Tensilon tonography in the diagnosis of myasthenia gravis. Joel S. Closer*
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1 Tensilon tonography in the diagnosis of myasthenia gravis Joel S. Closer* The concomitant intravenous administration of Tensilon during tonography was performed on a group of 5 myasthenic patients and ten "control" subjects, including patients with oculoparesis of known cause other than myasthenia. The myasthenic group uniformly responded with increases of intraocular pressure. There was no instance of this response in nonmyasthenic subjects when challenged with Tensilon. It is suggested that "Tensilon tonography" is a diagnostic procedure of greater sensitivity than the standard Tensilon test for myasthenia gravis with ocular involvement. T,.ensilon tonography is a new and easily performed procedure which enhances the appreciation of the response of extraocular muscles to an antimyasthenic agent. Often, the physician is faced with interpreting subtle responses obtained with standard Tensilon administration in cases of ptosis and ophthalmoplegia in which the physical findings are minimal. It is in this clinical situation that the value of the Tensilon tonograph may be of diagnostic significance. The variables inherent in the standard Tensilon test and the general unavailability of electromyographic apparatus led to the present study of a new procedure of high sensitivity and practical simplicity. The purpose of this report, therefore, is to describe the "Tensilon tonogram," a new approach utilizing the effect of the extraocular muscle cone on intraocular pres- From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, Fla. "Address: 68 N.W. th Ave., Miami, Fla sure to facilitate the diagnosis of myasthenia gravis. Methods and materials Fifteen myasthenic patients (Table I) and ten "control" patients (Table II) were subjects in this study. Tonography was performed on the myasthenic group following abstinence from all medication for a minimum of hours. The "control" group was selected from an outpatient clinic population and included persons having oculoparesis of known cause other than myasthenia gravis. With the patient in the supine position, a pediatric scalp-vein needle was introduced into the antecubital vein. A syringe containing normal saline and a second syringe containing Tensilon ( mg. per cubic centimeter) were connected to the indwelling needle utilizing a three-way stopcock. All tonography was performed with the V. Mueller electronic Schitz tonometer and a Leeds & Northrup recorder at a rate of 5 cm. per minute. With tonometry performed continuously, a stable pressure decay curve was established for the right eye (Fig. ). Normal saline, c.c, was administered intravenously and the effect monitored tonographically for a minimum of seconds. At this point, Tensilon, c.c. ( mg.) was delivered intravenously over a five-second period and tonography continuously recorded for a minimum of 6 seconds. After a five-minute hiatus, Downloaded From: on //8
2 6 Glaser Investigative Ophthalmology April 67 Table I. Myasthenic patients Case. 56 F. 66 M. 5 F. 5 F 5. 8 M F 7. 8 M 8. 5 F. 6 F. 8 M. 6 M. 5 M. 6 F. 6 F 5. F Duration (known) (yr.) 6? 7 5 Ocular Paresis Diplopia Paresis Diplopia Ptosis Ptosis, paresis Ptosis, paresis Ptosis, paresis Ptosis Ptosis Arms General Arms, legs Hyperthyroid Jaw, arms, legs Pharynx, arms, leg Resp., arms, leg Pharynx, arms, leg Legs? Pressure Response Saline (mm. Hg) * "In each case, the upper figure represents the right eye, the lower figure the left eye. Tensilon (mm. Hg) 5 5 Delay (sec.) Fasciculations ? 7? Table II. Control group Case. Traumatic third nerve.? etiology. Thyroid myopathy. Oculopharyngeal dystrophy 5. Multiple sclerosis 6. Congenital esotropia 7. Monocular cataract 8. Daughter of myasthenic. Normal. Normal Ocular R. third, residual Aberrant regeneration Exophthalmos, limited vert. Decreased versions Internuc. ophthalm. ET XT Pressure response Saline Tensilon Fasciculations Downloaded From: on //8
3 Volume 6 Number Tensilon tonography for myasthenia gravis 7 OD OS p i So ]' ne Saline I ^ Edrophonium i Edrophonium ^ Vw*- Fig.. Normal tonogram with infusion of saline and Tensilon. No change in intraocular pressure is observed. tonography with infusion of saline and Tensilon was repeated on the left eye. In addition to the tonographic record, observations were made of lacrimation and fasciculations of the orbicularis oculi as evidence of Tensilon effect. Results A total of 5 myasthenic patients with ocular involvement were tested. This material is summarized in Table I. In no instance was there any tonographically recordable response to intravenous saline. In all 5 patients, there was a demonstrable rise in intraocular pressure following Tensilon administration, at least monocularly. Of the tonograms performed on myasthenic eyes, only three failed to give evidence of increased intraocular tension. The greatest rise recorded was 5 mm. Hg in two instances (Cases and 7, Fig. ). The average increase was.8 mm. Hg. Fasciculations of the orbicularis oculi were not observed in any patient. The absence of fasciculations has been called by Osserman and Kaplan a "positive objective criterion" for the diagnosis of myasthenia gravis. Distinction is made between diplopia and ophthalmoplegia. On the day of observation, only of 5 myasthenics had clinical oculoparesis, while most had a positive past history of double vision. Standard Tensilon test response in the remaining patients without obvious motility dysfunction would have been most difficult to evaluate. Ptosis, although present in all but one patient, was often quite subtle. The myasthenic response to Tensilon recorded tonographically, on the other hand, resulted in finite objective endpoints which