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Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
Official Journal of the European Paediatric Neurology Society
Original article
Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature nchez b, A. Vidal Esteban a, D. Natera-de Benito a,*, D. Martı´nez Sa A. Reche Sainz c, M.R. Rodrı´guez Dı´az a, C.M. Alfaro Iznaola a, M.T. de Santos Moreno d a
Department of Pediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain Department of Dermatology, Hospital Universitario de Fuenlabrada, Madrid, Spain c Department of Ophtalmology, Hospital Universitario de Fuenlabrada, Madrid, Spain d Department of Pediatrics, Hospital Clı´nico San Carlos, Madrid, Spain b
article info
abstract
Article history:
Harlequin syndrome (HS) is a rare autonomic disorder due to a hemifacial cutaneous
Received 13 September 2015
sympathetic denervation. It is characterized by unilateral diminished sweating and
Accepted 7 February 2016
flushing of the face even though after heat or prolonged exercise. It is typically acquired. Congenital cases only represent a 6% of all individuals with HS. All congenital HS cases
Keywords:
reported so far showed a concomitant Horner syndrome, probably due to a stellate gan-
Harlequin syndrome
glion involvement. HS represents an uncommon autonomic disorder due to a hemifacial
Harlequin sign
cutaneous sympathetic denervation. It is clinically characterized by a dramatic alteration
Congenital
in facial appearance: ipsilateral denervated pale and dry half from the other intact red and
Facial flushing
moist half. Conclusion: We present, to the best of our knowledge, the first case of a patient
Autonomic neuropathy
with a congenital HS as an isolated phenomenon.
Autonomic nervous system
© 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
1.
Introduction
Harlequin syndrome (HS), first described by Lance et al. in 1988 represents an uncommon autonomic disorder due to an hemifacial cutaneous sympathetic denervation.1,2 It is clinically characterized by a dramatic alteration in facial appearance, in List of abbreviations: SD, Standard deviation; ESR, Erythrocyte sedimentation rate; HS, Harlequin syndrome; MR, Magnetic resonance. * Corresponding author. Tel.: þ34 606058561. E-mail addresses: [email protected] (A. Vidal Esteban), [email protected] (D. Natera-de Benito), diego. nchez), [email protected] (A. Reche Sainz), mariarocio.rodriguez@salud. [email protected] (D. Martı´nez Sa madrid.org (M.R. Rodrı´guez Dı´az), [email protected] (C.M. Alfaro Iznaola), [email protected] (M.T. de Santos Moreno). http://dx.doi.org/10.1016/j.ejpn.2016.02.004 1090-3798/© 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
2
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
“What is known” Harlequin syndrome represents an uncommon autonomic disorder due to a hemifacial cutaneous sympathetic denervation. It is clinically characterized by a dramatic alteration in facial appearance: ipsilateral denervated pale and dry half from the other intact red and moist half. “What is New” We present the first case of a patient with a congenital HS as an isolated phenomenon. Our observations indicate that congenital HS could appear without a concomitant Horner syndrome. To our knowledge, all congenital HS cases reported so far showed a concomitant Horner syndrome, probably due to a stellate ganglion involvement.
which a distinct line divides the ipsilateral denervated pale and dry half from the other intact red and moist half. This bipartite facial discoloration is named harlequin syndrome after the classical character in the Italian improvisational theater, the Commedia dell’Arte. In the recent literature the terms harlequin syndrome and harlequin sign have been used interchangeably. Moreover, the term harlequin color change is used to describe the transient hemibody flushing often seen in premature neonates due to immadurity of the hypothalamic centers.3 Congenital cases represents approximately a 6% of all the HS patients.4,5 To date it was thought that Horner syndrome was an obligatory concomitant syndrome in patients presenting a congenital HS. We present, to the best of our knowledge, the first case of a patient with a congenital HS as an isolated phenomenon.
2.
