OPTOMETRY
Horner syndrome
Yu X Kong* MBBS BMedSci Horner syndrome is an uncommon but important clinical entity, representing interrup-
Gavin Wright* MBBS FRACS tion of the sympathetic pathway to the eye and face. Horner syndrome is almost always
Konrad Pesudovs† BScOptom PhD FAAO diagnosed clinically, though pharmacological testing can be used to confirm the diag-
Justin O’Day§ || MBBS FRACS FRANZCO nosis. Imaging modalities such as PET, CT and MRI are important components of work-
AM up for patients presenting with acquired Horner syndrome. Our patient’s presentation
Zoe Wainer§ BMBS BHealthSci with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma
Harrison S Weisinger§ MScOptom MBBS and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these
PhD cancers resulted in complete resolution of the syndrome and disease-free survival at 18
* Cardiothoracic Care Centre, months. We review the anatomy and pathophysiology underlying this and other causes
§
St. Vincent’s Hospital, Fitzroy, Victoria, of Horner syndrome.
Australia
†
NH&MRC Centre for Clinical Eye
Research, Department of Ophthalmology,
Flinders Medical Centre, Flinders
University, Bedford Park, SA, Australia
||
Department of Neuro-ophthalmology,
Royal Victorian Eye and Ear Hospital, East
Melbourne, Victoria, Australia
E-mail: weisinger@mac.com
Key words: Horner syndrome, miosis, ptosis, superior pulmonary sulcus tumour, sympathetic nervous system
Horner syndrome is the collection of signs testing. Its causes range from benign to
CASE REPORT
produced by interruption of the sympa- life threatening. We present a case of
thetic pathway to the eye and face. It is Pancoast (superior pulmonary sulcus) JG, a 59-year-old clerical worker, was
defined clinically by ipsilateral miosis, par- tumour, in which acquired Horner syn- admitted to the Cardiothoracic Care Cen-
tial ptosis, apparent enophthalmos and drome was a feature at presentation and tre for investigation in July 2005, following
anhidrosis. The diagnosis of Horner syn- we discuss the pathophysiology and a diag- a three-month-history of gradually worsen-
drome is based on clinical observation but nostic approach for patients with Horner ing right arm pain and right hand weak-
may be confirmed by pharmacological syndrome. ness that were unresponsive to simple
Clinical and Experimental Optometry 90.5 September 2007 © 2007 The Authors
336 Journal compilation © 2007 Optometrists Association Australia
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
© 2007 The Authors Clinical and Experimental Optometry 90.5 September 2007
Journal compilation © 2007 Optometrists Association Australia 337
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
Pathophysiology of Horner
syndrome
The sympathetic pathway to the eye and
its adnexae is a three-neuron pathway,
which begins in the central nervous system
Figure 3A. Coronal CT, PET and fused scan images of upper thoracic region in July 2005, (Figure 4). The first-order neuronal fibres
demonstrating intense uptake in the right lung apex and apical segment of right lower arise from the postero-lateral hypothala-
lung lobe mus. They descend through the brainstem
to terminate in the spinal cord at the
ciliospinal centre (C8 - T2). The second-
order neuronal fibres (pre-ganglionic)
exit through T1 root and travel close to
the lung apex through the para-vertebral
sympathetic chain and the stellate gan-
glion and terminate in the superior
cervical ganglion. Tumours involving the
upper lobe of the lung and thoracic outlet
can interrupt the pathway at this level
because of their proximity to these
structures.
