Journal of Neuro-Ophthalmology, June 1988, Volume 8, Issue 2

Lyme Disease and Optic Neuritis

A 39-year-old black woman presented with a clinical picture of aseptic meningitis. She was subsequently found to have Lyme disease, a tick transmitted spirochetal disease not unlike syphilis. Approximately 1 month after intensive antibiotic therapy including 128 million units of intravenous penicillin and 28 g of oral tetracycline, she developed symptoms of classical optic neuritis with painful loss of vision and optic disc edema. A discussion of this patient's clinical course, as well as the dermatologic, neurologic, and ocular manifestations of Lyme disease are presented.

Journal of Clillical Neuro-ophlhalmology 8(2); 73-78, 1988. Lyme Disease and Optic Neuritis Bradley K Farris, M.D., and Randall M. Webb, M.D © 1988 Raven Press, Ltd, New York A 39-year-old black woman presented with a clinical pic­ture of aseptic meningitis. She was subsequently found to have Lyme disease, a tick transmitted spirochetal dis­ease not unlike syphilis. Approximately 1 month after intensive antibiotic therapy including 128 million units of intravenous penicillin and 28 g of oral tetracycline, she developed symptoms of classical optic neuritis with painful loss of vision and optic disc edema. A discussion of this patient's clinical course, as well as the dermato­logic, neurologic, and ocular manifestations of Lyme disease are presented. Key Words: Lyme disease-Optic neuritis-Erythema chronicum migrans-Spirochete- Meningitis - Syph­ilis- Cephtriaxone. From the Department of Ophthalmology, Dean A. McGee Eye Institute (B.K.F.) and Department of Neurology (R.M.W.), University of Oklahoma, Oklahoma City, Oklahoma. Address correspondence and reprint requests to Dr. B. K. Farris at 608 Stanton L. Young Blvd., Dean A. McGee Eye Insti­tute, Oklahoma City, OK 73104, U.S.A. 73 Lyme disease is a tick borne infection first de­scribed in 1975 among a group of children in Lyme, Connecticut (1). It was not until later, how­ever, that a spirochete was implicated in the dis­ease (2). Clinically, this disease is characterized by three distinct stages, including involvement of the skin, nervous system, and synovial joints. Ocular manifestations of Lyme disease have included de­creased vision, papilledema, optic atrophy, iritis, uveitis, and visual field defects (3-6). Although optic neuritis may have been present in previous reports (5,6), this is the first case, to our knowl­edge, of a more classical presentation of optic neu­ritis presumably caused by Lyme disease. CASE REPORT H. P. was a 39-year-old black woman with a past medical history of diabetes, hypertension, and angina. She initially presented to her local physician on February 17, 1986 complaining of a small red skin lesion on her right breast. No treat­ment was given at that time. She returned on March 14, 1986 complaining of a pruritic rash of 2 days duration over her upper extremities only. Due to the possibility of a drug rash, her hypertensive medications were discon­tinued. She was seen in follow-up 4 days later with a more generalized rash. Her temperature was noted to be elevated to 99.7°F. All other medi­cations were discontinued at that time. Interest­ingly, she had recently gone fishing at a local lake, but could not recall any insect (tick) bites. She was admitted to the hospital on March 21, 1986 with a chief complaint of abdominal pain associated with nausea, vomiting, and diarrhea. Diagnostic endos­copy confirmed gastritis. The skin rash completely resolved in the hospital without treatment. She was discharged and did well for several weeks. On May 9, 1986, she began to complain of dif­fuse pain, weakness, and numbness in her lower trunk and extremities. Examination by her local 74 B. K. FARRIS AND R. M. WEBB physician at that time was negative. She was hos­pitalized on May 16, 1986 for progression of these complaints. Initial neurologic examination re­vealed bilateral lower extremity weakness, as well as hyperreflexia and a right upgoing toe. Subjec­tive numbness below each breast was noted. Complaints of intermittent diplopia during her hospitalization revealed what was felt to be a par­tial bilateral lateral rectus paresis. Due to the lower extremity weakness and sus­pected T-6 sensory level, a myelogram was