Journal of Neuro-Ophthalmology, March 1987, Volume 7, Issue 1

Visual loss in cryptococcal meningitis.

Optic neuropathy with visual loss is a well-known complication of chronic elevated intracranial pressure. The association of visual loss with cryptococcal meningitis may reflect the intracranial hypertension often seen in this condition. However, the generally poor results of optic nerve sheath fenestration and analysis of autopsy cases have led to the suggestion that direct invasion of the visual system by organisms may be the more common mechanism of visual loss. We describe a patient with severe visual loss from cryptococcal meningitis in whom organisms were demonstrated in the optic nerve sheath obtained at the time of fenestration. This is the first report to demonstrate this finding in a living patient.

Journal of Clinical Neuro-ophthalmology ~f1): 45-48, 1987.. iii•.•.•.•.•.•.•.•.•·· © 1987 Raven I'ress; NewYork VisualL(jssj~ Cryptococcal Meningitis , . ,Steven'Ofner,M.b.,.~hd RoberfS.Baker,M;D.' .' , .' . Opticnetlropathy withvisual Jossisawell~knowncorn­plication of chronic elevated intracranial pressure. The association •• of •visual loss withcryptococcal rneningitis may reflect the intracraniaLhypertension often seen in this condition. However, .thegenerally poor restllts .of .optic nerve sheath fenestration and analysis of autopsy cases have led to the suggestion 'that direct invasion of the'visual systembyorganisrns m-ay be the more common mechanism-of visual loss. We describeapa­tient ,with severe visual loss from cryptococcalmenin­gitis'in whom organisms were demonstrated in the optic nerve sheath obtained at the time of fenestration; This is the first report·todemonstrate this finding ina living .. patient.' .. ' .. .. ' Key Words:' Cryptococcal meningitis~Intracranial pressure-Cryptdcoccusneoformans. ,'Ctyptococcalmeningitisisknown••• to. cause in­creasedintracranialpressure; thiS,in turn'IIlay prod~ce.optic.neuropathy. H0'-Vever, autopsy .. specimens{l) and animal studies (2) have. sug­' gested that visual loss incryptococcal meningitis is due primatilytodirect iiwasion of the optic nerve ,.. ,. she'ath,. opticrier'Ve,optit tract"or lateralgenicti- ,'late.by 'the organisms (1,3). Our 'paper supports this suggestionbyhistologic demonstration of cryptococcal organisms in sectiorisof arioptic nerve sheath ina patient with visual loss and cryptococcal meningitis. If direct invasion of the organism into the visual system is the mechanism . of visual loss, ifmay explain the low success rate ,. of optic nerve sheath 'fenestration in this disease (4,5) . ..~ , A 43-year-old, previously healthy, white man had severe headachesprogressirig to. anorexia, ·nausea;and vomiting inJ~IY1985.0nadmission to the hospital, his temperature was 99.6°P, blood ,·pressureJ18/80mm.Hg,respiratory. rate 20/min, 'and pulse 92/min. Neur6logic examination re­vealed disorientationandhyperreflexia.Anoph­. thalmology consult was not obtained aLthaltime: ' ," .,A lumb"ar puncture revealed, elevated intra.cranial pressure. India~inkstain of the spinal fluid was positive, and ·cultures' grew Cryptococcusneo~, formans:Treatment with intravenous amphotericin " .B was compliCated by transient disorientation arid· agitation. . , A repea.t spirial~fluid culture at the' tirrieof ad­mission to thishospitaI; 7 days after the'onsef of ' ,illness, grewCfyptococcus neoformans. Thespirial- " fluid cryptococcalantigen,fiter was 1:64. Comput-, ,. erized tomography (CT) scan of the head was' . 'normal. , . . . .The pati~rttw~sstarted'oni~tiavenollsall1~h()~ tetieinBand received a totalof3,280mg.During treatment, and for several"weeks after, the patient 45 . From the Departmenfof()phthalmology:Univer~ity()fKen­tucky Medical Center, Lexington, Kentucky. '/ Address correspondence and reprint requests to RobertS. , Baker, M.D., Department of Ophthalmology, University of ., Kentucky Medical Center, 800 Rose St., Lexington, KY 40536­0084, U.S.A 46 S.OFNER AND R. S. BAKER complained ofblurred VISIOn and duILeYe.pain. Six months after the onset of illness, he was re­ferred for ophthalmologic evaluation. Atthat time, visual acuity in bcHh eyes was hand motion at 2 feet and both discs were pale. The patientwas Un-' . able to perform standardized perimetry because of severely diminished visual acuity. ACT scan of the orbits revealed strikingly enlarged optic nerve images in both eyes (Fig,"I). A repeat lumbar punCture showed au opening .pressure of•350mm water.: Spinal-fluid .cultures showed· no growth .