were easily interpretable. A myasthenic response is represented by Case (Fig, ). Tensilon administration resulted in a rise of mm. Hg in the right eye and mm. Hg in the left eye. The increasing intraocular pressure was recorded 5 and seconds after Tensilon, right and left eyes, respectively. Clinically, this patient had no overt paresis and only minimal ptosis. A maximum response was recorded in Case (Fig. ). Ocular tension rose 5 mm. Hg in the right eye and mm. Hg in the left eye. Paradoxically, the less paretic eye demonstrated the greater rise in pressure upon Tensilon stimulation. The remaining tonogram (Fig. ) demonstrates a dissociation of response. In the right eye, there was no recordable increase in pressure, but a veiy strong response was elicited in the left eye. Clinically, there was only the most subtle ptosis and no oculoparesis. In the "control" group (Table II), there was no recordable elevation of intraocular pressure in response to Tensilon. Fasciculations of the orbicularis oculi were a constant observation in contradistinction to the myasthenic patients. Discussion Derivatives of physostigmine had been utilized therapeutically by Walker-' a and others, " 7 but the diagnostic value of a rapid test was not emphasized until Osserman and Kaplan described the intravenous use of Tensilon. This analogue of neostigmine is a rapid anticurare-like agent whose maximum effect usually occurs within one minute. Breinin s has evaluated anticholinesterase and anticurare agents by use of electromyography. He suggests the oc- Downloaded From: on //8
4 8 Glaser Investigative Ophthalmology April 67 Fig.. Tonogram of Case (niyasthenia). Tensilon administration results in and mm. Hg increases in intraocular pressure, right and left eyes, respectively. P Fig.. Tonogram of Case (niyasthenia). Maximum response is demonstrated by 5 mm, Hg rise in pressure in right eye following Tensilon. Downloaded From: on //8
5 Volume 6 Number Tensilon tonography for myasthenia gravis Edrophonium Fig.. Tonogram of Case 7 (myasthenia). Left eye response is maximal. No response to Tensilon infusion was observed in right eye. currence in myasthenic patients of characteristic patterns of innervation and drug response. Kornblueth and co-workers" demonstrated the effect on intraocular pressure of increased tonus of the oculorotary muscles in response to succinylcholine and Tensilon. In that study, Tensilon increased the activity of myasthenic muscles but not in normal subjects. "Tensilon tonography" represents a sensitive diagnostic procedure which records finite increases in intraocular pressure due to contraction of the myasthenic extraocular muscle cone. Standard Tensilon testing is often unsatisfactory by virtue of dependency upon the patient's subjective evaluation of the antimyasthenic response and the physician's often rough interpretation of subtle and inconstant oculoparesis or ptosis. The occurrence of a false-negative response to Tensilon is not uncommon. While electromyographic recordings of the response to Tensilon represent a higher order of sensitivity, the necessary equipment is not generally available. The technical difficulties and discomfort of intramusclar electrode placement may make such testing cumbersome and inapplicable as a practical diagnostic device. The value of "Tensilon tonography" lies in its ease of performance, availability of apparatus, and heightened sensitivity in recording the response of paretic ocular muscles. While the diagnosis of ocular myasthenia may be difficult early in the course of the disease, it is likewise obscured in cases of extensive bilateral ophthalmoplegia due to chronic myopathy. We have observed cases of myasthenic ophthalmoplegia sufficiently severe to be considered examples of so-called progressive "nuclear" ophthalmoplegia. In these patients, standard testing with Tensilon and prostigmin was unimpressive. Attempts to place electrodes in active muscle for electromyography were unrewarding. However, Tensilon administration during tonography clearly established the proper etiology. In this series of 5 myasthenic patients, the inconstancy of the oculoparesis at any Downloaded From: on //8
6 Glaser Investigative Ophthalmology April 67 one observation would have been sufficiently confusing to make standard Tensilon testing difficult. On the other hand, "Tensilon tonography" was easily interpretable. The data from this study suggest a high incidence of intraocular pressure response to Tensilon in myasthenics and no instances of "false-positive" responses in nonmyasthenic patients. REFERENCES. Osserman, K. E., and Kaplan, L. I.: Rapid diagnostic test for myasthenia gravis, J. A. M. A. 5: 65, 5.. Walker, M. B.: Case showing effect of prostigmin on myasthenia gravis, Proc. Roy. Soc. Med. 8: 75,.. Walker, M. B.: Treatment of myasthenia gravis with physostigmine, Lancet :,.. Pritchard, E. A. B.: "Prostigmin" in the treatment of myasthenia gravis, Lancet :, Hamill, P.: Further uses of prostigmin, Lancet : 575, Denny-Brown, D.: Physostigmine and belladonna by mouth in myasthenia gravis, Lancet : 767, Viets, H. R., and Schwab, R. S.: Prostigmin in the diagnosis of myasthenia gravis, New England J. Med. : 8, Breinin, G. M.: Electromyograph: A tool in ocular and neurological diagnosis, Arch. Ophth. 57: 6, 57.. Kornblueth, W., Jampolsky, A. J., Tamler, E., and Marg, E.: Contraction of the oculorotary muscles and intraocular pressure, Am. J. Ophth. : 8, 6. Discussion From the floor. I wonder if you have tested anyone without any past or present ocular involvement in myasthenia? Dr. Glaser. We have tested patients with myasthenia who, at the time of examination, had clinically no ocular myasthenia. The tests were positive. Downloaded From: on //8
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