Abstract
Background
Epicrania fugax consists of brief paroxysms of pain, which radiate in a line or in zigzag trajectory across the surface of the scalp or the face.
Methods
A prospective, descriptive study was performed in five patients presenting with an epicrania fugax-type pain with extracephalic irradiation.
Results
All patients were women, and the mean age at onset was 59.8 (standard deviation, 10.9). They had unilateral paroxysms of electrical pain starting at a particular point in the head (parietal, n = 3; vertex, n = 1; frontal, n = 1) and rapidly radiating downwards in a lineal trajectory to reach extracephalic regions (ipsilateral limbs, n = 2; shoulder, n = 2; low neck, n = 1) in 1–3 seconds. Pain intensity was moderate or severe. Three patients had nummular headache at the point where the paroxysms originated. One patient had spontaneous remission, and four patients achieved complete or almost complete response with therapy (onabotulinumtoxinA, n = 2; indomethacin, n = 1; amitriptyline, n = 1; lamotrigine, n = 1).
Conclusion
The spectrum of epicrania fugax may include paroxysms with extracephalic irradiation. The propagation of pain beyond the head and the face supports the involvement of central mechanisms in the pathophysiology of this entity.
Keywords
Introduction
Epicrania fugax (EF) is a primary headache disorder included in the appendix of the International Classification of Headache Disorders, 3rd edition (ICHD-3) (1). It consists of brief episodes of electric or stabbing paroxysmal pain running across the surface of the head through different nerve territories with a linear or zigzag trajectory. The dynamic topography has been pointed out as a distinctive attribute that can differentiate EF from other epicranial headaches and from the neuralgias or painful neuropathies. To date, more than 70 cases have been reported in the literature (2).
The most frequent and first described variant is forward EF, in which the pain arises from a localized area of the posterior scalp and moves anteriorly (3). Backward EF, in contrast, starts at the forehead, eye or nose and moves posteriorly (4). According to the ICHD-3 description, the paroxysms are strictly unilateral, although some patients have shifting sides. The attacks are normally spontaneous, but some patients identify triggers such as touch stimuli at the stemming point. During EF paroxysms, some patients have ipsilateral autonomic signs. Between attacks, some pain or tenderness may persist at the point of origin (2,3,5) or, more rarely, along the route of pain propagation (6).
Although most patients may be included among forward or backward EF, there have been some reports of patients with a paroxysmal EF-type pain whose topographical features deviate from the current diagnostic criteria of the ICHD-3. Among these atypical cases, one had a sagittal trajectory (7), four had coronal trajectories (8), and one had paroxysms running in multiple directions (9). A facial variant of EF has also been described in 15 patients, with the pain crossing several dermatomes of the face in an upward or downward direction (10–12). Yet, until very recently, all the described cases were circumscribed to trigeminal or occipital nerve territories. Lately, one case of a possible EF pain with an extracephalic trajectory has been reported; in this patient, the pain started at a point on the prethoracic area and reached the head surface with a lineal trajectory (13). Here we describe five additional patients with paroxysmal episodes of EF-type pain stemming from the head and radiating to extracephalic areas. We propose that this clinical picture could correspond to a new subtype of EF.
Patients and methods
We performed a prospective descriptive observational study of five consecutive patients attending the headache outpatient clinics of two tertiary hospitals in Spain from January 2014 to December 2019. Participant centres were Hospital Clínico San Carlos de Madrid (Patients 1–3) and Hospital Clínico Universitario de Valladolid (Patients 4–5), with a reference population of 600,000 and 280,000 people, respectively.
The study population encompassed patients with an EF-like pain that fulfilled the following inclusion criteria: i) recurrent head pain attacks lasting 1–10 seconds; ii) pain moving with a constant linear or zigzag trajectory across the cranial surface; iii) pain commencing and terminating in the distribution of different nerves; iv) irradiation of the pain to extracephalic areas, and v) symptoms presenting during at least 1 month. We excluded patients unable to describe the characteristics of the pain, patients with changing descriptions of pain phenotype, patients with a secondary headache according to the ICHD-3 or patients unable to differentiate it from other coexistent primary headaches. Recruitment was non-probabilistic by opportunism.
