Journal of Neuro-Ophthalmology, June 1982, Volume 2, Issue 2

Aspergillosis presenting as a corticosteroid-responsive optic neuropathy.

A case of orbital aspergillosis presenting as a steroid response of optic neuropathy is presented. The invasive and aggressive nature of this infection in the presence of systemic corticosteroids is documented by serial CT scans and necropsy examination. The authors urge inclusion of aspergilloma in the differential diagnosis of a steroid responsive optic neuropathy.

J. Clin. Neuro-ophth,l/moJ. 2: 103-107, 1982. Aspergillosis Presenting as a Corticosteroid-Responsive Optic Neuropathy THOMAS C. SPOOR, M.D. WALTER C. HARTEL, M.D. SALLY HARDING, M.D. GARY KOCHER, M.D. Abstract A c~se of orbital aspergillosis presenting ~s ~ steroid response of optic neurop~thy is presented. The inv~­sive ~nd ~ggressive nature of this infection in the presence of systemic corticosteroids is documented by seri~1 CT snns and necropsy ex~min~tion. The au­thors urge inclusion of ~spergillom~ in the differen­ti~ 1 di~gnosis of a steroid responsive optic neuropathy. Introduction Sudden, unilateral visual loss accompanied by signs of optic nerve dysfunction in a middle-aged patient suggests the diagnosis of inflammatory op­tic neuritis. Normalization of visual acuity and alleviation of discomfort after treatment with sys­temic corticosteroids support this diagnosis. We describe and document a patient whose optic neu­ritis completely responded to systemic cortico­steroids, recurred while tapering the steroid dosage and, again, responded temporarily to an increased dose of corticosteroids. Further deterioration of the visual function in spite of systemic corticosteroid therapy prompted further evaluation. The patient was found to have an aspergilloma of the orbital apex with intracranial extension. We urge the in­clusion of fungal infection in the differential diag­nosis of a steroid responsive optic neuropathy. Case Report A 49-year-old lady was referred for evaluation of "retrobulbar neuritis." Six weeks prior to refer­ral, best corrected visual acuity was 20/20 in both eyes. Despite new glasses, she noted blurred vision From the Division of Ophthalmology, Dl'partment of Surf\l'ry (TCS, WCH. GK) and thl' Department of l'atholoKY ISH). University of South Carolina School of Medicine, Columbia. South Carolina. June 1982 in the left eye. Three weeks later, periorbital pain and further decreased vision in the left eye prompted a return visit to her ophthalmologist and subsequent referral for neuro-ophthalmologic con­sultation. Pertinent past medical history included hysterectomy for uterine fibroids with postopera­tive maintenance on synthetic estrogen and pro­gesterone (premarin and Provera). She gave a (ong history of sinus disease treated with an over-the­counter sinus medication (Sine-Off) but was other­wise healthy. Neuro-ophthalmologic examination revealed a visual acuity of 20/20 in the right eye and count­fingers vision at 2 ft. in the left eye. A 3+ afferent pupillary defect was present. Goldmann perimetry was normal in the right eye. An absolute central