REVIEW ARTICLE
Horner Syndrome: A Practical Approach to Investigation and Management Zoe Gao, MBBS* and John L. Crompton, MBBS, FRANZCO, FRACS*Þ Abstract: Horner syndrome is typically described by the classic triad of blepharoptosis, miosis, and anhydrosis resulting from disruption along the oculosympathetic pathway. Because of the complex and extensive course of this pathway, there are a large number of causes of Horner syndrome ranging from benign to life-threatening diseases. This review article aims to provide a practical approach to investigation and management, including evaluation of the more recent use of apraclonidine for pharmacological testing. Key Words: Horner syndrome, oculosympathetic pathway (Asia-Pac J Ophthalmol 2012;1: 175Y179)
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orner syndrome is caused by disruption at some point along the oculosympathethic pathway from the hypothalamus to the eye, resulting in the clinical features of miosis, ptosis, and anhydrosis. It was first described by Francois Pourfour du Petit1 in 1727 when he noted changes in the eyes and snout of dogs after cutting the intercostal nerves in their necks. In 1852, Claude Bernard,2 a French physiologist, described the syndrome in more detail (and hence it is known as Bernard-Horner syndrome in France), and in 1864, 3 American army physicians Silas Weir Mitchell, William Keen, Jr, and George Read Morehouse published a clinical report of the syndrome in a man shot through the throat.3 However, it was only in 1869 that the Swiss ophthalmologist Johann Friedrich Horner described the classic triad of findings, and the syndrome subsequently bore his name.4 Because the oculosympathetic pathway has a long course, there is the potential for involvement by many different disease processes. However, given that some are potentially lifethreatening such as internal carotid dissection and malignancies, it is important to have a systematic approach to diagnosis and management. This review discusses the important anatomic features, clinical features, and investigations that should be ordered, as well as experience from our center over the last 30 years.
CLINICAL ANATOMY The oculosympathetic pathway consists of 3 orders of neurons. The first-order neuron, which if affected would result in a central Horner syndrome, originates in the posterior lateral aspect of the hypothalamus and descends uncrossed down the brainstem and terminates in the ciliospinal center of BudgeWaller. This spans the intermediolateral horn of the spinal cord from C8 to T2.5,6 From the *South Australian Institute of Ophthalmology, Adelaide, c/o Royal Adelaide Hospital; and †Discipline of Ophthalmology & Visual Sciences, University of Adelaide, North Terrace, South Australia, Australia. Received for publication February 4, 2012; accepted March 16, 2012. The authors have no funding or conflicts of interest to declare. Informed consent was obtained from all patients for use of images in this review. Reprints: Zoe Gao, MBBS, Royal Victorian Eye and Ear Hospital, 32 Gisborne St, E Melbourne, Victoria 3002, Australia. E-mail: [email protected]. Copyright * 2012 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.1097/APO.0b013e318256009d
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The second-order or preganglionic neuron leaves the ciliospinal center of Budge-Waller via the ventral spinal roots of C8-T2 and passes through the inferior and middle cervical ganglia before synapsing at the superior cervical ganglion in the neck. During its course, it is closely related to the apical pleura and can therefore be damaged by lung cancer (Pancoast tumor: Figure, Supplementary Digital Content 1; http://links.lww.com/ APJO/A12 and http://links.lww.com/APJO/A13). The superior cervical ganglion is located at the level of C2-C3 posterior to the carotid sheath at the level of the angle of the mandible. The sympathetic sudomotor and vasoconstrictor fibers to the face leave prior to the superior cervical ganglion at the bifurcation of the common carotid artery into the internal and external carotid arteries. Therefore, a postganglionic lesion will not be associated with significant anhydrosis.5,6 The postganglionic neuron ascends along the internal carotid artery as a plexus before dividing into a medial and lateral branch. The medial branch enters the cavernous sinus and joins the oculomotor nerve before innervating Mu¨ller muscle in the upper and lower lids. The lateral branch joins the abducens nerve briefly and then the ophthalmic division of the trigeminal nerve, before reaching the dilator pupillae of the iris via the nasociliary nerve and long ciliary nerves.5Y7 Given the long course of the oculosympathetic pathway, it is not surprising that the causes of Horner syndrome are diverse, and it may not be easy to determine the etiology (Table 1).
CLINICAL SIGNS Horner syndrome results in miosis and mild ptosis as a result of unopposed action of the sphincter pupillae and weakness of Mu¨ller muscle, respectively. These 2 signs are the most constant findings in Horner syndrome. The anisocoria is accentuated in dim light, and there is a dilation lag where the affected pupil dilates slower compared with the healthy pupil because of lack of pull from the dilator muscle.8 In addition, apparent enophthalmos due to ptosis (elevation) of the lower lid may be present. If the lesion is congenital or longstanding, there may be hypochromic heterochromia of the iris (Fig. 1). This sign is not, however, useful in the perinatal period because iris color is not established until several months of age (Supplementary Digital Content 2; http://links.lww.com/ APJO/A14). Anhydrosis is not always present and although helpful is rarely elicited.7 Harlequin sign refers to unilateral facial flushing that can occur in congenital Horner syndrome. The areas that do not flush correspond with anhydrotic areas. There is also a decrease in the skin temperature on the affected side. These findings are the result of impaired sympathetic vasodilatation.9 Conjunctival hyperemia may be present as an early transient sign in response to loss of sympathetic innervation to the conjunctival vessels resulting in vasodilation. This sign is rarely present for more than a few weeks.5 Rarely, Horner syndrome may alternate between the 2 sides. We have observed 2 such cases in quadriplegics with secondary syringobulbia (Fig. 2). Both of these patients developed miosis in the dependent eye, when changed from lying from one side to the
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TABLE 1. Breakdown of Causes of Horner Syndrome Based on Anatomic Location Anatomic Site Central
Preganglionic
Postganglionic
Etiologies Hypothalamus Stroke Tumor Brainstem disease StrokeVPICA/vertebral artery ) Lateral medullary syndrome Demyelination Tumor Syringomyelia Cervical/thoracic myelitis Spinal cord tumor Diabetic autonomic neuropathy AVM Tumor Thyroid/mediastinal Neuroblastoma Sympathetic schwannoma Pancoast Trauma, including birth trauma Brachial plexus injury Postsurgical/iatrogenic Sympathectomy for peripheral vascular disease, hyperhydrosis Surgery for thyroid and parathyroid disease Carotid and aortic/subclavian aneurysm and dissection Cervical rib Osteophytes Postsurgical/iatrogenic Trauma Cluster/migraine headaches Internal carotid artery dissection/aneurysm Jugular venous ectasia Fibromuscular dysplasia Skull base lesions Nasopharyngeal tumor Otitis media Cavernous sinus mass/inflammation/infection Internal carotid arteritis
Those in bold type are the more common causes. AVM indicates arteriovenous malformation; PICA, posterior inferior cerebellar artery.
