Isolated neurosarcoidosis presenting with multiple cranial nerve palsies
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1 OPEN ACCESS For entire Editoril Bord visit : Editor: Jmes I. Ausmn, MD, PhD University of Cliforni, Los Angeles, CA, USA Cse Report Isolted neurosroidosis presenting with multiple rnil nerve plsies Kiyohru Shimizu, Kiyoshi Yuki, Tkshi Sdtomo, Koru Kurisu 1 Deprtment of Neurosurgery, Higshihiroshim Medil Center, Higshihiroshim, 1 Deprtment of Neurosurgery, Grdute Shool of Biomedil Sienes, Hiroshim University, Hiroshim, Jpn E mil: *Kiyohru Shimizu shimizu_kiyohru@hiro hosp.jp; Kiyoshi Yuki yuki_kiyoshi@hiro hosp.jp; Tkshi Sdtomo sdtomo_tkshi@hiro hosp.jp; Koru Kurisu kuk422@hiroshim u..jp *Corresponding uthor Reeived: 12 August 15 Aepted: 19 Ferury 16 Pulished: 19 April 16 Astrt Bkground: As n extremely rre sutype of sroidosis tht develops exlusively in the nervous system, isolted neurosroidosis is diffiult to dignose. In ddition, its ext linil fetures re not known. Cse Desription: A 61 yer old mn presented with right er hering loss, diplopi, nd fever. Computed tomogrphy (CT) nd mgneti resonne imging reveled mss lesions in the right ereellum nd left side ody of the lterl ventrile. Neither systemi CT nor positron emission tomogrphy reveled extrrnil lesions. A neuroendosopi iopsy ws performed on the lterl ventrile lesion, nd histopthology nlysis reveled epithelioid grnulomtous inflmmtion. By systemti exlusion of other possile grnulomtous diseses, isolted neurosroidosis ws dignosed. The lesions disppered immeditely upon ortiosteroid (methylprednisolone) tretment nd hd not reurred s of 12 month follow up exmintion. Conlusions: Isolted neurosroidosis is diffiult to dignose. Suessful dignosis requires omptile linil findings, histologil demonstrtion of nonseting grnuloms, nd exlusion of other grnulomtous diseses. Isolted neurosroidosis hs reltively good linil prognosis, whih ould e hrteristi of the disese. Aess this rtile online Wesite: DOI: / Quik Response Code: Key Words: Crnil nerve plsy, grnulomtous inflmmtion, isolted neurosroidosis INTRODUCTION Sroidosis is multisystem grnulomtous disese of unknown etiology. Sroidosis n our in the entrl or peripherl nervous system with other orgn involvement (neurosroidosis), however, when sroidosis develops exlusively in the nervous system, it is lled isolted neurosroidosis. Although its preise prevlene hs not een determined, isolted neurosroidosis is estimted to ount for <1% of sroidosis ses. [18] Beuse of its rrity, it is diffiult to dignose nd its ext linil fetures re not known. In this se report, we desrie ptient with isolted neurosroidosis who presented with multiple rnil nerve plsies. This se followed good linil prognosis, whih ould e typil of this disese. This is n open ess rtile distriuted under the terms of the Cretive Commons Attriution NonCommeril ShreAlike 3.0 Liense, whih llows others to remix, twek, nd uild upon the work non ommerilly, s long s the uthor is redited nd the new retions re liensed under the identil terms. For reprints ontt: reprints@medknow.om How to ite this rtile: Shimizu K, Yuki K, Sdtomo T, Kurisu K. Isolted neurosroidosis presenting with multiple rnil nerve plsies. Surg Neurol Int 2016;7: Surgil Neurology Interntionl Pulished y Wolters Kluwer - Medknow
2 Surgil Neurology Interntionl 2016, 7:44 CASE REPORT A 61 yer old mn with history of hypertensive ereellr hemorrhge visited our hospitl euse of diplopi nd fever. The diplopi ws reognized when he gzed t the right side nd disppered with monoulr vision. In ddition, he eme wre of right er hering loss few months efore visiting the hospitl. He ws lert nd hd no prlysis. The deep tendon reflexes were norml, nd ny upper motor neuron pthologil reflexes were not seen. His tndem wlk ws distured nd lened to the right side. An oulr exmintion showed fint right lterl gze plsy. Fundus exmintion reveled ppilledem. Lortory results inluded the following: C retive protein 0.01 mg/dl (0 0.3 mg/dl), ltte dehydrogense 142 U/L ( U/L), erythroyte sedimenttion rte = 24 mm/1 h (0 10 mm/1 h), lumin = 3.8 g/dl ( g/dl), lium = 8.6 mg/dl ( mg/dl), ngiotensin onversion enzyme = 7.7 IU/L ( IU/L), solule interleukin 2 reeptor = 291 U/ml ( U/ml), nd immunogloulin G4 = 40.6 mg/dl ( mg/dl). Antinuler ntiody test ws negtive. QuntiFERON lood tests were negtive, nd tests for Epstein Brr virus, ytomeglovirus, toxoplsm, syphilis, heptitis B virus, heptitis C virus, nd humn immunodefiieny virus were ll negtive. Cererospinl fluid (CSF) study reveled lymphoytosis nd elevted protein levels: Cell ount 349/mm 3 (pleoyte 16/mm 3, lymphoyte 333/mm 3 ) nd totl protein 153 mg/dl. Oligolonl nd ws negtive. The hest X ry ws norml nd no ilterl hilr lymphdenopthy ws seen. Mgneti resonne imging (MRI) reveled intrrnil mss lesions in the right hemisphere of the ereellum nd the left ody of the lterl ventrile [Figure 1]. Systemi enhned omputed tomogrphy nd positron emission tomogrphy showed no extrrnil lesions. Two weeks lter, the right ereellr lesion disppered [Figure 2]; however, fter 2 more weeks, the lterl ventriulr lesion ws enlrged nd new mss lesions developed in the horoid plexus of the fourth ventrile [Figure 2 nd ]. A neuroendosopi iopsy ws performed on the lesion of the left ody of the lterl ventrile [Figure 3]. The histopthology studies reveled epithelioid grnulomtous inflmmtion nd lrge numers of lymphoytes nd plsm ells infiltrting perivsulr spes [Figure 4]. The iohemil exmintions nd lood nd CSF ulture reveled no orgnisms, nd the histopthology findings ruled out vsulitis. Bsed on the linil ourse nd the exlusion of these other grnulomtous diseses, isolted neurosroidosis ws dignosed. Methylprednisolone (1000 mg/dy) ws dministered for 3 dys, nd the intrrnil lesions lmost disppered [Figure 5]. Cortiosteroids were ontinued nd grdully tpered off over period of 12 months. No exertions or reurrenes were found even up to yer lter [Figure 6]. DISCUSSION Isolted neurosroidosis is n extremely rre disese, nd its urte dignosis is diffiult. The urte dignosis of isolted neurosroidosis requires omptile linil symptoms, histologil finding of nonseous grnulomtous inflmmtion, nd exlusion of other grnulomtous diseses. [19] In ddition, this disese is d e f Figure 1: Mgneti resonne imging on dmission. The two mss lesions in the left ody of the lterl ventrile nd the right ereellum hemisphere were isointense on T1-weighted imges ( nd d), nd hypointense on T2-weighted imges ( nd e). The lesions were enhned fter gdolinium-diethylenetrimine pentette injetion ( nd f)
3 Surgil Neurology Interntionl 2016, 7:44 Figure 2: Two weeks following hospitl dmission, the right ereellum lesion lmost disppered (). Two weeks lter, new enhned lesions emerged in the horoid plexus of the fourth ventrile (). Enlrged imge of the left ody of the lterl ventrile lesion () Figure 3: Intropertive neuroendosopi imge showed irregulr surfe in the lterl ventrile. Mny smll prtiles were floting in the ererospinl fluid, whih ws suggestive of leptomeningel dissemintion Figure 4: Pthologil findings: Originl mgnifition 20 (), 40 (). H nd E stining reveled epithelioid grnulomtous inflmmtion reported to hve etter linil prognosis ompred with systemi neurosroidosis. [12] The disorder s good linil ourse ould e typil feture of isolted neurosroidosis. An urte dignosis of isolted neurosroidosis requires hrteristi linil presenttions, the presene of grnulomtous inflmmtion on tissue iopsy, nd exlusion of other possile dignoses. Neurosroidosis ould our in ny prt of the nervous systems; however, the sl leptomeninges, the hypothlmus, nd the pituitry glnd re most ommonly involved. [6] Isolted neurosroidosis my hve more tendeny to involve the sl leptomeninges thn neurosroidosi. [12] Vrious neurologil symptoms ould e exhiited nd rnil nerve plsy, espeilly fil nerve plsy, is the most ommon linil mnifesttion. [11] Opti neuritis is the seond most ommon presenttion, nd other rnil nerve plsies n our ut re less ommon. [7] Eight rnil nerve re rrely involved nd typilly presented s sensorineurl hering loss. It is ommonly unilterl involvement; however, ilterl involvement is highly suggestive for neurosroidosis. [5] The etiology of sensorineurl hering loss is vrious nd unilterl Figure 5: (-) After steroid pulse tretment, the lesions lmost disppered involvement is ommon in most ses, with ilterl involvement reported in <5%. [13] Lyme disese is one of the importnt differentil dignosis for sensorineurl hering loss in the endemi re. Unilterl involvement is ommon feture nd ilterl involvement is never reported in Lyme disese. [15] Monornil nerve plsy is ommon symptom of neurosroidosis, wheres multiple rnil nerve plsies re rre mnifesttion. If multiple rnil nerve dysfuntion is onfirmed; however, it is highly suggestive of neurosroidosis, espeilly when fil or opti nerve is involved. [10] In this present se study, opti neuritis, undnt nerve plsy, nd ousti nerve plsy were noted nd ontriuted to the dignosis. There re no typil imging ptterns for neurosroidosis. It ould present s solitry or multiple enhning intrrnil prenhyml msses nd might e mistken for primry or seondry tumor or demyelinting disese in the entrl nervous system. [18]
4 Surgil Neurology Interntionl 2016, 7:44 Figure 6: (-) After 12 months, ll the lesions hd resolved nd hd not reurred In ddition, relpsing nd remitting ourses re reltively ommon in neurosroidosis. [17] In the present se study, there were enhned lesions on the MRI in the right ereellum t the time of hospitl dmission, nd they lmost disppered fter 2 weeks. Furthermore, the left lterl ventrile lesion followed relpsing nd remitting pttern. Although relpsing nd remitting ourses re lso ommon feture of multiple slerosis (MS), the durtion of the enhnement of lesions on the MRI in neurosroidosis ptients is reported to e longer thn tht in MS ptients. [17] Neurosroidosis ommonly exhiits enhnement of lesions for more thn few weeks. In ontrst, MS does so for less thn week. [17] In the present se study, the mss lesions exhiited enhnement for more thn month, whih is longer durtion thn tht in MS. CSF studies re not speifi for the dignosis of neurosroidosis ut very importnt for differentil dignosis. Typil CSF findings inlude elevted protein levels nd lymphoytosis, ut it is not insensitive nd out third of ptients with neurosroidosis hve norml CSF. Moreover, positive oligolonl nds re seen in 19 37% of neurosroidosis ses nd elevted IgG is seen in third of neurosroid ptients, whih mkes it diffiult to differentite neurosroidosis from MS. [9,18] Although CSF findings of neurosroidosis re not speifi, CSF nlysis should e performed to exlude other disorders inluding ryptool, tuerulous, nd lymphomtous meningitis. Cytology nd ultures of CSF my e useful. The nonseous grnulomtous inflmmtion exhiited in tissue iopsies is dignostilly suggestive of, ut not speifi feture of, sroidosis, so lterntive uses for grnulomtous inflmmtion need to e exluded. [8] In the present se study, typil grnulomtous inflmmtion ws evident in the pthology nlysis, so isolted neurosroidosis ws dignosed to the exlusion of other grnulomtous diseses (e.g., tuerulosis, other prsiti infetions, or vsulitis). The rrity of isolted neurosroidosis nd ertin other grnulomtous diseses n use misdignosis, s Riku et l. desried in se in whih germinom ws misdignosed s isolted neurosroidosis. [16] Thus, it is neessry to onsider other possile etiologies refully when grnulomtous inflmmtion is disovered through iopsy. Isolted neurosroidosis tends to hve more fvorle linil prognosis thn does neurosroidosis with extrrnil orgn involvement. [12] A previous study noted tht one third of neurosroidosis ptients hd refrtory illness ssoited with higher moridity nd mortlity. [1] Thus, the reltively good linil ourse ould e inditive of isolted neurosroidosis. It is noteworthy tht neurologil symptoms re the initil mnifesttion of sroidosis in pproximtely 50 70% of neurosroidosis ses. [4] In these ses, some ptients who re initilly dignosed with isolted neurosroidosis my eventully develop extr neurologil involvement, inluding the orrespondingly poorer linil outome ssoited with systemi neurosroidosis. Neurosroidosis ptients who truly hve the isolted form respond well to therpy. However, when the tretment is delyed, responsiveness to tretment my lso e redued. Brinr nd Hek reported on n isolted neurosroidosis se tht hd