Case report
A 14-month-old male who was referred to our neuropediatric outpatient clinic due to a history of anhidrosis and pallor affecting the right side of his face which contrasted with the flushing and sweating on the left side provoked by physical exercise. Relatives noticed this peculiar pattern of facial flushing since he started to walk. The male infant was born with spontaneous eutocic delivery at 38 weeks of gestation. He was the first child of a healthy, young Caucasian couple. Three previous firsttrimester miscarriages were reported. Rest of family history was unremarkable. The pregnancy history was normal and there was no known exposure to teratogens during pregnancy. The infant's birth weight was 2942 g, length was 50.5 cm and head circumference was 33.5 cm (p39, 0.29 SD). All within the standard range (10the90th centile) for male Spanish neonates. His psychomotor development was normal. His medical history was uneventful. He did not use any medication.
On examination at rest no asymmetric facial flushing or sweating was noted. Blood pressure and heart rate were normal for his age. Neurological examination did not reveal any other abnormalities. Cranial nerves, deep tendon reflexes of extremities, and pupil responses were normal. Signs of ptosis were absent. After physical exercise, progressive flushing and profuse sweating was seen on the left side of his face. The right side of his face remained pale and anhidrotic (Fig. 1). No asymmetric patterns were present on the upper limbs or chest. The clinical picture was compatible with the HS. His hemogram, glucose, electrolytes, ESR, renal, hepatic and thyroid function were normal as well as chest radiograph, cranial, cervical and thoracic spine MR, and MR angiography of the circle of Willis and vertebrobasilar circulation. Ophthalmologic examination at the age of 3 revealed an physiological anisochoria of 0.4 mm. It was identified as physiological since the difference between pupils was less than 1 mm, it was not more exacerbated in the dark than in light, and both pupils reacted normally to light stimulation: after a light stimulus, the pupils returned to their original darkness diameter in less than 8 s. Visual acuity and pupillary reflexes were normal in both eyes. After being diagnosed with HS, the family's concerns were relieved by explaining the benign nature of the condition. The patient is currently 7 years-old. Symptoms have remained unchanged, showing right-sided anhidrosis and pallor even though after prolonged exercise (Fig. 1). Ophthalmologic evaluation was completed at the age of 7. Autonomic pupillary function was assessed with pupillography and pharmalogical testing with topical apraclonidine. Horner syndrome was not detected: pupillary dilation lag in the dark was absent and the apraclonidine test was negative.
3.
Discussion
This patient represents an example of probable congenital HS. We assume that it is a congenital phenomenon as the clinical picture was noted as soon as the patient acquired ambulation and started to sweat profusely. He had never practiced physical exercise before and he had never shown a so generous sweating so it is unlikely that a congenital HS would be noted previously. Moreover, he was born after a non-instrumental delivery, no trauma history was reported and no structural underlying lesions could be found. Localization of the lesion in HS must be based on both the patient's clinical history and his constellation of symptoms.6,7 The site of the pathology can be anywhere along the sympathetic outflow to the face (Fig. 2). The first neuron of the sympathetic fibers begins in the posterior hypothalamus, traverses the midbrain and reticular substance of the pons, and ends in the anterior lateral gray substance of the spinal cord. It synapses somewhere between C8 and T2, at the ciliospinal center. The second neuron (preganglionic fibers) leaves the spinal cord at T2eT3 and synapse with the third neuron (postganglionic fibers) in the superior cervical ganglion. Postganglionic fibers that supply the medial forehead
Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
3
Fig. 1 e Frontal view of the male with harlequin syndrome after exercise when he was a) 3 years-old, and b) 7 years-old. Note the distinct line that divides the right denervated pale and dry half from the left intact red and moist half.
Fig. 2 e Schematic diagrams showing sympathetic fibers innervating the face and possible lesion sites.12 Scissors indicate possible sites of sympathetic lesions; see Table 1. An arrow indicates the hypothetic site of the lesion.
