In 1952, Neligan and Strang1 reported a summary of 22 infants with transient (30 seconds to 20 minutes) hemilateral skin color changes of no apparent pathologic significance and named this presentation Harlequin syndrome. Since that time, Harlequin syndrome has been reported in numerous case reports and reviews. Although most Harlequin syndrome reports relate to excessive heat or exercise2–6 and are considered benign, a few cases of Harlequin syndrome associated with structural lesions have been reported in both infants7–9 and adults.10–17
Harlequin syndrome has been reported after regional anesthesia after high thoracic paravertebral anesthesia,18 epidural anesthesia,19 or extrapleural bupivacaine infusion,20 with or without Horner syndrome. The mechanism by which regional anesthesia precipitates Harlequin syndrome is not understood. We present a case of Harlequin syndrome without miosis or ptosis after a thoracic paravertebral nerve block and review mechanisms by which interruption of the autonomic nervous system by regional anesthesia may cause Harlequin syndrome. We obtained written informed consent from the patient for publication of this case report.
A 64-year-old woman with hypertension and hyperlipidemia was scheduled for a left mastectomy for multifocal ductal adenocarcinoma. Her medications included lisinopril, hydrochlorothiazide, and simvastatin. The patient had an allergy to penicillin, which caused a rash. Her laboratory studies were unremarkable. The radiograph of her chest was within normal limits (Fig. 1). Before the procedure, her vital signs and neurologic examination were normal.
The patient underwent a left T3 paravertebral block before surgery. She was premedicated with fentanyl and midazolam. An ultrasound-guided, left paravertebral block was placed in the prone position at approximately T3. Twenty-five milliliters of 0.5% bupivacaine with 1:400,000 epinephrine was injected through a 22-gauge blunt-tipped hyperechoic Pajunk needle. After confirmation of a successful left-sided block by the pinprick method, her mastectomy was performed under general anesthesia without complication. Intraoperatively, the patient was noted to have right-sided facial redness (Fig. 2). The patient received 2 mg neostigmine and 0.2 mg glycopyrrolate for the reversal of muscle relaxation before extubation.
Postoperatively, sharply demarcated right-sided facial flushing was present without any signs of miosis, ptosis, or sweating. The disparity between the appearance of the left and right side of the face resolved slowly between 6 and 11 hours after the contralateral thoracic paravertebral block. This suggested an 11-hour sympathetic block on the side of the thoracic paravertebral block, with resolution of the sympathetic block before the resolution of the sensory block. No changes in vital signs were noted postoperatively. The patient was discharged home on the next day.
We report a patient with a unique presentation of Harlequin syndrome without Horner syndrome after contralateral paravertebral nerve block for a mastectomy. This rare case may help us to understand the function of the sympathetic efferent nerve fibers that innervate the face.
When looking at the face of an individual with Harlequin syndrome, the immediate observation is a sharply demarcated hemifacial erythema. Therefore, the first descriptions of Harlequin syndrome suggest that the hemifacial reddening is the pathologic reaction. However, Drummond and Lance21 made clear that the pathologic reaction in Harlequin syndrome is the pale side of the face after interruption of the sympathetic nerve fibers not the red side of the face with normal sympathetic innervation. In this report, the dysfunction of the ipsilateral efferents leads to the pale appearance of the face (Fig. 2). In other words, without the thoracic paravertebral block, our patient would most likely have had a uniformly reddened face. The exact mechanisms that cause Harlequin syndrome are still unclear. Both sympathetic and parasympathetic fibers may be involved in a partial autonomic neuropathy21 associated with Harlequin syndrome.22
The sympathetic outflow pathway comprises a 3-neuron chain (Fig. 3). The first neuron begins in the posterior and lateral hypothalamus and ends in the intermediolateral cell column of the upper thoracic spinal cord.23 The second neuron arises in the intermediolateral cell column of the spinal cord, transverses the ventral spinal root, exits as white rami communicantes,24 and follows the sympathetic trunk to synapse in the superior cervical ganglion.23 The second-order oculomotor fibers leave the spinal cord in the first thoracic root (T1). The stellate ganglion contains fibers from the lower cervical and first thoracic ganglia in 80% of the population.25 The preganglionic sudomotor and vasomotor fibers leave at the second and third thoracic roots (T2 and T3), respectively.