scotoma with relative peripheral constriction was present in the left eye. There were no other local­izing neuro-ophthalmologic signs. Slit-lamp ex­amination, intraocular pressure, and funduscopy were normal. B-scan ultrasonogram revealed no orbital masses or extraocular muscle enlargement. X-rays revealed clear sinuses without evidence for mucus membrane thickening or fluid levels. The left optic canal was poorly visualized on Rhese views. With a presumptive diagnosis of idiopdthic orbital infldmmation, she was given a trial of 80 mg prednisone daily. One week later, she reported total allevidtion of pain and markedly improved visual acuity. The prednisone was reduced to 40 mg/day. The follow­ing week, examination revealed a visual acuity of 20/20 in the right eye dnd 20/25 in the left eye. Color vision was equal and normdl; visudl fields were normdl in both eyes. A trace afferent pupil­lary defect WdS present in the left eye. The remain­der of the examindtion WdS normal and the pred­nisone dosdge was decreased to 20 mg/day. Four ddys later, at d dose of 10 mg of prednisone a day, she complained of pdin over the left side of her head dnd decreased visual acuity in the left eye. Visual acuity in the left eye hdd decreased to count 103 Figure I. Compul~d I,'mo~rdphl can demon>trdlin~ enlargement of Ihe left "pIlC Cdndl. Figure 2. Computed ti.lmll~r.Jphu.: ........In d("m'l.l[lstr.,)lIn~ (""I~'r~('mcnt "''"If thf' It'ft optic nerve. widening of the It·f! llplu. f.JnJI . .Jnd Inlr,H.:r.mtJl Inv,,,llv("mcnt. Journal of Clinical Neuro-ophthalmology fingers at 2 ft. and ,1 3+ ,lHerent pupill,lry Jl'fl'l't was again present. The relll,linJ('r llf the l'''',llllln,l­tion was unch,lIlged. The preJnislll1l' JllSl' W,lS increased to 100 mg/d,ly. A~.lin. she rq>llrted hlt.11 alleviation of pain .Ind imprl'Vement 11( visil1n. Three d'lyS bter, ViSU,ll .\\uity W,IS dlKllmentl,d ,It :!O/30 in thl.' left l'ye and .1 1+ ,lHerl'llt pupill.HY defect was evident. Cl)IllputNizl'li tllll\l1~r.1phy re­vealed ,1 slight l'nlargl'ment 11f the Il·ft I>ptil" (.111,11 and a question,lt-ll' ,lpic,ll density (Fig. I). Nil pre­chiasmaI m.lSS was evident. One WE'l'l-. l,ltN. ViSU.11 ,Kuity in the left eye once again detl'rillr,ltl'd tll (l)Unt fingers ,11 :! h. and the orbital p.lin recurred; but ,ldmissil.lIl fllr further evaluation was postponed 5 dJys ,It the p"tient's request. EXJminJtion on admission revealed an acutely ill lady with no light perception in thl' Il'ft eye. The left pupil was amaurotic. The visual field in the right eye was normal. A mild left sixth and fourth nerve paresis was evident a well as de­creased sensation over the distribution of both the first 'lIld second branches of the trigemindl nerve. Repeat CT scan (Fig. 2) demonstrdted enlargement of the left optic nerve dnd intracranial invasion through the orbital apex. Neurosurgical explora­tion was planned. CSF cytology demonstrated 200 ",hite cells with 99% segmented neutrophils. Bac­terial and fungal smears were negdtive. Cerebrdl angiography WdS negative except for narrowing of the left ophthalmic drtery. Twenty-four hour~ after angiography. he de­vl'lllprd ,I ri~ht hemiplegia and her mental status deterior,lted, Repeat lumbar puncture revedled 800 white bl,'od celb again with 99% segmented neu­tnlphil~. csr protein was slightly elevdted; but the ~Iun> e remained normal. Cytology WdS negative for ne,'plasm after millipore filtrdtion. SmedrS f I' b.1Ch·ri,l and fun~i were negative. Subsequent cul­tures were al'(1 negative. A fine needl,' aspiration biopsy of the now markedly enldrged left optIC nerve under computed tomography guidance re­v(' a[ed only segmented neulrophils and no evi­dence of neoplasia, Additional scans obtained dt this time demonstrdled a mass in the sphenoid sinus (Fig. 3). The following morning she underwent a naso­pharyngeal and sphen id sinus biopsy, Hi tologic examination of the nasopharyngeal specimens was unrevealing, but the sphenoid sinus exhibited nec­rotizing grdnulomata with septate dichotomously branching fungal hyphae present (Fig. 4). Subse­quent cultures confirmed the diagnosis of asper­gillosis with many colonies of Aspergi/Jus fumi­gdtuS isolated. She was started on a course of Amphotericin and Rifampin, but rapidly became less responsive and died Shortly thereafter. Ne­cropsy revcaled extensive involvement of the eth­moid and sphenoid sinuses, the orbital ape . vas­cular invasion by fungal hyphae of lhe left internal carotid artery. and dcute infarction of the left basal June 1982 lOS FigurE' ~. rhlltl'lml(r''I~r.'rh ,.If th() 'rl''H'nllld 'Inu'!O bU.lrsy ,hl\~\'ln~ A"'rt'r~llIu.. h\"rnJl' ~\'llhln .In .lr('J l'ilf nC'(fO$IS (PAS. f(l'duc{"d Ir,lm X5001 l'.lnl'Ii.l, the left midbr.lin. and multiple superfici.ll .l re.lS uf the cerebr.11 and cerebellar cortices. Discussion Our patient was unique in that he pr('sented with .l steroid re ponSlve optIC neur<'pathy, c1ini­c. llly tn ignific.lnl prClptllsis, .lnd norm.ll sinus x-r.lVG. ~l'('rnid r(' pun iv ,'pti n('ur<lp.lthil'~ usu.lllv h.lve .1 o('my('lin.lttn~ or infl.1mnl.ltOl"V etl<'logy Our p.lljent\ r.lpiJ .lnu Jr.lm.lli,' rl'~p,>nsl' t,l ;ys, len It (ortl(ostewiJs ;lren~thl'neJ <'ur clinl'·.ll ,mpre.."on "f .10 IIlfl.lmnl.lt"ry ,'plic neur,'p.lthv. It i.. well rl'(o~nizI'J th.11 ,'phc I1l'ur,'p.llhy fr,'m lum"r ""'lpl"l'so,,"n m.1V .11 ..., l"l'Sp,'nJ lemp<lr.1nl\, tll '<lrtlnl~t,·nIlJ ... ' 'M"lef h.ls p"stul.l!t'u th.lt the'r!' .H(' t\\l<l p,,~ ..,bll' me(h.lnisms f<1r lhi~ r('­" P<I" ..('.' O,lt' mvolvlll~ .10 intrinsic Inil.mlm.1t<'I",I' 'Cllllpllnl'nt presPllt ill 1ll.IIIV lum"". thl' <'th,'r .1 ",·,<I"J.lry 1"f1.lmm.lt<>ry l"l'''p,'nsl' .'1 th,' IIltl'rf.I((· lIf IUllwr .IIlJ ",'rm.ll tl~~U!'. C,'rti,·<'~t,'r"ids bv ".JlJ( 'lIg "lthn lIr b,'th illfl.lInm.lt"ry (,'mp"Ill'nl's 111.1V rt'dUll' (('Inlpn,·...... lvl· "'Ign~ .,nd ~yTllrh.'n'l~ rC'­" 1""1 ..11,1,, ill I",rl fllr tl", ,'ptl" Ill'unlp.lthy, One r111)',ht l"pl', 1 r.LlIlUI\llll,'''HI~ ~nf1.lT1Hll.lti,,'n sur-rounding .l nidus of fung.ll infection to also re­spond t<, .:ortlCosteroids. r!:>it.l1 involvement!:>y .lspergillosis is rare, usu­. llly .lcn'mp.ll1led by (oncomitanl paranasaJ sinus involvement·' .lnd often Without evidence of