and nose travel with the internal carotid artery, while fibers for other facial areas and the neck travel with the external carotid artery. Ocular sympathetic fibers most commonly leave the cord at T1. The upper trunk and extremities are provided with sympathetic outflow from T4 to T5. The upper extremity receives postganglionic fibers via the stellate ganglion. Table 1 shows the potential etiologies of HS according to the site of the sympathetic lesions. In the case presented, nor did we observe oculomotor changes (ptosis or miosis), and upper extremity sudomotor or vasomotor changes did not occur. It suggests that T1 and T4, respectively, are undamaged and delineates the site of
sympathetic injury at the level of the second or third thoracic segments of the spinal cord. A lesion immediately superior to the roots would involve to ocular sympathetic fibers and would imply ipsilateral ptosis and miosis, as preganglionic fibers arising from T2 and T3 travel to the superior cervical ganglion accompanied by ocular sympathetic fibers arising from T1. Lastly, a lesion located in the fibers that travel with the external carotid artery would not affect to medial forehead and nose, which are innervated by sudomotor fibers that travel with the internal carotid artery. On the basis of the pattern of symptoms in this particular case, it is possible to identify the site of the lesion at the level
Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
4
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
Table 1 e Etiology according to the site of sympathetic lesions.12 Numbers in brackets refer to sites in Fig. 2. Site of lesion Pons/cervical cord (1a/1b) Thoracic roots T2eT3 (3)
Thoracic roots T1eT3 (2 and 3) Sympathetic chain between T1 and T2 (5) Stellate ganglion (6) Sympathetic chain between stellate and middle cervical ganglion/middle and superior cervical ganglion (7a/7b) Sympathetic fibres travelling with the internal carotid artery (8)
of the second or third thoracic segments of spinal cord, in the intermediolateral cell column, or T2-T3 roots. Lance et al. suggested that an anterior radicular artery which supply only the T2 and T3 roots and do not contribute significantly to the spinal cord circulation could be occluded and result in an HS.5 It is thus possible that a congenital impaired perfusion of the anterior radicular artery that supplies blood specifically to T2 and T3 roots results in an agenesis or hypoplasia of the second neuron of the sympathetic fibers that would lead to a congenital HS without ocular signs of Horner syndrome. In addition to these observations, Tascilar et al. described patients with syringomyelia and Horner syndrome due to a syrinx at the level of thoracic segments.8 The possibility of a syrinx was ruled out in our patient by a cervical and thoracic spine MR. HS is typically acquired. Congenital cases only represent a 6% of all individuals with HS. To our knowledge, all congenital HS cases reported so far showed a concomitant Horner syndrome, probably due to a stellate ganglion involvement. In the case presented, absence of oculomotor changes indicates a stellate ganglion preservation. We hypothesize that a disorder in the preganglionic fibers arising from T2 and T3 could be a possible cause of the pure autonomic disorder of our patient. The precise etiology has still to be elucidated. Whereas HS is usually benign and imaging studies are unrevealing, it is worth noting that it may be caused by spaceoccupying lesions or infarction. Transient HS has also been described in the perioperative period after thoracic paravertebral blocks and after the insertion of lines into the internal jugular vein. Thorough investigation is required to rule out underlying structural lesions, some of which may lend themselves to surgical correction. HS overlaps with several other syndromes. Among them are Holmes-Adie syndrome9 and Ross syndrome.10,11 These syndromes may lie along the same nosologic spectrum. Most patients do not require medical or surgical treatment. Where embarrassment is significant and there is a need for psychological support, surgical sympathectomy ipsilateral to the side of the face that flushes and sweats must be considered.12 Repeated stellate ganglion blocks have been recently reported as either a screen for sympathectomy, or a less invasive alternative treatment.6 Our observations indicate that congenital HS could appear without a concomitant Horner syndrome. To our knowledge, all congenital HS cases reported so far showed a concomitant Horner syndrome. Localization of the lesion in HS must be
Aetiology Brainstem infarction/syringomyelia Pancoast tumour, post-thoracic surgery, superior mediastinal neurinoma, schwannoma at lung apex, selective radiculopathy following occlusion of anterior radicular artery Pancoast tumour Sympathectomy Ganglionectomy, ganglioneuroma, extending schwannoma Thyroid diseases (e.g. neurovascular compression by inferior thyroid artery, enlarged thyroid gland, post-thyroidectomy, goitre)
based on autonomic sympathetic innervation of the face. Thorough investigation is required to rule out underlying structural lesions. In idiopathic forms is essential to reinforce the idea of the benign nature of the disorder and its favorable prognosis.
4.
Conclusion
We established in our review that HS is a rare autonomic disorder. It is characterized by hemifacial anhidrosis due to an ipsilateral cutaneous sympathetic denervation. We present, to the best of our knowledge, the first case of a patient with a congenital HS as an isolated phenomenon.
