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대한임상신경생리학회지 8(1):58~62, 2006 ISSN 1229-6414 가천의과학대학교길병원신경과 Suspected Idiopathic Acute Transverse Myelitis : Retrospective Analysis of 27 Cases Dong-Chul Han, M.D., Jae-Hyuk Kim, M.D., Dong-Jin Shin, M.D., Hyeon-Mi Park, M.D., Yeong-Bae Lee, M.D. Department of Neurology, Gil Medical Center, Gachon University Background: Acute transverse myelitis(atm) is a group of disorders characterized by focal inflammation of the spinal cord and resultant neural injury. It can be diagnosed by Transverse Myelitis Consortium Working Group(TMCWG) criteria. But there are some cases which were not satisfied with idiopathic ATM criteria, both clinically and radiologically, especially in acute stage. So we analyzed 27 cases retrospectively, which were diagnosed as idiopathic ATM. Methods: All the records of the patients at Gil Medical Center with a diagnosis of idiopathic ATM from 2001 to 2005 were reviewed. And clinical manifestations including neurological examination, radiologic features and cerebrospinal fluid (CSF) findings were analyzed. Results: Among the patients(20 men and 7 women; mean age, 45.3 years), 11 cases could not be diagnosed as idiopathic ATM according to the TMCWG criteria ; 6 cases did not have well marginated upper sensory level and 5 cases were not satisfied with spinal cord inflammation. Conclusions: Although most cases of suspected idiopathic ATM were suitable for TMCWG criteria, some cases were not satisfied with this diagnostic criteria, especially in acute stage. Subsequent study might be needed to evaluate the reliability and clinical application of the criteria. Key Words: Acute Transverse Myelitis, Diagnosis, Analysis, Retrospective. 서 론 급성횡단성척수염 (acute transverse myelitis) 은척수의초점성염증으로인한신경손상을일으키는질환이다. 임상적으로는침범된척수분절이하의양측성운동장애, 감각장애및자율신경계이상이특징적이다. 1 신속한진단은급성기치료방향의결정및예후에중대한영향을미칠수있다. 진단기준으로이전에몇몇보고가있었으며, 최근 Transverse Myelitis Consortium Working Address for correspondence Yeong-Bae Lee, M.D. 1198 Guwol-Dong, Namdong-Gu, Incheon, Korea Department of Neurology, Gil Medical Center, Gachon University TEL: +82-32-460-3346 Fax: +82-32-460-3344 E-mail : lyb@gilhospital.com Group(TMCWG) 에서통합된하나의진단기준을제시하였다 (Table 1). 1 진단기준에는임상증상과경과, 감각경계, 신경영상그리고척수염증에대한내용이포함되어있다. 저자들은비록 TMCWG 가연구목적으로개발되었으나기존의 classic 한진단기준으로특발성 ATM 을진단하기에는한계가있으며, 현재 TMCWG 외에마땅한 criteria 가없는실정이므로가능하면정형화된최근기준에합당하게특발성 ATM 을진단하고자특발성 ATM 으로진단된환자를대상으로후향연구를실시하였다. 대상과방법 1. 대상 본연구는 2001 년 1 월부터 2005 년 12 월까지가천의과학대학교길병원응급실및신경과외래를통해특발성 58 Copyright 2006 by the Korean Society for Clinical Neurophysiology