per­formed. This was normal. Cerebrospinal fluid (CSF) drawn at that time revealed 261 white blood cells (WBCs), predominantly lymphocytes, with a protein of 59 ng/dl and glucose of 51 ng/dl. Myelin basic protein was weakly positive at 5.7. All other CSF studies, including cultures, were normal. A computed tomography (CT) scan of the head was normal. During hospitalization, the patient's dip­lopia, weakness, and numbness cleared without treatment. She received no antibiotic treatment for the presumed aseptic meningitis. A repeat lumbar puncture 5 days later revealed an opening pres­sure of 120 mm H20, with 117 WBCs per mm3 (90% lymphocytes), protein of 54 and glucose 67. All other CSF studies were normal. At the time of discharge, a serum Lyme quantitative immunoflu­orescent antibody test (IFA) revealed a titer of 1:128. The Center for Disease Control suggests a titer of greater than or equal to 1:256 for a pre­sumed diagnosis of Lyme disease. Subsequently, a serum Lyme enzyme-linked immunosorbent assay (ELISA) of IgG and IgM was performed. Although the serum IgG was negative, the serum IgM was strongly positive at 7.1, the upper limits of normal being less than 2.0. The positive serum (ELISA) IgM was felt to be diagnostic of Lyme disease. Due to the strongly positive IgM serology, the patient was readmitted to the hospital on June 24, 1986 for antibiotic treatment of Lyme disease. A lumbar puncture at that time revealed an opening pressure of 230 mm H20, with 20 WBCs (99% lymphocytes). She was begun on i.v. penicillin, 4 million units every 6 h. After 8 days of antibiotic therapy, or a total of 128 million units of penicillin, a rash developed that was thought to be a drug allergy. The penicillin was discontinued, and she was discharged on oral tetracycline 500 mg four times daily for the next 2 weeks. On July 31, 1986, the patient awoke with a "film" over her right eye. This cleared after several hours, however. Three days later, she noted a "green film" over her right eye. She awoke the next morning with no light perception in the right eye. She noted some soreness around her right eye at that time. Neuro-ophthalmologic examination on August 8, 1986 revealed a visual acuity of light perception only right eye, and 20/10 left eye. Pupillary exam revealed an afferent defect on the right. Visual field testing was normal on the left, and unobtain­able on the right. Funduscopic examination dem­onstrated optic nerve swelling with flame hemor­rhages and exudates on the right (see Fig. 1). No vitreous cells were noted. The left optic nerve was normal. A presumed diagnosis of optic neuritis on FIG. 1. Funduscopic examination of right eye (A) and left eye (8), demonstr~ting optic nerve swelling with flame he rnn rrhag8s and exuljates on the r'qht. The left optic nerve is normal. LYME DISEASE AND OPTIC NEURITIS 75 the right was made, and a subtenon injection of Kenalog (40 mg) was given in the right orbit. Follow-up neuro-ophthalmologic examination on September 5, 1986 showed a recovery of her vision in the right eye to 20/600. There was a dense central scotoma on the right. Resolution of the optic nerve swelling on the right was noted, with residual optic atrophy (see Fig. 2). A subsequent neuro-ophthalmologic examina­tion on December 16, 1986 revealed a best cor­rected visual acuity of 20/50 - 2 on the right. The optic atrophy on the right was unchanged. Although her neuro-ophthalmologic examina­tion has remained unchanged, she has continued to have intermittent joint and muscle pain, re­quiring readmission to the hospital on September 24, 1987. A repeat lumbar puncture was normal (see Table 1 for a summary of all CSF results). A serum fluorescent treponemal antibody absorp­tion test (FTA-ABS) was positive, although the serum VDRL was negative. Of interest was a posi­tive serum Treponema pallidum hemagglutination test (TPHA). The patient specifically denied a past history of venereal disease. A repeat serum Lyme quantitative immunofluorescent antibody test (IFA) revealed a titer of less than 1:64 (see Table 2 for a summary of serum Lyme and syphilis tests). A magnetic resonance imaging (MRI) scan of the brain prior to discharge revealed a single high in­tensity lesion in the left frontal lobe (see Fig. 3). She was discharged without further treatment. DISCUSSION