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Show ]. CIin. Neuro-ophthalmol. 3: 19-22, 1983. Clinical and Subclinical Oculomotor Findings in the Eaton-Lambert Syndrome MARC. P. CRUCIGER, M.D. BRIAN BROWN, Ph.D. ERIC H. DENYS, M.D. ELBERT MAGOON, M.D. PAUL J. WASSON NANCY M. NEWMAN, M.D. ALAN B. SCOTT, M.D. Abstract Five patients with the Eaton-lambert syndrome were examined neuro-ophthalmologically. Three were studied using electro-oculographic saccadic velocity recordings. Four complained of blurred vision and all complained of ptosis during the course of their disease. Clinical examination revealed mild ptosis in three of the five patients. Saccadic velocities before exercise were normal. After saccadic exercise, an increase in velocity of up to 40% was noted in two of the three patients studied. Introduction The Eaton-Lambert syndrome, or myasthenic syndrome, is a rare disorder of neuromuscular transmission which can be differentiated from myasthenia gravis on the basis of clinical and electromyographic findings. I, 2 One of the clinical distinctions between the Eaton-Lambert syndrome and myasthenia gravis is that ocular signs and symptoms are reportedly rare in the Eaton- Lambert syndrome in contrast to their frequent occurrence in myasthenia gravis.:l - X This report describes the clinical and the sub-clinical oculomotor findings in patients with the Eaton-Lambert syndrome and reports analysis of the saccadic eye movement velocities before and after exercise in three patients. Fellow in Strabismus and Neuro-ophthalmology (MPC), Senior Scientist (BB), Fellow in Strabismus (EM), and Associate Director (ABS), Smith Kettlewell Institute of Visual Sciences, San Francisco, California; Institute of Medical Sciences (EHD), San Francisco, California; medical student (PJW), Case Western Reserve University School of Medicine, Cleveland, Ohio; and Associate Professor and Director of Neuro-ophthalmology Unit (NMN), Department of Ophthalmology, Pacific Medical Center, San Francisco, California. March 1983 Patients and Methods Patients Four males and one female patient with the myasthenic syndrome were evaluated (Table 1). The diagnosis of myasthenic syndrome was well established by the clinical neurologic symptoms and characteristic electromyographic abnormalities. 9 The initial evoked muscle response in the hypothenar muscle following stimulation of the ulnar nerve was very small (0.2 mV; 1.6 mV; and 0.9 mV in RK, MR, and WC). In the other two patients (MK and TF), the initial evoked muscle response in the thenar muscle following stimulation of the ulnar nerve was 2.1 and 0.4 mV respectively. With repetitive stimulation at slow frequences (2/second), a further decline of the first few responses were seen in all patients. At high frequencies (SO/second), or following a brief period of exercise (15 seconds), marked facilitation was observed (from 4 to 20 times the initial response). All patients had been fully investigated for the presence of an underlying malignancy but none was found. All patients were participating in an experimental protocol of plasmapheresis and immunosuppressive treatment at the time of their neuro-ophthalmological evaluation. Medications included prednisone and azathioprine. The patients were not on guanidine. lo Anticholinesterase medication was withheld for at least 10 hours prior to testing. Methods The clinical neuro-ophthalmological examination assessed visual acuity, external appearance, especially the presence of ptosis, pupil function, confrontation visual fields, the ocular motor system including ocular rotations, pursuit and saccades, and the ocular fundi. Saccadic velocity measurements were obtained in three of the five patients (We, MK, and TF), 19 Eaton-Lambert Syndrome TABLE l. Oculomotor Findings in Myasthenic Syndrome Clinical Symptoms Patient Age Sex RK 47 M MR 48 M we 48 M MK 60 F TF 70 M Diplopia Blurred Ptosis Vision + + + + + + + + + + + + Clinical Findings Saccadic Velocity Ptosis Saccades Pursuit Preexercise Postexercise + N N nm nm N N nm nm + N N N /I N N N /I + slow N slow nc abduction Abbreviations: N = normal; + = present; - = absent; nc = no change; nm = not measured; /I = increased. with the Eaton-Lambert syndrome. Each patient was placed supine on a table to minimize head movement. Directly overhead at a distance of 5 ft. was an arc with independently controlled lightemitting diodes as fixation markers at 100 intervals. The skin was prepared with alcohol swabs to insure good contact and Beckman electrodes with Beckman electrode paste were placed at the medial and lateral canthi and above the eye brow of the right eye. Subjects looked at the zero position on the display while any DC offset in the recording system was nulled, and then at a target 200 eccentric while the gain of the system was adjusted to produce a standard output. The DC-EOG signal was electronically differentiated to produce a