Case report: Wallenberg’s syndrome,a possible cause of symptomatic epicrania fugax

Abstract

Background

Epicrania fugax has been described as a primary headache. Nevertheless, a symptomatic form was recently found in a patient with a skull base meningioma abutting the trigeminal nerve. Here we report on a patient with facial pain with the features of epicrania fugax occurring after Wallenberg’s syndrome.

Case report

A 53-year-old man suffered a right-sided dorsolateral medullary ischaemic stroke. Nine months later, he presented with brief electric shock-like paroxysms of pain stemming from the right eye and radiating to the ipsilateral forehead, the temple or the cheek in a zigzag trajectory. Some episodes were accompanied by ipsilateral conjunctival injection and eyelid oedema. Treatment with eslicarbazepine abolished the pain.

Conclusion

A pain with the features of epicrania fugax may be associated with medullary lesions. This finding suggests that the central trigeminal pathways and/or the spinal trigeminal nucleus may play an important role in the pathophysiology of this type of pain.

Introduction

Epicrania fugax (EF) is a headache disorder, the features of which have been in constant update since it was first proposed as a new syndrome by Pareja et al. in 2008 (1). The essential feature is the occurrence of dynamic painful paroxysms with a quick movement between distant points in different craniofacial dermatomes (2). The pain follows a linear or zigzag trajectory and, according to the direction of the pain, two variants (forward and backward) may be distinguished. During pain attacks, some patients have ocular or nasal autonomic accompaniments. In addition, some patients may experience interictal mild pain or tenderness at the site of origin (3). Initially, EF was described as involving the cranium; however, a facial location was later described (4,5).

In the Appendix of the International Classification of Headache Disorders, 3rd edition, beta version (ICHD-3 beta), EF was classified as a primary headache (2). Nevertheless, an EF-like phenotype was recently found in a patient who had received radiation therapy to a skull base meningioma that was compressing the trigeminal nerve (6). Here we report on a patient with a dorsolateral medullary infarct who later developed paroxysms of pain with features of EF.

Case report

A 53-year-old man, an active cigarette smoker with no other relevant past medical history, suffered a right-sided lateral medullary stroke caused by ipsilateral vertebral artery dissection. Brain magnetic resonance imaging (MRI) demonstrated the presence of an infarction in the right dorsolateral medulla as well as an absence of flow in the right vertebral artery (Figure 1). Nine months later, the patient presented with brief electric shock-like paroxysms of facial pain. The pain started in a fixed area over the right eye, and rapidly radiated to the ipsilateral forehead in a zigzag trajectory up to the hairline. Sometimes, the pain propagated in other directions, either to the temple or the cheek, also with a zigzag trail (Figure 2(a)). Pain quality was electric, and the intensity was 9 out of 10 on a numerical rating scale. These episodes lasted one second, and occurred three to four times a day without a clear circadian pattern. Occasionally, during attacks, the patient had associated autonomic symptoms consisting of ipsilateral conjunctival injection and eyelid oedema, without tearing or nasal congestion (Figure 2(b)). Between attacks, a stabbing pain persisted in the orbital and periorbital area at an intensity of 4 out of 10. Remarkably, painful stimuli over the left arm or forearm triggered some of the paroxysms. However, mechanical stimuli over the right orbital area or the face did not activate the pain.

Figure 1.

(a),(b) Coronal fat-saturated T2- weighted magnetic resonance imaging (MRI) (a) and axial fluid-attenuated recovery (FLAIR) MRI (b) demonstrating a hyperintense lesion in the right lateral and posterior medulla related to subacute ischaemic stroke. (c),(d) Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF MRA) demonstrating the absence of flow at the right vertebral artery.

Figure 2.

(a) Pain trajectories in our patient stemming from the right eye (V1) and radiating to the forehead (V1), the cheek (V2) or the temple (V3). (b). Ipsilateral eyelid oedema during a pain attack.

Physical examination revealed tenderness upon palpation of the periorbital nerves on the right side (supraorbital, supratrochlear, lacrimal and infraorbital). In addition, the examination showed persistent neurological sequelae of the stroke, including right Horner’s syndrome, multidirectional nystagmus, right facial hyperalgesia, left trunk and limb hyperalgesia, mild right central facial palsy, and mild right limb ataxia. A new MRI study showed the old medullary infarct but did not detect any new findings.

