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Show f. Clin. Neuro-ophthalmol. 3: 5-8, 1983. Progressive Visual Loss in Syphilitic Optic Atrophy JOEL G. SACKS, M.D. ROBERT H. OSHER, M.D. HOWARD ELCONIN, M.D. Abstract A 62-year-old man had progressive visual loss from neurosyphilis while his optic disks appeared atrophic. At no time was there evidence of inflammation of the globe or of either optic disk. The presence of an extremely high IgG index and five oligocIonal bands in the cerebrospinal fluid indicated that the central nervous system was synthesizing antibody specific to Treponema pallidum. Recent investigations indicate that much larger doses of penicillin are necessary for adequate treatment of neurosyphilis than have been recommended previously. In the past, visual loss produced by the optic neuropathy of neurosyphilis has been described as having an abrupt onset associated with swelling and engorgement of the optic disk.I-!i Optic atrophy may ensue. We recently cared for a patient who upon initial presentation had bilateral optic atrophy with no evidence of ocular inflammation. His vision subsequently deteriorated over several months until the diagnosis of neurosyphilis was established. We are unaware of any previous report of progressive visual loss during the atrophic stage of syphilitic optic neuropathy. Case Report A 62-year-old man was first seen at the University of Cincinnati in November 1981 because of progressive loss of vision in the left eye that had begun a year earlier. Vision in the right eye deteriorated some time thereafter. He first sought care about 6 months after visual problems began. At that time, visual acuity was 20/50 in the right eye and 20/400 in the left eye. Both disks were pale. The following month, vision had decreased to 20/70 in the right eye, while the left eye was limited to counting of fingers at 3 ft. From the Department of Ophthalmology (JGS), and Division of Neurosurgery (HE), University of Cincinnati College of Medicine, Cincinnati, Ohio; and the Department of Ophthalmology (RHO), Ohio State University, Cincinnati, Ohio. March 1983 The visual fields showed generalized constriction in the right eye in association with an inferior arcuate defect; in the left eye, only a small inferotemporal island remained (Fig. 1). The right optic disk was excavated, with a pale neural rim. The left disk was flat and diffusely pale. The arterioles were moderately attenuated on the surface of each nerve head. Computerized tomography and evaluation by an internist failed to reveal the cause of visual loss. The patient denied previous serious illness or hospitalization, although questioning disclosed a history of possible venereal disease in 1945. The social history was unremarkable. After discharge from the armed forces at the end of World War II, the patient lived at home with his wife and worked regularly. He smoked one or two cigarettes a day on and off for many years and was a social drinker. His diet was well-balanced. At the time of examination in November 1981, vision was reduced to counting fingers at 12 in. in the right eye and questionable perception of light inferotemporally in the left eye. Visual field examination disclosed severe constriction of field in the right eye; no consistent responses were obtainable in the left eye (Fig. 2). The pupils were middilated and reacted weakly only when light was shone into the right eye. The appearance of the optic disks was unchanged. There was no evidence of ocular inflammation or retinal disease. Electroretinography was normal. Fluorescein retinal angiography showed only a paucity of disk capillaries. Because of the unexplained progressive visual loss, the patient was admitted to the University of Cincinnati Hospital for further evaluation. Routine physical examination on admission disclosed no abnormalities. The neurology consultant discovered peripheral neuropathy in addition to bilateral optic atrophy. All of the routine hematologic and chemical studies were normal, but the fluorescent treponemal antibody absorption test was positive on two separate occasions, and the rapid protein reagin test was positive in a titer of 1:128 on one occasion and 1:64 on another. Computerized tomography of the brain and orbits was normal. 5 Syphilitic Optic Atrophy o.,.