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-Sympathetic innervation of the face and arm (adapted from Wasner et al 7 ). Myelinated fibers project from the anterior cingulate cortex via the hypothalamus to the centrum ciliospinale within the spinal cord (1 st order neuron). From thereon, fibers radiate via the anterior horn to ganglions in the sympathetic trunk (2 nd order neuron): from C8-Th1 fibers travel to the face and from Th2-Th8 fibers travel to the arm. Unmyelinated fibers, separate for vasomotor and sudomotor activity, accompany peripheral nerves from the truncal ganglions to the organs (3 rd neuron). Facial sympathetic innervation originates in the ganglion cervical superius. Fibers partially travel along either the internal carotid artery (innervation of the medial side of the forehead, eyes, and nostrils) or along the external carotid artery (rest of the face) and are distributed over the face alongside the branches of the trigeminal nerve. The cheeks are innervated in both ways. Sympathetic innervation of the arm and hand continues from the roots Th2-Th8, via the ganglion cervicothoracicum (stellatum) to the plexus brachialis and further alongside peripheral nerves.
Source publication
Background:
The harlequin sign or syndrome is a rare cranial autonomic condition characterized by unilateral diminished flushing and sweating of the face (and sometimes arm), in response to heat or exercise. It results from autonomic, mainly sympathetic dysfunction. Although the idiopathic form is the most common, underlying structural abnormaliti...
Context in source publication
Context 1
... are both functions of the sympathetic nervous system, of which the vasomotor and sudomotor innervation origin from the hypothalamus (Fig. 1). From here myelinated axons project caudally to the ganglions within the sympathetic trunk: the centrum ciliospinale at the level of C8-Th1 (facial innervation) and at Th1-Th4 (innervation of the arm) (Fig. 2). Sympathetic dysfunction and the symptoms described above can result from a dissection of the carotid artery, an aneurysm of the cerebral vessels, or a (space-occupying) lesion in the brainstem, neck, apex of the lung or mediastinum (trajectory of the vagal nerve or sympathetic trunk). 1,7 For exclusion of underlying causes, an MR scan ...
Citations
... While other features of cranial autonomic dysfunction, such as Horner's syndrome, are well described in patients with trigeminal autonomic dysfunction, only 11 cases with harlequin syndrome and a primary headache disorder have been published. Of these cases two patients had cluster headaches [4,5], eight patients suffered from migraine [2,[6][7][8][9], and one patient had post-traumatic headache (with phenotype of tension-type headache) [1]. Four of 11 patients were reported to have an additional primary exertional headache, which, therefore, was more prevalent in this patient collective than in the general population, where its frequency ranges from 1% [10,11] to 12.3% [12,13] with female predominance. ...
Background
The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported.
Case presentation
This work describes the case of a 42‐year‐old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner’s syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren’s syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren’s syndrome.
Conclusions
This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches.
... Moreover, a relationship between Harlequin syndrome and headache was suggested in the literature. To date, approximately 90 cases of Harlequin syndrome are reported in the literature [28] and 11 of them showed comorbidity with headaches [28,29]. Migraine is the most common headache in this population; however, pathological association between these two disorders is doubtful. ...
... Moreover, a relationship between Harlequin syndrome and headache was suggested in the literature. To date, approximately 90 cases of Harlequin syndrome are reported in the literature [28] and 11 of them showed comorbidity with headaches [28,29]. Migraine is the most common headache in this population; however, pathological association between these two disorders is doubtful. ...
... Migraine is the most common headache in this population; however, pathological association between these two disorders is doubtful. In most presented cases as well as in our case, migraine started years before the development of Harlequin syndrome and autonomic symptoms were not simultaneous with headache attacks [28,30]. Two case reports raised the possibility of the association between cluster and Harlequin syndrome [28,31]. ...
Background and Objectives: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory disturbances in the trunk, proximal limbs, face, or mouth in a patchy and asymmetrical pattern. Harlequin syndrome is characterized by unilateral flushing and sweating of the face, neck, and upper chest, concurrent with contralateral anhidrosis. Here, we present and discuss a clinical case of sarcoidosis-associated ganglionopathy and Harlequin syndrome. Case presentation: A 31-year-old woman complained of burning pain in the right side of the upper chest and the feet. She also experienced episodes of intense flushing and sweating on the right side of her face, neck, and upper chest. Three years before these symptoms began, the patient was diagnosed with pulmonary sarcoidosis. On neurological examination, sensory disturbances were present. In the trunk, the patient reported pronounced hyperalgesia and allodynia in the upper part of the right chest and some patches on the right side of the upper back. In the extremities, hypoalgesia in the tips of the fingers and hyperalgesia in the feet were noted. An extensive diagnostic workup was performed to eliminate other possible causes of these disorders. A broad range of possible metabolic, immunological, and structural causes were ruled out. Thus, the final clinical diagnosis of sarcoidosis-induced sensory ganglionopathy, small-fiber neuropathy, and Harlequin syndrome was made. Initially, the patient was treated with pregabalin and amitriptyline, but the effect was inadequate for the ganglionopathy-induced pain. Therefore, therapeutic plasma exchange as an immune-modulating treatment was selected, leading to partial pain relief. Conclusions: This case report demonstrates the possible autoimmune origin of both sensory ganglionopathy and Harlequin syndrome. It suggests that an autoimmune etiology for these disorders should be considered and the diagnostic workup should include screening for the most common autoimmune conditions.
... Postganglionic sympathetic lesions cause Horner's syndrome similar to what CH patients often experience during and sometimes in-between attacks [95,102,103]. Occasionally, interictal sympathetic dysfunction in the face also leads to Harlequin syndrome, characterized by reduced ipsilateral facial sweating and flushing [104]. ...
Patients’ accounts of cluster headache attacks, ictal restlessness, and electrophysiological studies suggest that the pathophysiology involves Aδ-fibre nociceptors and the network processing their input. Continuous activity of the trigeminal autonomic reflex throughout the in-bout period results in central sensitization of these networks in many patients. It is likely that several factors force circadian rhythmicity upon the disease. In addition to sensitization, circadian changes in pain perception and autonomic innervation might influence the excitability of the trigeminal cervical complex. Summation of several factors influencing pain perception might render neurons vulnerable to spontaneous depolarization, particularly at the beginning of rapid drops of the pain threshold (“summation headache”). In light of studies suggesting an impairment of short-term synaptic plasticity in CH patients, we suggest that the physiologic basis of CH attacks might be network overactivity—similarly to epileptic seizures. Case reports documenting cluster-like attacks support the idea of distinct factors being transiently able to induce attacks and being relevant in the pathophysiology of the disorder. A sustained and recurring proneness to attacks likely requires changes in the activity of other structures among which the hypothalamus is the most probable candidate.
Harlequin syndrome is a rare disorder of the autonomic nervous system, presenting as unilateral reduced flushing and sweating of the face induced by exercise, stress, or heat. It is caused by a cervical sympathetic deficit located at the preganglionic or postganglionic level on the non‐flushing side. We present a case of an 8 year old with harlequin syndrome and review the other dermatological conditions for which the term “harlequin” is part of the nomenclature.