sys­temic JiseJse Aspergillus fumlgdtu is an oppor­tunistic fung.ll p.lthl'gen th.lt can colonize the phar­yn, .lnd 5l11uses. If invasive infection develops in the sllluses. it n1JY spre.ld to the orbit secondarily. Subsequently, it IS Ill't Cl'ns,Jered a primary orbit.l! ;nfe(ti<'n." Re(urr('nt sinUSitis ,lnd a hot humid l'II\'lfl,nment ,He th,'ught to be contributing factors Itl .m .Isper~illus infection of the sinuses." and both WE're present 111 our C.l. e. Aspergillosis of the orbil is (lsu.llly .l .:hr,'nic gr.lnu!om.Jtous disease slowly sprl'.lJing fr<1m the adj.lcent sinus('s over many nlllnths 1<' VNr..ri.' Subsequently, the majority of (.ISt'S repMteo in the ophth.llmic literdture involve sl<'wly pr<'gressive proptosis with or without visual svmpt<'ms .mo Cl'ncomilJnt sinus involvement.:' Th~' [NT liter.lture describes aspergillosis dS usu.1l1y .Iffecting <l single sinus causing a chronic sinusitis in .ln olherwise healthy individual.l'-II The ,'r~11 is often .involved by direc~ ~xtension causin~ p.lIn, proptOSIs and decreased VISIon. Green et .11.; in .1 review l1f 37 CJses. found all but one to have involvement of the nose dnd mdxilldry sinus. Or- Journal of Clinical Neuro-ophthalmology bital involvement W.1S presellt ill :?:? \If 37 with \1111' extending intr.lCr,lni.llly. NOIll' of tlws\' p.lti\·llb had underlying debilit.lting dise.lse. Aspergillosis 1ll.1Y .llso present .IS pn'pt"sis wit h subsequent p.lr.lIus.ll sinlls inv\llv\'llwlll. ['.Iill .1IlJ amaurosis due to cell tr.lI retill.ll .Hh'ry \lcdusi\lll have been reportedl~fwm .1 l\lC.llil.cd .\Sper~i1hllll.1 causing optic forJmen enl.Jrgellwnt .1Ild Illilllid.ill~ an intracanalicul.Jr meningi\lm.l. Our p.lticilt pre­sented with ,\ simil.H picture \If borderlinc pwp­tosis, pdin, and visu.l1 1\1S!'. Thl' sysh'lllic c\lrtic\l­steroids which c.lUsed such .1 dr.llll.ltic illlpn,vl'­ment in her vision 1T1.1y well h.lVc (\lIlVcrteJ her infection to the ,lggressive inv.lsiv!.' type .15 evi­denced by her termin.ll (ourSt'. A simil.lr impwve­ment in vision .lfter c\lrtiC\lster\lid .Idministr.ltinll has been reported in .l patient with .In Aspert{il/us intrasell.ar abcess.1-l Hedges .lnd Leung1·1 reportt'd a patient with chronic headache who developt'd unilateral visual loss and a partial orbital apex syndrome. This patient was also treated with sys­temic corticosteroids (40 mg prednisone/day) with no improvement in vision or motility. She r.lpidly developed a complete orbital apt'x syndrome and total amaurosis on the affected side. Intracranial extension was documented at craniotomy and As­pergillus was proven to be the etiologic infectious agent. This patient experienced a terminal course similar to our's consisting of rapidly developing contralateral hemiplegia, lethargy, febrile episodes. polymorphoneutrophils in the CSF, and a rapid demise in spite of antifungal therapy. Our patient presented with initial symptoms of pain and decreased vision. No radiographic evi­dence for sinus involvement was evident on two occasions prior to her preterminal course. Initial orbital x-rays demonstrated some obscuration of the