Journal of Neuro-Ophthalmology, December 1993, Volume 13, Issue 4

Visual loss due to progressive multifocal leukoencephalopathy in a heart transplant patient.

A 59-year-old male heart transplant recipient experienced progressive visual loss following routine cataract surgery with intraocular lens implantation. Cranial magnetic resonance (MR) imaging suggested and brain biopsy confirmed the cause to be progressive multifocal leukoencephalopathy (PML). The patient died 2 months following cataract surgery. This case illustrates that visual failure may be the initial manifestation of PML, and the ophthalmologist should be aware of this central demyelinating disorder when dealing with immunocompromised patients.

Journal of Clinical Neuro-ophthalmology 13(4): 237-241, 1993. Visual Loss Due to Progressive Multifocal Leukoencephalopathy in a Heart Transplant Patient Angela R. Lewis, M.D., Lanning B. Kline, M.D., and Nanette B. Pinkard, M.D. © 1993 Raven Press, Ltd., New York A 59-year-old male heart transplant recipient experi­enced progressive visual loss following routine cataract surgery with intraocular lens implantation. Cranial mag­netic resonance (MR) imaging suggested and brain bi­opsy confirmed the cause to be progressive multifocal leukoencephalopathy (PML). The patient died 2 months following cataract surgery. This case illustrates that vi­sual failure may be the initial manifestation of PML, and the ophthalmologist should be aware of this central de­myelinating disorder when dealing with immunocom­promised patients. Key Words: Magnetic resonance scanning-Immuno­suppression- IC virus-Progressive visual loss-AIDS. From the Departments of Ophthalmology (A.R.L., L.B.K.) and Pathology (N.B.P.), University of Alabama at Birmingham, Birmingham, Alabama, U.S.A. Address correspondence and reprint requests to Dr. Lanning B. Kline, 1000 South 19th Street, Birmingham, AL 35205, U.S.A. 237 Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection of immunocom­promised patients caused by the IC virus, a poly­omavirus. It was first recognized as a clinical entity by Astrom and colleagues (1) in 1958. Prior to 1983, PML was most often associated with lymphopro­liferative disorders, particularly Hodgkin's lym­phoma, protracted granulomatous states such as tuberculosis and sarcoidosis, and allogenic organ transplantation (2-4). Since 1983, the most com­mon immunodeficient state associated with PML is the acquired immunodeficiency syndrome (AIDS) (4). As the number of immunocompromised pa­tients increases, PML will become a more common disorder. This case report demonstrates that be­cause of visual involvement, the ophthalmologist may be the first clinician to deal with this unusual infection of the central nervous system. CASE REPORT A 59-year-old man complained of decreasing vi­sual acuity bilaterally for 1 year. His past medical history included a myocardial infarction in 1970, coronary artery bypass grafting in 1980, orthotopic cardiac transplantation in 1988, and repair of an abdominal aortic aneurysm in 1990. Medications were prednisone, cyclosporin, mevacor, hydral­azine, furosemide, and zovirax. Ophthalmologic examination revealed best cor­rected visual acuity of 20170 in both eyes, with pos­terior subcapsular cataracts OU. Color vision, pu­pillary reactions, and fundi were normal. The patient underwent uneventful cataract ex­traction in the right eye with implantation of a pos­terior chamber lens. On the first postoperative day 238 A. R. LEWIS ET AI. visual acuity on the right was 20/30. At 13 days after surgery the visual acuity was 20/60 right eye and 20/70 left eye with normal pupillary reactions. Color vision was reduced bilaterally, and the fundi were normal. Because of mild anterior chamber in­flammation topical corticosteroid drops were in­creased in the right eye. At 31 days after surgery the visual acuity was counting fingers au. Pupil­lary reactions, extraocular movements, intraocular pressures, and fundi were normal. The anterior chamber reaction in