A detailed history was obtained in all cases. We recorded demographic data such as current age, gender and age at onset, as well as the time of evolution. We gathered information about prior medical history and history of other headache disorders. Patients with other primary headache disorders were asked to clearly differentiate between the previous and the current headache. Pain characteristics were collected in a systematic way, including pain quality, pain intensity on a 0–10 numerical rating scale (NRS: 0, no pain; 10, worst possible pain), the irradiation pattern, duration of episodes, frequency of paroxysms, and presence of any accompanying symptoms. The presence of triggers was also evaluated. To depict the irradiation of the pain, patients were asked to describe it in detail and to draw their pain trajectory on a model.
All the included patients underwent general and neurological examination, giving special attention to the area where the pain commenced. Blood tests including erythrocyte sedimentation rate (ESR), immunological screening and cranial magnetic resonance imaging (MRI) were obtained in all cases. When considered to be indicated for excluding other conditions, patients underwent cervical MRI, electroencephalogram (EEG), electromyogram (ENG/EMG) or somatosensory evoked potentials (SSEP).
The prescribed treatments were recorded as well as the patients’ response in terms of frequency and intensity of the episodes. The treatment was not established beforehand but was chosen by the attending physician based on the individual evaluation of each patient. All patients agreed to participate and signed an informed consent form.
Results
Among a total of 99 patients presenting with symptoms suggestive of EF during the study period, five met the inclusion criteria. All patients were female. The mean age at onset of the pain was 59.8 (standard deviation, 10.9). Table 1 summarizes the demographic and clinical features of the patients. Figure 1 shows the trajectory of pain in each case.
Demographic and clinical features of the five patients with EF-type paroxysms with extracephalic irradiation.
*Numerical rating scale (NRS): 0, no pain; 10, the worst imaginable pain.
bid: twice a day; EF: epicrania fugax; NH: nummular headache; OnabotA: onabotulimtoxinA; qd: once a day; qtly: quarterly; tid; three times a day.
Trajectory of pain in the five patients. (a) Left parietal scalp to third finger of left hand, sometimes continuing to second toe of left foot. (b) Left parietal scalp to ipsilateral shoulder. (c) Vertex to first toe of left foot and/or dorsum of left hand. (d) Right frontal area to right low neck. (e) Right parietal scalp to ipsilateral shoulder. Red circles represent areas of nummular headache.
Patient 1 was a 69-year-old female, with a history of hypertension, dyslipidemia, bronchial asthma, rheumatoid arthritis, chorioadenoma destruens and migraine with aura. From the age of 65, she experienced episodes of paroxysmal pain, which always stemmed from the left parietal region and radiated linearly along the left side of the neck, the shoulder and the dorsal area of the arm and forearm to reach the third finger of the left hand in just 1 second. About one-fifth of the episodes continued with the pain radiating along the left side of the trunk, thigh and leg, and the dorsal aspect of the left foot towards the second toe (Figure 1(a)). This irradiated pain had electrical quality and severe intensity (8–9 on the NRS). The frequency was quite variable, from one attack per month to five attacks per day. After each paroxysm, a moderate-to-severe pressing pain (6–7 on the NRS) persisted in a well-defined 2-cm circular area located at the point of origin during 3–5 minutes. This area remained tender between the paroxysms and had 1–2 episodes per week of circumscribed pain with pressing quality and an intensity of 3–4 on the NRS lasting up to 24 hours. Physical examination revealed allodynia and hyperalgesia within this area, as well as a 0.7-cm area of skin depression in the centre, which was consistent with nummular headache (NH). Blood tests at the time of assessment did not show any relevant abnormalities. Cranial and cervical MRI, 4-hour video-EEG, EMG/ENG and PESS were also obtained, with normal results. Treatment was initiated with onabotulinumtoxinA (OnabotA) injections (30 U) in the NH area. Both the allodynia and the trophic changes decreased significantly while the localized pain was reduced to occasional stabs lasting seconds. The paroxysms of irradiated pain disappeared completely and did not recur during a 2-year follow-up. Throughout the follow-up, OnabotA injections in the NH area were repeated quarterly.