The third neuron originates from postganglionic neurons in the rostral and caudal end of the superior cervical ganglion. These fibers form a plexus around the carotid artery.27 Sudomotor and vasomotor fibers to the cheeks and forehead separate at the bifurcation of the common carotid artery. The medial part of the forehead and side of the nose are innervated by the fibers that travel with oculosympathetic fibers, which innervate the dilator muscles along the internal carotid artery. The rest of the face is innervated by fibers that follow the external carotid artery before joining the branches of the trigeminal nerve through which they are distributed to the skin.18
The upper extremity receives postganglionic fibers from the stellate ganglion. A lesion in or proximal to the stellate ganglion would disrupt sudomotor and vasomotor responses to the arm, neck, upper extremity, and upper part of the trunk. A lesion distal to the stellate ganglion would affect only the face.26
The location of sympathetic nerve interruption in the current patient is most likely preganglionic, because hemifacial involvement indicates an interruption of the preganglionic neurons below the superior cervical ganglion.28 Most of the pupillary fibers leave the spinal cord in the Tl ventral root29 (Fig. 3). Facial erythema without Horner syndrome in our patient indicates that the sympathetic nerve was blocked distal to the exit of the sympathetic pupillomotor fibers from the spinal cord (T1). The interruption was at the level of the vasomotor and sudomotor sympathetic fibers (T2–T3),26,30,31 which correlates with the level of paravertebral block (T3) performed in our patient. Although we cannot exclude an effect of the glycopyrrolate in the current patient, it has been reported to have no prolonged effects on mydriasis.32 Facial erythema persisted and resolved slowly between 6 and 11 hours after the contralateral thoracic paravertebral block. The incidence of Harlequin syndrome after thoracic paravertebral block combined with general anesthesia is not significantly higher in comparison with general anesthesia alone.33 Therefore, it is likely that preganglionic T2 to T3 sympathetic blockade, not the effect of glycopyrrolate, contributed to the development of hemifacial erythema without miosis or ptosis in the current patient.
There are several previous case reports of regional anesthesia and Harlequin syndrome, with and without Horner syndrome. A detailed case report of Harlequin syndrome with coexisting Horner syndrome after high thoracic paravertebral block18 has been described. Other reports consist of brief correspondences (a report of Harlequin syndrome without Horner syndrome after T3/4 paravertebral block30 or low thoracic epidural block34) or case reports without pupil sizes.19,20
Subclinical Harlequin syndrome may be more common than we realize after regional blocks of spinal nerves. We detected Harlequin syndrome clinically because of the contralateral reddened face with a clear midline demarcation. It would be of interest to measure skin temperature or laser Doppler flowmetry on both sides of the face in each patient after thoracic paravertebral block to determine more about the incidence of Harlequin syndrome.
In general, after sympathectomy, more α-adrenoceptors are expressed in denervated vessels leading to an increased sensitivity to circulating catecholamines, which results in increased vasoconstriction.35,36 Postganglionic sympathetic fibers are typically vasoconstrictor nerves.37 Vessels of the different target organs, such as the skin for thermoregulation and the muscles for blood pressure regulation, constrict after increased sympathetic activity and dilate with less sympathetic activity. This mechanism develops over a period of time and cannot account for any acute changes. Many cases of Harlequin syndrome described in the literature are chronic.3,15–17,38 In contrast, the pathologic pale face after acute sympathetic denervation in this report may not have been due to interruption of active sympathetic vasodilation, but rather resulted from excessive vasoconstriction secondary to the adrenergic denervation. Other etiologies of vasodilation such as parasympathetic stimulation or the influence of nitric oxide cannot be excluded.39 However, the reported acute facial vasoconstriction after regional block likely gives evidence for the interruption of active sympathetic vasodilator neurons, which have been reported rarely.40
In summary, we describe a case of transient Harlequin syndrome without Horner syndrome after thoracic paravertebral block. Acute Harlequin syndrome without a structural lesion seems to be benign and transient, as we observed in our patient.
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