Contribution of each co-author 1. Mrs Arantxa Vidal Esteban. Pediatrician who performs patient reviews. 2. Mr Daniel Natera de Benito. Pediatrician who performs patient reviews. nchez. Dermatologist who helped 3. Mr Diego Martı´nez Sa with the diagnosis. 4. Mr Alberto Reche Sainz. Ophtalmologist who helped the diagnosis and ruled Horner syndrome. 5. Mrs Marı´a Rocı´o Rodrı´guez Dı´az. Pediatrician who performs patient reviews. 6. Mrs Cristina Marı´a Alfaro Iznaola. Pediatrician who performs patient reviews. 7. Mrs Marı´a Teresa de Santos Moreno. Pediatrician responsible for the final diagnosis.
Conflict of interest The author has declared that no conflict of interest exists.
references
1. Bremner F, Smith S. Pupillographic findings in 39 consecutive cases of harlequin syndrome. J Neuroophthalmol 2008;28:171e7.
Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
2. Cheshire Jr WP, Low PA. Harlequin syndrome: still only half understood. J Neuroophthalmol 2008 Sep;28(3):169e70. 3. Drummond PD, Finch PM. Reflex control of facial flushing during body heating in man. Brain 1989;112:1351e8. 4. Drummond PD, Edis RH. Loss of facial sweating and flushing in Holmes-Adie syndrome. Neurology 1990;40:847e9. 5. Lance JW, Drummond PD, Gandevia SC, et al. Harlequin syndrome: the sudden onset of unilateral flushing and sweating. J Neurol Neurosurg Psychiatry 1988;51:635e42. 6. Neligan GA, Strang LBA. “Harlequin” colour change in the newborn. Lancet 1952;260:1005e7. 7. Reddy H, Fatah S, Gulve A, Carmichael AJ. Novel management of harlequin syndrome with stellate ganglion block. Br J Dermatol 2013;169(4):954e6.
5
8. Tascilar N, Tekin NS, Erdem Z, Alpay A, Emre U. Unnoticed dysautonomic syndrome of the face: Harlequin syndrome. Auton Neurosci 2007;137(1e2):1e9. 9. Shin RK, Galetta SL, Ting TY, et al. Ross syndrome plus: beyond Horner, Holmes-Adie, and harlequin. Neurology 2000;55:1841e6. 10. Sribnick EA, Boulis NM. Treatment of Harlequin syndrome by costo transversectomy and sympathectomy: case report. Neurosurgery 2011;69(1):E257e9. 11. Wasner G, Maag R, Ludwig J, Binder A, Schattschneider J, Stingele R, Baron R. Harlequin syndrome: one face of many etiologies. Nat Clin Pract Neurol 2005;1(1):54e9. 12. Willaert WI, Scheltinga MR, Steenhuisen SF, Hiel JA. Harlequin syndrome: two new cases and a management proposal. Acta Neurol Belg 2009;109(3):214e20.
Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
Official Journal of the European Paediatric Neurology Society
Original article
Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature nchez b, A. Vidal Esteban a, D. Natera-de Benito a,*, D. Martı´nez Sa A. Reche Sainz c, M.R. Rodrı´guez Dı´az a, C.M. Alfaro Iznaola a, M.T. de Santos Moreno d a
Department of Pediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain Department of Dermatology, Hospital Universitario de Fuenlabrada, Madrid, Spain c Department of Ophtalmology, Hospital Universitario de Fuenlabrada, Madrid, Spain d Department of Pediatrics, Hospital Clı´nico San Carlos, Madrid, Spain b
article info
abstract
Article history:
Harlequin syndrome (HS) is a rare autonomic disorder due to a hemifacial cutaneous
Received 13 September 2015
sympathetic denervation. It is characterized by unilateral diminished sweating and
Accepted 7 February 2016
flushing of the face even though after heat or prolonged exercise. It is typically acquired. Congenital cases only represent a 6% of all individuals with HS. All congenital HS cases
Keywords:
reported so far showed a concomitant Horner syndrome, probably due to a stellate gan-
Harlequin syndrome
glion involvement. HS represents an uncommon autonomic disorder due to a hemifacial
Harlequin sign
cutaneous sympathetic denervation. It is clinically characterized by a dramatic alteration
Congenital
in facial appearance: ipsilateral denervated pale and dry half from the other intact red and
Facial flushing
moist half. Conclusion: We present, to the best of our knowledge, the first case of a patient
Autonomic neuropathy
with a congenital HS as an isolated phenomenon.
