Horner's syndrome

Journal of the Neurological Sciences, 1982,56:293-298

293

Elsevier BiomedicalPress

HORNER'S SYNDROME Criteria for Oculosympathetic Denervation

H.L. VAN DER WlEL and J. VAN GIJN Department of Neurology, University Hospital Rotterdam (Dijkzigt), Rotterdam (The Netherlands)

(Received 21 January, 1982) (Accepted 5 April, 1982)

SUMMARY The darkness reflex of the pupil was examined by taking photographs under standard bright lighting conditions, and after 5 and 10 s of uninterrupted darkness. The study involved 40 control subjects and 12 patients with a presumed Horner's syndrome. No control subject showed a dilatation lag (compared with the other eye) of 0.5 mm or more in the first 5 s of darkness. This criterion allows exclusion of a fortuitous combination of "physiological anisocoria" and "physiological ptosis".

INTRODUCTION Pupils affected by sympathetic denervation show not only miosis but also a delay of dilatation in darkness after exposure to a bright light (Riley and Moyer 1970; Pilley and Thompson 1975; Loewenfeld 1977). The pupil eventually dilates to some extent, by a decrease of parasympathetic tone (L6wenstein and Loewenfeld 1950a,b, 1962), and pupillographic studies indicate that the "dilatation lag" from sympathetic denervation is maximal after about 5 s of darkness (Riley and Moyer 1970; Pilley and Thompson 1975). Pilley and Thompson tried to make an easy distinction between patients with a unilateral sympathetic denervation and patients with "simple" anisocoria, by taking Polaroid flash photographs. They found a significant difference in anisocoria between the two groups after 4-5 s of darkness, a difference not found in light or after 10-12 s of darkness. Address correspondence and reprint requests to Dr. Van der Wiel, Department of Neurology, UniversityHospital Rotterdam (Dijkzigt),40 Dr. Molewaterplein,3015 GD Rotterdam, The Netherlands. 0022-510X/82/0000-0000/$02.75 © 1982 ElsevierBiomedicalPress

294 In individual cases, however, it is still not clear what degree of "dilatatiow~ lag" distinguishes pupils with sympathetic denervation from normal pupils. Therefore, we studied the darkness reflex with flash photographs not only in patients with presumed oculosympathetic denervation, but also in a large group of controls. We eliminated the role of "physiological" anisocoria by measuring absolute values of pupillary dilatation after fixed time intervals. Finally, the use of a more accurate technique was necessary because with polaroid prints, our measuring error of pupil size appeared considerably larger than the error of 0.1 mm which has been described by Pilley and Thompson. M E T H O D S A N D SUBJECTS

Photographic apparatus We used an Asahi Pentax ME camera with an Asahi Pentax auto-bellows and a telescopic lens SMC Pentax-M 1:4, 200 mm. The flashlight, a Philips Flash 20B, was positioned near the camera body. The flash time was 0.001 s, which is far shorter than the latency of the pupillary reflex (0.2 s or more, L6wenstein and Loewenfeld 1962). A Philips bulb of 60 W with inbuilt mirror illuminated the subject, and was fastened at the same distance behind the lens as the flashlight. Its luminance was 18.10 4 cd/m 2, measured at the position of the eyes by a Tektronic j 6523-2 1° narrow angle luminance probe. The same instrument detected no light in the darkened test room. To achieve an accuracy of 0.1 mm, we had to use positive film (Kodak Ektachrome 64 professional film, for daylight); this was satisfactory even in subjects with dark-brown irises. A NE 555 timer drove the camera and winder. A double pole switch triggered the timer a n d turned off the light; after exactly 5 or 10 s the timer released the shutter.

Measurements Each subject was photographed under standard lighting conditions, then after 5 s of darkness and finally after 10 s of uninterrupted darkness (Fig. 1). This sequence was repeated once. We measured the pupils from projected films. with correction of magnification. Values used for calculations are the means of two measurements from the corresponding pictures of the two series. F r o m these mean diameters we calculated: (1)anisocoria; (2) dilatation after 5 and after 10 s of darkness; (3) the ratio between pupillary dilatation after 5 s of darkness and dilatation after 10 s of darkness ("velocity index"): (4) difference in dilatation between the two eyes ("dilatation lag") after 5 s of darkness and also for the period between 5 and 10 s of darkness; as the error of measurement was approximately 0.1 mm the maximal error of the dilatation lag is 0.4 mm. The patpebral fissure was measured through the midline of the pupil, and ptosis was defined as the difference between the two sides. The relation between pupil size and ptosls was calculated from single films, the relation between ptosis and "dilatation lag'" from the mean of two values.

295 DIAMETER OF PUPIL in m m

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Fig. 1. In this example, the arrows indicate the time (on the horizontal) and conditions under which the three measurements of pupillary diameter (on the vertical axis) are taken. It is clear that the pupillary diameter at 10 s is measured separately after uninterrupted darkness and is not influenced by constriction through the flashlight at 5 s.