een initilly dignosed s tuerulosis. [2] In tht se, the dignosis of isolted neurosroidosis ws onfirmed fter 21 yers of linil follow up, ut ortiosteroids or other immune modulting/ytotoxi gents were not effetive. This demonstrtes tht the prognosis ould e poor unless tretment egins immeditely. In ddition, it is noteworthy tht some other lesions suh s primry nervous system lymphom (PCNSL) n respond to steroids. Renl ell rinoms, neurolstoms, mlignnt melnoms, nd germ ell tumors re reported to e le to respond to ortiosteroid therpy. [14] However, in these ses, the regression is trnsient nd relpse n our fter some durtions. The medin durtion of remission of PCNSL fter steroid dministrtion is reported to e 7 months. [3] Therefore, reful oservtion fter steroids dministrtion ould e helpful for differentiting other lesions whih n respond to steroids from isolted neurosroidosis. The dignosis of isolted neurosroidosis requires omptile linil findings, histologil demonstrtion of nonseting grnuloms, nd exlusion of other grnulomtous diseses. In the present se study, multiple rnil nerve plsies, relpsing nd remitting linil ourse, nd grnulomtous inflmmtion in the tissue iopsy ontriuted to the dignosis. Isolted neurosroidosis tends to hve more fvorle linil outomes thn neurosroidosis with extrrnil orgn involvement. Suh good prognosis ws experiened y our ptient, nd this informtion ould e useful to liniins seeking to mitigte stress relted omplitions
5 Surgil Neurology Interntionl 2016, 7:44 in ptients nxious over the symptoms they re experiening. Finnil support nd sponsorship Nil. Conflits of interest There re no onflits of interest. REFERENCES 1. Agogu BN, Stern BJ, Sewell C, Yng G. Therpeuti onsidertions in ptients with refrtory neurosroidosis. Arh Neurol 1995;52: Brinr VV, Hek M. Isolted entrl nervous system sroidosis: A gret mimiker. Clin Neurol Neurosurg 2008;110: Bromerg JE, Siemers MD, Tphoorn MJ. Is vnishing tumor lwys lymphom? Neurology 2002;59: Ferriy D, de Seze J, Stojkovi T, Hhull E, Wllert B, Destée A, et l. Long term follow up of neurosroidosis. Neurology 2001;57: Gullplli D, Phillips LH 2 nd. Neurologi mnifesttions of sroidosis. Neurol Clin 2002;20:59 83, vi. 6. Hoitsm E, Fer CG, Drent M, Shrm OP. Neurosroidosis: A linil Dilemm. Lnet Neurol 2004;3: Joseph FG, Solding NJ. Neurosroidosis: A study of 30 new ses. J Neurol Neurosurg Psyhitry 2009;80: Judson MA. The dignosis of sroidosis. Clin Chest Med 2008;29:415 27, viii. 9. Kellinghus C, Shilling M, Lüdemnn P. Neurosroidosis: Clinil experiene nd dignosti pitflls. Eur Neurol 2004;51: Loor RG, vn Tongeren J, Derks W. Multiple rnil nerve dysfuntion used y neurosroidosis. Am J Otolryngol 2012;33: Nowk DA, Widenk DC. Neurosroidosis: A review of its intrrnil mnifesttion. J Neurol 2001;248: Nozki K, Sott TF, Sohn M, Judson MA. Isolted neurosroidosis: Cse series in 2 sroidosis enters. Neurologist 2012;18: Oh JH, Prk K, Lee SJ, Shin YR, Choung YH. Bilterl versus unilterl sudden sensorineurl hering loss. Otolryngol Hed Nek Surg 2007;136: Okit Y, Nrit Y, Miykit Y, Ohno M, Fukushim S, Meshim A, et l. Long term follow up of vnishing tumors in the rin: How should lesion mimiking primry CNS lymphom e mnged? Clin Neurol Neurosurg 2012;114: Peltom M, Pyykkö I, Sppälä I, Viitnen L, Viljnen M. Lyme orreliosis, n etiologil ftor in sensorineurl hering loss? Eur Arh Otorhinolryngol 2000;257: Riku Y, Ito M, Atsut N, Wtne H, Momot H, Soue G. Intrrnil germinom msquerding s grnulomtous inflmmtion, dignosti filure fter rin iopsy. Rinsho Shinkeigku 2013;53: Sott TF, Yndor K, Kunshner LJ, Shrmke C. Neurosroidosis mimiry of multiple slerosis: Clinil, lortory, nd imging hrteristis. Neurologist 2010;16: Smith JK, Mtheus MG, Cstillo M. Imging mnifesttions of neurosroidosis. AJR Am J Roentgenol 2004;182: Sttement on sroidosis. Joint Sttement of the Amerin Thori Soiety (ATS), the Europen Respirtory Soiety (ERS) nd the World Assoition of Sroidosis nd Other Grnulomtous Disorders (WASOG) dopted y the ATS Bord of Diretors nd y the ERS Exeutive Committee, Ferury Am J Respir Crit Cre Med 1999;160:
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