other, thought to be due to pressure of the cerebrospinal fluid in the syrinx on the sympathetic fibers running down the midbrain. Although the above signs describe Horner syndrome, in clinical practice, it is other features on history and examination that will guide further investigation and management. This is highlighted below with photographs of some clinical cases the author (J.L.C.) has been involved with. A central Horner syndrome is unlikely to be in isolation because of the close proximity of other structures within the hypothalamus, brainstem, and spinal cord10 (Supplementary Digital Content 3; http:// links.lww.com/APJO/A15). Patients may present with vertigo, ataxia, contralateral loss of pain and temperature sensation,
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FIGURE 1. Congenital right Horner syndrome from right brachial plexus birth trauma. Her right iris never developed pigmentation.
swallowing difficulties, or unilateral facial numbness. The causes of a preganglionic Horner are often trauma (Fig. 3) or iatrogenic (Fig. 4), which should be elicited from a thorough history.11Y13 Postganglionic Horner syndrome may have localizing signs such as involvement of other cranial nerves secondary to cavernous sinus pathology. For example, cavernous sinus masses from metastases, pituitary tumor invasion, or aneurysms can cause Horner syndrome and isolated abducens nerve palsy. A Horner syndrome associated with pain in the face and neckV Raeder paratrigeminal syndromeVcan be associated with the serious diagnosis of a carotid artery dissection. Although there are other more benign causes such as cluster headache, Raeder syndrome should alert the clinician toward requiring further investigations.11 Enquiries should be made about any recent neck manipulation or activity resulting in prolonged neck extension and rotation. Clinical cases have been noted following chiropractic treatment, prolonged insertion of ceiling tiles, a novice windsurfing, and so on.
INVESTIGATIONS Traditionally, confirmation of Horner syndrome was performed using topical cocaine 4% or 10% and hydroxyamphetamine 1% localization. Recently, the use of apraclonidine 1% has been advocated as a viable alternative to cocaine largely because of the difficulty in accessing cocaine legally. Hydroxyamphetamine has also become unavailable commercially. Neuroimaging has largely overtaken pharmacological testing for investigating the site of lesion causing Horner syndrome.14
Pharmacological In an eye unaffected by Horner syndrome, noradrenaline is normally released and reuptaken at postganglionic sympathetic nerve endings. This is blocked by cocaine. Therefore, in a normal eye, noradrenaline accumulates and results in prolonged dilatation. In a Horner syndrome pupil, there is no noradrenaline
FIGURE 2. Alternating Horner syndrome in a quadriplegicVlying on left side, lying on right side. * 2012 Asia Pacific Academy of Ophthalmology
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released, and therefore, the cocaine has no effect15 (Fig. 3). Evaluation of cocaine has shown that 0.8 mm of anisocoria after instillation of cocaine 10% makes Horner syndrome highly likely with a mean odds ratio of 1050:1.16 Hydroxyamphetamine potentiates the release of noradrenaline from postganglionic nerve endings resulting in pupil dilatation. In a postganglionic lesion, the neuron is destroyed, and there is no noradrenaline to be released, and hence, the Horner pupil will not dilate. In a preganglionic lesion, both pupils will dilate as noradrenaline is still present in the unaffected postganglionic neuron.17 Hydroxyamphetamine must be instilled 72 hours after the cocaine test because cocaine blocks the effectiveness of hydroxyamphetamine.7 It takes 1 week for the noradrenaline stores to be depleted, and so instilling hydroxyamphetamine within 1 week of the onset of Horner syndrome may result in spurious results.18 These potential limitations mean that, in an acute setting, the use of pharmacological testing to localize a Horner lesion may not be practical, and hence, neuroimaging may be more appropriate. Adrenaline 1:1000 or phenylephrine 1% has also been used to localize a Horner pupil. One percent phenylephrine has been found to be comparable to hydroxyamphetamine in terms of sensitivity and specificity and is readily available in most ophthalmic practices.19 The dilator pupillae muscle develops denervation hypersensitivity when it is deprived of its motor supply. Therefore, it will display heightened sensitivity to any adrenergic neurotransmitter. In a preganglionic lesion, this does not occur because the postganglionic neuron is intact, and so neither pupil will dilate (Supplementary Digital Content 4; http://links.lww.com/APJO/A16). The adrenaline is rapidly destroyed by monoamine oxidase produced by the postganglionic neuron. In a postganglionic lesion, however, the Horner pupil will dilate because of the absence of monoamine oxidase. The ptosis may also improve. This explains why Horner syndrome can improve with stress and the release of endogenous catecholamines.19 Apraclonidine 1% has recently been described as an alternative to cocaine for the diagnosis of Horner syndrome. It was first described by Morales et al20 in 2000. Apraclonidine is primarily an >2 agonist acting on the ciliary body to decrease aqueous production. However, it also exhibits weak >1 activity causing pupil dilation. It is proposed to work because of denervation hypersensitivity and upregulation in the number of >1 receptors in a Horner pupil, which results in dilation with instillation compared with no change or even constriction in the unaffected eye.20 However, it is not clear at what point after the onset of the Horner syndrome that this hypersensitivity
FIGURE 3. Right traumatic Horner syndrome from brachial plexus injury after a motorbike accident. Note that only the normal left pupil dilated on instillation of cocaine 10% drops. * 2012 Asia Pacific Academy of Ophthalmology
Horner Syndrome
FIGURE 4. Bilateral iatrogenic Horner syndrome after bilateral surgical sympathectomies for peripheral vascular disease.
