Clinical Radiology (2008) 63, 499e505

REVIEW

Imaging of Horner’s syndrome
A. George, A.A. Haydar, W.M. Adams*
Derriford Hospital Plymouth, Derriford, Plymouth, UK
Received 25 September 2007; received in revised form 10 December 2007; accepted 14 December 2007

Horner’s syndrome, or oculosympathetic paresis, results from interruption of the sympathetic trunk innervation to the eye and presents typically with meiosis, ptosis and facial anhydrosis on the affected side.1 The pathological process ranges from benign, such as cluster headache, or life threatening, such as lung malignancy. Appropriate imaging requires an anatomical appreciation of the complex and circuitous route the neuronal pathway takes as it passes from the central nervous system to the eye. ª 2007 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction
The first description of the syndrome of oculosympathetic paresis occurred as early as 1727 by Francois Pourfour du Petit after experimental transection of the intercostal nerves of dogs. In 1852 Claude Bernard, vivisector and son of a French winegrower, gave a more complete description of the syndrome, which the French recognize as BernardeHorner syndrome. Johann Friedrich Horner, a Swiss ophthalmologist practising in Zurich and one of the first to associate diseases of the eye with other disorders of the body, described the classical features of the syndrome in 1869.2 Horner’s syndrome results from interruption of the sympathetic innervation to the eye and presents typically with meiosis (a constricted pupil), blepharoptosis (a drooping eyelid), enophthalmos (a sunken globe), a narrow palpebral fissure and facial anhydrosis on the affected side.1 A number of pathologies can affect the oculosympathetic pathway ranging from the benign, such as cluster headache, or life threatening, such as an apical Pancoast’s tumour. Appropriate imaging requires both close liaison with the physicians and an accurate
* Guarantor and correspondent: W.M. Adams, Derriford Hospital Plymouth, Derriford, Plymouth PL6 8DH, UK. Tel.: þ44 1752 517917; fax: þ44 1752 763277. E-mail address: william.adams@phnt.swest.nhs.uk (W.M. Adams).

anatomical appreciation of the complex and circuitous route the neuronal pathway takes as it passes from the central nervous system to the eye.

Anatomy
The three-neuron oculosympathetic pathway begins in the hypothalamus and ends in the eye (Fig. 1).

Central
First-order neurons descend caudally from the dorsolateral hypothalamus into the midbrain, passing lateral to the nucleus of the fourth nerve. The fibres traverse anteriorly at the level of the pontomedullary junction from the region of the locus ceruleus in the floor of the fourth ventricle to lie anterior to the inferior olivary nucleus.1 The ipsilateral spinothalamic tract and vestibular structures are in close proximity at this point. On reaching the cervical spinal cord, the first-order fibres pass lateral to the dorsal grey matter to the first synapse located at levels C8-T2 (also called the ciliospinal centre of Budge).

Preganglionic
Second-order neurons exit the spinal cord at the level of the C8 to T2 ventral roots. The fibres

0009-9260/$ - see front matter ª 2007 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2007.12.006