급성횡단성척수염이의심되는환자 27 명을대상으로하였다. 포함기준으로는첫째, 급격히발생한척수성운동장애, 감각장애혹은배뇨장애가있고, 둘째, 상기증상들이 4 주이상진행하지않으면서, 셋째, 종양이나퇴행성척추병변과같은압박성병변으로인한경우가아니며, 넷째, 방사선조사의병력, 다발성경화증, 동정맥기형과같은척수의혈관성병변, 척수공동증, 신경계매독, 유육종증과같이척수증을일으킬수있는기존의알려진신경계질환에의하지않는특발성인경우에한하였다. 2. 검사방법 내원시환자의신경학적검사는신경과학을전공하는전공의혹은전문의에의해이루어졌으며전공의가시행한신경학적검사는전문의에의해확인을받았고, 이를바탕으로감각, 운동, 자율신경계의임상증상및감각경계유무를알아보았다. 감각증상은통각, 냉, 온각, 위치각혹은진동각의소실이있는경우감각이상이있다고판별하였으며, 정상감각기능또는주관적이상감각은동반되 어있으나신경학적검사상확실한감각장애가없는경우는정상이라판별하였다. 운동은 modifed Medical Research Council (MRC) grading 에따라양측상하지근력을평가하였으며 grade V 인경우는정상, 그외에는이상이있다고판별하였다. 그리고자율신경계증상은긴박뇨, 요저류, 요실금혹은변실금이있는경우이상이있다고판정하였다. 자세한병력청취를통해방사선조사력, 시신경염을알아보았고, 병변이의심되는척수병변은내원후늦어도 48 시간이내에 MRI (SIMENS MAG- NETOM VISION PLUS 1.5T) 를통해확인하였고영상의학과전문의가판독하였다. 영상의학과전문의는시상면에서병변위치, 길이, 병변부위의척수의크기및병변의다발성여부를평가하였으며 Gadolinium 조영증강을시행한경우는조영증강여부및양상을함께기술하였다. 항핵항체 (Antinuclear Antibody), 인체면역결핍바이러스, 간염, VDRL, 결핵의중합효소연쇄반응 (Polymerase Chain Reaction) 검사를시행하였으며, 항핵항체가양성반응시항 ds DNA, anti Ro/La anti- Table 1. Criteria for idiopathic acute transverse myelitis Inclusion criteria Development of sensory, motor, or autonomic dysfunction attributable to the spinal cord Bilateral signs and/or symptoms(though not necessarily symmetric) Clearly defined sensory level Exclusion of extra-axial compressive etiology by neuroimaging(mri or myelography; CT of spine not adequate) Inflammation within the spinal cord demonstrated by CSF pleocytosis or elevated IgG index or gadolinium enhancement. If none of the inflammatory criteria is met at symptom onset, repeat MRI and lumbar puncture evaluation between 2 and 7 d following symptom onset meet criteria Progression to nadir between 4h and 21 d following the onset of symptoms(if patient awakens with symptoms, symptoms must become pronounced from point of awakening) Exclusion criteria History of previous radiation to the spine within the last 10 y Clear arterial distribution clinical deficit consistent with thrombosis of the anterior spinal artery Abnormal flow voids on the surface of the spinal cord c/w AVM Serologic or clinical evidence of connective tissue disease(sarcoidosis, Behcet s disease, Sjogren s syndrome, SLE, mixed connective tissue disorder, etc.)