(.f cryptocbCCUS.· organisms: .. The spinal-fluid white blood cell Cbunt was 64, 980/0mbnonuclear and 2 %pblyrnbrphbnuclear . cells. The glucose was48mg/dl(serum glucbse 115 .mg/dl); protein 143 mg/dl,and spinal-fluid cryptbc coccal antigen titer L32. • " . Atthecol11pletion of intravenotIssystel11ic' therapy, the patient' s cryptococcal antigen titer was 1:64. The persistent low positive antigen titer raised the possibility of either a subdinicalinfec­tion with a live organism or an aJitigenicresponse to remaining dead organisms in the cerebrbspinal fluid. Because the patient described/a rapidlyprbgres~ sive loss of vision and had documented increased intracranial pressure and no cryptococcalgrowth .' on spinal-Huidculture, an optic nerve sheath fen-' :.~estrationwasperformed.6n theJeft eye with the' '.. hope that visual loss could be stopped or even rec . . versed. We Were aware that elevatedinhacrariial· .pressurel11ight nbthave been the mechanism of visual loss and that,evenjf it was, too much nerve ··.damagealready might have occurred to expect re· covery of visual function; We offered the patient a netvesheath fenesttationaspossibly beneficial in . this' otherwise hopeless situation. An unusually large outflowb£ spinal fluid occurred at the time the sheath was cut. Extensive adhesions were present-betWeen -the"dural sheath and the optic nerve. An optic nerve sheath biopsy specimen re­vealed several periodic acid-Schiff reagent and' mucicarmine positive yeast forms consistent with· CryptococclIsneof0rlnans (Fig. 2). Whether these organisms were active or dead .' . was unknown: Since the.possibilityofanactive )nfectiousprocessexisted, .the patientwasstarted·.· on intravenous amphotericin Band Hucytosine. DISCUSSION Ctyptococcosis isasystemic fungal. disease caused by the encapsulated yeastGyptococclIsneo~ forml1ns.lnfection is thought to be acquired through inhalatibn oHhe fungus ihtothelungs:·· Pulmonaryihvolvement is usually asymptomatic' and self-limited. However, untrea ted tentral nervous system dissemination-is uniformly fatal.' These patients often present with symptoms of headache, nausea, mental status'changes, and changes )ngait; and most have-a predisposing condition, such as lymphoma, sarcoidosis, or im­munosuppression. Visual signs and symptoms are •. also commonly described. Eye findings were 'present in 16 of 36 patients with cryptococcal men­ingitis described by Okun and ButIer(3).Blurred '.• PiG,.2. AnopllcnervesneatnOlOpsyspecimen shOWing mucicarmine staining yeast forms consistent . with Cryptococcus neoformans(arrows). VISUAL LOSS IN CRYPTOCOCCAL MENINGITIS 47 vision was the most common symptom, followed by retrobulbar pain, diplopia, and photophobia. The most common sign was papilledema, fol­lowed by increased blind spot, decreased visual acuity, extraocular muscle paresis, and optic at­rophy. The patients with the most severe visual loss had either optic atrophy or papilledema asso­ciated with cryptococcal invasion of the visual pathways found at autopsy. Six of 22 surviving pa­tients had severe visual damage. Of these, four had permanent visual loss from optic atrophy. Eight other patients had either mild residual optic atrophy or papilledema. Less frequently seen are internuclear and supranuclear ophthalmoplegias (6) and Horner's syndrome (7). The most serious ophthalmologic sequela of cryptococcal meningitis is due to involvement of the visual sensory pathway. The exact mechanism of visual loss is uncertain, but two plausible theo­ries exist: the organism may invade the visual pathway primarily with resultant cellular destruc­tion; alternatively, increased intracranial pressure may damage the optic nerve, as is known to occur in pseudotumor cerebri (8). By decreasing extra­cellular fluid pressure and normalizing axoplasmic flow, optic nerve sheath fenestration is thought to relieve papilledema and prevent