Plymouth. The posterior cord is often fenestrated to enclose the vertebral artery.4 Sympathetic denervation to the corresponding muscle of the inferior eyelid produces lower lid elevation. The ptosis occurs as a result of denervation of Muller’s muscle. George et al. a narrow palpebral fissure with or without loss of ipsilateral sweating (facial anhydrosis). The fibres synapse in the superior cervical ganglion. The middle cervical ganglion is connected to the inferior cervical ganglion by two or more cords. those for the remainder of the face follow the external carotid plexus. If the disruption is traverse the inferior (often fused with the first thoracic ganglion to form the cervico-thoracic or stellate ganglion) and middle cervical ganglia to synapse in the superior cervical ganglion. Within the orbit: (1) Sympathetic branches of the nasociliary nerve supply the dilator pupillae. salivary gland secretion. Figure 1 Anatomical pathway of the sympathetic supply to the pupil and eyelids. Anterior to it lie the vertebral artery and veins and inferiorly the lung apex. reduced ipsilateral sweating occurs. UK. ophthalmic. The medial branch lies medial to the internal carotid artery within the cavernous sinus. Because it is responsible for about 2 mm of elevation. Sudomotor fibres responsible for vasoconstriction and sweating in the forehead follow the internal carotid plexus. This is because fibres supplying the sweat glands follow the course of the external carotid artery. Courtesy: Medical Illustrations. pupillary dilatation. a contracted pupil (meiosis). the . and the smooth muscles in the upper and lower eyelids. These ganglia are in effect the continuation of the sympathetic trunk. Anisocoria (the difference in size between the affected and non-affected pupil) is accentuated in dim light. and (3) Sympathetic fibres innervate the lacrimal gland. which acts as an accessory elevator of the upper eyelid. Derriford Hospital. The anterior cord (ansa subclavia) passes over the cervical pleura and then inferior to the first part of the subclavian artery. Postganglionic Third-order neurons leave the superior cervical ganglion to form a sympathetic plexus. The inferior cervical ganglion lies between the base of the transverse process of the seventh cervical vertebra and the neck of the first rib. Pupillary meiosis is a consequence of loss of the balance between the sympathetic system controlling the iris dilator muscle and the parasympathetic system supplying the iris constrictor muscle.500 A. which can have a varied course.3 Fibres continue without synapsing through the superior orbital fissure and ciliary ganglion into the orbit to supply the blood vessels of the eyeball. The postganglionic branches influence vasoconstriction and sweating in the face and neck. On entering the bony carotid canal. It supplies branches to the oculomotor. If the oculosympathetic pathway is interrupted below the superior cervical ganglion (central or preganglionic). the resultant ptosis is subtle. the internal carotid nerve divides into medial and lateral branches forming the carotid plexus. a sunken globe (enophthalmos). Sympathetic innervation of pupillary muscles Müller’s muscle Sudomotor and vasoconstrictor fibres to forehead Hypothalamus Pons Pupil dilator Long ciliary nerve Ophthalmic artery V * Medulla Nasociliary nerve Carotid plexus Postganglionic neuron Sudomotor and vasoconstrictor fibres to face Superior cervical ganglion Internal carotid artery External carotid artery Preganglionic neuron Central neuron Inferior cervical ganglion Subclavian artery Lung Ciliospinal centre of Budge internal carotid nerve. and also the ciliary ganglion. The lateral branch communicates with the trigeminal ganglion and the abducens nerve. located near the angle of the mandible and the bifurcation of the common carotid artery. trochlear. and abducens nerves. (2) Fibres from the oculomotor nerve supply small smooth muscles in both the upper and lower eyelids responsible for a minor portion of upper lid elevation (Mu ¨ller’s muscle) and retraction. Clinical features Disruption of the oculosympathetic pathway anywhere along its course results in mild drooping of the ipsilateral upper eyelid (ptosis).

lymphoma) Cavernous sinus lesion Tumours Invasive pituitary tumour Inflammation Thrombosis Carotid aneurysm .12 Table 1 Causes of Horner’s syndrome in adults Preganglionic (second order) Postganglionic (third order) Central (first order) Hypothalamus Tumour Stroke Brainstem Demyelination Stroke Tumour Cervicothoracic spinal cord Myelitis Syringomyelia Arteriovenous malformation Demyelination Infarction Tumour Trauma Pulmonary apical lesions Subclavian artery aneurysm Apical lung tumour (Pancoast tumour) Mediastinal tumours Cervical rib Iatrogenic Thyroid malignancy Superior cervical ganglion Trauma Jugular venous ectasia Iatrogenic (surgical neck dissection) Internal carotid artery Dissection Aneurysm Trauma Arteritis Thrombosis Tumour Skull-base lesions (nasopharyngeal carcinoma. unilateral facial numbness. however. in clinical practice pharmacological testing is rarely applied. pre and postganglionic disease is reliant on recognizing the clinical clues available.. 5th and 6th cranial nerves. which can involve both the brain and spinal cord. a patient presenting with a lesion in the cavernous sinus will often have accompanying deficits affecting to varying degree the 3rd. 4th. Horner’s syndrome may be an additional feature of a Pancoast tumour. and loss of pain and temperature sensation in the opposite limbs.10 Tumour. and other vascular diseases. 2). brainstem or spinal cord central Horner’s syndrome in isolation is unlikely. Therefore. presumed related to vascular disease. of cases of Horner’s syndrome had an unknown diagnosis. this area being supplied by some third order fibres.9. i. and 43% to a thirdorder (postganglionic) lesion. have all been implicated. 13% were related to a first-order (central) lesion. contralateral fourth nerve palsy. Most patients who present with Horner’s syndrome in isolation without additional clinical features will have a postganglionic lesion5 or may be idiopathic. this distinction between preganglionic and postganglionic supply is not a reliable clinical feature. For example.8 Crossed sensory or motor signs are highly suggestive of a brainstem lesion.7 The most frequently identified central causes are infarction of the posterior inferior cerebellar artery (PICA) or distal vertebral artery occlusion producing lateral medullary syndrome (Fig. swallowing difficulties. 44% to a secondorder (preganglionic) lesion. In the remaining 270 patients. Rarer causes include acute disseminated encephalomyelitis11 and syrinx of the spinal cord. stroke. In one large case series6 40% Central (Table 1) Because of the proximity of other structures within the hypothalamus. trauma. In practice. Pathology within the midbrain may produce an accompanying. Causes and investigation of Horner’s syndrome Testing the pupils with 4% cocaine eye drops can confirm a diagnosis of Horner’s syndrome. In a patient with known lung malignancy presenting with shoulder and arm pain.Imaging of Horner’s syndrome 501 postganglionic. then only the medial part of the upper forehead may be affected. no imaging abnormality can be demonstrated. One percent hydroxyamphetamine can be used to distinguish central and preganglionic from postganglionic lesions4.e. distinguishing between central. such as arteriovenous malformation (AVM). These patients may also have vertigo. In children causes of Horner’s syndrome are mainly related to either congenital or acquired/postsurgical lesions.