The third-order sympathetic fibres
(post-ganglionic) exit the ganglion to
form a plexus surrounding the internal
carotid artery. Dissection of the internal
carotid artery is a very important cause
that can lead to interruption of the path-
way at this level.5 The plexus then ascends
into the cavernous sinus, runs a short
course on the sixth cranial nerve and then
follows the ophthalmic division of the
trigeminal nerve (V1) to the orbit, where
they supply the iris dilator muscles and the
smooth muscle fibres of upper and lower
Figure 3B. Coronal CT, PET and fused scan images of upper thoracic region in Septem- lid. Vasomotor and sweat gland fibres to
ber 2005 (two months following chemo-radio-therapy) demonstrating marked reduction the face follow a different course after
in the uptake by the right apical lung lesion leaving the ganglion. They follow the
Clinical and Experimental Optometry 90.5 September 2007 © 2007 The Authors
338 Journal compilation © 2007 Optometrists Association Australia
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
© 2007 The Authors Clinical and Experimental Optometry 90.5 September 2007
Journal compilation © 2007 Optometrists Association Australia 339
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
Clinical and Experimental Optometry 90.5 September 2007 © 2007 The Authors
340 Journal compilation © 2007 Optometrists Association Australia
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
SECOND-ORDER NEURON
Figure 6. Congenital Horner syndrome with iris heterochromia; the affected side has the (‘PRE-GANGLIONIC’)
blue iris (photograph courtesy of Photographic Case Library, Department of Ophthal- Tumour of the lung apex is a common
mology, Flinders Medical Centre) and life-threatening presentation of pre-
© 2007 The Authors Clinical and Experimental Optometry 90.5 September 2007
Journal compilation © 2007 Optometrists Association Australia 341
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
ganglionic Horner syndrome. It presents being replaced by non-invasive imaging serious pathology such as neuroblastoma
classically with Pancoast syndrome, which techniques, such as duplex ultrasound, and other tumours.57,58 Children present-
includes symptoms and signs of ipsilateral MRI of the carotid vessel (to visualise dis- ing with Horner syndrome should have
Horner syndrome accompanied by persis- section), MRI angiography or CT angio- head, neck and thoracic MRI as well as
tent shoulder and arm pain and brachial graphy.45 The current recommended measurement of urinary catecholamine
plexus palsy.29 Unfortunately, the diagno- medical management of carotid dissection levels,55,59 as the catecholamine vanillyl-
sis of superior pulmonary sulcus tumour involves anticoagulation or antiplatelet mandelic acid is raised in up to 95 per cent
is often delayed as many patients are medications for three to six months.46,47 of cases of neuroblastoma.60,61 Early detec-
treated for the more common cervical Surgical intervention is often reserved for tion of primary mediastinal neuroblas-
osteoarthritis or shoulder bursitis before cases where medical management has toma is critical, as the cure rate is
the diagnosis is made.30 Patients suspected failed or there is absolute contraindica- approaches 100 per cent when treated in
of having superior pulmonary sulcus tion to anticoagulation, as the incidence the first year of life.62
tumour should be referred urgently for of post-operative stroke is high.48 Endovas-
medical management with initial work-up cular stenting for acute dissection is being REFERENCES
including chest X-ray and CT scan of tho- trialled and is showing some promising 1. Kwong KF, Edelman MJ, Suntharalingam
rax and abdomen. Further investigations results.49 M, Cooper LB, Gamliel Z, Burrows W,
Hausner P, Doyle LA, Krasna MJ. High-dose
at a tertiary referral centre often include Another relatively common presenta- radiotherapy in trimodality treatment of
MRI scan of neck and thorax because it tion of post-ganglionic Horner syndrome Pancoast tumors results in high pathologic
has superiority over CT scan in showing is in association with cluster headaches complete response rates and excellent
the involvement of the brachial plexus (episodic, excruciating unilateral head- long-term survival. J Thorac Cardiovasc Surg
and subclavian vessels and in evaluating ache, ipsilateral lacrimation, conjunctival 2005; 129: 1250–1257.
2. Gandara DR, Chansky K, Albain KS, Gaspar
vertebral bodies and the spinal canal for injection, rhinorrhoea, and nasal conges- LE, Lara PN Jr, Kelly K, Crowley J, Living-
tumour extension.31,32 Definitive patholog- tion).50 This condition is benign and can ston R. Long-term survival with concurrent
ical diagnosis is made with image-guided be managed with abortive and preventive chemoradiation therapy followed by con-
needle biopsy.33 CT or MRI of the brain is medications. Focal neurological symp- solidation docetaxel in stage IIIB non-
performed prior to treatment because toms other than Horner syndrome are small-cell lung cancer: a phase II Southwest
Oncology Group Study (S9504). Clin Lung
superior pulmonary sulcus tumours have rare; if present, a more life-threatening Cancer 2006; 8: 116–121.
a predilection for cerebral metastasis.34 diagnosis such as carotid dissection or 3. van der Wiel HL. Johann Friedrich Horner
Treatment options depend on the individ- lesion in the middle cranial fossa should (1831–1886). J Neurol 2002; 249: 636–637.
ual case but often involve chemo- be suspected.51,52 Indeed, the diagnosis 4. Walton KA, Buono LM. Horner syndrome.
radiotherapy prior to surgery.35,36 of cluster headache can be made only Curr Opin Ophthalmol 2003; 14: 357–363.