occurs. The majority of case series that have shown success with apraclonidine have tested patients at least 1 month after the onset of symptoms, and although they have shown favorable results, the series of patients were small.21Y24 Other case reports have shown mixed results, with 1 patient having a positive apraclonidine test only 36 hours after a dorsolateral pontomedullary stroke25 and yet another with a negative apraclonidine test 16 days after an internal carotid artery dissection.26 There has also been concern due to recent reports of serious idiosyncratic adverse effects of apraclonidine, especially in children younger than 6 months. Adverse effects include excessive drowsiness, bradycardia, hypertension, and decreased oxygen saturations.27 Its use in children is therefore contraindicated. These preliminary results suggest that cocaine 10% for confirmation of Horner syndrome is still the criterion standard. However, given the difficulty in its access, it would be reasonable to use apraclonidine as an alternative in adults, keeping in mind that, early in the disease process, denervation hypersensitivity may not have occurred, leading to false negatives.
Neuroimaging Although neuroimaging can be extremely useful in helping to determine the etiology of Horner syndrome, it is very important that the imaging is targeted. It would be expensive and time consuming to try and image the entire oculosympathetic pathway. This again highlights the need and importance of taking an adequate history and examination to help determine the site of the suspected lesion along the pathway. If suspecting a central lesion, magnetic resonance imaging (MRI) T magnetic resonance angiography (MRA) is the imaging of choice that avoids the beam hardening artifact of computed tomography (CT) and allows clear resolution of the hypothalamus and midbrain structures. Diffusion-weighted imaging can also be useful in diagnosing stroke.11 In a preganglionic Horner syndrome, if a lung, anterior neck, or mediastinal mass is suspected on history, a contrast-enhanced CT is the imaging of choice. If there are brachial plexus or cervical/upper thoracic neurological symptoms or signs, an MRI should be considered.11 Magnetic resonance angiography or CT angiography (CTA) has largely superseded traditional angiography and is appropriate if suspecting a carotid artery dissection.10,11 Given the urgency of this diagnosis, it is often practically easier to obtain a CTA. In infants, where there is no reasonable explanation for Horner syndrome on history such as birth trauma, the current recommendation for investigation is urine catecholamine testing and MRI of the brain, neck, and chest looking for neuroblastoma.28 www.apjo.org
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TABLE 2. Breakdown of Site of Lesion in Horner Syndrome Case Series
2 3 11 20 17 12 12 77
A recent review of 52 patients referred for neuroophthalmology evaluation of Horner syndrome by Almog et al29 found that, in two thirds of patients, the cause of Horner syndrome will already be known at the time of the first consultation. These etiologies consisted of surgery or trauma to the neck, head, or chest; dorsolateral medullary stroke; or carotid dissection. Of the remaining third of patients, one half of these will have clinical clues that will allow localization of the lesion, and in these patients, targeted imaging will usually find the lesion. In the rest of the patients, nontargeted imaging will rarely find a responsible lesion. However, it is still necessary because life-threatening lesions such as malignancy can be detected. This highlights that although all of the above investigations are at a clinician’s disposal, not all are necessary or appropriate for each patient. With a thorough history and examination, it may be possible to avoid any investigations in up to two thirds of patients and only targeted investigations for one sixth.
CASE SERIES From 1979 to 2010, one of the authors (J.L.C.) has seen more than 70 patients with Horner syndrome. A retrospective review of the case notes of these patients was performed. A total of 77 patients were identified with Horner syndrome. Fifty-three of these patients had cocaine testing, which confirmed the diagnosis. The remainder were diagnosed based on clinical history and examination. Sixteen of the patients underwent pharmacological testing with either hydroxyamphetamine or phenylephrine to localize the lesion. Table 2 shows the breakdown of this testing. In the majority of patients, history and examination alone were enough to localize the lesion. There was an even distribution between central, preganglionic, and postganglionic Horner syn-
TABLE 3. Breakdown of Etiology in Horner Syndrome Case Series Cause
N
Trauma Surgery/iatrogenic Vascular Tumor Migraine/cluster headache Miscellaneous Unknown Total
15 6 18 7 6 3 22 77
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TABLE 4. Neuroimaging Approach n
Site of lesionVpharmacologically tested Central Preganglionic Postganglionic Site of lesionVpresumed based on history/examination Central Preganglionic Postganglionic Unknown Total
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Central Stroke Preganglionic Neck/mediastinal/lung pathology Brachial plexus/spinal cord Postganglionic Carotid dissection Infants
MRI T MRA Diffusion-weighted imaging Contrast-enhanced CT MRI MRA or CTA MRI + urine catecholamines
drome, which differs from other case series, which have shown a much lower prevalence of central Horner syndrome.12,13 Perhaps this reflects the tertiary nature of the referral pattern in our series from a major neurosciences and trauma hospital. Table 3 shows the breakdown of etiologies in our case series. Vascular causes accounted for 18 cases with an equal number of stroke and carotid dissections. There were 13 cases of trauma in adults and 2 in childrenVboth birth trauma. There were 6 cases of surgical/iatrogenic Horner syndromeVthese cases being as a result of intervention in the anterior neck. There were 7 tumors, 6 cases of migraine/cluster headache, and the miscellaneous cases of syringobulbia and multiple sclerosis. Twenty-two patients had an unknown etiology for Horner syndrome after investigation, which is a similar percentage to other studies.12,13,29 The majority of the patients did not require any further intervention or follow-up once diagnosis was established. There were a few patients who underwent ptosis surgery, but the majority of patients were not troubled by the anisocoria.
