Electroretinographic abnormalities and advanced multiple sclerosis James Pitzer Gills, Jr. Reduced electroretinographic responses were present in patients with advanced multiple sclerosis. The observed electroretinographic reduction, in general, paralleled the severity and duration of the optic atrophy. These decreased electroretinographic responses in patients with advanced multiple sclerosis were not in keeping with the normal or elevated electroretinographic responses observed in patients with sectioned optic nerves. These findings suggest that with multiple sclerosis there may be other factors affecting the retina than the lesions of the optic nerve..he purpose of this paper is to describe the electroretinographic responses of patients with advanced multiple sclerosis. Multiple sclerosis is characterized by demyelinating lesions in the white matter of the central nervous system. The associated loss of vision usually results from demyelination of the optic nerve. A review of the literature shows that normal and elevated ERG responses have been observed in cases of acute optic neuritis. " There are no reports of ERG findings in patients with chronic optic atrophy associated with multiple sclerosis. Although the exact origin of the components of the electroretinogram is disputed, rom the Department of Ophthalmology, Duke University Medical Center, Durham, N. C. This project was supported, in part, by the Neurological and Sensory Disease Service Program, United States Public Health Service, Grant N A6, and by the National Institutes of Health Training Grant TINB -6. Presented at The Southeastern Association for Research in Ophthalmology in Charleston, S. C, March, 66. there is general agreement that the ganglion cells do not contribute. The a wave probably originates in the visual cell layer (rods, cones, and their nuclei), and the b wave in the synapses to the bipolar cells, or in the bipolar cells themselves.' ' n> c Critical flicker fusion frequencies have been found to be progressively decreased in patients with advancing multiple sclerosis. Kurachr suggested that decreased critical flicker fusion resulted from functional deterioration in the neuronal network of bipolar cells. Gartner has described the histologic appearance of the retina and optic nerve in fourteen autopsied eyes of patients with multiple sclerosis. He noted optic atrophy and loss of ganglion cells which was best seen near the macula. Although the other layers of the retina appeared normal in most cases, a few showed a small loss of cells in the inner nuclear layer. Gartner suggested that this might be artifact. rom earlier work, one would conclude that the inner nuclear layer of the retina in multiple sclerosis patients is normal. Downloaded rom: http://iovs.arvojournals.org/pdfaccess.ashxurl=/data/journals/iovs// on //
6 Gills Investigative Ophthalmology December 66 Method Electroretinographic recordings were obtained from both eyes of patients with multiple sclerosis. The diagnosis of multiple sclerosis was based upon complete neurological evaluation. Twenty of the patients were bedridden as a result of their disease. Complete ophthalmologic and neurologic examinations were performed, including color vision testings with Ishihara and Hardy Rand Rittler color plates. Visual field testing was performed when possible. The pupils were dilated for electroretinography and ophthalmoscopy. A Grass model P stimulator was used with intensity settings of and 6, the photic flash was positioned feet from the patient. Light-adapted and dark-adapted responses ( minutes) were recorded. The flicker responses were recorded from white flash stimuli (intensity, at per cent second). Ruedemann contact lens electrodes were used and ERG responses were amplified by Tektronix preamplifiers (model ) and recorded on a Tektronix oscilloscope (type 6). Permanent records were made on Polaroid film. Amplitude measurements were made from the bottom of the a wave to the top of the b wave. The electroretinographic responses from eyes of a pair were usually equal in amplitude and were averaged. The responses obtained from the multiple sclerosis group were compared to tracings obtained with the same techniques from normal subjects. Results In of the patients with multiple sclerosis, there was a reduction of two or more standard deviations in some or all components of the electroretinographic responses. Typical individual examples of the reduced electroretinographic responses are shown in the tracings of ig.. The reduction in ERG responses, in a general way, paralleled the extent and duration of the optic atrophy and systemic involvement. The electroretinographic responses, sex, age, mental status, duration of multiple sclerosis, duration of visual symptoms, vision, state of the optic nerve, color visual fields of patients, are recorded in chart form (Table I). Line graphs compare the ERG responses in multiple sclerosis patients to those of the control group of normal subjects (ig. ). LIGHT i.v/cm ADAPTED WHITE LICKER DARK ADAPTED ( (i.»/em )* RED 6 BLUE 6* WHITE «6* ig.. Electroretinographic tracings from individual patients with multiple sclerosis. A, responses. B, Decreased flicker response, photopic responses, and scotopic red responses. C, D, and E, Progressive reduction in all responses, particularly photopic components. Note the photopic responses to be the earliest and most severely reduced. Downloaded rom: http://iovs.arvojournals.org/pdfaccess.ashxurl=/data/journals/iovs// on //
