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Show It) 1986 Raven Press, New York The Pupil Cycle Time In Horner's Syndrome Sergiu C. Blumen, M.D., Vera Feiler-Ofry, M.D., and Amos D. Korczyn, M.D., M.Sc. Edge-light pupil cycle time has been introduced recently as a simple method for examining parasympathetic pupillary innervation. Since the sympathetic system is not thought to be involved in the light reflex, it was assumed that edge-light pupil cycle time would be unimpaired in lesions of the sympathetic pathways. In 12 patients with unilateral Horner's syndrome of different etiologies, the edge-light pupil cycle time was determined in both eyes. In all cases the edge-light pupil cycle time was significantly prolonged on the abnormal side. Patients with central, preganglionic, or postganglionic lesions showed the differences consistently. These data support the notion that the sympathetic system plays a role in the pupillo-dilating phase of edge-light pupil cycle time, presumably by exerting a tonic mydriatic effect. Since this tonic effect is lost in Horner's syndrome, leading to slowed redilatation, the edge-light pupil cycle time becomes prolonged. Thus, edge-light pupil cycle time may prove to be a valuable diagnostic test for Horner's syndrome. Key Words: Autonomic nervous system-Homer's syndrome- Pupil cycle time-Sympathetic denervation. From the Departments of Neurology (S.C.B., A.D.K.) and Ophthalmology (V.F.O.), Tel Aviv University Medical Cl'nter, and the Departml'nt (,( Physiology and Pharmacology (A.D.K.), Sackll'r Faculty of Medicine, Ramat Aviv, Israel. An abstract of this work has bl'en presented at thl' 39th Annual Meeting of the American Acadl'my of Neurology, New Orleans, Louisiana, IlJH6. Address cllrrespondl'nce and rl'print rl'Ljul'sts to A. D. Korczyn. Department of Physiology and Pharmacology, Sackler Faculty of Medicine', Ramat Aviv 69978. Israel. 232 When a beam of light is directed to the pupillary margin it induces pupillary constriction; when constricted, the retina no longer "sees" the light and the pupil redilates. By the end of the dilatation the pupillary margin is again in contact with the projected light and a new cycle begins. In this way it is possible to produce clearly visible pupillary oscillations, as long as the light is projected at the edge of the dilated pupil (1). The time required to complete such a cycle, the edge-light pupil cycle time, is remarkably stable for the same eye over extended periods of time. In a group of normal subjects 12-50 years of age the edge-light pupil cycle time had values of 822 ::!: 69 ms (mean::!: SO) (1); in other studies it was 870 ::!: 148 and 980 ::!: 97 ms, respectively (2,3). The maximum betweenmeasurement variation was on the order of 3%, and the difference between the two eyes was generally less than 70 ms (1). It is generally agreed that the edge-light pupil cycle time increases with advancing age (4). Variations in the intensity of the stimulus light (in the useful range) have a negligible effect. Edge-light pupil cycle is quite stable over prolonged stimulation (150 cycles or more); there is no significant light adaptation. Also, it is not significantly affected by visual acuity, refractive error, pupil size at the beginning of the examination, or presence and amplitude of hippus (1). . The edge~light pupil cycle time depends upon mtactness at the light reflex arc; it has been shown to be prolonged when either the afferent or the efferent limb of the pupillary light reflex is impaired: in optic neuritis (5,6), optic nerve compression (7,8), and recently in patients with diseases of the parasympathetic nervous system (9,10). Its behavior in oculosympathetic paresis (Horner's syndrome) has not been reported. PATIENTS AND METHODS .Twelve patients (seven women and five men) WIth Horner's syndrome of various etiologies were included in the present study. The age of the pa- PUPIL CYCLE TIME IN HORNER'S SYNDROME 233 tients ranged from 46 to 83 yt'ars (mean 66 years). All the patients had intact visual fields; they did not suffer from any eye disease other than minor refractive deficiencies (in four patients) and did not exhibit afferent pupillary defects. Four patients suffered from preganglionic lesions due to lateral nlt'dull,lrv syndrome and t11l'ir clinical diagnoses were c1t.'dr cut; two other patients