CONCLUSIONS Our approach to a patient presenting with suspected Horner syndrome would be to first take a thorough history and examination looking for associated symptoms or signs that will help localize the site of a lesion. The presence of Horner syndrome should be confirmed through the clinical features described but also with topical cocaine 10% if possible, as this still remains the criterion standard. Given the concerns with safety, apraclonidine is not recommended in young children and/or infants. If cocaine is not available, apraclonidine is a reasonable alternative in adults. However, one should be aware that there may be false negatives early in the disease process. If there is enough information on history and examination to explain the diagnosis, no further investigations are required. However, if a diagnosis cannot be made although there are localizing signs, targeted imaging as outlined in Table 4 should be performed. The timing of imaging will depend on the suspected diagnosis. For example, carotid artery dissection is an urgent diagnosis to be excluded, and a suspected Pancoast tumor is also relatively urgent. Finally, if there are no clues as to making a diagnosis, topical phenylephrine may be useful in differentiating postganglionic lesions, although patients often end up requiring nonselective imaging from the upper chest to the brain. Although this has a low yield, it can rarely detect life-threatening lesions and so is still worthwhile. Given the limited availability of hydroxyamphetamine, phenylephrine is preferred. REFERENCES 1. du Petit FP. Me´moire dans lequel il est de´montre´ que les nerfs intercostaux fournissent des rameaux que portent des esprits dans les yeux. Hist Acad Roy Sci. 1727:1Y19.
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2. Bernard C. Des phe´nome`nes oculo-pupillaires produits par la section du nerf sympathique cervical: ils sont inde´pendants des phe´nome`nes vasculaires calorifi ques de la teˆte. Comptes Rendus Acad Sci. 1852;55:381Y388. 3. Weir Mitchell S, Keen W Jr, Morehouse GR. Gunshot Wounds and Other Injuries of Nerves. Philadelphia, PA: Lippincott; 1864. (Reprinted: San Francisco: Norman Publishing; 1989.) 4. Horner JF. On a form of ptosis. Klin Monatsbl Augenheilkd. 1869;7:193Y198. 5. Thompson HS. The pupil. In: Adler’s Physiology of the Eye. 9th ed. Hart WM Jr, ed. St Louis, MO: Mosby-Year Book; 1992:412Y441. 6. Snell RS, Lemp MA. Clinical Anatomy of the Eye. 2nd ed. Boston, MA: Blackwell Publishing; 1998:352Y358. 7. Reede DL, Garcon E, Smoker WR, et al. Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am. 2008;18:369Y385, xi. 8. Pilley SF, Thompson HS. Pupillary ‘‘dilatation lag’’ in Horner’s syndrome. Br J Ophthalmol. 1975;59:731Y735. 9. Morrison DA, Bibby K, Woodruff G. The ‘‘harlequin’’ sign and congenital Horner’s syndrome. J Neurol Neurosurg Psychiatry. 1997;62:626Y628.
Horner Syndrome
cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol. 1990;108:384Y387. 17. Cremer SA, Thompson HS, Digre KB, et al. Hydroxyamphetamine mydriasis in Horner’s syndrome. Am J Ophthalmol. 1990;110:71Y76. 18. Donahue SP, Lavin PJ, Digre K. False negative hydroxyamphetamine test in acute Horner’s syndrome. Am J Ophthalmol. 1996;122:900Y901. 19. Danesh-Meyer HV, Savino P, Sergott R. The correlation of phenylephrine 1% with hydroxyamphetamine 1% in Horner’s syndrome. Br J Ophthalmol. 2004;88:592Y593. 20. Morales J, Brown S, Abdul-Rahim A, et al. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol. 2000;118:951Y954. 21. Brown S, Aouchich R, Freedman K. The utility of 0.5% apraclonidine in the diagnosis of Horner syndrome. Arch Ophthalmol. 2003;121:1201Y1203. 22. Bacal D, Levy S. The use of apraclonidine in the diagnosis of Horner syndrome in paediatric patients. Arch Ophthalmol. 2004;122:276Y279. 23. Koc F, Kavuncu S, Kansu T, et al. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol. 2005;89:1442Y1444.
10. George A, Haydar AA, Adams WM. Imaging of Horner’s syndrome. Clin Radiol. 2008;63:499Y505.
24. Chen PL, Hsiao CH, Chen JT, et al. Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol. 2006;142:469Y474.
11. Lee JH, Lee HK, Lee DH, et al. Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. AJR Am J Roentgenol. 2007;188:W74YW81.
25. Lebas M, Seror J, Debroucker T. Positive apraclonidine test 36 hours after acute onset of Horner syndrome in dorsolateral pontomedullary stroke. J Neuroophthal. 2010;30:12Y17.
12. Maloney WF, Younge BR, Moyer NJ. Evaluation of the causes and accuracy of pharmacologic localization in Horner’s syndrome. Am J Ophthalmol. 1980;90:394Y402.
26. Dewan MA, Harrison AR, Lee MS. False-negative apraclonidine testing in acute Horner syndrome. Can J Ophthalmol. 2009;44:109Y110.
13. Giles CL, Henderson JW. Horner’s syndrome: an analysis of 216 cases. Am J Ophthalmol. 1958;46:289Y296. 14. Mughal M, Longmuir R. Current pharmacological testing for Horner syndrome. Curr Neurol Neurosci Rep. 2009;9:384Y389. 15. Kardon RH. The pupils and accommodation. In: Principles and Practice of Ophthalmology. 2nd ed. Albert DM, Jakobiec FA, eds. Philadelphia, PA: WB Saunders Co; 2000:4029Y4051. 16. Kardon RH, Denison CE, Brown CK, et al. Critical evaluation of the
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27. Watts P, Satterfield D, Lim MK. Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants. J AAPOS. 2007;11:282Y283. 28. Mahoney NR, Liu GT, Menacker SJ, et al. Pediatric Horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol. 2006;142:651Y659. 29. Almog Y, Gepstein R, Kelser A. Diagnostic value of imaging in Horner Syndrome in adults. J Neurophthal. 2010;30:7Y11.
