Eyedrop testing in Horner Syndrome Eugene F May
- Slides: 35
Eyedrop testing in Horner Syndrome Eugene F. May, MD Neuro-ophthalmic Consultants Northwest Seattle Neuroscience Institute at Swedish Medical Center University of Washington Seattle, WA
• Horner JF. Über eine Form von Ptosis. Klinische Monatsblätter für Augenheilkunde. 1869; 7: 193198. – No references – Described by Claude Bernard (1850) – Described by Francois Pourfour de Petit (1727)
Anatomy
Pharmacology
Findings • Ptosis – upper eyelid ptosis – inverse ptosis – narrowing of the palpebral fissure • facial anhidrosis • miosis – > 1. 0 mm – dilatation lag • any combination of the above – van der Wiel HL The diagnosis of Horner’s syndrome. Clin Neurol Neurosurg. 1988; 90: 103 -108.
Miosis • Ptosis – iris constrictor unopposed – 1 - 1. 5 mm miosis • greatest in dim illumination • dilation lag – pupil dilation is passive
Is there a chance combination of the ptosis and miosis? • No anhidrosis • No associated neurologic symptoms or findings
Historical Background • • Dilute epinephrine test Cocaine test Hydroxyamphetamine test Apraclonidine test
Cocaine test • Cocaine hydrochloride, 10% • one or two drops in each eye – perhaps several minutes apart • measure pupil size before and 50 -60 minutes later – maintain stable ambient lighting (what level? ) – control near response – ? measure post-drop anisocoria – ? measure change in anisocoria pre- vs. post-drop
Cocaine test • Normal eyes – post-cocaine anisocoria < 0. 5 mm – pupils of Afro-americans react poorly to cocaine – Friedman JR et al. The cocaine test in normal patients. Am J Ophthalmol. 1984; 98: 808 -810 • Horner syndrome – anisocoria of 1. 0 mm or more is consistent – normal result does not exclude Horner’s – Van der Wiel HL, Van Gijn J. The diagnosis of Horner’s syndrome: use and limitations of the cocaine test. J Neurol Sci. 1986; 74: 311316.
Cocaine test • Chances of a Horner syndrome increase with anisocoria – anisocoria of 0. 8 mm = odds ratio of 1050: 1 – anisocoria of 1. 0 mm = odds ratio of 6000: 1 • but measured anisocoria of up to 0. 9 mm in normals • anisocoria as little as 0. 3 mm in Horner group Kardon RH et al. Critical evaluation of the cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol. 1990; 108: 384 -387.
Cocaine test – Absolute anisocoria more predictive than change in anisocoria • less overlap between groups – physiologic anisocoria • anisocoria actually decreased in most Kardon RH et al. Critical evaluation of the cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol. 1990; 108: 384 -387.
Cocaine test Alternatives • Why not cocaine? – difficult to obtain (? ) – expensive (? ) – short shelf life (? ) – parents hesitant (? ) – positive urine test (? )
Cocaine test Alternatives • Apraclonidine 0. 5%, 1% (Iopidine) – α 2 > α 1 adrenergic agonist • approved for treatment of IOP after trabeculoplasty • receptors upregulate after 5 -8 days – reversal of anisocoria in several studies • 0. 5% and 1. 0% • denervation supersensitivity – actively dilates the abnormal pupil
Apraclonidine • Studies show good sensitivity – 1. 00 (1%) and 0. 88 (0. 5%) – Morales J et al. Arch Ophthalmol. 2000; 118: 951 -954. – Brown SM et al. Arch Ophthalmol. 2003; 121: 1201 -1203. – physiologic anisocoria: no reversal of anisocoria • Comparison studies – 0. 5% vs 4% cocaine in children • equally sensitive • Chen P et al. J Ocular Pharm and Therapeutics. 2006; 22: 182 -187.
Apraclonidine • must have high level of illumination • sometimes normal pupil dilates
Apraclonidine • Side effects – in children with glaucoma • apnea, bradycardia, hypotension, somnolence, fatigue – in children with Horner syndrome • conjunctival hyperemia • sleepiness
Localization
Hydroxyamphetamine test • Pivotal study – more reliable than dilute epinephrine testing – Thompson HS and Mensher JH. Adrenergic mydriasis in Horner’s syndrome. Hydroxyamphetamine test for diagnosis of postganglionic defects. Am J Ophthalmol 1971; 72: 472 -480.
Hydroxyamphetamine test • Post-drop anisocoria – difference in dilation • 1. 0 mm: 85% chance of post-ganglionic lesion • 1. 5 mm: 96% chance of post-ganglionic lesion Cremer SA, et al. Hydroxyamphetamine mydriasis in Horner’s syndrome. Am J Ophthalmol. 1990; 110: 66 -70.
Hydroxyamphetamine test • Problems – range of variability exists • even in normals – Cremer et al. Hydroxyamphetamine mydriasis in normal subjects. Am J Ophthalmol. 1990; 110: 66 -70. • extent of deficit influences test results – false negative in acute Horner’s • one week before NE stores are exhausted – must wait two days after cocaine test
Hydroxyamphetamine test • False positive – if second and third order neuron involved • extensive tumor • radiation – blood supply to the SCG arises lower in the neck – congenital • trans-synaptic degeneration of 2 o neuron
Hydroxyamphetamine test Alternatives • Hydroxyamphetamine not always available • Denervation supersensitivity – Dilute epinephrine • 55% false positives • 61% false negatives – Hydroxyamphetamine • 16% false positives • 4% false negatives – Maloney WF, et al. Am J Ophthalmol. 1980; 90: 394 -402.
Hydroxyamphetamine test Alternatives • Dilute (1%) phenylephrine – sensitivity 81%; specificity 100% – effects vary according to integrity of corneal epithelium • hydroxyamphetamine not dose-dependent – partial postganglionic lesion may not be distinguished from preganglionic lesion Danesh-Meyer HV et al. The correlation of phenylephrine 1% with hydroxyamphetamine 1% in Horner’s syndrome. Br J Ophthalmol. 2004; 88: 592 -3.
Hydroxyamphetamine test Alternatives • Problems with supersensitivity testing – dilution of eyedrop – degree of supersensitivity • preganglionic lesions cause relative supersensitivity – dilute solutions more dependent on corneal parameters – supersensitivity of the iris dilator increases with age
Hydroxyamphetamine test Alternatives • Not generally available in US: – Tyramine hydrochloride (5%) – Hydroxymethylamphetamine (Pholedrine)
Conclusions • A combination of characteristic symptoms and signs allows a diagnosis of Horner syndrome
Conclusions • Cocaine testing is the eyedrop test of choice for diagnosing anisocoria due to Horner syndrome – 1. 0 mm anisocoria after the eyedrops is a useful cutoff – apraclonidine testing is very helpful and the eyedrop is more readily available • bright light
Conclusions • Hydroxyamphetamine testing helps localize the Horner syndrome to the third order neuron – 1. 0 mm difference in dilation a useful cutoff – beware of false positives – dilute phenylephrine if hydroxyamphetamine not available
Thank you!
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