Autonomic nervous system
© 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
1.
Introduction
Harlequin syndrome (HS), first described by Lance et al. in 1988 represents an uncommon autonomic disorder due to an hemifacial cutaneous sympathetic denervation.1,2 It is clinically characterized by a dramatic alteration in facial appearance, in List of abbreviations: SD, Standard deviation; ESR, Erythrocyte sedimentation rate; HS, Harlequin syndrome; MR, Magnetic resonance. * Corresponding author. Tel.: þ34 606058561. E-mail addresses: [email protected] (A. Vidal Esteban), [email protected] (D. Natera-de Benito), diego. nchez), [email protected] (A. Reche Sainz), mariarocio.rodriguez@salud. [email protected] (D. Martı´nez Sa madrid.org (M.R. Rodrı´guez Dı´az), [email protected] (C.M. Alfaro Iznaola), [email protected] (M.T. de Santos Moreno). http://dx.doi.org/10.1016/j.ejpn.2016.02.004 1090-3798/© 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
2
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
“What is known” Harlequin syndrome represents an uncommon autonomic disorder due to a hemifacial cutaneous sympathetic denervation. It is clinically characterized by a dramatic alteration in facial appearance: ipsilateral denervated pale and dry half from the other intact red and moist half. “What is New” We present the first case of a patient with a congenital HS as an isolated phenomenon. Our observations indicate that congenital HS could appear without a concomitant Horner syndrome. To our knowledge, all congenital HS cases reported so far showed a concomitant Horner syndrome, probably due to a stellate ganglion involvement.
which a distinct line divides the ipsilateral denervated pale and dry half from the other intact red and moist half. This bipartite facial discoloration is named harlequin syndrome after the classical character in the Italian improvisational theater, the Commedia dell’Arte. In the recent literature the terms harlequin syndrome and harlequin sign have been used interchangeably. Moreover, the term harlequin color change is used to describe the transient hemibody flushing often seen in premature neonates due to immadurity of the hypothalamic centers.3 Congenital cases represents approximately a 6% of all the HS patients.4,5 To date it was thought that Horner syndrome was an obligatory concomitant syndrome in patients presenting a congenital HS. We present, to the best of our knowledge, the first case of a patient with a congenital HS as an isolated phenomenon.
2.
Case report
A 14-month-old male who was referred to our neuropediatric outpatient clinic due to a history of anhidrosis and pallor affecting the right side of his face which contrasted with the flushing and sweating on the left side provoked by physical exercise. Relatives noticed this peculiar pattern of facial flushing since he started to walk. The male infant was born with spontaneous eutocic delivery at 38 weeks of gestation. He was the first child of a healthy, young Caucasian couple. Three previous firsttrimester miscarriages were reported. Rest of family history was unremarkable. The pregnancy history was normal and there was no known exposure to teratogens during pregnancy. The infant's birth weight was 2942 g, length was 50.5 cm and head circumference was 33.5 cm (p39, 0.29 SD). All within the standard range (10the90th centile) for male Spanish neonates. His psychomotor development was normal. His medical history was uneventful. He did not use any medication.