the right eye had resolved. Goldmann visual field testing showed generalized constriction with dense central scotomas bilaterally (Fig. 1). Cranial magnetic resonance (MR) scanning dem­onstrated areas of increased signal in both occipital regions, both frontal regions, the right optic radi­ation, and the right basal ganglia (Fig. 2). The pa­tient was felt to have sustained multiple cerebro­vascular accidents, and was hospitalized and anti­coagulated. However, his symptoms progressed, and he developed left hemiparesis and deteriora­tion of cognitive abilities. The patient underwent a stereotactic brain biopsy of the lesion in the right occipital lobe. The histologic findings were consis­tent with PML (Fig. 3). The patient's neurologic status continued to de­teriorate. On the request of his family he was dis­charged home, where he expired 2 months after his cataract surgery. DISCUSSION Since being described in 1958, PML has been recognized as an opportunistic infection caused by a virus in patients with impaired immune systems. PML is due to central nervous invasion of the JC virus, a member of the polyoma subgroup of the genus Papovaviridae (5). Serologic surveys have demonstrated that the acquisition of antibodies to the JC virus begins in childhood, and by young adulthood, 60--90% of people worldwide have anti­JC virus antibodies (6). Despite the common occur­rence of this infection, little is known of the patho­physiology of PML. Studies have demonstrated urinary excretion of the virus during pregnancy and periods of immunosuppression (6). Autopsy studies have recovered the JC virus from the brain and kidney in patients who did not have PML (7). Based on the fact that the JC virus is a ubiquitous agent that has been recovered from patients who did not have PML, it is postulated that the infec­tion occurs in childhood and becomes dormant in the kidneys and/or brain. Then, subsequent epi­sodes of prolonged immunodeficiency or direct in­teraction with an immunocompromising agent ac­tivate the latent virus, leading to the development of PML (5,7). The fundamental pathologic process of this con­dition is destruction of oligodendrocytes, the my­elin- producing cells of the central nervous system (3). The areas of the brain most often affected are the cerebral hemispheres, especially the parieto­occipital region, followed by the cerebellum and the brainstem. The spinal cord is usually spared (2). On gross examination of the brain, the cortex, meninges, and deep gray matter structures are normal. Myelin loss appears as gray foci in white matter and/or nonhemorrhagic softening of the ::I:IItt-+t+-+-+-+-t--i 0 LEFT RIGHT CF CF ~IG ..1. Visual fi.elds demonstrate dense homonymous central scotomas with generalized constriction. CF t-mg fmgers acuity. ' coun JGin Neuro-ophthalmol, Vol. 13, No.4, 1993 VISUAL LOSS IN PML 239 FIG.2. Cranial magnetic resonance imaging. Proton-density (left) and T2-weighted (right) axial scans reveal areas of increased signal in the white matter of both occipital lobes. white matter (3). Microscopically, the disease is characterized by a triad (5) (Fig. 3): 1. Multifocal sites of demyelination with spar­ing ofaxons 2. Giant bizarre astrocytes with large pleomor­phic nuclei 3. Large hyperchromatic oligodendrocytes at the periphery of the lesion The oligodendrocytes contain large, round nuclei packed with viral particles. In addition, lipid-laden macrophages and small numbers of lymphocytes may be distributed in a perivascular fashion. Rarely will there be a significant inflammatory re­sponse. The clinical signs of PML begin insidiously. In the early stages, alterations in personality are com­mon. Blunting of intellect, and dementia occurs as the disease progresses. Visual field abnormalities occur in 50% of patients (2,8). Other signs include aphasia, hemiplegia, gait disturbances, headache, dysarthria, and seizures (2,9). PML is character­ized by a relentless progression of signs and symp­toms that ultimately end in death. MR is the preferred