W. RICHARDGREEN MD
Horner syndrome refers to a condition where oculosympathetic pathwaydamage or dysfunction can cause ptosis, miosis of the pupil, and anhydrosis.1 Congenital Horner syndrome is most commonly idiopathicor due to a traumatic birth. Acquired Horner syndrome in children is oftenpostsurgical. Other causes include neuroblastoma, trauma, and brainstem processes.2
The diagnosis of this condition may be confirmed by instilling topicalcocaine in each eye. The Horner pupil dilates poorly in comparison with thehealthy pupil.3
Apraclonidine hydrochloride is an α-adrenergic receptor agonistthat is approved for the treatment of elevated intraocular pressure followingargon laser trabeculoplasty. A prior study4 of6 adult patients with Horner syndrome showed that instillation of 1% apraclonidineinto both eyes produced mydriasis in the affected eye only. In fact, all patientsexperienced a reversal of their baseline anisocoria. In every case, the mioticpupil on the Horner side dilated to become larger than the healthy side, whereasthe size of the pupil on the unaffected side remained unchanged. Four patientshad postganglionic Horner syndrome (third-order neuron) and 2 had preganglionicHorner syndrome (first-order and second-order neurons).
We discuss 4 pediatric patients with a diagnosis of Horner syndromewho underwent pharmacologic testing with apraclonidine. For comparison, wediscuss 2 children pharmacologically tested with apraclonidine who had anisocoriabut did not have Horner syndrome. To our knowledge, there is no prior reportof the use of apraclonidine as a diagnostic test in a pediatric patient.
Case 1 A 6-month-old boy was first seen in our office because of a 2-month history of anisocoria. He was the product of an uncomplicated pregnancy andwas born full-term by vaginal delivery. Forceps were not used during the delivery.There was some fetal bradycardia related to contractions toward the end ofthe labor. He was found to have a nuchal cord and mild neck bruising. Therewas no evidence of shoulder dystocia, and his health had been good. His developmentwas age-appropriate, and he reached for objects preferentially with his righthand. His parents reported that they did not notice any anisocoria beforethe infant was 4 months of age.
On examination, his vision was central, steady, and maintained in botheyes. In normal room lighting, the pupils measured 3 mm OD and 2 mm OS. Inthe dark, the size of the pupils changed to 5 mm OD and 3 mm OS. No inverseptosis (elevation of the lower lid) was present, but there was approximately1 mm of left upper lid ptosis. The conjunctiva, cornea, iris, and lens appearedhealthy in both eyes. Motility was full, and the patient was orthotropic atnearby light reflex testing. Neurologic evaluation showed full range of motionof his neck and back. The patient kept his left hand fisted with flexion contracturesof the third, fourth, and fifth fingers.
We instilled 1% apraclonidine in each eye prior to any other pharmacologicagent that day. The patient was evaluated 1 hour later, and in normal roomlighting, the right pupil remained 3 mm. The left pupil increased from 2 mmto 4 mm, resulting in a reversal of the anisocoria. The patient's mother reportedthat he was sleepier than usual that afternoon, but by evening his activitylevel had returned to baseline.
Computed tomography findings of the head, cervical spine, and neck werecompletely normal. Computed tomography results of the abdomen and pelvis werenormal with no masses. Because of the left upper extremity weakness, a magneticresonance image of the cervical and thoracic spine was ordered. These resultswere also normal. A diagnosis of Klumpke paralysis was made by the neurologist.The anisocoria secondary to a left-sided Horner syndrome was confirmed on3 separate office visits.
Case 2. A 4-month-old boy was born by complicated vaginaldelivery with a resultant brachial plexus injury on the left side. He displayedleft upper extremity weakness with almost no motor strength in the left hand.His left pupil was noted to be smaller than his right pupil by his mother.
On examination, his vision was central, steady, and maintained in botheyes. There was 1 mm of left upper lid ptosis and 1 mm of left lower lid inverseptosis. In bright lighting, the pupils measured 4 mm OD and 3 mm OS. In adarkened room, the pupil size changed to 6 mm OD and 4 mm OS. One hour afterthe instillation of 1% apraclonidine in each eye, the right pupil measured4 mm and the left pupil measured 5 mm, resulting in a reversal of anisocoria.The infant displayed no adverse effects from the topical medication.
Case 3. A 14-year-old boy was first seen in our officebecause of a 2-year history of anisocoria. His medical history was only remarkablefor a positive purified protein derivative, which was treated with a 6-monthcourse of antibiotics. A family photo album was reviewed and pictures of theboy prior to age 12 years failed to show anisocoria or ptosis, whereas photographsof the boy at age 12 years and older did show mild ptosis and anisocoria.On examination, he displayed a miotic right pupil with a greater amount ofanisocoria in the dark. Mild right upper lid ptosis was present, as well asright lower lid inverse ptosis. No iris heterochromia was present.
One hour after instillation of 1% apraclonidine in each eye, the rightpupil size increased from 2 mm to 4.5 mm, and the left pupil remained unchangedat 4 mm (Figure 1). Results frommagnetic resonance imaging of his neck and chest radiography were normal,with no masses noted. The family declined any additional workup because ofthe chronicity of the condition.
Case 3. Left, Miotic right pupil.Right, Reversal of anisocoria 1 hour after instilling 1% apraclonidine inboth eyes.