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Horner Syndrome: A Practical Approach to Investigation and Management Zoe Gao, MBBS* and John L. Crompton, MBBS, FRANZCO, FRACS*Þ Abstract: Horner syndrome is typically described by the classic triad of blepharoptosis, miosis, and anhydrosis resulting from disruption along the oculosympathetic pathway. Because of the complex and extensive course of this pathway, there are a large number of causes of Horner syndrome ranging from benign to life-threatening diseases. This review article aims to provide a practical approach to investigation and management, including evaluation of the more recent use of apraclonidine for pharmacological testing. Key Words: Horner syndrome, oculosympathetic pathway (Asia-Pac J Ophthalmol 2012;1: 175Y179)
H
orner syndrome is caused by disruption at some point along the oculosympathethic pathway from the hypothalamus to the eye, resulting in the clinical features of miosis, ptosis, and anhydrosis. It was first described by Francois Pourfour du Petit1 in 1727 when he noted changes in the eyes and snout of dogs after cutting the intercostal nerves in their necks. In 1852, Claude Bernard,2 a French physiologist, described the syndrome in more detail (and hence it is known as Bernard-Horner syndrome in France), and in 1864, 3 American army physicians Silas Weir Mitchell, William Keen, Jr, and George Read Morehouse published a clinical report of the syndrome in a man shot through the throat.3 However, it was only in 1869 that the Swiss ophthalmologist Johann Friedrich Horner described the classic triad of findings, and the syndrome subsequently bore his name.4 Because the oculosympathetic pathway has a long course, there is the potential for involvement by many different disease processes. However, given that some are potentially lifethreatening such as internal carotid dissection and malignancies, it is important to have a systematic approach to diagnosis and management. This review discusses the important anatomic features, clinical features, and investigations that should be ordered, as well as experience from our center over the last 30 years.
CLINICAL ANATOMY The oculosympathetic pathway consists of 3 orders of neurons. The first-order neuron, which if affected would result in a central Horner syndrome, originates in the posterior lateral aspect of the hypothalamus and descends uncrossed down the brainstem and terminates in the ciliospinal center of BudgeWaller. This spans the intermediolateral horn of the spinal cord from C8 to T2.5,6 From the *South Australian Institute of Ophthalmology, Adelaide, c/o Royal Adelaide Hospital; and †Discipline of Ophthalmology & Visual Sciences, University of Adelaide, North Terrace, South Australia, Australia. Received for publication February 4, 2012; accepted March 16, 2012. The authors have no funding or conflicts of interest to declare. Informed consent was obtained from all patients for use of images in this review. Reprints: Zoe Gao, MBBS, Royal Victorian Eye and Ear Hospital, 32 Gisborne St, E Melbourne, Victoria 3002, Australia. E-mail: [email protected]. Copyright * 2012 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.1097/APO.0b013e318256009d
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The second-order or preganglionic neuron leaves the ciliospinal center of Budge-Waller via the ventral spinal roots of C8-T2 and passes through the inferior and middle cervical ganglia before synapsing at the superior cervical ganglion in the neck. During its course, it is closely related to the apical pleura and can therefore be damaged by lung cancer (Pancoast tumor: Figure, Supplementary Digital Content 1; http://links.lww.com/ APJO/A12 and http://links.lww.com/APJO/A13). The superior cervical ganglion is located at the level of C2-C3 posterior to the carotid sheath at the level of the angle of the mandible. The sympathetic sudomotor and vasoconstrictor fibers to the face leave prior to the superior cervical ganglion at the bifurcation of the common carotid artery into the internal and external carotid arteries. Therefore, a postganglionic lesion will not be associated with significant anhydrosis.5,6 The postganglionic neuron ascends along the internal carotid artery as a plexus before dividing into a medial and lateral branch. The medial branch enters the cavernous sinus and joins the oculomotor nerve before innervating Mu¨ller muscle in the upper and lower lids. The lateral branch joins the abducens nerve briefly and then the ophthalmic division of the trigeminal nerve, before reaching the dilator pupillae of the iris via the nasociliary nerve and long ciliary nerves.5Y7 Given the long course of the oculosympathetic pathway, it is not surprising that the causes of Horner syndrome are diverse, and it may not be easy to determine the etiology (Table 1).
CLINICAL SIGNS Horner syndrome results in miosis and mild ptosis as a result of unopposed action of the sphincter pupillae and weakness of Mu¨ller muscle, respectively. These 2 signs are the most constant findings in Horner syndrome. The anisocoria is accentuated in dim light, and there is a dilation lag where the affected pupil dilates slower compared with the healthy pupil because of lack of pull from the dilator muscle.8 In addition, apparent enophthalmos due to ptosis (elevation) of the lower lid may be present. If the lesion is congenital or longstanding, there may be hypochromic heterochromia of the iris (Fig. 1). This sign is not, however, useful in the perinatal period because iris color is not established until several months of age (Supplementary Digital Content 2; http://links.lww.com/ APJO/A14). Anhydrosis is not always present and although helpful is rarely elicited.7 Harlequin sign refers to unilateral facial flushing that can occur in congenital Horner syndrome. The areas that do not flush correspond with anhydrotic areas. There is also a decrease in the skin temperature on the affected side. These findings are the result of impaired sympathetic vasodilatation.9 Conjunctival hyperemia may be present as an early transient sign in response to loss of sympathetic innervation to the conjunctival vessels resulting in vasodilation. This sign is rarely present for more than a few weeks.5 Rarely, Horner syndrome may alternate between the 2 sides. We have observed 2 such cases in quadriplegics with secondary syringobulbia (Fig. 2). Both of these patients developed miosis in the dependent eye, when changed from lying from one side to the
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TABLE 1. Breakdown of Causes of Horner Syndrome Based on Anatomic Location Anatomic Site Central
Preganglionic
Postganglionic
Etiologies Hypothalamus Stroke Tumor Brainstem disease StrokeVPICA/vertebral artery ) Lateral medullary syndrome Demyelination Tumor Syringomyelia Cervical/thoracic myelitis Spinal cord tumor Diabetic autonomic neuropathy AVM Tumor Thyroid/mediastinal Neuroblastoma Sympathetic schwannoma Pancoast Trauma, including birth trauma Brachial plexus injury Postsurgical/iatrogenic Sympathectomy for peripheral vascular disease, hyperhydrosis Surgery for thyroid and parathyroid disease Carotid and aortic/subclavian aneurysm and dissection Cervical rib Osteophytes Postsurgical/iatrogenic Trauma Cluster/migraine headaches Internal carotid artery dissection/aneurysm Jugular venous ectasia Fibromuscular dysplasia Skull base lesions Nasopharyngeal tumor Otitis media Cavernous sinus mass/inflammation/infection Internal carotid arteritis
Those in bold type are the more common causes. AVM indicates arteriovenous malformation; PICA, posterior inferior cerebellar artery.