left optic foramen on Rhese projections and the initial computed tomographiC scan demonstrated minimal changes in the left optic canal. The aggressive nature of this infection in the presence of corticosteroids is documented by com­puted tomographic changes over a 3-week period. Computed tomographic scans also demonstrate the probable origin of the invasive infection dt the orbital apex and rapid extension distally along the optic nerve and proximdlly into the sphenoid sinus where a positive biopsy was subsequently ob­tained. This supports lakobiec's contention thJt in up to 75% of patients, proptosiS is the presenting sign of aspergillosis in the orbit followed by signs of paranasal disease.'; June 1982 ~rmlr, HMtd. H.lrdlng. Kocher Wc ur~{' lhl' inclu~ion of .lspergillosis in the Jiff{·rpn\i.11 di.ly;no... is Df ,I p.linful, teroid respon­siv{' \)ptic Ileurup.lthy, especidlly in a patient with .1 histury uf ehronit' ... inu.,itis. I~eferences l. ~(·IH'lid,. R.C ..IIlJ V,IIl Dyk, H.I.L: Chromt1phobC' .,Jel1orll., m.l~qu(·r.IJlIlg .l~ \ (lrtl\<)~t('rllld-r('~pon,ivl' \lptll Ill·uriti,. Am. f. C)phth,llnlOJ. 78: 4~5. 1974. , K.lmin. I).r.. ,lIlJ Hepler. RS. ~olit.. ry IIltr.JUdnldl I'J."rn.ll-yhHTI.l mist.JkC'f) for rt'trubulbdr f)euriti~. Am. f. Ophth.J1nwl. 73: S~4. 1972. 3. l(el1lll'rJ(·II, J.~ .. l.lnlwttJ. 1'.1.. JnJ John~on. BL: A .,teH'iJ ·,C'n.,itive ,olit.lry intrJ\ rJni,11 pla~mJryh,rnd. Arch. OphthJ/nwl. 92: 393, 1974. .\. Hir~l. L.W.. Millt>r. N.R., Kumdr. A I.. Jnd Udvdr­hC'lyi. C.B: Mt'dullobl.lstoma CdUSlllg.J ort•.0­5ten> id-re~plln~ivt' opti\ neuropathy. Am. }. Oph­th. J/mo/. 89: 437. (980. 5. Greel). W.R .. Font. R.L. dnd Zimmerman. L.E: As­pergi lI11si~ of the orbit. Report of len cases dnd rt'view of the lilerJlure. Ar h. Ophthd/mol. 82: 302. !Qoo. o. JJkobiec. r.A .. dnd Jones. 1.5.: Orbital Inflamma­tions. In Clinicdl Ophthd/mo/ogy. Vol. 2. T.D. Duane. Ed. Harper & Row. Hdgerstown. Md.. 1978, Chdp. 35. pp. 52-59. 7. Rudwdy, M.A.. and Sheikh. H.A.: Aspergillomd of pMdndSJI sinuse'. A common cause of unddterdl proptosis in Suddn. ClIO. RJdio/. 27: 497, 1970. 8. Agarwal. L.P.. M.llik. 5.R.K., Mohan. M.. and Ma­hopdtra. L.N.: Orbitdl a pergillosis. Br. }. OphthJI­mol. 46: 50 9. 1902. 9. Warder. FR.. Chlkes. P. ).. Jnd Hudson, W.R.: A ­pergillosi of the par.lnaSdl sinuses. Arch. O/\"Jr­yngol, 101: 083. 1075. 10. Stevens, M.H.: A pergill{)sis of the frontJI 5InUS. Arch. OlolJryngol. 104: 153, 1978. II. Miglets. A.W.. Saunder . W.H.. dnd Ayers, L.. As­pergillosis of the sphenoid sinus. Arch. Ot<"Jryn~oJ. 104: -l7. 10 78. 12. Crivdli. G. Jnd Riviera, L.c.: Unil.lterJI blindness fnlfll ,1sperKillonlJ .It the riKht \'ptir f\H.lmell. I. NCUn>surg. 33: 207, 1070. 13. Coldll.lmmC'r. Y.. Smith. LL.. .lIld Y.ltes. B.M.: Mv­el, tir intrJs"II.H .Ibsl'ess. Am.'. Ophth.llnl\ll. 78: 478. 1074. 14. Hedgt's, T.R.. ,lI1d Leung. LE.: J'Jr.lsell.lr .llld \lrbitdl JpPX syndnlme (,I used by .1.,pergdl\lSi~. Neur,'h'g~' 26: 117. 10 70. Write /,lr r('print>- I,,: Th"m.ls C. Sf,,'\lr. M.D.. 3321 M,·Ji\.1I I'.lrk ({",HI. ~lIltC' JL1ll, ·\llumbi.l. S\lllth e.l("lin,1 20 203. 107