* CNS manifestations of syphilis, Lyme disease, HIV, HTLV-1, Mycoplasma, other viral infection(e.g. HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, enteroviruses)* Brain MRI abnormalities suggestive of MS* History of clinically apparent optic neuritis* *Do not exclude disease-associated acute transverse myelitis. AVM = arteriovenous malformation; SLE = systemic lupus erythematosus; HTLV-1 = human T-cell lymphotropic virus-1; HSV = herpes simplex virus; VZV = varicella zoster virus; EBV = Epstein-Barr virus; CMV = cytomegalovirus; HHV = human herpes virus. Source : Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002;59:499-505. J Korean Society for Clinical Neurophysiology / Volume 8 / June, 2006 59

bodies, anti Smith antibodies, Lupus coagulant 에대한검사를추가하였고본원류마티스내과와상의후결합조직질환을배제하였다. 또한요추천자는내원 24 시간이내시행하여뇌척수액의세포수및 IgG index, oligoclonal band 등의검사를확인하였다. 결 과 남자는 20 명, 여자는 7 명이었으며평균연령은 45.3± 10 세 (44.6 세 & 47.6 세, 남녀각각 ) 였다. 각환자별특징은 Table 2 에기술하였다. 임상증상은감각, 운동, 자율신경장애가있는경우 6 예 (22.2%), 감각장애, 감각과운동장애가있는경우각각 10 예 (37.0%) 이었으며감각과자율신경장애가 1 예 (3.7%) 였다. 환자모두에게서대칭성의증상이나타났으며 21 예 (77.8%) 는감각경계가명확하였으나 6 예 (22.2%) 는그렇지않았다 (Table 3). 명확한감각경계는 21 예 ( 흉추부 19 예 (70.4%), 요추부 2 예 (7.4%)) 였으며침범된척수는경추부 10 예 (37.0%), 흉추부 20 예 (74.0%), 요추부 2 예 (7.4%) 로, 흉추부침범이더많았으며, 경추와흉추를동시에침범한경우 2 예 (7.4%), 흉추와요추를같이침범한경우 1 예 (3.7%), 경추, 흉추, 요추를모두침범한경우도 1 예 (3.7%) 있었다. 척수염증은뇌척수액세포증가증이있거나, IgG index 가증가되어있거나, 혹은척수자기공명영상에서 gadolinium 조영증강이있는경우에국한하였으며 5 예 (19%) 의경우는척수염증소견을보이지않아급성기진단이어려웠으나모두 T2 강조영상에서고신호병변을보이고있었다. 이와같이특발성 ATM 27 예의환자를후향적으로분석하였으나 6 예 (22.2%) 는신경학적검사에서감각경계가명확하지않았고, 5 예 (19%) 는척수염증이보이지않아, 모두 11 예 (40.7%) 에서 TMCWG 진단기준에부합되지않았다. 고 찰 급성횡단성척수염 (acute transverse myelitis, ATM) Table 2. Retrospcective review of 27 cases of acute transverse myelitis including age, sex, symptoms, sensory level, involving spine, spinal inflammation Age(y) Sex Symptom Sensory level Involving spine Spinal inflammation Case 1 48 Female S T10 T unknown Case 2 39 Male S,M,A T4 T unknown Case 3 49 Male S,M negative C yes Case 4 33 Male S,M,A T8 T yes Case 5 31 Male S T7 T unknown Case 6 36 Female S,M T4 T no Case 7 46 Male S,M T8 C yes Case 8 33 Male S,A negative C unknown Case 9 51 Male S T10 T unknown Case 10 43 Male S negative T yes Case 11 48 Male S T12 T no Case 12 46 Male S,M T8 T yes Case 13 57 Male S,M T5 C no Case 14 52 Male S,M T6 C yes Case 15 44 Male S,M,A T6 C,T no Case 16 47 Female S,M T5 T yes Case 17 53 Female S,M T10 T yes Case 18 54 Female S T12 C,T yes Case 19 73 Male S,M,A L1 T,L yes Case 20 44 Male S T10 T yes Case 21 24 Male S,M,A L3 C,T,L yes Case 22 58 Female S negative C unknown Case 23 41 Male S T4 T yes Case 24 45 Male S,M negative T unknown Case 25 61 Male S T4 T yes Case 26 31 Male S,M T6 T no Case 27 37 Female S,M,A negative C yes S; sensory, M; motor, A; autonomic, C; cervical, T; thoracic, L; lumbar 60 J Korean Society for Clinical Neurophysiology / Volume 8 / June, 2006