other, thought to be due to pressure of the cerebrospinal fluid in the syrinx on the sympathetic fibers running down the midbrain. Although the above signs describe Horner syndrome, in clinical practice, it is other features on history and examination that will guide further investigation and management. This is highlighted below with photographs of some clinical cases the author (J.L.C.) has been involved with. A central Horner syndrome is unlikely to be in isolation because of the close proximity of other structures within the hypothalamus, brainstem, and spinal cord10 (Supplementary Digital Content 3; http:// links.lww.com/APJO/A15). Patients may present with vertigo, ataxia, contralateral loss of pain and temperature sensation,
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FIGURE 1. Congenital right Horner syndrome from right brachial plexus birth trauma. Her right iris never developed pigmentation.
swallowing difficulties, or unilateral facial numbness. The causes of a preganglionic Horner are often trauma (Fig. 3) or iatrogenic (Fig. 4), which should be elicited from a thorough history.11Y13 Postganglionic Horner syndrome may have localizing signs such as involvement of other cranial nerves secondary to cavernous sinus pathology. For example, cavernous sinus masses from metastases, pituitary tumor invasion, or aneurysms can cause Horner syndrome and isolated abducens nerve palsy. A Horner syndrome associated with pain in the face and neckV Raeder paratrigeminal syndromeVcan be associated with the serious diagnosis of a carotid artery dissection. Although there are other more benign causes such as cluster headache, Raeder syndrome should alert the clinician toward requiring further investigations.11 Enquiries should be made about any recent neck manipulation or activity resulting in prolonged neck extension and rotation. Clinical cases have been noted following chiropractic treatment, prolonged insertion of ceiling tiles, a novice windsurfing, and so on.
INVESTIGATIONS Traditionally, confirmation of Horner syndrome was performed using topical cocaine 4% or 10% and hydroxyamphetamine 1% localization. Recently, the use of apraclonidine 1% has been advocated as a viable alternative to cocaine largely because of the difficulty in accessing cocaine legally. Hydroxyamphetamine has also become unavailable commercially. Neuroimaging has largely overtaken pharmacological testing for investigating the site of lesion causing Horner syndrome.14
Pharmacological In an eye unaffected by Horner syndrome, noradrenaline is normally released and reuptaken at postganglionic sympathetic nerve endings. This is blocked by cocaine. Therefore, in a normal eye, noradrenaline accumulates and results in prolonged dilatation. In a Horner syndrome pupil, there is no noradrenaline
FIGURE 2. Alternating Horner syndrome in a quadriplegicVlying on left side, lying on right side. * 2012 Asia Pacific Academy of Ophthalmology
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released, and therefore, the cocaine has no effect15 (Fig. 3). Evaluation of cocaine has shown that 0.8 mm of anisocoria after instillation of cocaine 10% makes Horner syndrome highly likely with a mean odds ratio of 1050:1.16 Hydroxyamphetamine potentiates the release of noradrenaline from postganglionic nerve endings resulting in pupil dilatation. In a postganglionic lesion, the neuron is destroyed, and there is no noradrenaline to be released, and hence, the Horner pupil will not dilate. In a preganglionic lesion, both pupils will dilate as noradrenaline is still present in the unaffected postganglionic neuron.17 Hydroxyamphetamine must be instilled 72 hours after the cocaine test because cocaine blocks the effectiveness of hydroxyamphetamine.7 It takes 1 week for the noradrenaline stores to be depleted, and so instilling hydroxyamphetamine within 1 week of the onset of Horner syndrome may result in spurious results.18 These potential limitations mean that, in an acute setting, the use of pharmacological testing to localize a Horner lesion may not be practical, and hence, neuroimaging may be more appropriate. Adrenaline 1:1000 or phenylephrine 1% has also been used to localize a Horner pupil. One percent phenylephrine has been found to be comparable to hydroxyamphetamine in terms of sensitivity and specificity and is readily available in most ophthalmic practices.19 The dilator pupillae muscle develops denervation hypersensitivity when it is deprived of its motor supply. Therefore, it will display heightened sensitivity to any adrenergic neurotransmitter. In a preganglionic lesion, this does not occur because the postganglionic neuron is intact, and so neither pupil will dilate (Supplementary Digital Content 4; http://links.lww.com/APJO/A16). The adrenaline is rapidly destroyed by monoamine oxidase produced by the postganglionic neuron. In a postganglionic lesion, however, the Horner pupil will dilate because of the absence of monoamine oxidase. The ptosis may also improve. This explains why Horner syndrome can improve with stress and the release of endogenous catecholamines.19 Apraclonidine 1% has recently been described as an alternative to cocaine for the diagnosis of Horner syndrome. It was first described by Morales et al20 in 2000. Apraclonidine is primarily an >2 agonist acting on the ciliary body to decrease aqueous production. However, it also exhibits weak >1 activity causing pupil dilation. It is proposed to work because of denervation hypersensitivity and upregulation in the number of >1 receptors in a Horner pupil, which results in dilation with instillation compared with no change or even constriction in the unaffected eye.20 However, it is not clear at what point after the onset of the Horner syndrome that this hypersensitivity
FIGURE 3. Right traumatic Horner syndrome from brachial plexus injury after a motorbike accident. Note that only the normal left pupil dilated on instillation of cocaine 10% drops. * 2012 Asia Pacific Academy of Ophthalmology
Horner Syndrome
FIGURE 4. Bilateral iatrogenic Horner syndrome after bilateral surgical sympathectomies for peripheral vascular disease.