The spirochete Borrelia burgdorferi has been rec­ognized as the responsible organism for Lyme dis­ease (1,2,7). The vector for this spirochete, a tick that prefers deer and mice, is known as Ixodes dammini in the Midwest and northeast, Ixodes paci­ficus in the northwest, and Ixodes ricinus in Europe (8). The illness in humans is typically character­ized in three stages. These stages tend to vary, with a typical clinical history of exacerbations and remissions, similar to other spirochetal diseases (9). The first stage is characterized by a skin lesion known as erythema chronicum migrans, or ECM. This pruritic lesion begins near the initial tick bite, and gradually expands. Several days later, mul­tiple secondary annular lesions may arise (9). Often associated with this rash, and sometimes preceding it, are nonspecific symptoms such as headache, fever, chills, neck stiffness, and gener­alized malaise (9). Painful lymphadenopathy, splenomegaly, hepatomegaly, and various gastro­intestinal disorders have also been reported (3,8,9). FIG. 2. Funduscopic examination of right eye, dem­onstrating resolution of the optic nerve swelling with residual optic atrophy. The second stage of Lyme disease usually de­velops from 1 week to 5 months after the first stage (3,9). This stage is characterized by neuro­logical and cardiac disorders (3,10). Neurologic symptoms can include a meningoencephalitis or aseptic meningitis (3,5,8,9,11,15), isolated cranial nerve palsies (12,13), radiculoneuropathies (3,8,12,13), Guillain- Barre-like syndrome (14), cerebellar ataxia, chorea, polyneuropathies, mon­oneuritis multiplex, and cranial arteritis (3,5,8,9,11-15). It is in this second stage of Lyme disease that ophthalmologic disorders usually occur. Other than conjunctivitis (9), these are rela­tively rare. The third stage of Lyme disease is characterized by mono- or oligoarticular arthritis in up to 60(;" of patients (13). This usually occurs several months to years after the onset of the skin rash. The joint pain is suspected to result from persistent circu­lating immune complexes (16). TABLE 1. Cerebrospinal fluid results Opening pressure Date (mm H2O) Cells Protein Glucose VDRL 5/17/86 NA 261 59 51 (-) 5/22/86 120 117 54 67 (-) 6/05/86 NA 100 42 109 NA 6/24/86 230 20 30 76 NA 7/04/86 238 10 29 119 (-) 9/24/87 NA 4 31 101 (-) NA, not performed. I Clill Neuro-opl.t1wlmol. Vol. 8. No.2, 1988 76 B. K. FARRIS AND R. M. WEBB TABLE 2. Serum Iyme and syphilis tests Lyme Lyme Lyme Date IFA IgG IgM VDRL FTA MHA-TP 5/22/86 1:128 (-) 7.1 (-) NA NA 9/24/87 1:64 NA NA (-) (+) (+) NA. not performed. Reik et al. initially described 18 patients with neurologic abnormalities associated with Lyme disease (3). Of these, five patients were noted to present with transient obscurations of vision. Five others had papilledema, but only one patient had documented increased intracranial pressure. Spe­cific visual acuities were not reported. Two pa­tients complained of diplopia. In a more recent review of eight patients with neurologic symptoms and high Lyme titers, Reik et al. later noted two patients with papilledema and one with optic atrophy (17). One patient also developed an Argyll Robertson pupil. Only one of the two patients with papilledema was noted to have increased intracranial pressure. An interesting case of Lyme disease causing iritis and subsequent uveitis was reported by Steere et al. (4). Despite aggressive medical and surgical intervention, the patient required removal of the eye. Pathological examination of vitreous debris after enucleation revealed several intact spi­rochetes. The authors recommended the consider­ation of Lyme disease in any undiagnosed case of uveitis. Schechter has reported a 53-year-old patient with Lyme disease who experienced a sudden loss of vision with optic nerve swelling (6). Visual field testing demonstrated an inferior altitudinal defect. Several weeks later, the patient developed a sim­ilar visual field defect in the other eye. Although FIG. 3. Magnetic resonance imaging scan of the brain prior to discharge, revealing a single high density lesion in the left frontal lobe. LYME DISEASE AND OPTIC NEURITIS 77 no visual acuity was reported, the author felt that this patient most likely had suffered an episode of bilateral ischemic optic neuropathy. Wu