--,=2",-,/2~3",,1,-,,8<--,1,-__ LEFT RIGHT Figure 1. Visual fields at the first examination. An inferior arcuate scotoma and generalized constriction .ue present in the right eye. Only an island of vision is present inferotemporally in the left eye. 0... ----'.1-'.1'-'/2"'3""/:..:8:..1'--_ LEFT RIGHT Figure 2. Visual fields 9 months later. The field in the right eye is markedly constricted. No field was recordable in the left eye. Examination of the cerebrospinal fluid disclosed a protein concentration of 90 mg/IOO ml; glucose, 38 mg/IOO ml; red cells, 2080/mm3 ; and 66 other cells the differential count of which showed 82% lymphocytes, SOlo neutrophils, 2% band cells, and 6 11% pia-arachnoid cells. The VORL test on spinal fluid was positive at 1:16. The lumbar puncture was repeated 6 days later and demonstrated less peripheral blood contamination. The IgG was 42.7 mg/IOO ml (upper limit Journal of Clinical Neuro-ophthalmology of normal, 3.6 mg/100 ml) and the IgG index was 4.8 (upper limit of normal, 0.58 mg/100 ml). Five abnormal oligoclonal bands were present in the spinal fluid. The proteins in the peripheral blood were all normal. The patient was treated with penicillin G sodium, 24 million units a day, by intravenous infusion for 14 days. During treatment, the penicillin level in the cerebrospinal fluid was 1.28 /lm/ml. The patient's laboratory studies were repeated 14 weeks after penicillin therapy. The RPR on serum was positive at 1:128. All of the abnormal values on cerebrospinal fluid improved: the VORL was reactive at 1:4; protein, 50 mg/100 ml; IgG, 25.6 mg/100 ml; and the IgG index, 4.39. Only four oligoclonal bands were present. The cell count was down to l1/mm:J, the differential of which was 78% lymphocytes, 10% neutrophils, 5% band cells 2% eosinophils, and 4% pia-arachnoid cells. Neither the patient's visual acuity nor visual fields have improved since he was first hospitalized. The appearance of his optic discs is also unchanged. Discussion This case report emphasizes three important features of management of neurosyphilis. First, vision continued to deteriorate during the period in which the optic disks were atrophic. Second, the abnormal oligoclonal bands in the spinal fluid and the elevated IgG index strongly suggest the synthesis of specific antibody to T. pallidum in the central nervous system. Third, recent reports indicate that large doses of penicillin may be necessary for adequate treatment of neurosyphilis. This patient must be considered as having had optic atrophy resulting from neurosyphilis. The inferior arcuate field defect that was initially found in his right eye is definite evidence of primary optic nerve dysfunction. He thinks that he was infected 36 years ago, a time interval which is compatible with development of central nervous system syphilis. The optic nerve involvement is probably a manifestation of meningovascular neurosyphilis rather than parenchymatous syphilis, the latter of which is more typical of general paresis and tabes dorsalis.4-~ We have been unable to find any report of a patient with neurosyphilis whose vision continued to worsen after the optic disks became pale. Visual loss usually occurs during an episode of acuite papillitis. I - 5 It is possible that our patient had bilateral disk swelling when the vision first failed, yet a dramatic progressive visual loss was documented despite the stable appearance of the atrophic disks. We are not aware of any other reported cases in which modern immunochemical analyses have been performed on a patient with syphilitic optic atrophy. The extremely high IgG index points to- March 1983 Sacks, Osher, Eleonin ward the synthesis of immunoglobulins within the central nervous system.7 The index is calculated as a fraction in which the numerator is the ratio of the IgG in the cerebrospinal fluid to that in the serum and the denominator is the ratio of the albumin in the cerebrospinal fluid to that in the serum. This calculated value corrects for variation of albumin and IgG concentrations in serum and produces a value that correlates positively with the synthesis of immunoglobin within the central nervous system. Oligoclonal IgG was identified in five abnormal electrophoretic bands in our patient. Vartdal and coworkers8 studied three patients with neurosyphilis and