d. + PGB 75 mg t.i.d. + LCS 100 t.i.d.	OXC 300 mg t.i.d. +  LCS 150 mg t.i.d. +  BoNTA 7 × 5U
Response to therapy	Complete	Complete	Complete	Complete	Complete	Complete	Partial	Almost complete

All patients presented with strictly unilateral pain paroxysms in the face, six of them on the right side and two of them on the left (Figure 1). In all cases, the pain described a linear trajectory across different dermatomes, with either upward (n = 6) or downward (n = 2) radiation. In the patients with upward radiation, the pain stemmed from the lower dental arch –V3 dermatome (n = 3), the submandibular and mandibular angle –C2 (n = 2), or the upper dental arch –V2 (n = 1), and moved up to reach the forehead –V1 (n = 3), the vertex –V1 (n = 1), the cheek –V2 (n = 1), or the temple –V3 (n = 1). In the patients with downward radiation, the pain started at the forehead –V1 (n = 1) or the cheek –V2 (n = 1) and moved down to end at the chin –V3 (n = 1) or the lower dental arch –V3 (n = 1) . The mean duration of the paroxysms was 3.6 seconds (SD 5.9; median 3; range 1–10 seconds), and the average intensity of the pain was 9.4 on a numerical point scale ranging from 0 to 10 (SD 1.5; median 9; range 8–10). Pain quality was described as electric by four patients, stabbing by three patients, and both burning and electric by one patient. The frequency of episodes had high intra-individual and inter-individual variability, ranging from 2–3 to uncountable attacks per day. OPEN IN VIEWER

Four patients presented with autonomic phenomena associated with the pain, and in all of them the pain crossed the orbital or periorbital area: one had both lacrimation and ptosis, one had lacrimation and conjunctival injection, one had lacrimation alone, and a last one had rhinorrhoea. All patients identified triggers, which included touching the involved area (n = 8), chewing (n = 5), speaking (n = 3), coughing, extreme temperatures, strong wind, and orofacial movements (n = 1). Half of the patients had remaining postictal pain at the stemming area, which was mild in two cases, moderate in one, and severe in another, and lasted from minutes (n = 1) to hours (n = 3). Cranial MRI with FIESTA sequence showed neurovascular compression of the superior cerebellar artery with imprinting over the trigeminal nerve on the symptomatic side in three patients, and neurovascular contact without imprinting in one additional patient.

All patients required therapy for their pain, and all of them were treated with antiepileptics. Three patients were pain-free on monotherapy (pregabalin, n = 1; gabapentin, n = 1; eslicarbazepine, n = 1), while the remaining five patients had combination therapy with several drugs (including pregabalin, gabapentin, eslicarbazepine, lamotrigine, lacosamide, carbamazepine and oxcarbazepine). One of the patients obtained additional benefit from the injection of onabotulinumtoxinA 35 U around the stemming area. Seven patients had a complete or almost complete response, and one patient had partial relief. The clinical course was quite heterogeneous. Three patients had long-lasting remissions with no need for therapy, but eventually had a recurrence.

Patient three experienced some changes in her clinical features. Nine years before assessment, she had brief pain paroxysms with origin at the right submandibular area (C2), describing a linear trajectory across the temple (V3) to end at the parietal parasagittal region (V1). The pain was extremely intense (10 out of 10) and electrical in quality, and occurred with a frequency of five to tens of episodes per day, commonly with triggers. There were no autonomic accompaniments. MRI with FIESTA sequences revealed a neurovascular compression with imprinting of the superior cerebellar artery over the trigeminal root on the symptomatic side. The pain was refractory to several drugs (gabapentin, carbamazepine, tiapride), and she underwent microvascular decompression surgery with the Janetta procedure. After the intervention, she became asymptomatic for the next three years. Then the pain recurred, and its features changed. It started at the same point (right submandibular area) with a new trajectory across the jaw (V3) to the cheek (V2). Moreover, she started to have associated autonomic signs (conjunctival injection and lacrimation). She became asymptomatic with eslicarbazepine and gabapentin.

Discussion

We describe a series of eight patients presenting with dynamic facial pain paroxysms of short duration, starting at a fixed point in the face and moving up or down with a linear trajectory across different dermatomes. Based on previous descriptions, this may correspond to the facial variant of EF. Six cases had an upward radiation resembling the former description of facial EF (9). However, in two patients the pain paroxysms had an upper origin and moved downwards to the lower face. This might be considered a new type of facial EF with downward radiation, just as the backward type of EF was recognized after the original description with forward radiation (2).