occurs. The majority of case series that have shown success with apraclonidine have tested patients at least 1 month after the onset of symptoms, and although they have shown favorable results, the series of patients were small.21Y24 Other case reports have shown mixed results, with 1 patient having a positive apraclonidine test only 36 hours after a dorsolateral pontomedullary stroke25 and yet another with a negative apraclonidine test 16 days after an internal carotid artery dissection.26 There has also been concern due to recent reports of serious idiosyncratic adverse effects of apraclonidine, especially in children younger than 6 months. Adverse effects include excessive drowsiness, bradycardia, hypertension, and decreased oxygen saturations.27 Its use in children is therefore contraindicated. These preliminary results suggest that cocaine 10% for confirmation of Horner syndrome is still the criterion standard. However, given the difficulty in its access, it would be reasonable to use apraclonidine as an alternative in adults, keeping in mind that, early in the disease process, denervation hypersensitivity may not have occurred, leading to false negatives.
Neuroimaging Although neuroimaging can be extremely useful in helping to determine the etiology of Horner syndrome, it is very important that the imaging is targeted. It would be expensive and time consuming to try and image the entire oculosympathetic pathway. This again highlights the need and importance of taking an adequate history and examination to help determine the site of the suspected lesion along the pathway. If suspecting a central lesion, magnetic resonance imaging (MRI) T magnetic resonance angiography (MRA) is the imaging of choice that avoids the beam hardening artifact of computed tomography (CT) and allows clear resolution of the hypothalamus and midbrain structures. Diffusion-weighted imaging can also be useful in diagnosing stroke.11 In a preganglionic Horner syndrome, if a lung, anterior neck, or mediastinal mass is suspected on history, a contrast-enhanced CT is the imaging of choice. If there are brachial plexus or cervical/upper thoracic neurological symptoms or signs, an MRI should be considered.11 Magnetic resonance angiography or CT angiography (CTA) has largely superseded traditional angiography and is appropriate if suspecting a carotid artery dissection.10,11 Given the urgency of this diagnosis, it is often practically easier to obtain a CTA. In infants, where there is no reasonable explanation for Horner syndrome on history such as birth trauma, the current recommendation for investigation is urine catecholamine testing and MRI of the brain, neck, and chest looking for neuroblastoma.28 www.apjo.org
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Gao and Crompton
TABLE 2. Breakdown of Site of Lesion in Horner Syndrome Case Series
2 3 11 20 17 12 12 77
A recent review of 52 patients referred for neuroophthalmology evaluation of Horner syndrome by Almog et al29 found that, in two thirds of patients, the cause of Horner syndrome will already be known at the time of the first consultation. These etiologies consisted of surgery or trauma to the neck, head, or chest; dorsolateral medullary stroke; or carotid dissection. Of the remaining third of patients, one half of these will have clinical clues that will allow localization of the lesion, and in these patients, targeted imaging will usually find the lesion. In the rest of the patients, nontargeted imaging will rarely find a responsible lesion. However, it is still necessary because life-threatening lesions such as malignancy can be detected. This highlights that although all of the above investigations are at a clinician’s disposal, not all are necessary or appropriate for each patient. With a thorough history and examination, it may be possible to avoid any investigations in up to two thirds of patients and only targeted investigations for one sixth.
CASE SERIES From 1979 to 2010, one of the authors (J.L.C.) has seen more than 70 patients with Horner syndrome. A retrospective review of the case notes of these patients was performed. A total of 77 patients were identified with Horner syndrome. Fifty-three of these patients had cocaine testing, which confirmed the diagnosis. The remainder were diagnosed based on clinical history and examination. Sixteen of the patients underwent pharmacological testing with either hydroxyamphetamine or phenylephrine to localize the lesion. Table 2 shows the breakdown of this testing. In the majority of patients, history and examination alone were enough to localize the lesion. There was an even distribution between central, preganglionic, and postganglionic Horner syn-
TABLE 3. Breakdown of Etiology in Horner Syndrome Case Series Cause
N
Trauma Surgery/iatrogenic Vascular Tumor Migraine/cluster headache Miscellaneous Unknown Total
15 6 18 7 6 3 22 77
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TABLE 4. Neuroimaging Approach n
Site of lesionVpharmacologically tested Central Preganglionic Postganglionic Site of lesionVpresumed based on history/examination Central Preganglionic Postganglionic Unknown Total
&
Central Stroke Preganglionic Neck/mediastinal/lung pathology Brachial plexus/spinal cord Postganglionic Carotid dissection Infants
MRI T MRA Diffusion-weighted imaging Contrast-enhanced CT MRI MRA or CTA MRI + urine catecholamines
drome, which differs from other case series, which have shown a much lower prevalence of central Horner syndrome.12,13 Perhaps this reflects the tertiary nature of the referral pattern in our series from a major neurosciences and trauma hospital. Table 3 shows the breakdown of etiologies in our case series. Vascular causes accounted for 18 cases with an equal number of stroke and carotid dissections. There were 13 cases of trauma in adults and 2 in childrenVboth birth trauma. There were 6 cases of surgical/iatrogenic Horner syndromeVthese cases being as a result of intervention in the anterior neck. There were 7 tumors, 6 cases of migraine/cluster headache, and the miscellaneous cases of syringobulbia and multiple sclerosis. Twenty-two patients had an unknown etiology for Horner syndrome after investigation, which is a similar percentage to other studies.12,13,29 The majority of the patients did not require any further intervention or follow-up once diagnosis was established. There were a few patients who underwent ptosis surgery, but the majority of patients were not troubled by the anisocoria.