et al. recently reported a 7-year-old child who presented with Lyme disease and bilateral optic disc edema (5). Upon presentation, the child was noted to have an aseptic meningitis, normal opening pressure on lumbar puncture, and normal visual acuity in each eye in spite of bilat­eral macular exudates. Vision did diminish on the 12th hospital day to 20/40 O. U. Visual field testing revealed bilateral centrocecal scotomas. On a 1 year follow-up examination, the vision had re­turned to near normal. This case may have in fact represented optic perineuritis, instead of a more typical optic neuritis. Neuroradiological studies of Lyme patients, al­though limited, have recently been reported (18). Wokke et al., in a review of three patients with a chronic form of Lyme disease, demonstrated focal low density paraventricular lesions on CT scan­ning in two patients, as well as high intensity par­aventricular lesions on MRI scanning in one pa­tient. SUMMARY Our patient is interesting in that she presented with a classical presentation of optic neuritis 15 days after the completion of 128 million units of i.v. penicillin and 28 g of oral tetracycline for what was considered adequate treatment of Lyme dis­ease. The optic neuritis was typical in that it pre­sented as a "smoldering" loss of vision over sev­eral days, climaxing with a catastrophic loss of vi­sion within the first week. The optic disc edema was marked, and scattered exudates suggested an inflammatory component. Whether the steroid therapy was of any value is open for debate. In any event, she had a gradual return of vision over the next several months. The residual optic at­rophy was certainly typical of optic neuritis. Of equal interest is that, to our knowledge, Lyme disease has not heretofore been reported in the state of Oklahoma, although scattered cases are known to exist (personal communication with the Oklahoma State Department of Health). There have been several reported cases in Texas, how­ever (19). The neurological symptoms demonstrated by Our patient included a radicular sensory neurop­athy, aseptic meningitis, upper motor neuron le­sions manifested by hyperreflexia, and an upgoing toe, as well as probable bilateral sixth cranial nerve involvement. She now seems to exhibit a low grade, intermittent arthritis, typical of the third stage of Lyme disease. Cross reactivity of the Lyme immunofluorescent antibody (IFA) test and syphilis FTA-ABS test has been reported in 22.5% to 54% of patients (20,21). Cross reactivity of the Lyme enzyme-linked im­munosorbent assay (ELISA) with the FTA-ABS was somewhat less (32%) (21). If both the serum FTA-ABS test and Lyme serology (IFA or ELISA) are positive, a negative serum microhemagglutin­ation test for Treponoma pallidum (MHA-TP) and rapid plasma reagin (RPR) for syphilis would strongly suggest a diagnosis of Lyme disease (20,21). Interestingly, our patient had a negative RPR but positive MHA-TP. Therefore, we cannot entirely exclude the possibility of coexisting Lyme disease and syphilis, or simply syphilis with a false positive Lyme serology. The fact that our pa­tient developed typical optic neuritis 2 weeks after what would be considered adequate treatment for syphilis (128 million units penicillin and 28 g of tetracycline) may be more consistent with a diag­nosis of Lyme disease. Although high dose penicillin has been advo­cated for the acute treatment of Lyme disease (22,23), ceftriaxone (Rocephin) has recently been shown to be at least as effective as penicillin in the acute stages, and perhaps more so in the chronic form (24,25). Tetracycline has also been found to be effective (23). In summary, the consideration for Lyme disease should be made in any patient who presents with an undiagnosed encephalitis, aseptic meningitis, lymphadenopathy, neurologic deficit including sensory or motor abnormalities, specific cranial nerve palsies induding Bell's palsy, and inflamma­tory ocular disorders induding iritis, uveitis, con­junctivitis, or optic neuritis. More specifically, any disease process that may implicate a spirochetal etiology, whether it be syphilis or Lyme disease, should be investigated with both syphilis and Lyme serology. REFERENCES 1. Steere AC, Malawista SE, Snydman DR, et al. 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