concluded that the oligoclonal IgG in the cerebrospinal fluid of patients with neurosyphilis represents a specific antibody directed toward T. pallidum. This is in contrast to the IgG in the spinal fluid of patients with multiple sclerosis, which is also synthesized intracerebrally but is not associated with demonstrable antigenic specificity.9 Recent reports suggest that much higher doses of penicillin are required to treat neurosyphilis effectively than was thought previously. Short and coworkers lO have challenged the adequacy of the commonly recommended penicillin schedules for treatment of neurosyphilis. Penicillin therapy may not be infallible in syphilis. 11 In 1980, Greene, Miller, and Bynum12 reported a case in which 7.2 million units of benzathine penicillin G failed to cure neurosyphilis. Ducas and Robsonl:J emphasized that conventional dosage schedules failed to produce an acceptably high level of penicillin within the central nervous system in patients with neurosyphilis. The ideal therapeutic concentration of penicillin in spinal fluid for treatment of neurosyphilis is not known, but it is probably in the range of 0.1-0.4 /lg/mI. 14 The therapeutic regimen given to our patient achieved levels of 1.28 /lm/ml, which should have been sufficient to eradicate the organism. Even "appropriate" treatment of primary syphilis may not be adequate to prevent neurosyphilis. Moskovitz and coworkers!5 recently described the development of meningovascular syphilis in a patient whose primary lesion had been treated with 2.4 million units of benzathine penicillin G in accordance with the recommendation of the Centers for Disease Control. This case emphasizes that adequate treatment with penicillin is essential in order to minimize the risk of subsequent progressive visual loss in patients with syphilitic optic atrophy. References 1. Graveson, G.S.: Syphilitic optic neuritis. f. Neurol. Neurosurg. Psychiatry 13: 216-224, 1950. 2. Kline, L.B., and Jackson W.G.: Syphilitic optic perineuritis and uveitis. In Neuro-Ophthalmology Focus 7 8 Syphilitic Optic Atrophy 1980, J.L. Smith, Ed. Masson Publishing USA, Inc., New York, 1979, pp. 77-84. 3. Schatz, N.J., and Smith, J.L.: Non-tumor causes of the Foster Kennedy syndrome. ]. Neurosurg. 27: 37-44, 1967. 4. Walsh, F.B.: Syphilis of the optic nerve. Trans. Am. Acad. Ophthalmol. Otolaryngol. 60: OP39-42, 1956. 5. Weinstein, J.M., Lexow, S.5., Ho, P., and Spickards, A.: Acute syphilitic optic neuritis. Arch. Ophthalmol. 99: 1392-1395, 1981. 6. Tramont, E.C: Treponema pallidum. In Principles and Practice of Infectious Diseases, G.L. Mandell, R.G. Douglas, Jr., and J.E. Bennett, Eds. John Wiley and Sons, Inc., New York, 1979, pp. 1820-1837. 7. Tibbling, G., Link, H., and Ohman, S.: Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand. ]. C1in. Lab. Invest. 37: 385-390, 1977. 8. VartdaJ, F., Vandvik, B., Michaelson, T.E., Loe, K., and Norrby, E.: Neurosyphilis: Intrathecal synthesis of oligoclonal antibodies to Treponema pallid urn. Ann. Neural. 11: 35-40, 1982. 9. Paterson, P. Y., and Whitacre, CC: The enigma of oligoclonal immunoglobulin G in cerebrospinal fluid from multiple sclerosis patients. Immuno/. Today 2: 111-117, 1981. 10. Short, D.H., Knox, J.M., and Glickman, J.: Neuro-syphilis, the search for adequate treatment. Arch. Dermatol. 93: 87-91,1966. 11. Collart, P., and Poitevin, M.: Is penicillin therapy always infaJlable in syphilis? ]. C1in. Neuro-ophthalmol. 2: 77-83, 1982. 12. Greene, B.M., Miller, N.R., and Bynum, T.E.: Failure of penicillin G benzathine in the treatment of neurosyphilis. Arch. Intern. Med. 140: 1117-1118, 1980. 13. Ducas, J., and Robson, H.G.: Cerebrospinal fluid penicillin levels during therapy for latent syphilis. ].A.M.A. 246: 2583-2584, 1981. 14. Rein, M.F.: Treatment of neurosyphilis. ].A.M.A. 246: 2613, 1981. 15. Moskovitz, B.L., Klimek, J.J., Goldman, R.L., Fiumara, N.J., and Quintiliani, R.: Meningovascular syphilis after "appropriate" treatment of primary syphilis. Arch. Intern. Med. 142: 139-140, 1982. Acknowledgment This study was supported in part by a grant from the Ohio Lions Eye Research Foundation, awarded to Dr. Sacks. Write for reprints to: Joel G. Sacks, MD., Mail Location 527, 231 Bethesda Avenue, Cincinnati, Ohio 45267. Journal of Clinical Neuro-ophthalmology |