progression of vis­ualloss (9). In some patients, this does not lower intracranial pressure (10), but, in others, it is thought to lower intracranial pressure by a persis­tent leak of cerebrospinal fluid through the optic nerve sheath window (11). The first documented case of relief of papilledema with optic nerve sheath fenestration was reported by Smith and as­sociates in 1968 (12). Subsequently, others have found similar results (9,13). Previous attempts to treat visual loss in crypto­coccal meningitis by optic nerve sheath fenestra­tion have been unsuccessful (4,5). It has been sug­gested that this poor result is due to direct inva- , sion of the optic nerve or tract by the organism. Examination of autopsy specimens has shown cryptococcal invasion of the optic nerve from the central nervous system (1,3). Birkmann and Ben­nett (14) described cryptococcal meningitis devel­oping 9 months after enucleation of an eye with cryptococcal endophthalmitis from a penetrating injury. They postulated direct entrance into the central nervous system through the optic nerve sheath. Blouin and Cello (2) showed, by histologic examination, a high incidence of cryptococci in the optic nerve meninges of intracerebrally infected mice and cats. They suggested that optic nerve meningitis develops by extension from the central nervous system. Our patient showed no return of visual function following optic nerve sheath fenestration. Micro­scopic examination of the optic nerve sheath re­vealed intact organisms. This supports the sug­gestion that visual loss is by direct invasion of the optic nerve meninges, presumably via the cerebro­spinal fluid. The work of Kupfer and McCrane (1) showed that further invasion by the organism throughout the visual pathway may occur. It is likely that restoring axoplasmic flow by an optic nerve sheath fenestration has no effect on a nerve sheath invaded by the organism. The small numbers of cases reported to date make it difficult to make specific recommendations regarding the efficacy of optic nerve sheath fenes­tration in cryptococcal meningitis. It seems reason­able to assume that optic nerve sheath fenestration will benefit patients with cryptococcal meningitis whose visual loss is from increased intracranial pressure rather than from direct invasion of the nerve sheath by the organism. Predicting which mechanism is involved in the visual loss of a par­ticular patient is difficult. Examination of the CT images of the optic nerve (Fig. 1) may help the cli­nician determine whether the optic nerve me­ninges are involved. The differential diagnosis of enlarged optic nerve images is limited to inflamed meninges. Other possibilities, such as menin­gioma, glioma, etc., are unlikely in this clinical setting. Thickened meninges, as seen in this case, may indicate invasion of the anterior visual system by organisms, making an optic nerve sheath fen­estration inadvisable. This is the first case to show histologically the organism in the optic nerve sheath in a living pa­tient with cryptococcal meningitis. The mecha­nism of optic atrophy in cryptococcal meningitis has been suggested to be the result of direct inva­sion and destruction of the optic nerve by the or­ganism (1,3). The clinical and histologic findings in our patient are consistent with such a mecha­nism. 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Gutgold-Glen H, Kattah Je. Chavis RM. Reversible visual loss in pseudotumor cerebri. Arch Ophthalmol 1984;102: 403-6. 10. Kaye AH, Galbraith JEK, King J. Intracranial pressure fol­lowing optic nerve decompression for benign intracranial hypertension. JNellrosurg 1981;55:453-6. 1(.1/," 11. Kilpatrick q, Kaufman DV, Galbraith JEK, King JO. Optic nerve decompression in benign intracranial hypertension. Clin Exp NeuroI1981;18:161-8. 12. Smith JL, Hoyt WF, Newton TH. Optic nerve sheath de­compression for relief of chronic monocular choked disc. Am JOphthalmoI1968;68(4):633-9. 13. Galbraith JEK, Sullivan JH. Decompression of the perioptic meninges for relief of papilledema. Am J Ophthalmol 1973;76(5):687-92. 14. Birkmann LW, Bennett DR. Meningoencephalitis follOWing enucleation for cryptococcal endophthalmitis. Ann Neurol 1978;4(5):476-7.