Case 4. A 2-month-old boy was first seen in our officefor a nasolacrimal duct obstruction. His mother also stated that asymmetryof the pupil size had been noticed for at least 1 month. On examination, therewas left upper lid ptosis of 2 mm and left lower lid inverse ptosis. The rightpupil was 4 mm and increased to 6 mm in dim light. The left pupil was 3 mmand did not change in dim light. The rest of the results of the ocular examinationwere normal except for eyelid crusting. The patient returned another day fortesting with 1% apraclonidine. One hour after instillation, the right pupilchanged from 4.5 mm to 4 mm, whereas the left pupil increased from 2.5 mmto 7 mm.
The patient then underwent urine testing. The results showed creatine(Cr) levels of 0.06 g/dL (normal range, 0.02-0.32 g/dL), homovanillic acidlevels of 65.6 mg/g of Cr (normal range, 9.1-36.0 mg/g of Cr), and vanillylmandelicacid levels of 112.7 mg/g of Cr (normal range, 5.5-26.0 mg/g of Cr).
Because of the abnormal urine test results, computed tomography of hisneck, chest, abdomen, and pelvis was performed, which revealed a 2-cm massextending superiorly to the middle left thyroid lobe. The mass was resectedand found to be a stage 1 neuroblastoma.
Case 5. A 5-month-old healthy full-term girl was firstseen in our office with at least a 2-month history of anisocoria. On examination,there was no ptosis or inverse ptosis. The pupils measured 5 mm OD and 3 mmOS. Both pupils became 1 mm larger in dim lighting. The rest of the ophthalmicexamination was unremarkable. Two days later, 1% apraclonidine was instilledin each eye. One hour later, there was no change in pupil size.
Case 6. A 7-year-old boy returned for a routine follow-upexamination of anisocoria. At the time of his initial examination in 1999,he underwent magnetic resonance imaging of his head and neck and radiographyof the chest. He also had creatine and vanillylmandelic acid urine tests.All test results were normal.
His right pupil measured 2 mm in room lighting and dilated to 3 mm indim illumination. His left pupil measured 4 mm in room lighting and dilatedto 6 mm in dim illumination. He had no ptosis, inverse ptosis, or iris heterochromia.The rest of the results from his ocular examination were unremarkable.
The patient received 1 drop of 1% apraclonidine in both eyes and returnedto our office 1 hour later. There was no change in pupil size (Figure 2).
Case 6. Left, Miotic right pupil.Right, Right pupil is still miotic compared with the left pupil 1 hour afterinstillation of 1% apraclonidine in both eyes.
Pharmacologic diagnosis of Horner syndrome with the use of topical 5%or 10% cocaine has been the standard for years.5 Cocaineis a controlled substance that must be prepared by individual pharmacies forlocal use and has become more difficult to obtain in recent years. We havefound the parents of children with anisocoria and possible Horner syndromeare often hesitant to allow the use of cocaine as a diagnostic tool when suggested.
In healthy eyes, 1% apraclonidine produces little or no dilation ofthe pupils. However, a previous study4 showedthat 1 hour after 1% apraclonidine was instilled in both eyes of 6 adult patientswith Horner syndrome, a reversal of anisocoria occurred. This occurred whetherthe Horner syndrome was preganglionic or postganglionic. The mydriatic responseobserved in eyes affected with Horner syndrome is due to the denervation supersensitivityof the α-1 receptors on the iris dilator muscle.4
Topical apraclonidine is readily available and has been used in thepast to treat glaucoma with minimal adverse effects. To our knowledge, wereport the first use of this agent in the pharmacologic diagnosis of pediatricHorner syndrome. We discussed 4 patients (cases 1-4) with Horner syndrome,all of whom experienced a reversal of anisocoria after receiving 1% apraclonidine.To contrast this, we discussed an additional 2 patients with anisocoria notrelated to Horner syndrome (cases 5 and 6), who experienced no change in pupilsize. This reversal of anisocoria is easier to observe clinically than theasymmetric mydriasis cocaine produces.
Based on the findings in our cases and the prior article with 6 adultpatients with Horner syndrome, apraclonidine may play a role in the diagnosisof Horner syndrome. In fact, the diagnosis of neuroblastoma in case 4 mayhave been delayed if we had not tested the patient with 1% apraclonidine.
If it could be shown that 0.5% apraclonidine is as effective in causinga reversal of anisocoria in Horner syndrome as 1% apraclonidine, it wouldbe an even more attractive agent to use for this purpose. Adverse effectswould be minimized, and 0.5% apraclonidine is more readily available. Althoughthe previously published article using apraclonidine to diagnose adults withHorner syndrome had cases of preganglionic and postganglionic lesions, thenumber of patients was small. Sensitivity and specificity of this diagnostictest need to be investigated. Also, with all pharmacologic tests based ondenervation hypersensitivity, a false-negative result may occur in the acutesetting (where denervation hypersensitivity has not yet developed).
Further studies are also necessary to evaluate the safety profile ofthe instillation of this agent in infants. Another α-adrenergic receptoragonist used to lower intraocular pressure, 0.2% brimonidine tartrate, hascaused apnea, bradycardia, hypotension, somnolence, and lethargy in children.6 One of the infants in our study who received 1drop of 1% apraclonidine in both eyes was somewhat sleepier than usual thatafternoon, but this resolved without adverse sequelae. The other patientsdid not experience any adverse effects.
The authors have no relevant financial interest in this article.
Corresponding author and reprints: Darron A. Bacal, MD, Eye Physicians& Surgeons, PC, 202 Cherry St, Milford, CT 06460 (e-mail: firstname.lastname@example.org).
Bacal DA, Levy SR. The Use of Apraclonidine in the Diagnosis of Horner Syndrome in PediatricPatients. Arch Ophthalmol. 2004;122(2):276-279. doi:10.1001/archopht.122.2.276