Journal of Neuro-Ophthalmology, December 1989, Volume 9, Issue 4

Isolated, pupil-sparing third nerve palsy as initial manifestation of systemic lupus erythematosus.

A 29-year-old woman had an isolated, pupil-sparing third cranial nerve palsy. Serologic and CSF abnormalities and the subsequent course were consistent with systemic lupus erythematosus. Corticosteroid therapy resulted in improvement of ocular palsy within 4 weeks. The pathogenesis of cranial neuropathy in systemic lupus erythematosus and the unique presentation in this patient are discussed.

Journal of Clinical Neuro- ophthalmology 9( 4): 285- 288, 1989. Isolated, Pupil- Sparing Third Nerve Palsy as Initial Manifestation of Systemic Lupus Erythematosus Elliot D. Rosenstein, M. D., Joseph Sobelman, M. D., and Neil Kramer, M. D. © 1989 Raven Press, Ltd., New York A 29- year- old woman had an isolated, pupil- sparing third cranial nerve palsy, Serologic and CSF abnormali­ties and the subsequent course were consistent with sys­temic lUpus erythematosus, Corticosteroid therapy re­sulted in improvement of ocular palsy within 4 weeks, The pathogenesis of cranial neuropathy in systemic lu­pus erythematosus and the unique presentation in this patient are discussed, Key Words: Systemic lUpus erythematosus- Cranial neuropathy- Oculomotor nerve, From the Division of Rheumatology and Department of Neu­rology, UMDNJ- New Jersey Medical Center, Newark, New Jer­sey, U. S, A, Address correspondence and reprint requests to Dr. E, D. Rosenstein at Division of Rheumatology and Chmcal Immunol­ogy, Newark Beth Israel Medical Center, 201 Lyons Ave" New­ark, NJ 07112, U. S, A. 285 Systemic lupus erythematosus is a chronic in­flammatory disease of unknown etiology, charac­terized by autoantibody formation and immune complex deposition resulting in diverse and vari­able clinical presentation. Neurologic manifestations of systemic lupus erythematosus are often prominent and dramatic and have been appreciated since the earliest de­scriptions by Kaposi ( 1) and Osler ( 2). Since the original descriptions, a wide spectrum of neuro­logic findings have been reported involving almost every level of the neuraxis, from disorders of cor­tical function ( e, g., psychosis or dementia) to the neuromuscular junction ( e. g., myasthenia gravis), Cranial neuropathies, consisting most commonly of ophthalmoplegias, trigeminal neuralgia, or fa­cial palsy, have been reported in 3- 16% of patients in several large series ( 3- 5), In our case, a common neuro- ophthalmologic abnormality, an isolated third nerve palsy with pupillary sparing, repre­sents a novel initial manifestation of systemic lu­pus erythematosus, CASE REPORT A previously well 29- year- old woman presented in September 1985 with progressive horizontal and vertical diplopia with associated dizziness for sev­eral weeks, unresponSive to trifluoperazine and meclizine. Single binocular vision occurred only in left lateral gaze, There was no prior personal or family history of diabetes, hypertension, hyper­cholesterolemia, or vascular disease. The patient smoked one pack of cigarettes daily for 12 years. There was no use of oral contraceptive medica­tions. Physical examination was notable for normal visual acuity. Pupils were equal in size and reacted to light and accommodation. Visual fields were 286 E. D. ROSENSTEIN ET AL. full. Ptosis was present on the left. The left eye was deviated outward and slightly depressed. There was inability to move the eye upward or down­ward. There was no nystagmus, and ocular motil­ity was full in the right eye. The remainder of the neurologic and general physical examination was normal. There was no improvement in ocular mo­tility after administration of edrophonium chlo­ride. Computed tomography of the head and orbits, with and without contrast, and cerebral angiogra­phy were normal. Cerebral spinal fluid analysis revealed protein 76 mg/ dl ( normal, 14- 45 mg/ dl) and slight lymphocytosis, 12 cells/ mm3 ; oligoclonal bands were