에대한몇몇증례는 1882년기술되었으며, 1920년대예방접종후발생한뇌척수염의병리학적소견은혈관성질환보다는염증세포혹은탈수초성질환때문이라는보고가있었다. 1 근래에는 ATM의주된병인은전신성질환 (systemic disease), 척수경색 (spinal cord infarct), 염증성질환, 다발성경화증등이있으며원인이없을경우특발성이라언급하였고, 2,3 다양한면역병리기전으로인해명확한치료법은없는상태이다. 3 그후 1981년 Berman 등, 4 1990년 Christensen 등, 1993년 Jeffery 등여러저자들이 ATM의진단기준에대해언급하였다. 이후통일된기준을마련하고자 2002년 TMCWG에의해특발성급성횡단성척수염의진단기준이새로이제시되었다 (Table 1). 1 하지만진단기준중척수염증소견에대해 MRI 혹은뇌척수액검사결과가충족되지않을경우, possible ATM 이라고언급하였다. Seze 등 2 은 idiopathic ATM 의 1/3에서는척수염증이보이지않았으며, MRI에서 gadolinium 조영증강이되는경우는 38% 였다고보고하였으며, Kim 등 5 은 47% 에서척수염증이 MRI에서관찰된다고보고하였다. TMCWG에서는척수염증소견이보이지않을경우 2~7일이내에 MRI 혹은요추천자의추적검사를권하나여러현실적이유로이를시행하기쉽지않으며, 이는조기진단의지연으로인해질병의치료및예후에영향을미칠수있다. ATM의 classic criteria의경우임상증상은감각, 운동및자율신경장애가모두있어야하지만, TMCWG의경우는감각, 운동혹은자율신경장애로변경되었으며, 본연구에서 ATM으로진단한환자들이모두임상증상이적합하였다. 그외대칭성의증상및징후, 압박성원인의배제, 4일에서 21일최대악화등의기준들또한모두 TMCWG의진단기준에적합하였다. 그러나감각증상은 6 예 (22.2%) 에서명확한감각경계부위가관찰되지않았으며, 척수염증을나타내는뇌척수액세포증가증, IgG index 증가, gadolinium 조영증강소견은 5 예 (19%) 에서나타나지않았으나모두 T2 강조영상에서는고신호병변을나타내었다. 따라서감각증상및척수염증소견을종합하여볼때, 본원에서특발성 ATM 환자중 11 예 (40.7%) 는진단기준에부합되지않았고, 현실적이유등으로추적검사를할수없어조기진단에어려움이있었다. 이에저자들은특발성 ATM 이의심되는환자에서조기진단을위해일률적으로 TMCWG 의기준을적용하기에는어려움이있다고생각하였다. ATM 의초기임상증상으로보면이상감각이높은비중을차지하며 6, Ropper 등 7 은초기임상증상을이상감각, 통증, 양측성하지위약감, 요저류로나누었으며 52 예중이상감각이 24 예 (46.2%) 으로가장많았고이는감각증상의위쪽경계가불분명하다는것을보고했다. Defresne 등 8 도 29 예의급성횡단성척수염연구에서 4 예 (13.8%) 는감각경계가명확치않다고하였으며, Berman 등 4 도 16% 에서는정확한감각경계를알수없다고보고하였다. 본연구에서도임상증상중감각경계가불분명한 6 예 (22.2%) 가있었으며, 위쪽경계가없다는이유로 ATM 의진단기준에서제외하는것은무리가있다고생각한다. 횡단성척수염에대한척수자기공명영상을살펴보면 T2 강조영상에서척수내고신호강도소견과일부환자에서의병변부위척수팽창및조영증강소견등의비특이적인소견에대한언급이있었으며, 9-13 비교적증례수가많은보고에의하면척수중심부에위치하고횡단면상척수의 3 분의 2 이상을침범하며, 시상면상 3 개내지 4 개의척수분절을침범하는비교적광범위한병변이 T2 강조영상에서고신호강도로 T1 강조영상에서동등신호강도및저신호강도를보인다고하였으며약반수에서병변부위에 Table 3. Clinical features and laboratory findings of 27 patients with ATM Clinical feature & laboratory findings Cases Clinical symptoms Sensory 10 Sensory + motor 10 Sensory + autonomic 1 Sensory + motor + autonomic 6 Bilateral signs and symptoms 27 Cleary defined sensory level 21 Exclusion of extra-axial compressive etiology 27 Spinal cord inflammation CSF pleocytosis 6 Elevated lgg index 5 Gadolinium enhancement 6 Progression to nadir between 4 hours and 21 days 27 J Korean Society for Clinical Neurophysiology / Volume 8 / June, 2006 61