On examination at rest no asymmetric facial flushing or sweating was noted. Blood pressure and heart rate were normal for his age. Neurological examination did not reveal any other abnormalities. Cranial nerves, deep tendon reflexes of extremities, and pupil responses were normal. Signs of ptosis were absent. After physical exercise, progressive flushing and profuse sweating was seen on the left side of his face. The right side of his face remained pale and anhidrotic (Fig. 1). No asymmetric patterns were present on the upper limbs or chest. The clinical picture was compatible with the HS. His hemogram, glucose, electrolytes, ESR, renal, hepatic and thyroid function were normal as well as chest radiograph, cranial, cervical and thoracic spine MR, and MR angiography of the circle of Willis and vertebrobasilar circulation. Ophthalmologic examination at the age of 3 revealed an physiological anisochoria of 0.4 mm. It was identified as physiological since the difference between pupils was less than 1 mm, it was not more exacerbated in the dark than in light, and both pupils reacted normally to light stimulation: after a light stimulus, the pupils returned to their original darkness diameter in less than 8 s. Visual acuity and pupillary reflexes were normal in both eyes. After being diagnosed with HS, the family's concerns were relieved by explaining the benign nature of the condition. The patient is currently 7 years-old. Symptoms have remained unchanged, showing right-sided anhidrosis and pallor even though after prolonged exercise (Fig. 1). Ophthalmologic evaluation was completed at the age of 7. Autonomic pupillary function was assessed with pupillography and pharmalogical testing with topical apraclonidine. Horner syndrome was not detected: pupillary dilation lag in the dark was absent and the apraclonidine test was negative.
3.
Discussion
This patient represents an example of probable congenital HS. We assume that it is a congenital phenomenon as the clinical picture was noted as soon as the patient acquired ambulation and started to sweat profusely. He had never practiced physical exercise before and he had never shown a so generous sweating so it is unlikely that a congenital HS would be noted previously. Moreover, he was born after a non-instrumental delivery, no trauma history was reported and no structural underlying lesions could be found. Localization of the lesion in HS must be based on both the patient's clinical history and his constellation of symptoms.6,7 The site of the pathology can be anywhere along the sympathetic outflow to the face (Fig. 2). The first neuron of the sympathetic fibers begins in the posterior hypothalamus, traverses the midbrain and reticular substance of the pons, and ends in the anterior lateral gray substance of the spinal cord. It synapses somewhere between C8 and T2, at the ciliospinal center. The second neuron (preganglionic fibers) leaves the spinal cord at T2eT3 and synapse with the third neuron (postganglionic fibers) in the superior cervical ganglion. Postganglionic fibers that supply the medial forehead
Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
3
Fig. 1 e Frontal view of the male with harlequin syndrome after exercise when he was a) 3 years-old, and b) 7 years-old. Note the distinct line that divides the right denervated pale and dry half from the left intact red and moist half.
Fig. 2 e Schematic diagrams showing sympathetic fibers innervating the face and possible lesion sites.12 Scissors indicate possible sites of sympathetic lesions; see Table 1. An arrow indicates the hypothetic site of the lesion.
and nose travel with the internal carotid artery, while fibers for other facial areas and the neck travel with the external carotid artery. Ocular sympathetic fibers most commonly leave the cord at T1. The upper trunk and extremities are provided with sympathetic outflow from T4 to T5. The upper extremity receives postganglionic fibers via the stellate ganglion. Table 1 shows the potential etiologies of HS according to the site of the sympathetic lesions. In the case presented, nor did we observe oculomotor changes (ptosis or miosis), and upper extremity sudomotor or vasomotor changes did not occur. It suggests that T1 and T4, respectively, are undamaged and delineates the site of
sympathetic injury at the level of the second or third thoracic segments of the spinal cord. A lesion immediately superior to the roots would involve to ocular sympathetic fibers and would imply ipsilateral ptosis and miosis, as preganglionic fibers arising from T2 and T3 travel to the superior cervical ganglion accompanied by ocular sympathetic fibers arising from T1. Lastly, a lesion located in the fibers that travel with the external carotid artery would not affect to medial forehead and nose, which are innervated by sudomotor fibers that travel with the internal carotid artery. On the basis of the pattern of symptoms in this particular case, it is possible to identify the site of the lesion at the level
Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
4
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 6 ) 1 e5