absent. Erythrocyte sedimentation rate was 63 mm/ h ( Westergren). Complete blood count, 4- h glucose tolerance, and thyroid function tests were normal. Serologic testing for syphilis [ rapid plasma reagin ( RPR)] and Lyme disease [ enzyme- linked immunosorbent assay ( ELISA)] were negative. LE prep was positive. Anti- nuclear antibody was positive at titer 1: 2,560, homoge­neous pattern; antibodies to DNA, RNP, Smith, SS- A ( Ro), and SS- B ( La) were absent. Anti­cardiolipin antibody determination was not done. The level of C3 was 65 mg/ dl ( normal, 84- 140 mg/ dl), C4 was 12 mg/ dl ( normal 18- 45 mg/ dl). Prednisone, 1 mg/ kg, was administered with im­provement of gaze palsy within 3- 4 weeks. During the following 4 months, her regimen was reduced to alternate day corticosteroids and eventually dis­continued. During the next 8- 12 months, she subsequently noted the onset of periods of morning stiffness with painful swelling of her digits; cold- and emo­tion- induced Raynaud's phenomenon of her fin­gers; pleuritic chest pain without documented ef­fusion- all of which have been treated with non­steroidal medications and supportive measures. Renal function and urinalysis remained normal. There has been no recurrence of her ocular palsy or development of other neurologic findings. DISCUSSION Isolated pupil- sparing third nerve palsies in adults are most often caused by microvascular in­farction ( 6). In the patient presented here, there was no identifiable vasculopathic risk factor other than the history of smoking. The presence of tu­mor or aneurysm was excluded by the radio­graphiC procedures. Systemic lupus erythemato­sus seemed the most plausible explanation for her presenta tion. Neuro- ophthalmologic manifestations of lupus I Gin Neuro- ophthalmol, Vol. 9, No. 3, 1989 are diverse and include disorders of the orbits, vi­sual system, and oculomotor pathways. These ab­normalities are listed in Table 1, based on anatomic localization. We are aware of only one prior report of ocular palsy as the sole initial clinical manifestation of lu­pus. Sedwick and Burde ( 18) reported a young women with an isolated sixth nerve palsy who ad­ditionally had leukopenia and positive fluorescent antinuclear antibody, consistent with lupus. Her symptoms improved without treatment, and she subsequently showed no further evidence of active lupus. Third nerve palsy has been noted in only a few previous reports ( 5,19,20). The best substantiated case was reported by Johnson and Richardson ( 5) ( case 3), who noted a transient, pupil- sparing, third nerve palsy in a patient with multisystem involvement due to lupus. Death was attributed to renal failure 7 years later, and postmortem exam­ination revealed a totally normal brainstem. The peripheral portion of the cranial nerve was not ex­amined. Isolated, nontraumatic, third nerve palsy, spar­ing the pupil, has traditionally been ascribed to microinfarction due to diabetes, hypertension, or atherosclerosis. The classic oculomotor lesion, as seen in diabetes, involves the nerve at the brain stern level in its subarachnoid and cavernous por­tion. Asbury et al. ( 21) found hyalinization and endothelial proliferation resulting in luminal nar­rowing in some of these vessels. Due to involve­ment of the vasa nervorum, central axons and my­elin sheaths were destroyed. The nerve periphery, where the pupillary- motor fibers dominate and which receives its blood supply from the arachnoi­dal vessels, was spared. TABLE 1. Neuro- ophthalmologic manifestations of systemic lupus erythematosus Orbital lesions Orbital pseudotumor ( 7) Tolosa- Hunt syndrome ( 8) Anterior visual pathway Papilledema ( 9) Pseudotumor cerebri ( 10,11) Optic neu ropathy ( 12) Retinal vascular disease ( 13) Retrochiasmatic pathway Visual field defects ( 14) Cerebral blindness ( 14) Visual hallucinations and transient obscuration with or without migraine ( 14,15) Brainstem lesions Unilateral internuclear ophthalmoplegia ( 16) Bilateral internuclear ophthalmoplegia ( 17) Isolated