neuroimaging procedure for evaluating patients with PML (10,11). Characteris­tic findings are lesions limited to the white matter, which have long Tl- and T2-relaxation times. The involvement is often asymmetric and distant from the periventricular region. These lesions do not produce mass effect nor do they enhance following intravenous gadolinium. Other clinical studies are of little help in establishing the diagnosis of PML. Cerebrospinal fluid analysis is normal and electro­encephalography demonstrates nonspecific gener­alized slowing. Histopathologic examination of brain tissue is the definitive diagnostic procedure (2). The differential diagnosis of multiple white mat­ter lesions within the central nervous system in­cludes multiple sclerosis, lymphoma, stroke, and infectious diseases such as tuberculosis, toxoplas­mosis, cryptococcosis, and HIV encephalitis. Currently, there is no proven therapy for PML. There have been anecdotal reports of PML remit­ting either spontaneously or in response to with­drawal of immunosuppressive drugs (2,9). Over­all, the prognosis is dismal; PML is a lethal disease. The average survival time after diagnosis is 4 months. In our patient, PML led to progressive visual loss following cataract surgery. This clinical setting initially led to diagnostic delay, as visual failure was attributed to postoperative inflammation. It was only dramatic loss of vision in both eyes that prompted further patient evaluation. The diagno­sis of PML was not thought of early in the clinical course, because the patient was otherwise intact neurologically. This case emphasizes the need to suspect PML when evaluating immunocompro­mised patients complaining of diminished vision. I Clin Neuro-{)phthalmol, Vol. 13, No.4, 1993 240 A. R. LEWIS ET AL. FIG. 3. Pathologic findings of progressive multifocal leukoencephalopathy. A: Whole-mount section of oc­cipital cortex reveals demyelination of white matter. The adjacent smaller gyri appear normal (hematoxylin & eosin). B: At periphery of area of demyelination sev­eral enlarged oligodendrocytes (arrows) are seen with coarsely hyperchromatic nuclei typical of viral cyto­pathic change (hematoxylin & eosin; X1000). C: Large. bizarre astrocyte adjacent to viral-infected oli­godendrocytes (hematoxylin &eosin; X1000). B c J Clin Neuro-ophthalmol, Vol. 13, No.4, 1993 VISUAL LOSS IN PML 241 REFERENCES 1. Astrom KE, Mancall EL, Richardson EP Jr. Progressive mul­tifocalleukoencephalopathy. Brain 1958;81:93-111. 2. Greenlee JE. Progressive multifocal leukoencephalopathy. Curr Clin Top Infect Dis 1989;10:140-56. 3. Raine CS. Demyelinating Disease. In Davis RL, Robertson DM, eds. Textbook of neuropathology. Baltimore: Williams & Wilkins; 1991:535-620. 4. Holman RC, Janssen RS, Buehler JW, Zelasky MT, Hooper We. Epidemiology of progressive multifocalleukoenceph­alopathy in the United States: analysis of national mortality and AIDS surveillance data. Neurology 1991;11:1733-36. 5. Major EO, Vacante DA, Houff SA. Human papovaviruses. In: Spector S, Bendinelli M, Friedman H, eds. Neuropatho­genic viruses and immunity. New York: Plenum Press; 1992: 207-27. 6. Chaisson RE, Griffin DE. Progressive multifocal leukoen­cephalopathy in AIDS. ]AMA 1990;1:79-82. 7. White FA, Isaq M, Stoner GL, Frisque RJ. JC virus DNA is present in many brain samples from patients without pro­gressive multifocal leukoencephalopathy. ] Virol 1992;10: 5726-34. 8. Slavin ML, Mallin JE, Jacob HS. Isolated homonymous hemianopsia in the acquired immunodeficiency syndrome. Am] OphthalmoI1989;2:198-200. 9. Flomenbaum MA, Jarcho JA, Schoen FJ. Progressive mul­tifocalleukoencephalopathy fifty-seven months after heart transplantation. ] Heart Lung Transplant 1991;6:888--93. 10. Whiteman ML, Post MJ, Berger JR, et al. Progressive mul­tifocal leukoencephalopathy in 47 HIV-seropositive pa­tients: neuroimaging with clinical and pathologic correla­tion. Radiology 1993;1:233-40. 11. Guilleva M, Steiner RE, Young IR. 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