5. Chan CC, Paine M, O’Day J. Carotid dissec-
Other causes of pre-ganglionic Horner following the exclusion of carotid artery tion: a common cause of Horner syndrome.
syndrome may be iatrogenic and include dissection. Clin Experiment Ophthalmol 2001; 29: 411–
brachial plexus trauma, recent thoracic Other causes of post-ganglionic Horner 415.
or neck surgery,37 central venous cathe- syndrome include carotid artery thrombo- 6. Maloney WF, Younge BR, Moyer N. Evalua-
terisation38 and chest tube insertion.39 sis, lesions in the cavernous sinus53 or the tion of the causes and accuracy of pharma-
cologic localization in Horner syndrome.
orbit. Horner syndrome with visual loss Am J Ophthalmol 1980; 90: 394–402.
THIRD-ORDER NEURON should raise the suspicion of a space- 7. Mojon DS, Stehberger B. Diagnosis of Hor-
(‘POST-GANGLIONIC’) occupying lesion in the orbital apex. It has ner syndrome by pupil dilation lag. Klin
Carotid artery dissection is one of the been suggested that in complete clinico- Monatsbl Augenheilkd 2005; 222: 211–213.
most common and most important causes pathological isolation, third-order lesions 8. Lepore FE. Enophthalmos and Horner’s
syndrome. Arch Neurol 1983; 40: 460.
of post-ganglionic Horner syndrome.5 require no further investigation.54 9. Daroff R. Enophthalmos is not present in
Stroke is the major concern with carotid Horner syndrome. PLoS Med 2005; 2: e120.
artery dissection, which can occur in more Paediatric Horner syndrome 10. Glaser JS. The pupils and accommodation.
than half of these patients.40 Horner syn- Congenital Horner syndrome is usually id- In: Glaser JS, ed. Neuro-ophthalmology,
drome is present in about 50 per cent of iopathic or associated with birth trauma.55 3rd ed. Philadelphia: Lippincott Williams &
Wilkins, 1999. p 527–552.
cases of carotid artery dissection.41 Other Other causes such as agenesis of the inter- 11. Morrison DA, Bibby K, Woodruff G. The
symptoms and signs include acute unilat- nal carotid artery56 are rare and are often ‘harlequin’ sign and congenital Horner’s
eral face or neck pain, amaurosis fugax symptomatic. Therefore, extensive medi- syndrome. J Neurol Neurosurg Psychiatry
and cranial nerve palsies.42,43 Dissection cal imaging is not recommended in iso- 1997; 62: 626–628.
can occur with minor trauma or spontane- lated Horner syndrome in the absence of 12. Wallis DH, Granet DB, Levi L. When the
darker eye has the smaller pupil. J AAPOS
ously in people with connective tissue dis- cervical or abdominal masses or cranial 2003; 7: 215–216.
orders or syphilis.44 The diagnostic gold nerve palsies,55 however, in children, Hor- 13. Diesenhouse MC, Palay DA, Newman NJ,
standard is carotid angiography, which is ner syndrome can be a presentation of To K, Albert DM. Acquired heterochromia
Clinical and Experimental Optometry 90.5 September 2007 © 2007 The Authors
342 Journal compilation © 2007 Optometrists Association Australia
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
with Horner syndrome in two adults. Oph- case reports and review of the literature. J of silent carotid dissection. PLoS Med 2005;
thalmology 1992; 99: 1815–1817. Trauma 2001; 51: 400–404. 2: e19.
14. Imesch PD, Wallow IH, Albert DM. The 29. Arcasoy SM, Jett JR. Superior pulmonary 44. Brandt T, Orberk E, Weber R, Werner I,
color of the human eye: a review of mor- sulcus tumors and Pancoast’s syndrome. N Busse O, Muller BT, Wigger F, Grau A,
phologic correlates and of some conditions Engl J Med 1997; 337: 1370–1376. Grond-Ginsbach C, Hausser I. Pathogenesis
that affect iridial pigmentation. Surv Oph- 30. Hepper NG, Herskovic T, Witten DM, of cervical artery dissections: association
thalmol 1997; 41 (Suppl 2): S117–S123. Mulder DW, Woolner LB. Thoracic inlet with connective tissue abnormalities. Neu-
15. Kardon RH, Denison CE, Brown CK, tumors. Ann Intern Med 1966; 64: 979–989. rology 2001; 57: 24–30.
Thompson HS. Critical evaluation of the 31. Webb WR, Gatsonis C, Zerhouni EA, 45. Flis CM, Jager HR, Sidhu PS. Carotid and
cocaine test in the diagnosis of Horner’s Heelan RT, Glazer GM, Francis IR, McNeil vertebral artery dissections: clinical aspects,
syndrome. Arch Ophthalmol 1990; 108: 384– BJ. CT and MR imaging in staging non- imaging features and endovascular treat-
387. small cell bronchogenic carcinoma: report ment. Eur Radiol 2006: 17: 820–834.