서척수의팽창및조영증강소견이관찰되었다. 14-16 본연구에서는특발성 ATM 으로진단하였던환자들은모두자기공명영상 T2 강조영상에서척수의고신호병변및 T1 강조영상에서동등신호혹은저신호강도의병변이관찰되었으며 gadolinium 조영제를시행한자기공명영상 19 예중 11 예 (57.9%) 에서만조영증강이관찰되었다. TMCWG 진단기준항목에서명확한감각경계는신경학적검사로판단할수있었으나실제로그렇지않은경우가있었고, 척수염증은뇌척수액및자기공명영상을통해확인할수있었으나조기에척수염증소견이나타나지않는경우가있었으며, 추적검사가필요하지만경제적이유등의현실적문제로추적검사가쉽지않아저자들은 TMCWG 진단기준적용시특발성 ATM 을조기에진단하는데어려움이있을것으로생각하였다. 결론적으로저자들은연구를위해개발되었으나현재최근의 TMCWG 진단기준을적용시임상적으로몇몇예에서 ATM 의조기진단이어려웠음을강조하며, 향후조기진단에민감한세밀한기준에대한연구가필요하리라생각한다. REFERENCES 01. Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002;59:499-505. 02. Seze J, Lanctin C, et al. Idiopathic acute transverse myelitis: application of the recent diagnostic criteria. Neurology 2005;65 1950-1953. 03. Kerr DA, Ayetey H. Immunopathogenesis of acute transverse myelitis. Curr Opin Neurol 2002;15(3):339-347. 04. Berman M, Feldman S, Alter M, Zilber N, Kahana E. Acute transverse myelitis: incidence and etiologic considerations. Neurology 1981;31:966-971. 05. Kim KK. Idiopathic Recurrent Transverse Myelitis. Arch Neurol. 2003;60:1290-1294. 06. Dunne K, Hopkins IJ, Shield LK. Acute transverse myelopathy in childhood. Dev Med Child Neurol. 1986 ;28(2):198-204. 07. Ropper AH, Poskanzer DC. The prognosis of acute and subacute transverse myelopathy based on early signs and symptoms. Ann Neurol 1978;4:51-59. 08. Defresne P, Meyer L, Tardieu M, et al. Landrieu P, Kadhim H, Sebire G. Efficacy of high dose steroid therapy in children with severe acute transverse myelitis. J Neurol Neurosurg Psychiatry 2001;71:272-274. 09. Kim JS, Han MH, Choi CG, Na DG, Chang KH, Kim JH. MR Findings of Transverse Myelitis and its Clinical Correlation. J Korean Radiol Soc 1995;32:201-207. 10. Sanders KA, Khandji AG, Mohr JP. Gadolinium-MRI in acute transverse myelopathy. Neurology 1990;40:1614-1616. 11. Barakos JA, Mark AS, Dillon WP, Norman D. MR imaging of acute transverse myelitis and AIDS myelopathy. J Comput Assist Tomogr 1990;14:45-50. 12. Austin SG, Zee CS, Waters C. The role of magnetic resonance imaging in acute transverse myelitis. Can J Neurol Sci 1992;19:508-511. 13. Pardatscher K, Fiore DL, Lavano A. MR imaging of transverse myelitis using Gd-DTPA. J Neuroradiol 1992;19:63-67. 14. Choi KH, Lee KS, Chung SO, et al. Idiopathic transverse myelitis : MR characteristics. Am J Neuroradiol 1996;17:1151-1160. 15. Al Deeb SM, Yaqub BA, Bruyn GW, Biary NM. Acute transverse myelitis. A localized form of postinfectious encephalomyelitis. Brain 1997;120:1115-22. 16. Choi HY, Park H, Chung TS. MR Findings of Transverse Myelitis : Focusing on T2WI. J Korean Radiol Soc 1996 ;34:193-199. 62 J Korean Society for Clinical Neurophysiology / Volume 8 / June, 2006