Anaesthetic blockades of the tender nerves provided the patient with pain relief for less than 24 hours. Oral treatment with lamotrigine and pregabalin was not effective. Long-term remission was eventually achieved with eslicarbazepine 800 mg per day. The effect was maintained during a four month follow-up, and an attempt to reduce the dose was followed by a recurrence.

Discussion

Central post-stroke pain is a recognized complication of dorsolateral medullary infarction. It usually starts within the first six months after stroke, and most frequently affects the ipsilateral periorbital region (7,8). Some patients feel a constant, boring, pain, while others describe a paroxysmal pain (8). Trigeminal neuralgia (TN) (9,10), short-lasting unilateral neuralgiform pain with conjunctival injection and tearing (SUNCT) (11), and even co-existent SUNCT and TN (12) have been described in patients who suffered Wallenberg’s syndrome. In our patient, the paroxysms of facial pain were most likely due to the previous medullary infarction, but pain features were suggestive of EF. Indeed, the pain had a dynamic character along the surface of the face moving with a zigzag trajectory and sometimes crossing the territory of different dermatomes (V1 to V2; V1 to V3). These features help to differentiate this patient’s syndrome from other headache disorders, namely TN and either SUNCT or SUNA (short-lasting unilateral neuralgiform headache attacks with autonomic symptoms). Although TN involving one or more dermatomes has been occasionally attributed to a brainstem infarction (9,10), the zigzag trajectory together with the presence of prominent autonomic symptoms are not characteristic of TN (2). Moreover, although some of the paroxysms of our patient had autonomic accompaniments and could meet the criteria for SUNA, the pain in SUNCT or SUNA does not move in a zigzag pattern (2).

The pathogenesis of EF remains unknown, and both peripheral and central mechanisms have been proposed (3). Although the first EF descriptions were thought to be idiopathic (1,3), a symptomatic form was later described in a patient with a skull base meningioma located next to the trigeminal nerve after radiation therapy (6). A peripheral generator may possibly be initiated by a trigeminal nerve injury of any origin, such as the compressive effect of the tumour or the radiation in the former case. A similar mechanism could have been responsible for the pain in those cases of EF in which a neurovascular contact has been demonstrated with appropriate MRI sequences (5). However, a central generator is also plausible, and the medullary lesion in our patient could illustrate this hypothesis.

There are two mechanisms proposed to explain facial pain after a dorsolateral medullary infarction. First, Fitzek et al. proposed that the pain arose from injuries of the trigeminal tract and nucleus with sparing of the subnucleus caudalis (the most caudal subdivision of the trigeminal spinal nucleus), which predominantly processes nociceptive and thermal inputs from trigeminal areas. If lesions involve the subnucleus interpolaris and the subnucleus oralis (the other two subdivisions of the trigeminal spinal nucleus) together with the part of the spinal trigeminal tract next to them, the nociceptive trigeminal neurons of the spared subnucleus caudalis could become deafferented. After deafferentation, abnormal spontaneous activity may be projected via the intact trigeminothalamic tract to the contralateral thalamus and beyond, leading to pain episodes (8). Second, the demyelination in the central trigeminal pathways could cause ectopic generation of spontaneous nerve impulses and ephaptic transmission to and from adjacent fibers in the spinal trigeminal tract (first-order nerve fibers) or the trigeminothalamic tract prior to its decussation (second-order fibers) (9). Cross-excitation may even involve the spinothalamic tract, which conveys pain and temperature sensations from the contralateral side of the body; in the patient presented this hypothesis is supported, since painful stimuli on the contralateral upper extremity could trigger the paroxysms of right facial pain.

In conclusion, a pain with the features of EF may be associated with structural lesions of the medulla oblongata, and specifically with a dorsolateral medullary infarction. This finding suggests that the central trigeminal pathways and/or the spinal trigeminal nucleus may play an important role in the pathophysiology of EF.

Clinical implications

A paroxysmal facial pain with the features of epicrania fugax (EF) occurred in connection with Wallenberg’s syndrome.

EF-type pain may be occasionally related to structural lesions of the brainstem.

Patient consent

Informed consent was obtained from the patient reported in this case report.