16. Freedman KA, Brown SM. Topical apra- of the Radiologic Diagnostic Oncology 46. Georgiadis D, Caso V, Baumgartner RW.
clonidine in the diagnosis of suspected Group. Radiology 1991; 178: 705–713. Acute therapy and prevention of stroke in
Horner syndrome. J Neuroophthalmol 2005; 32. Pennes DR, Glazer GM, Wimbish KJ, Gross spontaneous carotid dissection. Clin Exp
25: 83–85. BH, Long RW, Orringer MB. Chest wall Hypertens 2006; 28: 365–370.
17. Brown SM. The utility of 0.5% apracloni- invasion by lung cancer: limitations of CT 47. Beletsky V, Nadareishvili Z, Lynch J, Shuaib
dine in the diagnosis of Horner syndrome. evaluation. AJR Am J Roentgenol 1985; 144: A, Woolfenden A, Norris JW. Cervical arte-
Arch Ophthalmol 2005; 123: 578. 507–511. rial dissection: time for a therapeutic trial?
18. Koc F, Kavuncu S, Kansu T, Acaroglu G, 33. Paulson DL, Weed TE, Rian RL. Cervical Stroke 2003; 34: 2856–2860.
Firat E. The sensitivity and specificity of approach for percutaneous needle biopsy 48. Schievink WI, Piepgras DG, McCaffrey TV,
0.5% apraclonidine in the diagnosis of ocu- of Pancoast tumors. Ann Thorac Surg 1985; Mokri B. Surgical treatment of extracranial
losympathetic paresis. Br J Ophthalmol 2005; 39: 586–587. internal carotid artery dissecting aneu-
89: 1442–1444. 34. Komaki R, Derus SB, Perez-Tamayo C, rysms. Neurosurgery 1994; 35: 809–815.
19. Kardon R. Are we ready to replace cocaine Byhardt RW, Hartz A, Cox JD. Brain 49. Vazquez Rodriguez C, Lemaire V, Renard
with apraclonidine in the pharmacologic metastasis in patients with superior sulcus F, De Keuleneer R. Primary stenting for
diagnosis of Horner syndrome? J Neurooph- tumors. Cancer 1987; 59: 1649–1653. the acute treatment of carotid artery dis-
thalmol 2005; 25: 69–70. 35. Sartori F, Rea F, Calabro F, Mazzucco C, section. Eur J Vasc Endovasc Surg 2005; 29:
20. Chen PL, Hsiao CH, Chen JT, Lu DW, Bortolotti L, Tomio L. Carcinoma of the 350–352.
Chen WY. Efficacy of apraclonidine 0.5% in superior pulmonary sulcus. Results of irra- 50. May A. Cluster headache: pathogenesis,
the diagnosis of Horner syndrome in pedi- diation and radical resection. J Thorac Car- diagnosis, and management. Lancet 2005;
atric patients under low or high illumina- diovasc Surg 1992; 104: 679–683. 366: 843–855.
tion. Am J Ophthalmol 2006; 142: 469–474. 36. Martinod E, D’Audiffret A, Thomas P, 51. Goadsby PJ. Raeder’s syndrome [cor-
21. Chen PL, Chen JT, Lu DW, Chen YC, Hsiao Wurtz AJ, Dahan M, Riquet M, Dujon A, rected]: paratrigeminal paralysis of the
CH. Comparing efficacies of 0.5% apra- Jancovici R, Giudicelli R, Fuentes P, Azorin oculopupillary sympathetic system. J Neurol
clonidine with 4% cocaine in the diagnosis JF. Management of superior sulcus tumors: Neurosurg Psychiatry 2002; 72: 297–299.
of Horner syndrome in pediatric patients. J experience with 139 cases treated by surgi- 52. Kashihara K, Ito H, Yamamoto S, Yamano
Ocul Pharmacol Ther 2006; 22: 182–1827. cal resection. Ann Thorac Surg 2002; 73: K. Raeder’s syndrome associated with
22. Bacal DA, Levy SR. The use of apracloni- 1534–1539. intracranial internal carotid artery aneu-
dine in the diagnosis of Horner syndrome 37. Grocott HP, Clark JA, Homi HM, Sharma rysm. Neurosurgery 1987; 20: 49–51.