Like other primary headaches – such as migraine and the trigeminal autonomic cephalalgias (10–12) – EF may occasionally appear as facial pain. When comparing the 13 reported cases of facial EF from the previous series (9) and the current one with the published cases of classic EF (with forward or backward radiation across one hemicranium) (7), we find an older age at onset in the facial variant (63.3 versus 45.2 years) and a higher female preponderance (a ratio of 7:1 versus 1.7:1). All patients with facial EF described strictly unilateral pain paroxysms with a linear trajectory, while 27.1% of the patients with the classic form had shifting sides or simultaneous paroxysms on both sides of the head, and 5.7% described a zigzag trajectory. Pain quality and duration were similar, but pain intensity was consistently severe in the facial type (range 8–10 out of 10), in contrast to the classic form in which it was moderate to severe (range 3–10 out of 10). Triggers have been identified in all patients with EF of facial location, a higher proportion than that of the classic type, which was 23.9%. Half of the patients with facial paroxysms had associated autonomic accompaniments, while they were present in 34.3% of patients with EF at other locations (42% in forward EF, and 15% in backward EF). Thus, autonomic symptoms seem more likely when the periorbital area is involved. Postictal disturbances at the stemming area were similar among all patients. The natural history of EF is similar in all variants. A significant number of patients experience spontaneous remissions and long periods without recurrences after withdrawal of treatment. Drug therapy with antiepileptics seems to be effective in all types of EF.

Differential diagnosis of facial EF should be established with other craniofacial types of pain. Trigeminal neuralgia (TN) causes brief shocks of facial pain, usually triggered by touch or orofacial movements. However, the pain runs along one or more divisions of the trigeminal nerve (usually V2 or V3), and does not affect the C2 dermatome (13–15). This differs from facial EF, in which the pain moves vertically and may involve C2. Moreover, TN attacks may extend to more than one trigeminal branch months or years after onset in contrast to facial EF, in which the origin and trajectory of the pain remain constant on follow-up (13). An exception would be patient three, in whom the trajectory of the pain changed after the Janetta procedure, which could have modulated the characteristics of the pain through the manipulation of the trigeminal pathway. Otherwise, autonomic accompaniments are common in facial EF and are never prominent in TN (16). Distinguishing facial EF from terminal branch neuropathies may be easier, since their pain is located in the territory of the affected nerve and is commonly persistent (17–19). The same happens with nummular headache, in which a circumscribed rounded painful area is usually persistent, with or without exacerbations (17). As some patients with facial EF have autonomic accompaniments, SUNCT (short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (short lasting unilateral headache attacks with cranial autonomic features) should be considered in the differential diagnosis. However, SUNCT and SUNA episodes last longer, are characterized by more diffuse periorbital pain, and do not have the dynamic character that defines EF (20). Finally, primary stabbing headache is characterized by brief and well-localized pain attacks, which occasionally may change location giving a false illusion of pain movement, but never draw a linear trajectory along the cranium or the face (21).

The pathogenesis of EF remains unknown. There may be a peripheral origin of the pain, since pain attacks always start in a fixed area and may be triggered by different external stimuli. This peripheral generator could be superficial/epicranial (terminal branches of the occipital or trigeminal nerves), or could be located internally at the trigeminal nerve root. The recently reported case of an EF-type pain occurring after radiation therapy of a skull base meningioma may support a pathogenic role of the trigeminal root, at least in some cases (22). The latter may be supported by the high prevalence of neurovascular compression with imprinting over the trigeminal root found in our series, which was 37.5% in comparison with the prevalence in the asymptomatic population, which is approximately 1 to 5% (23,24). Furthermore, in patient three the trajectory of the pain changed and autonomic symptoms appeared after the Janetta procedure, thus reinforcing the role of the trigeminal pathway in the pathogenesis of EF.

After initiation of the pain, transmission may be due to central and/or peripheral mechanisms. It has been proposed that pain irradiation could be due to ephaptic or paracrine transmission through terminal sensitive fibres. Anyhow, there are several facts that support a central component. First, the trajectory of the pain across different dermatomes, not only facial but also cervical, could be explained by the anatomical and functional convergence of trigeminal and cervical afferents at the trigeminal nucleus caudalis (25). In addition, some patients have autonomic symptoms, which probably involve a trigeminofacial reflex (26). Interestingly, patient three started having autonomic features – which were previously absent – after Janetta’s intervention. This surgical procedure could have modified the trigeminofacial loop, with the subsequent emergence of autonomic symptoms.

In conclusion, we report eight patients presenting with facial pain paroxysms that fulfill the characteristics of EF of facial location. This reinforces the facial location as a variant of EF, and contributes to enriching the differential diagnosis of facial pain. In addition, two of the cases in this new series presented with downward radiation, thus extending the phenotype of facial EF. The high prevalence of neurovascular compression with imprinting over the trigeminal root might support a peripheral component in the pathogenesis of EF, although further research is needed to clarify its role.

Clinical implications

Pain paroxysms consistent with a facial variant of epicrania fugax (EF) are reported in eight patients, with the pain crossing dermatomes in either the upward or downward direction.