Axial T2-weighted image showing localized high signal change within the right hemi-medulla respecting the mid-line in keeping with recent infarction. (c) Parasagittal oblique T2-weighted MRI image demonstrates the 4 cm apical mass. Other cited causes include paragangliomas of the sympathetic chain17. which provides good soft-tissue contrast and spatial resolution. In the newborn. A 37-year-old woman presented with gradual onset right-sided neck pain and ipsilateral Horner’s syndrome. which is prone to beam hardening artefact in the posterior fossa. Of tumours at the lung apex. Preganglionic (Table 1) Preganglionic Horner’s syndrome is frequently caused by tumour or trauma. T1-weighted sequences with and without gadolinium enhancement may allow the detection of tumour or metastasis. nystagmus. Unenhanced CT. There was no communication with the exit foramina or spinal canal. It is of mixed signal and exhibits some intra-lesional necrosis. (a) Chest radiograph shows a smoothly demarcated mass lesion at the medial aspect of the apex of the right upper lobe. A CT image taken 2 days prior to the MRI examination was normal. Pancoast tumour and neurogenic tumours (Fig.502 A. George et al. and an ipsilateral Horner’s syndrome. right-sided weakness. in the cervical cord the use of DWI to detect ischaemic lesions is limited because of the small size of the cord. and medulla and avoid the beam-hardening Figure 3 Apical neuroma. These are more likely to be malignant than benign. . A 47-year-old man presented acutely with slurred speech. cerebrospinal fluid (CSF) flow and susceptibility artefact from adjacent structures.15 Nerve root avulsion disrupting the sympathetic pathway may produce symptoms referred to the brachial plexus distribution. and conventional spin-echo (SE) T2-weighted or fluid-attenuated inversion recovery sequences (FLAIR) sequences can fail to detect infarction occurring within the first 12e24 h. Figure 2 Right posterior inferior cerebellar infarct. (b) Multiplanar parasagittal oblique reformat contrast-enhanced CT image of the neck demonstrates both vascular detail and the relationship of the mass to the vertebral bodies at the level of the upper thoracic spine. iatrogenic causes such as forceps delivery can be responsible. 3)16 are most frequently associated. Magnetic resonance imaging (MRI).13 However.14 SE and fast SE (FSE) sequences suffer less from susceptibility artefact than gradient-echo techniques and are favoured for assessing anatomical detail within the cord. is the most appropriate method of imaging the central neuroaxis to include the hypothalamus. Diffusion-weighted imaging (DWI) has more application for the early assessment of acute stroke. Imaging in at least two orthogonal planes is recommended. pons. artefact seen on computed tomography (CT).