CONCLUSIONS Our approach to a patient presenting with suspected Horner syndrome would be to first take a thorough history and examination looking for associated symptoms or signs that will help localize the site of a lesion. The presence of Horner syndrome should be confirmed through the clinical features described but also with topical cocaine 10% if possible, as this still remains the criterion standard. Given the concerns with safety, apraclonidine is not recommended in young children and/or infants. If cocaine is not available, apraclonidine is a reasonable alternative in adults. However, one should be aware that there may be false negatives early in the disease process. If there is enough information on history and examination to explain the diagnosis, no further investigations are required. However, if a diagnosis cannot be made although there are localizing signs, targeted imaging as outlined in Table 4 should be performed. The timing of imaging will depend on the suspected diagnosis. For example, carotid artery dissection is an urgent diagnosis to be excluded, and a suspected Pancoast tumor is also relatively urgent. Finally, if there are no clues as to making a diagnosis, topical phenylephrine may be useful in differentiating postganglionic lesions, although patients often end up requiring nonselective imaging from the upper chest to the brain. Although this has a low yield, it can rarely detect life-threatening lesions and so is still worthwhile. Given the limited availability of hydroxyamphetamine, phenylephrine is preferred. REFERENCES 1. du Petit FP. Me´moire dans lequel il est de´montre´ que les nerfs intercostaux fournissent des rameaux que portent des esprits dans les yeux. Hist Acad Roy Sci. 1727:1Y19.
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2. Bernard C. Des phe´nome`nes oculo-pupillaires produits par la section du nerf sympathique cervical: ils sont inde´pendants des phe´nome`nes vasculaires calorifi ques de la teˆte. Comptes Rendus Acad Sci. 1852;55:381Y388. 3. Weir Mitchell S, Keen W Jr, Morehouse GR. Gunshot Wounds and Other Injuries of Nerves. Philadelphia, PA: Lippincott; 1864. (Reprinted: San Francisco: Norman Publishing; 1989.) 4. Horner JF. On a form of ptosis. Klin Monatsbl Augenheilkd. 1869;7:193Y198. 5. Thompson HS. The pupil. In: Adler’s Physiology of the Eye. 9th ed. Hart WM Jr, ed. St Louis, MO: Mosby-Year Book; 1992:412Y441. 6. Snell RS, Lemp MA. Clinical Anatomy of the Eye. 2nd ed. Boston, MA: Blackwell Publishing; 1998:352Y358. 7. Reede DL, Garcon E, Smoker WR, et al. Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am. 2008;18:369Y385, xi. 8. Pilley SF, Thompson HS. Pupillary ‘‘dilatation lag’’ in Horner’s syndrome. Br J Ophthalmol. 1975;59:731Y735. 9. Morrison DA, Bibby K, Woodruff G. The ‘‘harlequin’’ sign and congenital Horner’s syndrome. J Neurol Neurosurg Psychiatry. 1997;62:626Y628.
Horner Syndrome
cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol. 1990;108:384Y387. 17. Cremer SA, Thompson HS, Digre KB, et al. Hydroxyamphetamine mydriasis in Horner’s syndrome. Am J Ophthalmol. 1990;110:71Y76. 18. Donahue SP, Lavin PJ, Digre K. False negative hydroxyamphetamine test in acute Horner’s syndrome. Am J Ophthalmol. 1996;122:900Y901. 19. Danesh-Meyer HV, Savino P, Sergott R. The correlation of phenylephrine 1% with hydroxyamphetamine 1% in Horner’s syndrome. Br J Ophthalmol. 2004;88:592Y593. 20. Morales J, Brown S, Abdul-Rahim A, et al. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol. 2000;118:951Y954. 21. Brown S, Aouchich R, Freedman K. The utility of 0.5% apraclonidine in the diagnosis of Horner syndrome. Arch Ophthalmol. 2003;121:1201Y1203. 22. Bacal D, Levy S. The use of apraclonidine in the diagnosis of Horner syndrome in paediatric patients. Arch Ophthalmol. 2004;122:276Y279. 23. Koc F, Kavuncu S, Kansu T, et al. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol. 2005;89:1442Y1444.
10. George A, Haydar AA, Adams WM. Imaging of Horner’s syndrome. Clin Radiol. 2008;63:499Y505.
24. Chen PL, Hsiao CH, Chen JT, et al. Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol. 2006;142:469Y474.
11. Lee JH, Lee HK, Lee DH, et al. Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. AJR Am J Roentgenol. 2007;188:W74YW81.
25. Lebas M, Seror J, Debroucker T. Positive apraclonidine test 36 hours after acute onset of Horner syndrome in dorsolateral pontomedullary stroke. J Neuroophthal. 2010;30:12Y17.
12. Maloney WF, Younge BR, Moyer NJ. Evaluation of the causes and accuracy of pharmacologic localization in Horner’s syndrome. Am J Ophthalmol. 1980;90:394Y402.
26. Dewan MA, Harrison AR, Lee MS. False-negative apraclonidine testing in acute Horner syndrome. Can J Ophthalmol. 2009;44:109Y110.
13. Giles CL, Henderson JW. Horner’s syndrome: an analysis of 216 cases. Am J Ophthalmol. 1958;46:289Y296. 14. Mughal M, Longmuir R. Current pharmacological testing for Horner syndrome. Curr Neurol Neurosci Rep. 2009;9:384Y389. 15. Kardon RH. The pupils and accommodation. In: Principles and Practice of Ophthalmology. 2nd ed. Albert DM, Jakobiec FA, eds. Philadelphia, PA: WB Saunders Co; 2000:4029Y4051. 16. Kardon RH, Denison CE, Brown CK, et al. Critical evaluation of the
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27. Watts P, Satterfield D, Lim MK. Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants. J AAPOS. 2007;11:282Y283. 28. Mahoney NR, Liu GT, Menacker SJ, et al. Pediatric Horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol. 2006;142:651Y659. 29. Almog Y, Gepstein R, Kelser A. Diagnostic value of imaging in Horner Syndrome in adults. J Neurophthal. 2010;30:7Y11.
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