sixth nerve palsy ( 18) Isolated third nerve palsy ( present case) SYSTEMIC LUPUS ERYTHEMATOSUS 287 In systemic lupus erythematosus, the pathogen­esis of CNS manifestations has been similarly felt to be due to vaso- occlusive phenomenon in small vessels. As opposed to the characteristic inflamma­tory cell infiltration of blood vessel walls and fi­brinoid necrosis, pathologic studies of patients with CNS lupus infrequently show these features. More typically, a bland vasculopathy with degen­erative and proliferative changes in small vessels, similar to those seen in hypertensive encephalop­athy, would be present ( 5,22). Since vasculitic lesions are conspicuously ab­sent, alternative explanations for vaso- occlusive phenomenon have been examined. Recent inves­tigations have suggested that even in the absence of local immune complex deposition, profound complement activation can result in a release of chemotactic factors ( C3a and C5a) resulting in the aggregation and activation of platelets and neutro­phils, with subsequent release of toxic oxygen spe­cies and proteolytic enzymes, causing endothelial injury and vascular obstruction ( 23). Alternatively, thrombotic and/ or embolic events related to the presence of anti- phospholipid anti­bodies ( lupus anticoagulant, anti- cardiolipin) have been postulated ( 24). Other less likely causes of vascular compromise might include embolic phe­nomenon related to the presence of verrucous ( Libman- Sachs) endocarditis ( 25) and the presence of thrombotic thrombocytopenic purpura, which has been documented in a number of patients with lupus ( 26). This patient's serologic abnormalities and subse­quent course satisfies ARA criteria for the diagno­sis of systemic lupus erythematosus ( 27). How­ever, her initial presentation was most uncharac­teristic of patients with CNS involvement. Although neuropsychiatric manifestations may oc­cur before or after the diagnosis of lupus is made, in only - 5% of patients are they the sole present­ing features of the disease ( 28). In the series ~ f Feinglass ( 3), among 33 patients with neuropsychI­atric manifestations preceding or occurring in the first year subsequent to the diagnosis of lupus, 32 had associated clinical symptoms or findings more suggestive of lupus. Furthermore, among those patients with cranial nerve findings, 88% had other acute neurologic features ( 3). The patient de­scribed here reported no other manifestations of lupus until 1 year after her initial presentation. The use of corticosteroids in this patient was predicated on not only the ocular palsy, but the serologic and CSF abnormalities suggesting more generalized lupus activity and possibly diffuse ce­rebral dysfunction. The patient's rapid improve-ment and benign course may indicate responsive­ness to corticosteroid therapy. Since vasculopathic palsy often resolves spontaneously in ~ 12 weeks without treatment, we cannot be certain if this may have occurred, similar to the patient reported by Sedwick and Burde ( 18). Although some series have shown no alteration in morbidity ( 3), neuropsychiatric manifestations of systemic lupus erythematosus are generally re­garded as a poor prognostic indicator, with cranial neuropathy having a particularly low 5- year sur­vival rate ( 4). However, when cranial neuropathy presents in isolation, unassociated with signs of generalized cerebral dysfunction and without evi­dence of significant visceral involvement, the clin­ical course may be surprisingly benign. In 3 years of continued care, our patient has shown only mi­nor extraneurologic manifestations of lupus and continues to thrive with only symptomatic ther­apy. REFERENCES 1. Kaposi M. Neue beitrage zur kenntnis des lupus erythema­tosus. Archir plr Dennatologie und Syphilis 1872; 4: 36- 78. 2. Osler W. On the visceral complications of erythema exuda­tiuum multiforme. Am JMed Sci 1895; 110: 629- 46. 3. Feinglass EJ, Arnett Fe, Dorsch CA, Zizic TM, Stevens MB. 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