Imaging of Horner’s syndrome 503 hydatid cyst18. often accompanied by carotydynia (pain of face and neck). (b) Axial T1-weighted enhanced MRI image demonstrates the dissection flap and high signal within the narrowed true lumen (white arrow). Formal catheter digital subtraction angiography is a valuable technique for the detection of internal carotid artery dissection. severe unilateral. . Pain is often an accompanying feature.24 Digre et al. (a) Axial T2-weighted MRI image at the level of the skull base shows high signal change replacing the normal flow void within the right extracranial internal carotid artery (white arrow). fatsuppressed sequences and magnetic resonance angiography (MRA) will detect most internal carotid artery dissections. In affected patients the history is often typical. to include the upper thoracic spine and thoracic inlet. Coverage of the entire cervical spine in three orthogonal planes is recommended. The presence of 3rd. short-lived headaches localized to the orbital. Both tumour and trauma can disrupt third-order neurons within the skull base and cavernous sinus (Fig. 5). 4). temporal and mid-face areas in which imaging is not helpful. 5th or 6th cranial nerve palsies points to a lesion within the cavernous sinus or superior orbital fissure.5 Generally. 4th.25 An orbital apex lesion might also be expected to produce visual loss in addition. such as fibromuscular dysplasia or Ehlerse Danlos syndrome. intercostal drain insertion19.27 On a T1-weighted sequence thrombosis within the false lumen of a carotid Figure 4 Internal carotid artery dissection.23 and even disc prolapse. Coronal sequences with and without fat suppression can also provide detail of any coexistent brachial plexus injury. The sagittal images can be offset to the side of interest. regional anaesthetic blocks. A 50-yearold woman presented with carotydynia and right-sided Horner’s syndrome. the cavernous sinus and the orbital apex.21 subclavian artery aneurysm. Imaging Department. By far the most common cause is spontaneous or traumatic carotid artery dissection (Fig. axial contrast-enhanced CT may be required. imaging has a greater positive yield in postganglionic disease if symptoms are acute rather than chronic. may be more susceptible.26 An axial MRI of the neck with T1-weighted. but is being superseded by both MR and CT angiography. If an apical lung lesion or a tumour within the upper mediastinum or anterior neck is considered likely. Cluster headaches are thought to be due to injury of the sympathetic fibres within the bony carotid canal.20 sympathectomy.5 provide a suggested protocol for the MRI investigation of preganglionic Horner’s syndrome. Postganglionic (Table 1) Postganglionic Horner’s syndrome can be caused by conditions ranging from the relatively trivial to life threatening. Patients with connective tissue disorders. Courtesy: Royal Cornwall Hospitals NHS Trust.22 thyroid malignancy. Thrombosis within the vessel may induce contralateral hemiplegia. The anatomical distribution extends from the internal carotid artery to the skull base.

Rinsho Shinkeigaku 1989. (b) Axial T1-weighted MRI image after intravenous gadolinium demonstrates avid enhancement of the cavernous sinus mass. . Younge BR.133:702e4. et al. Gray’s anatomy. Kira J.29:1013e6. Isolated Horner syndrome and syrinx of the spinal cord. Am J Ophthalmol 1989. Bello JA. Buono LM.html> [accessed 25. Am J Ophthalmol 2002. Williams PL. et al.169: 581e4. Nagy AN. Edinburgh: Churchill Livingstone.com/doctor. Mickle JP.cfm/1044. Contralateral trochlear nerve paresis and ipsilateral Horner’s syndrome. Horner syndrome. Curr Opin Ophthalmol 2003. Sorensen G.whonamedit.107:73e6. Selective MR imaging approach for patients with Horner’s syndrome. although CT can be compromised by beam hardening artefact and the presence of dental amalgam.com/synd. 11. Imaging of the parasellar region and skull base can be performed with both MRI and CT. References 1.13:223e7. Pomeranz H. Warwick R. AJR Am J Roentgenol 1997.html>. et al. Johnston P. <http://www. 6.90:394. <http://www.14:357e63. et al.4. A 55-year-old man with a known history of nasopharyngeal carcinoma developed Horner’s syndrome on the right side associated with ophthalmoplegia. J Neurol Neurosurg Psychiatry 2000. Day AL. Advanced MR techniques. Horner’s syndrome due to first-order neuron lesions of the oculosympathetic pathway. which is a T1-weighted technique. George et al. 2005. Wu O. Maloney WF. Edinburgh: Churchill Livingstone. Neuroimaging Clin N Am 1999. 13. The intracavernous internal carotid artery is partly compressed. 9. Hayman LA. Evaluation of the causes and accuracy of pharmacologic localization in Horner’s syndrome. Diaz-Marchan PJ. multidetector CT using a bone algorithm allowing reconstruction in multiple planes. 5. (a) Axial T1-weighted MRI image of the head through the level of skull base shows a soft-tissue mass isointense to brain filling the right cavernous sinus and extending along the floor of the middle cranial fossa. Sacco RL. Arch Neurol 1993.25 The appropriate investigation of Horner’s syndrome is as heavily reliant on history and examination as imaging and requires close liaison between the physician and radiologist. Skull base fractures are readily identified using high-resolution. Accompanying physical signs may allow precise localization but occasionally imaging of the entire oculosympathetic pathway may be required. dissection may appear hyperintense due to the presence of methaemoglobin. Walton KA. Moyer NJ. Standing S. Wallenberg’s syndrome. Freddo L. 4. 12. 39th ed. 1980. Gray’s anatomy. 10. Wallenbergs lateral medullary syndrome e clinicalemagnetic resonance imaging correlations. Am J Ophthalmol 1980. 2.cfm/1056.504 A. 8. Yoshimura T.9.2007] 3. may register this as normal flow unless supplemented with other sequences. Figure 5 Cavernous sinus metastasis.28 To view the cavernous sinus the coronal and axial planes are most useful. Acute disseminated encephalomyelitis affecting medulla and upper cervical cord. Unenhanced and enhanced T1-weighted sequences are often necessary for the identification of subtle lesions. Smoker WR. Pearce JM. Yoshiura T. et al.50:609e14. Time-of-flight (TOF) MRA. 7. AJNR Am J Neuroradiol 1992.whonamedit. Guy J. Muramoto T. 36th ed.9:439e53. Digre KB.68:570.