I. Data ()n multiple sclerosis patients with various ERG responses Case Patient Age Sex Mental state Duration of multiple sclerosis (years) Duration of visual symptoms Vision Right Left State of optic nerve Number correct on color vision test 6 plates Right Left Visual fields M M Euphoric- 6 / / /- /- / / / /6 Atrophic S.I. pale ine 6 M 6 V /- / / / / / /- / c tion 6 M 6 6 / / / / / /- / 6/ / /- / /- /+ /- / / Mvopic, RE Myopic lized tion 6 M M M 6 M 6 6 M M / / / / / / - /- / /- / / / Myopic Downloaded rom: http://iovs.arvojournals.org/pdfaccess.ashxurl=/data/journals/iovs// on //
Downloaded rom: http://iovs.arvojournals.org/pdfaccess.ashxurl=/data/journals/iovs// on //
Volume Number 6 Electroretinographic responses in multiple sclerosis other chronic lesions involving optic nerve fibers, " " and with long-standing absolute glaucoma. The electroretinographic findings of the eyes with chronic optic atrophy from multiple sclerosis were not the same as recorded from the eyes with surgical sections of the optic nerves. In two such cases, unilateral elevated electroretinographic responses were recorded from eyes with chronic surgical sections ( and years) of the optic nerve. The retinal blood supply was intact. Thus, retrograde transsynaptic degeneration of the inner nuclear layer is probably not the etiology of the decreased ERG responses in patients with chronic atrophy associated with multiple sclerosis. Bornstein and Crain noted serum from two patients during acute exacerbations of multiple sclerosis produced marked alterations in electrical responses of cultured cerebral and spinal cord tissues of the mouse. Cert and Carels have noted with application of serum from patients with multiple sclerosis to the spinal cord of a frog a depression of polysynaptic reflex responses. "Exposure of the frog spinal cord to serum from patients diagnosed as having multiple sclerosis, on the basis of history and clinical examination, resulted in significant depression of the polysnaptic reflex discharge. The active factor in serum appears to depend on the presence of complement." Possibly the abnormal serum in patients with multiple sclerosis is responsible for their reduced electroretinographic responses. This circulating factor that produces a reversible synaptic blocking effect in multiple sclerosis explains the ocular symptomatology and electroretinographic responses which are not entirely accounted for by pathologic findings of demyelinization. resh serum from patients with multiple sclerosis was injected into the carotid artery of cats and monkeys without any significant reduction in the electroretinographic responses. The effect of multiple sclerosis rom Cerf and Carels: Science : 66, 66. serum on isolated retina must be studied. The effect of higher concentrations of serum over a longer period of time in the monkey would also be of interest. It is a pleasure to acknowledge the expert technical assistance of Mr. Robert Hobson of the Electroretinography Laboratory of the Wilmer Institute, The Johns Hopkins Hospital, Baltimore, Md., where all the electroretinography was performed. The guidance of Dr. rank Walsh, Wilmer Institute, is appreciated. I would also like to thank Mrs. Richard Schulze and Dr. Marion Bryson for statistical assistance. REERENCES. Karpe, C: Basis of clinical electroretinography, Acta ophth. : (suppl.).. Ruedemann, A., Jr.: Personal communications.. Gills, J. P., Jr.: The electroretinogram after section of the optic nerve in man, Am. J. Ophth. 6:, 66.. Tomita, T.: urther study on the origin of the so-called cone action potential (S-potential); its histological determination, Jap. J. Physiol. : 6,.. Hashimoto, Y.: Localization of the ERG by aid of histological method, Jap. J. Physiol. : 6, 6. 6. Brown, K. T., and Weisel, T. N.: Localization of origins of electroretinogram components by intraretinal recording in the intact cat eye, J. Physiol. :, 6.. Thorner, M. W., and Berk, M. E.: licker fusion test, Arch. Ophth. :, 6.. Kurachi, Y., and Yonemura, D.: Critical flicker fusion in retrobulbar neuritis, Arch. Ophth. :, 6.. Gartner, S.: Optic neuropathy in multiple sclerosis, Arch. Ophth. :,.. Van Buren, J.: The retinal ganglion cell layer, Springfield,., 6, Charles C Thomas, Publisher.. Haschke, W., and Sickel, W.: The ERG of man in the absence of the ganglion cells and partial damage of the bipolar cells, Acta ophth. : (suppl.) 6, 6.. Gills, J. P., Jr.: Retrograde trans-synaptic degeneration of the inner nuclear layer of the retina, American Ophthalmological Society, 66.. Bornstein, M. B., and Crain, S. M.: unctional studies of cultured brain tissues as related to "Demyelinative disorders," Science :, 6.. Cerf, J. A., and Carels, C.: Multiple sclerosis: Serum factor producing reversible alterations in bioelectric responses, Science : 66, 66. Downloaded rom: http://iovs.arvojournals.org/pdfaccess.ashxurl=/data/journals/iovs// on //