Patient 2 was a female, with prior history of hypertension, type-2 diabetes, dyslipidemia and bronchial asthma. At the age of 73, she started experiencing a circumscribed pain consistent with NH. This pain was located in a 5-cm round area over the left parietal scalp and occurred in episodes lasting several minutes 15 days per month. The quality of this pain was stabbing, and the intensity was severe (8 on the NRS). Examination of the symptomatic area revealed hypoaesthesia, erythema and local increase of temperature. One year after onset, NH disappeared after a single injection of onabotulinumtoxinA (40 U). Aged 75, the patient came to our office for a new type of pain presenting in brief paroxysms. The pain started in the same area and moved downwards in a linear trajectory to the left side of the neck and the left shoulder in 3 seconds (Figure 1(b)). For this new pain, the quality was electric, and the intensity was 9 out of 10. The paroxysms occurred once every other day for 1 month, always triggered by neck movements. At that time, physical examination was normal. Blood tests and cranial and cervical MRI were unremarkable. The patient was on indomethacin 25 mg three times daily for 1 month, and the paroxysms completely disappeared. Six months later, both the NH and the paroxysmal irradiated pain reappeared with the previous features. The nummular pain had daily frequency while the irradiated pain occurred 2–4 times per month. OnabotA injections (40 U) were performed every 3 months, with a complete response of both types of pain lasting 2–3 months after each procedure. Two years later all the symptoms disappeared, and the treatment was discontinued.
Patient 3 was a 46-year-old female with a medical history of parathyroid adenoma, treated with hemithyroidectomy, post-surgical hypothyroidism and migraine with aura. Three months before assessment, she started to experience paroxysmal episodes of pain always beginning in the vertex and rapidly radiating downwards in a linear trajectory through the left hemifacies, the front left side of the neck, the trunk and the left inferior limb, finally reaching the dorsal aspect of the first toe of her left foot in 2–3 seconds. More rarely (about 20% of the time), she had similar discharges also stemming from the vertex that moved linearly through her left upper limb towards the left dorsal aspect of her hand, either in isolation or in combination with one of the paroxysms that moved towards the foot (Figure 1(c)). Overall, she had 2–3 episodes per day. Pain quality was described as electric, and pain intensity was rated as 8–9 on the NRS. Physical and neurological exams were normal. Patient’s evaluation included blood tests, cranial and cervical MRI, 4-hour video-EEG monitoring – which coincided with one of the episodes – and ENG/EMG, all without relevant findings. She was first treated with amitriptyline 10 mg per day, with significant reduction of pain intensity (>50%) and pain frequency (to one episode per day). Amitriptyline was then raised to a dose of 25 mg per day, and pain frequency dropped to 1–6 episodes per month. The patient preferred not to withdraw the treatment during the 2 years of follow-up.
Patient 4 was a 59-year-old female, with a medical history of migraine without aura. When aged 50, she had 1–2 daily episodes of pain consistent with facial EF for 6 months. She described a lancinating pain of moderate intensity (5 out of 10) that stemmed from her right forehead and moved downwards to reach her right chin in 2–3 seconds following a linear trajectory. The symptoms remitted spontaneously. At the age of 58, she started to experience a paroxysmal pain of similar features. The pain also began at her right frontal region and descended through the right side of her face, but its path continued until it reached the lowest part of her neck (Figure 1(d)). Pain episodes lasted 2–3 seconds and occurred 2–4 times per week. Pain quality was electric and pain intensity was rated as 5 on the NRS. Around 25% of the episodes were accompanied by ipsilateral lacrimation. The patient was assessed 6 months after onset. Physical and neurological examination was normal. Blood tests and a cranial and cervical MRI were also normal. Pain episodes disappeared after starting treatment with lamotrigine 50 mg bid. Treatment was maintained without interruption over 1 year of follow-up.