had undergone surgical explorations of tilt' neck (one woman who had radical Ilt'ck dissl'ctinn after necrosis following radical m,lstectomy ,llso had ipsilateral phrenic tlt'n'e par,llvsis); two otlll'r patients had pulmonary space-occupying lesions: one had a Pancoast tumor, the otl1t'r had metastatic involvement of the apical pleura. Four patients had postganglionic lesions (distal to the superior cervical ganglion) as indicated by clinical history and pharmacologic tests (one patient had Horner's syndrome secondary to internal carotid artery obstruction; three idiopathic). In every patient the edge-light pupil cycle time was measured in both eyes. A Haag-Streit slit lamp (Berne, Switzerland) was used; the patients were examined after removing their glasses with a horizontal slit beam of light (thickness 0.5 mm) directed to the lower margin of the pupil. In every eye, three cycle rounds of 30 s each were produced and the average edge-light pupil cycle time in milliseconds was obtained by dividing the time (90 s) by the total number of cycles elicited. The patients were instructed to blink as little as possible. The statistical method for estimating results was the Student's t test for paired samples, comparing the two eyes. RESULTS The ed~e-light pupil cycle time results are summarized in Tabll' }. The mean edge-light pupil cycle on thl' Horner's syndrome side was 1,594 :!: 220 ms and was significantly different from the mean edge-light pupil cycle time of the healthy t.·ye (1,016 :!: 7'-J ms) (Student's paired t test, p < 0.0(11). The upper limit of the interocular difference in healthy persons (1) is considered to be 70 ms, and the difference between eyes in Horner's syndrome (579 :!: 207 ms) was more than eightfold larger. The mean edge-light pupil cycle time in every subgroup of Horner's syndrome patients was significantly increased when compared with the healthy eye (p < 0.001 for every subgroup). On the healthy side there was no edge-light pupil cycle time longer than 1,150 ms; on the Horner's syndrome side no edge-light pupil cycle was shorter than 1,304 ms. Thus, there was no overlap between values in normal and abnormal eyes. DISCUSSION The edge-light pupil cycle time for the healthy eyes in our group was on average longer than in TABLE 1. Edge-light pupil cycle time in 12 patients with unilateral Horner's syndrome Pupil cycle time Case Horner Contralateral Difference no. Diagnosis side side between eyes 1 Wallenberg syndrome 1,428 967 461 2 Wallenberg syndrome 1,400 930 470 3 Wallenberg syndrome 2,000 1,040 960 4 Wallenberg syndrome 1,428 1,000 428 1-4 First neuron 1,564 :!: 291 984 :!: 47 580 :!: 254 5 State following neck surgery 1,667 1,034 633 6 State following neck surgery 1,764 882 882 7 Lung tumor, apical 1,304 967 337 8 Lung tumor, apical 1,428 1,000 428 5-8 Preganglionic 1.541 :!: 212 971 :!: 65 570 :!: 242 9 Idiopathic 1,428 1,034 394 10 Idiopathic 1,760 1.150 610 11 Idiopathic 1,860 1,034 826 12 Carotid obstruction 1,667 1,150 517 9-12 Postganglionic 1,679 :!: 185 1.092 :!: 67 587 :!: 182 Total, 12 1,594 :!: 220 1.016 :!: 79 579 :!: 207 Values are given in milliseconds, mean + SO. I Clill Nt'II",-o!,"t"al",ol, Vol. 6, No ..J. 1986 S. C. BLUMEN ET AL. prt'vious studies (1-3), probably due to the older age of our patients. In all the patients the edge-light pupil cycle time on the Horner's syndrome side showed a highly significant increase when compared with the healthy side, and differences between eyes in the same patient were also highly significant when compared to the upper limit in a normal population (1). In addition, the lack of overlap between edge-light pupil cycle time values in healthy and sympathoparetic eyes makes the test sensitive and reliable. It is known that pupils in Horner's syndrome show, besides miosis, normal response to light but a delayed redilatation in darkness; after sympathetic denervation redilatation depends on the decrease of the parasympathetic tone and mechanical factors of the iris (11-13). The dilatation delay is maximal after 5 s of darkness: this is the period of time in which an average normal pupil reaches 73% of its total dilatation. This ratio is known as "velocity index" and has been shown in a recent article to be significantly smaller (54(7(,) in 12 presumed sympathetically denervated pupils (11). However, in the same article