in pediatric patients. Arch Ophthalmol 2004; A. ‘Other’ neurologic complications after 53. Tsuda H, Ishikawa H, Asayama K, Saito T,
122: 276–279. cardiac surgery. Semin Cardiothorac Vasc Endo S, Mizutani T. Abducens nerve palsy
23. Moster ML, Galiani D, Garfinkle W. False Anesth 2004; 8: 213–226. and Horner syndrome due to metastatic
negative hydroxyamphetamine test in Hor- 38. Mastan M. Carotid artery pseudoaneurysm tumor in the cavernous sinus. Intern Med
ner syndrome caused by acute internal with Horner’s syndrome: delayed complica- 2005; 44: 644–646.
carotid artery dissection. J Neuroophthalmol tion of internal jugular venous cannulation. 54. Burde RM, Savino PJ, Trobe JD. Clinical
2003; 23: 22–23. Hosp Med 2005; 66: 314–315. Decisions in Neuro-ophthalmology, 3rd ed.
24. Danesh-Meyer HV, Savino P, Sergott R. The 39. Kaya SO, Liman ST, Bir LS, Yuncu G, Erbay St Louis: Mosby Year Book, 2002.
correlation of phenylephrine 1% with HR, Unsal S. Horner’s syndrome as a com- 55. George ND, Gonzalez G, Hoyt CS. Does
hydroxyamphetamine 1% in Horner’s syn- plication in thoracic surgical practice. Eur J Horner’s syndrome in infancy require
drome. Br J Ophthalmol 2004; 88: 592–593. Cardiothorac Surg 2003; 24: 1025–1028. investigation? Br J Ophthalmol 1998; 82: 51–
25. Sacco RL, Freddo L, Bello JA, Odel JG, 40. Biousse V, D’Anglejan-Chatillon J, Touboul 54.
Onesti ST, Mohr JP. Wallenberg’s lateral PJ, Amarenco P, Bousser MG. Time course 56. Ryan FH, Kline LB, Gomez C. Congenital
medullary syndrome. Clinical-magnetic res- of symptoms in extracranial carotid artery Horner’s syndrome resulting from agenesis
onance imaging correlations. Arch Neurol dissections. A series of 80 patients. Stroke of the internal carotid artery. Ophthalmology
1993; 50: 609–614. 1995; 26: 235–239. 2000; 107: 185–188.
26. Kerrison JB, Biousse V, Newman NJ. Iso- 41. Mokri B, Sundt TM Jr, Houser OW. Spon- 57. Mahoney NR, Liu GT, Menacker SJ, Wilson
lated Horner’s syndrome and syringomye- taneous internal carotid dissection, hemic- MC, Hogarty MD, Maris JM. Pediatric
lia. J Neurol Neurosurg Psychiatry 2000; 69: rania, and Horner’s syndrome. Arch Neurol Horner syndrome: etiologies and roles of
131–132. 1979; 36: 677–680. imaging and urine studies to detect neuro-
27. Pomeranz H. Isolated Horner syndrome 42. McCorry D, Bamford J. Painful Horner’s blastoma and other responsible mass
and syrinx of the cervical spinal cord. Am J syndrome caused by carotid dissection. Post- lesions. Am J Ophthalmol 2006; 142: 651–659.
Ophthalmol 2002; 133: 702–704. grad Med J 2004; 80: 164. 58. Sauer C, Levingohn MW. Horner’s syn-
28. Bell RL, Atweh N, Ivy ME, Possenti P. Trau- 43. Nautiyal A, Singh S, DiSalle M, O’Sullivan drome in childhood. Neurology 1976; 26:
matic and iatrogenic Horner syndrome: J. Painful Horner syndrome as a harbinger 216–220.
© 2007 The Authors Clinical and Experimental Optometry 90.5 September 2007
Journal compilation © 2007 Optometrists Association Australia 343
Horner syndrome Kong, Wright, Pesudovs, O’Day, Wainer and Weisinger
Corresponding author:
Dr Harrison S Weisinger
St Vincent’s Hospital Melbourne
Fitzroy VIC 3065
AUSTRALIA
E-mail: weisinger@mac.com
Clinical and Experimental Optometry 90.5 September 2007 © 2007 The Authors
344 Journal compilation © 2007 Optometrists Association Australia