Patient 5 was a 55-year-old female with a medical history of hypertension, type-2 diabetes and migraine without aura. At age 53, she began to feel a circumscribed pain in the right parietal region with features typical of NH. She described a continuous stabbing pain in a well-defined circular area, 4 cm in diameter, with an intensity of 5 on the NRS. Two years later, for 1 month, she experienced bursts of radiating pain. Those episodes consisted of an electrical pain of moderate intensity (5 out of 10) that stemmed from the NH area and moved along the side of the neck and the ipsilateral shoulder in a linear trajectory (Figure 1(e)) in just 3 seconds. The frequency was quite variable (1–20 episodes per day). The paroxysms remitted spontaneously, while the pain of NH persisted. Two months later, the physical exam only showed allodynia and hyperalgesia at the right parietal region within the painful area. Blood tests and cranial and cervical MRI did not show any abnormalities. The patient chose not to receive any treatment for her headaches, and the NH remained. However, she did not have new paroxysms of irradiated pain over 2 years of follow-up.
Discussion
Here we report five patients presenting with unilateral paroxysms of electrical EF-type pain starting in the head and rapidly radiating downwards to reach extracephalic regions. This clinical picture could not be accounted for by other conditions and might correspond to a new variant of EF.
Only one case of a possible EF pain with extracephalic manifestations has been described in the literature (13). Wang et al. reported a 76-year-old woman who had episodes of a lancinating pain that started at a point above the nipple in the left thoracic region and rapidly moved upwards in a linear trajectory along the ipsilateral neck, face, auditory canal and temporal region, reaching the parietal region in 2–3 seconds; a good response was achieved with carbamazepine. Our patients had a clinical picture with similar features, but the pain began in the head and followed a downward direction, finally ending in extracephalic regions. Otherwise, all our cases presented typical EF features, with pain moving through the territories of different nerves, linear trajectory and short duration of the episodes (1–3 seconds). Pain quality was electric, and pain intensity was moderate or severe, as described in most EF cases. It is known that EF may occasionally have autonomic accompaniments (2,3), and one of our patients had tearing with some of her pain episodes. Four patients required treatment, and they showed a good response to drugs previously used in EF (2,6,10,11).
The association of EF with other headaches is not rare, particularly with migraine and NH (3,6,14–18). It is therefore not surprising that four of our patients had a history of migraine and three had concomitant NH. There seems to be a close link between EF and NH. In patients in whom both headaches are comorbid, NH is the site of origin of the pain paroxysms of EF. This occurred in the three patients having NH in our series as well as in all published cases with the two conditions combined (6,14–16).
EF pathogenesis is still unknown. Initially, an epicranial origin was proposed, which would presumably affect some terminal branches of the pericranial nerves (3). This hypothesis would be in line with the frequent coexistence of NH. However, symptomatic cases of EF have been associated with intracranial lesions in the posterior fossa, including a radiotherapy-treated meningioma adjacent to the trigeminal root, a lateral medullary infarction and a cerebellar abscess (19–21). EF is probably not a restricted ‘peripheral’ or ‘central’ disorder, and the origin of the pain might be equally due to peripheral or central generators. What seems unlikely is that pain irradiation is due to purely peripheral mechanisms. The wide movement of some of the reported forms of EF with the pain crossing different structures of the head and the face would support a central pathogenesis. The cases described here have an even wider spread, with a pseudo-Lhermitte cranio-caudal extension, sometimes reaching the hands or the feet. Such a long pain irradiation might possibly be due to hyperexcitability and/or ephaptic transmission involving the pain pathways within the thalamus, brainstem and/or the spinal cord.
Our study is limited by the small sample size, the lack of objective biomarkers and the possibility that spontaneous remissions could influence the observed therapeutic response. Therefore, all the conclusions of the study should be interpreted cautiously. On the other hand, this is the first series described so far of an EF-type pain with downward extracephalic irradiation. Our description not only broadens the clinical spectrum of EF but also sheds some light on possible pathophysiological mechanisms of this polymorph entity. Future studies should try to identify objective biomarkers or changes occurring in the central nervous system of EF patients.
Clinical implications
Paroxysmal episodes of pain starting as epicrania fugax (EF) and having extracephalic irradiation are reported in five patients. EF with extracephalic irradiation might be a new variant of this disorder. The wide irradiation of the pain would support an essential role of central structures in the pathogenesis of EF.
Footnotes
Acknowledgements
This study was presented in part at the LXX Annual Meeting of the Spanish Neurological Society (Seville, Spain, November 20–24, 2018).
Patient consent
All the patients read and signed an informed consent.
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.