velocity signal which was passed to a peak detector and "sample and hold" circuitry. The resulting scaled voltage value was displayed as peak saccadic velocity. Simultaneous position and velocity traces were recorded on a Gould Model 220 chart recorder. The patient was asked to make horizontal saccades of 20° amplitude for baseline saccadic velocity measurement. The patient was then asked to make horizontal saccades of 400 as rapidly as possible (about 2/second) for 20 seconds. Within 5 to 10 seconds after this"exercise," successive 20° saccades were then remeasured. The trial of preexercise velocity, exercise, and postexercise saccadic velocity was repeated twice. Five normal subjects were tested in a similar manner. Results Ptosis was the primary clinical neuro-ophthalmological finding in the group of five patients with the Eaton-Lambert syndrome studied. Three of the five patients demonstrated a unilateral ptosis of no more than 2 to 3 mm. Clinical fluctuation of ptosis was unremarkable during the examination; however, each patient reported an increase in ptosis, usually in the evening. However, at no time was the ptosis marked. Although four of the five patients complained of intermittent diplopia and blurred vision, on clinical examination no patient demonstrated either diplo- 20 pia or reduced visual acuity by conventional testing. The blurred vision complained of was primarily at near. One patient, (WC), had reduced near acuity which was optically correctable. Qualitative examination of the patient's amplitude of horizontal eye movements, saccades, and pursuit appeared normal except in one patient (TF). In this patient the abduction saccades appeared slowed, and the amplitude of abduction was slightly diminished. Table 1 summarizes the clinical symptoms and signs of these five patients. Quantitative analysis of the horizontal saccades of three of the patients with the Eaton-Lambert syndrome did, however, demonstrate interesting abnormalities. In all the patients the saccadic velocity in the preexercise state was within our normal range for 20° saccades. Following the exercise period with 40 0 saccades, an increase in saccadic velocity was noted in two of the patients. The increase was about 40% in the first patient and 20% in the second. Figure 1 shows the pre- and postexercise values for the first patient. The increase in saccadic velocity slowly decayed to initial levels after 6 to 8 saccades. For this patient, student's ttest demonstrated significant differences between pre- and postexercise saccadic velocities (p < 0.01). The increase in saccadic velocity was shown for both abduction and adduction saccades. The second patient showed a 20% increase in saccadic velocity after saccadic exercise; this difference was also significant by t-test (p < 0.01). For all of these sets of saccades, obviously hypometric saccades were eliminated from the analysis, so that these changes in saccadic velocity cannot be attributed to increased saccade size after exercise. There were no obvious changes in the size of saccades after exercise. One patient (TF) did not demonstrate an increase in postexercise saccadic velocity. There was no significant change in saccadic velocities in five normal patients tested after similar saccadic exercise. Discussion Although saccadic eye movement studies have been performed on patients with myasthenia Journal of Clinical Neuro-ophthalmology 350 U <l> ~ 01 :3 300 uo~ .>! "0 ~ 250 ('f") 0--0 Set 1 - Se12 if) <l> "0 '" UU ('f") o o o"" <l> if) U OJ w'" Cruciger, et aL 200 L-L-.l-.-.l-.-i.--'------'------'----'-----"---"---'---j'-'------L----'---'----'----' 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10 11 Saccade Number Figure 1. Saccadic velocity (deg./second) as a function of saccade number, before (left) and after (right) "saccadic exercise," in which the patient (We) made 40° saccades as rapidly as possible, for about 20 seconds. Postexercise saccadic velocities are significantly elevated. (Student's t-test, p < 0.01.) gravis,11-14 we know of no oculographic studies conducted on patients with Eaton-Lambert syndrome. Our findings suggest that in patients with the Eaton-Lambert syndrome, there is a subclinical increase in saccadic velocity following "saccadic exercise." In two of the three patients studied (WC and MK), the preexercise saccadic velocities were within normal ranges for 20° horizontal saccades.5. 