four pupils with Horner's syndrome had a velocity index within the normal range. Measurement of redilatation, therefore, is not specific. Moreover, the method is not very simple since the measurement of the dilatation after 5 and 10 s of darkness requires taking three photographs with a special apparatus. According to our results, the edge-light pupil cycle time seems to be more sensitive, simpler, and faster in the diagnosis of Horner's syndrome. It also has the advantage of being objective and quantitative. Pharmacological confirmation of the existence of Horner's syndrome (particularly of central or preganglionic origin) depends he~vilv on comparison with the normal fellow eye. Edg~light pupil cycle time should therefore be particularly helpful in patients in whom such a comparison is impossible, either because the contralateral eye is also suspected of being sympathetically denervated or is otherwise diseased. In a recent work (14) and in our own observations (not reported) the edge-light pupil cycle time was found to be prolonged in patients with familial dysautonomia; this finding was thought to represent either functional cholinergic denervation or an abnormal iris muscle. In view of our results, together with previous findings (15) in which we did not find evidence of pupillary parasympathetic denervation in this disease, it is more I (li" Neuro-ophthalmol, Vol. 6, No.4. 198b likely that edge-light pupil cycle time prolongation is due to sympathetic rather than parasympathetic denervation. In familial dysautonomia, loss of neurons in superior cervical ganglia has been demonstrated, whereas no loss was observed in the ciliary ganglia (16,17). Recently, Martin (9) reported increased edgelight pupil cycle time in diabetic patients, which correlates well with tests of autonomic function based on cardiovascular reflexes. Since the pupillary reaction to light was normal in these cases and since some cardiovascular reflexes test the function of sympathetic nerves, it is interesting to speculate that the edge-light pupil cycle time prolongation in diabetes is at least partly due to sympathetic denervation, rather than due to parasympathetic dysfunction as proposed by Martin (9). REFERENCES 1. Miller SO, Thompson HS. Edge-light pupil cycle time. Br r Ophtha/mo/ 1978;62:0195- 500 2. Campbell FW, WhiteSide TCD. Induced pupillary oscillations. Br r Ophthalmt,1 1950;301:180-9. 3. Wvbar KC Ocular manifestations of disseminated sclero~ is. Proc R Soc Med 1952;-15:315-20 01 Manor RS, Yassur Y, Siegal R, Ben-Sira I. The pupil cycle time test: age variations in normal patients. Br rOphtha/mo/ 1981;65:750-3 5. Miller SO, Thompson HS. Pupil cycle time in optic neuritis. Am r Ophthall1/l11 1978;85:635-012. 6. Manor RS, Yassur Y, Ben-Sira I. Pupil cycle time in noncompressive optic neuropathy. Ann Ophtha/mol 1982;101: 5016-50. 7. Weinstein jM. Van Gilder Jc. Thompson HS. Pupil cycle time In optIC nerve CL1mpression. Am r Ophthalmo/ 1980;89: 263-7 8. Manor RS, Yassur Y, Ben-Sira I. Pupil cycle time in space occupnng leSions ot anterior optic pathways. Arlll Oph-tha/ moI1982;lo1:1030-o1 . 9. Martin CN. Edge-light pupil cvcle time: a quantifiable autonomic retle" [Abstract]. r .\'clIrl,1 .'\ellroslIr..; PSlfchiatrlf 1985;-18:6021. c. • 10. The autonomic nervous sYstem and the eye [Editorial]. LlIlcet 1985;2:591-2. . 11. Van der \Viel HL, Van Gijn J. Horner's syndrome: criteria tor oculosYmpathetic denervation. r NellYol Sci 1982'56: 293-8 ' 12. Pilley ~FJ, Thompson HS. Pupillary "dilatation lag" in Horner s syndfllme. Ilr r Ophtha/mol 1975;59:731-5. 13. Lowenstein 0, Loewenteld IE. Mutual role of sympathetic and parasympathetic In shaping of the pupillary reflex to light. Arch NellYl'/ PSI/chiatn/ 1950;M:341-77. 101. Gadoth N, Schalen' N, Maschowsky 0, Bechar M. The ~upil cycle time in familial dysautonomia. Metab Pediatr Syst Ophtha/1I/l1/1983;7:131-o1. 15. Korczyn AD, Rubenstein AE, Yahr MD, Axelrod FD. The pupd In tamilial dysautonomia. Neur%gy 1981;31:628-9. 16. Pearson J, BudnlovlCh G, Finegold MJ- Sensory, motor and autonomous dysfunction: the nervous system in familial dysautonomia. Nellrology 1971;21:486-93. 17. Pearson J, Pyfel BA. Quantitative studies of sympathetic ganglia and spinal cord intermedia lateral gray columns in familial dysautonomia. rNellYol Sci 1978;39:47-59. /-----.....,...,--- |