Table 1 e Etiology according to the site of sympathetic lesions.12 Numbers in brackets refer to sites in Fig. 2. Site of lesion Pons/cervical cord (1a/1b) Thoracic roots T2eT3 (3)
Thoracic roots T1eT3 (2 and 3) Sympathetic chain between T1 and T2 (5) Stellate ganglion (6) Sympathetic chain between stellate and middle cervical ganglion/middle and superior cervical ganglion (7a/7b) Sympathetic fibres travelling with the internal carotid artery (8)
of the second or third thoracic segments of spinal cord, in the intermediolateral cell column, or T2-T3 roots. Lance et al. suggested that an anterior radicular artery which supply only the T2 and T3 roots and do not contribute significantly to the spinal cord circulation could be occluded and result in an HS.5 It is thus possible that a congenital impaired perfusion of the anterior radicular artery that supplies blood specifically to T2 and T3 roots results in an agenesis or hypoplasia of the second neuron of the sympathetic fibers that would lead to a congenital HS without ocular signs of Horner syndrome. In addition to these observations, Tascilar et al. described patients with syringomyelia and Horner syndrome due to a syrinx at the level of thoracic segments.8 The possibility of a syrinx was ruled out in our patient by a cervical and thoracic spine MR. HS is typically acquired. Congenital cases only represent a 6% of all individuals with HS. To our knowledge, all congenital HS cases reported so far showed a concomitant Horner syndrome, probably due to a stellate ganglion involvement. In the case presented, absence of oculomotor changes indicates a stellate ganglion preservation. We hypothesize that a disorder in the preganglionic fibers arising from T2 and T3 could be a possible cause of the pure autonomic disorder of our patient. The precise etiology has still to be elucidated. Whereas HS is usually benign and imaging studies are unrevealing, it is worth noting that it may be caused by spaceoccupying lesions or infarction. Transient HS has also been described in the perioperative period after thoracic paravertebral blocks and after the insertion of lines into the internal jugular vein. Thorough investigation is required to rule out underlying structural lesions, some of which may lend themselves to surgical correction. HS overlaps with several other syndromes. Among them are Holmes-Adie syndrome9 and Ross syndrome.10,11 These syndromes may lie along the same nosologic spectrum. Most patients do not require medical or surgical treatment. Where embarrassment is significant and there is a need for psychological support, surgical sympathectomy ipsilateral to the side of the face that flushes and sweats must be considered.12 Repeated stellate ganglion blocks have been recently reported as either a screen for sympathectomy, or a less invasive alternative treatment.6 Our observations indicate that congenital HS could appear without a concomitant Horner syndrome. To our knowledge, all congenital HS cases reported so far showed a concomitant Horner syndrome. Localization of the lesion in HS must be
Aetiology Brainstem infarction/syringomyelia Pancoast tumour, post-thoracic surgery, superior mediastinal neurinoma, schwannoma at lung apex, selective radiculopathy following occlusion of anterior radicular artery Pancoast tumour Sympathectomy Ganglionectomy, ganglioneuroma, extending schwannoma Thyroid diseases (e.g. neurovascular compression by inferior thyroid artery, enlarged thyroid gland, post-thyroidectomy, goitre)
based on autonomic sympathetic innervation of the face. Thorough investigation is required to rule out underlying structural lesions. In idiopathic forms is essential to reinforce the idea of the benign nature of the disorder and its favorable prognosis.
4.
Conclusion
We established in our review that HS is a rare autonomic disorder. It is characterized by hemifacial anhidrosis due to an ipsilateral cutaneous sympathetic denervation. We present, to the best of our knowledge, the first case of a patient with a congenital HS as an isolated phenomenon.
Contribution of each co-author 1. Mrs Arantxa Vidal Esteban. Pediatrician who performs patient reviews. 2. Mr Daniel Natera de Benito. Pediatrician who performs patient reviews. nchez. Dermatologist who helped 3. Mr Diego Martı´nez Sa with the diagnosis. 4. Mr Alberto Reche Sainz. Ophtalmologist who helped the diagnosis and ruled Horner syndrome. 5. Mrs Marı´a Rocı´o Rodrı´guez Dı´az. Pediatrician who performs patient reviews. 6. Mrs Cristina Marı´a Alfaro Iznaola. Pediatrician who performs patient reviews. 7. Mrs Marı´a Teresa de Santos Moreno. Pediatrician responsible for the final diagnosis.
Conflict of interest The author has declared that no conflict of interest exists.
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Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004
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Please cite this article in press as: Vidal Esteban A, et al., Congenital Harlequin syndrome as an isolated phenomenon: A case report and review of the literature, European Journal of Paediatric Neurology (2016), http://dx.doi.org/10.1016/j.ejpn.2016.02.004