15-19 The third patient (TF) was the only patient with clinically abnormal saccades; he had subnormal horizontal saccadic velocities and did not exhibit a postexercise velocity increase. In the two patients demonstrating an increased velocity with saccadic exercise, the first postexercise saccade velocity was increased. This increase in saccadic velocity was not maintained, but it slowly diminished after 6 to 8 saccades. The increase in velocity following exercise distinguishes the eye movements of the Eaton-Lambert syndrome from those of myasthenia gravis. In a recent report, Abel et aI. ll emphasized that in myasthenia gravis, saccadic velocity is normal for small amplitude eye movements and that the amplitude limitation is the primary defect. Clinically, eye movements in our patients appeared neither slowed nor limited in amplitude. This was also the experience at the Mayo Clinic where in 40 patients with Eaton-Lambert syndrome, the only eye findings were ptosis and intermittent blurred vision. Elmqvist concluded that ocular symptoms" ... either do not occur or are mild and transient and seldom present at the time March 1983 of the examination of patients with the Eaton-Lambert syndrome.',:l Blurred vision, commonly reported in the Mayo Clinic series, was noted intermittently by all but one of our patients. Only one of them specifically stated that the blurred vision was worse at near, and with the appropriate optical correction, his symptom was relieved. Since the Eaton-Lambert syndrome is most common in patients 40 years of age or older, the blurred vision in some cases may be physiologic for age, and not a manifestation of the disease itself. Our data support the view that there is a paucity of obvious clinical ocular findings in the Eaton-Lambert syndrome. However, in two of the three patients studied the saccadic velocities after exercise increased. This parallels the improvement in strength seen in peripheral muscles which is demonstrated electromyographically as facilitation. This suggests the electrooculographic recording of saccadic velocities is of potential value in diagnosis of complex cases of the Eaton-Lambert syndrome." References 1. Denys, E.H., Dau, P.c., and Lindstrom, ].M.: Neuromuscular transmission before and after plasmapheresis in myasthenia gravis and the myasthenic syndrome. In Plasmapheresis and the Immunobiology of Myasthenia Gravis, P.c. Dau, Ed. HoughtonMifflin, 1979, pp. 248-257. 21 Eaton-Lambert Syndrome 2. Desmedt, }.E., and Borenstein, S.: The testing of neuromuscular transmission. In Handbook oE Clinical Neurology, P.}. Vincken, G.W. Bruvn, Eds. North Holland Publishing Company, 1970, pp. 104-115. 3. Elmqvist, D., and Lambert, E.H.: Detailed analysis of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin. Proc. 43: 689-713, 1968. 4. Hedges, T.R.: Ophthalmoplegia of myasthenia and bronchial neoplasm. Arch. Ophthalmol. 70: 333-334, 1963. 5. Mastaglia, F.L., Black, }.L., and Collins, D.W.K.: Quantitative studies of saccadic and pursuit eye movements in multiple sclerosis. Brain 102: 817-834, 1979. 6. Schwartz, M.s., and Stalberg, E.: Myasthenia gravis with features of the myasthenic syndrome. Neurology 25: 80-84, 1975. 7. Stalberg, E., Ekstedt, J" and Broman, A: Neuromuscular transmission in myasthenia gravis studied with single fibre electromyography. ]. Neurol. Neurosurg. Psychiatry 37: 540-547, 1974. 8. Walsh, F.B., and Hoyt, W.F.: Clinical Neuro-Ophthalmology, Vol. 2. Williams and Wilkins, Baltimore, 1969, pp. 1194-1195. 9. Eaton, L.M., and Lambert, E.H.: Electromyography and electrical stimulation of nerves in diseases of motor unit. rAM.A. 163: 1117-1124, 1957. 10. Cherington, D.: Guanidine and germine in Eaton-Lambert syndrome. Neurology 26: 944-946, 1976. 11. Abel, L.A, DelrOsso, L.F., Schmidt, D., and Darof£, R.B.: Myasthenia gravis: analog computer model. Exp. Neurol. 68: 378-389, 1980. 12. Metz, H.S., Scott, AB., and O'Meara, D.M.: Saccadic eye movements in myasthenia gravis. Arch. Ophthalmol. 88: 9-11, 1972. 13. Schmidt, D., DelrOsso, L.F., Abel, L.A, and Darof£, R.B.: Myasthenia gravis: saccadic eye movement waveforms. Exp. Neurol. 68: 346-364, 1980. 14. Schmidt, D., Dell'Osso, L.F., Abel, L.A., and DaroE£, R.B.: Myasthenia gravis: Dynamic changes in saccadic waveform, gain and velocity. Exp. Neurol. 68: 365-377, 1980. 15. Bahill, AT., Clark, M.R., and Stark, L.: The main sequence, a tool for studying human eye movements. Math. 8iosci. 24: 191-204, 1975. 16. Baloh, R.W., Konrad, H.R., Sills, AW., and Honrubia, V.: The saccadic velocity test. Neurology 25: 1071-1076, 1975. 17. Bird, AC., and Leech, }.: Internuclear ophthalmoplegia; an electrooculographic study of peak angular saccadic velocities. 8r. ]. Ophthalmol. 60: 645-651, 1976. 18. Feldon, S.E., Hoyt, W.F., and Stark, L.: Disordered inhibition in internuclear ophthalmoplegia: Analysis of eye movement recordings with computer simulations. Brain 103: 113-137, 1980. 19. Schmidt, D., Abel, L.A ., DelrOsso, L.F., and Darof£, R.B.: Saccadic velocity characteristics, intrinsic variability and fatigue. Aviat. Space Environ. Med. 50: 393-395, 1979. Acknowledgment This research was funded in part by a National Eye Institute Training Grant 5T32-EY-07027-05; and Research to Prevent Blindness. Write Eor reprints to: Nancy M. Newman, M.D., Department of Ophthalmology, 2340 Clay at Webster, San Francisco, California 94115. Journal of Clinical Neuro-ophlhalmology |