et al. Bone I. Intervertebral disc prolapse as an unusual cause of Horner’s Syndrome. Imaging of suprasellar and parasellar tumours. Craniocervical artery dissection: diagnosis and follow-up with MR imaging and MR angiography. Lee DH. Bradford CR. sympathetic chain reconstruction after a one-stage removal of the tumor. Augustin M. Ann Fr Anesth Reanim 1998. Lee JH.153:353e9. et al. Segura P. 19. Simper LB. Moyer JS. Craniocervical artery dissection: MR imaging and MR angiographic findings. 18. 151:949e50. 20. Magnaes B. Extensive or partial microsurgical sympathectomy of the arm by supraclavicular route for primary or secondary Raynaud symptoms. Claude Bernarde Horner syndrome and its opposite Pourfour du petit syndrome in anaesthesia and intensive care. Thorax 1989. et al.68:620. Miura J.44:305e6. cerebello-pontine angle. 21. A rare cause of Horner’s syndrome: subclavian artery aneurysm. Neuroimaging Clin N Am 1999. 25. 26. .9:1385e91. 16. J Neurol Neurosurg Psychiatry 2005. Acta Chir Scand 1987. Oelerich M. Neuroimaging Clin N Am 2007. 28. Kitis O. Sympathetic paraganglioma as an unusual cause of Horner’s syndrome. Spine 2003. Levent E. Posacioglu H.74:442e5. Doita M.105:221e3. Speeg-Schatz C. Aydin E. Syndromes of the orbital fissure. Sto ¨gbauer F. 3):iii29eiii38. Wagner JM. Respiration 2001. Hadley DM. Vertinsky AT. Kurlemann G. et al. Calli C. AJR Am J Roentgenol 2007. Lee HK.10:MT109. 15. ANZ J Surg 2004. Horner’s syndrome caused by a thoracic dumbbell-shaped schwannoma.28(2):E33e6.17:707e24.188:W74e81. Campbell P.76(Suppl. Jorgensen AK. and skull base. Sywak MS. Harding JL. 24. et al. 17. Sirmali M. Wake PN. Horner syndrome in association with thyroid and parathyroid disease. Neil T. Eur Radiol 1999. 23. Gezer S. cavernous sinus. Krasnokutsky MV. Med Sci Monit 2004.23: 338e42. et al. Horner’s syndrome caused by an intercostal chest drain. Giant primary mediastinal hydatid cyst causing Horner’s syndrome: report of a case. Miyata K. Gelal FM. Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. et al.Imaging of Horner’s syndrome 505 14. 27.9:717e32.17:117e36. Sidhu S. Ugeskr Laeger 1989. Simonetta AB. 22. Head Neck 2001. Spinal imaging: overview and update. Acta Chir Belg 2005.