Sblbjccts Forty hospital employees served as controls. To be accepted they had to be free from eye disease (including strabismus) or neurological symptoms. Their ages varied between 19 and 50 years (mean 30 years). Patients with the clinical diagnosis of oculosympathetic denervation were accepted only when at least miosis and ptosis were present. Formal sweat testing was not performed. We studied 12 patients, with a mean age of 38 years (12-67 years). RESULTS

The 80 pupils of the control subjects had a m e a n diameter of 2.8 mm in light, 4.8 mm after 5 s of darkness, and 5.5 mm after 10 s of darkness. Accordingly, the mean pupil attained within 5 s of darkness 73~o of the total dilatation achieved in 10 s. Figure 2 illustrates that the values per eye for this "velocity index" show a normal distribution around the mean (SD: 8~). There was no difference between right and left eyes. The 12 patients with presumed oculosympathetic denervation showed the same values for their normal eyes, whereas the velocity index for the smaller pupils (also shown in Fig. 2) had a mean value of 54~, SD 12~. The difference between the indexes of the normal and presumably affected pupils in the patients was significant (P < 0.001, Student's t-test for paired samples). The velocity indexes of 4 smaller pupils, however, were well within the control range. Part of this overlap might be due to the fact that absolute measures for dilatation velocity fail to detect slight weakness in a patient whose pupil previously was at the "fast end" of the normal distribution. Therefore, we have compared the degree of dilatation within each pair of eyes, for the first 5 s of darkness as well as for the period between 5 and 10 s of darkness. Figure 3 shows the dilatation lag for each of these two intervals.

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Fig. 2. Velocity index (ratio - - in percentage - - between pupillary dilatation after 5 s of darkness and dilatation after 10 s) in 80 eyes of control subjects (above the horizontal) and 12 eyes with presumed oculosympathetic denervation (below the horizontal). Dilatation lag in ram, 5-10 s.

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Fig. 3. Dilatation lag (difference in pupillary dilatation between the two eyes of each individual) in mm for 40 controls (dots) and 12 patients with presumed oculosympathetic denervation (triangles). Differences for the first 5 s of darkness are shown on the horizontal axis. For the slower pupil of this first interval (or the right pupil if dilatation was equal), the dilatation lag between 5 and 10 s of darkness •

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297 Above the horizontal zero line in Fig. 3 are 10 control pupils which dilated less than the other side in the first period of 5 s, and again in the second period. Below the horizontal are pupils in which a "dilatation lag" within the first 5 s of darkness is partially or wholly compensated in the second interval. Such "catching up" or at least absence of a further lag after 5 s is a prerequisite for a diagnosis of oculosympathetic denervation (Pilley and Thompson 1975; Loewenfeld 1977). Nevertheless, some control subjects showed the same sequence of events, with an initial dilatation lag up to 0.4 mm (which equals the maximal deviation from cumulative errors of measurement). Three of the 12 patients who were thought to have oculosympathetic denervation failed to exceed a dilatation lag of 0.4 mm in the first 5 s of darkness, despite the presence of seemingly appropriate lesions: a pontine lesion, probably demyelination, in one patient, a traumatic cord injury in another, and abnormal sympathetic innervation of the forehead in the third case. The degree of ptosis in control eyes showed no statistical correlation with miosis, nor with dilatation lag (Spearman-Rank correlation test). DISCUSSION

The cardinal feature of oculosympathetic denervation is slowness of dilatation. Our results in control subjects indicate that this can be diagnosed with confidence only if the dilatation lag is 0.5 mm or more after 5 s of darkness. A further condition is that there should be no further lag between 5 and 10 s (Pilley and Thompson 1975 ; Loewenfeld 1977). The usefulness of these criteria is illustrated by the finding that they were not met by 3 of our 12 patients with clinically presumed oculosympathetic denervation, and we cannot but conclude that these cases represented a fortuitous combination of "physiological anisocoria" and "physiological ptosis". We showed in the control group that these variables are independent, which contrasts with the findings of Meyer (1947). If no normal eye is available for comparison because of possible bilateral oculosympathetic involvement, enucleation, or strabismus, a velocity index of less than 49~o (mean minus 3 SD) can be used as an alternative but less sensitive criterion. Our photographic technique for measuring the pupillary diameter after fixed intervals of darkness is relatively simple and can easily be reproduced. Even if pharmacological tests can reliably distinguish between pre- and postganglionic lesions of the oculosympathetic system (Thompson and Mensher 1971), unequivocal demonstration of dilatator weakness is a necessary first step. REFERENCES Loewenfeld, I.E. (1977) "Simple central" anisocoria - - A c o m m o n condition, seldom recognized, Trans. Amer. Acad. Ophthal. Otolaryng., 83: 832-839. L6wenstein, O. a n d I. E. Loewenfeld (1950a) Role of sympathetic and parasympathetic systems in reflex dilatation of the pupil, Arch. Neurol. Psychiat. (Chic.), 64: 313-340.

298 L6wenstein, O. and I.E. Loewenfeld (1950b) Mutual role of sympathetic and parasympathetic i~, shaping of the pupillary reflex to light, .4r~h. Neurol. P.*£ehiat. (Chic.), 64:341 377. L6wenstein, O. and I.E. Loewenfeld (1962) The pupil. In: Davson (Ed.), The EL'e, Vol. 3, Academic Press, New York, NY, pp. 231-267. Meyer, B. V. (1947) Incidence of anisocoria and difference in size of palpebral fissures in tire hundred normal subjects, Arch. NeuroL Ps3'chiat. (Chic.), 57: 464-468. Pilley, S.F.J. and H.S. Thompson (1975) Pupillary "dilatation lag'" in Horner's syndrome, Brit..! Ophthal., 59:731 735. Riley, F.C. and N.J. Moyer (1970) Experimental Homer's syndrome -~ A pupillographic evaluation of guanethidine-induced adrenergic blockade in humans, Amer. ,l. Ophthal., 69: 442-447. Thompson, H.S. and J.H. Mensher (1971) Adrenergic mydriasis in Horner's syndrome, Amer. ,L Ophthal., 72:472 480.