CASE REPORT J Neurocrit Care 2016;9(1): eissn: 추적뇌자기공명영상으로진단된메트로니다졸에의한뇌병증 영남대학교의과대학신경과학교실 조진

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1 CASE REPORT J Neurocrit Care 2016;9(1): eissn: 추적뇌자기공명영상으로진단된메트로니다졸에의한뇌병증 영남대학교의과대학신경과학교실 조진혁 이세진 Metronidazole-Induced Encephalopathy Diagnosed by Follow-Up Brain Magnetic Resonance Imaging Jinhyuk Cho, MD and Se-Jin Lee, MD, PhD Department of Neurology, Yeungnam University College of Medicine, Daegu, Korea Background: Metronidazole-induced encephalopathy (MIE) is caused by consumption of an excessive dose or prolonged use of metronidazole. Case Report: An 83-year-old female presented with left side ataxia and dysarthria. Initial brain magnetic resonance imaging (MRI) showed subtle high signal intensity in the splenium of corpus callosum. Three days later, she developed confused mental status. Followup brain MRI showed bilateral high signal intensities in the dentate nuclei of the cerebellum, splenium, insula, and subcortical white matter. She had infectious spondylitis and was taking metronidazole 1 g/day for 44 days. After discontinuation of metronidazole, her mental status and ataxia improved. Conclusion: Although initial brain MRI does not show typical lesions in a patient with clinically suspected MIE, follow-up brain MRI is recommended. J Neurocrit Care 2016;9(1):16-17 Key Words: Metronidazole; Encephalopathy; Brain MRI 서 론 메트로니다졸 (metronidazole) 은 5-nitromidazole 유도체로서 혐기세균, 헬리코박터필로리, 질편모충증, 아메바증, 람블편모 충증등과같은감염질환의치료에널리이용되는약제이다. 1,2 메트로니다졸은비교적안전한약물이지만고용량으로또는 장기간투여하면말초신경병, 소뇌기능이상, 뇌병증, 발작등 과같은신경독성이발생할수있다. 2,3 메트로니다졸에의한뇌 병증은매우드문질환이며자기공명영상 (magnetic resonance imaging, MRI) 에서주로소뇌치상핵, 뇌량팽대 (splenium) 및 뇌간에좌우대칭적인병변이발생한다. 2,3 저자들은초기 MRI Received: February 27, 2016 / Revised: April 15, 2016 Accepted: May 23, 2016 Address for correspondence: Se-Jin Lee, MD, PhD Department of Neurology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea Tel: , Fax: sejinmayo@ynu.ac.kr 에는뇌량팽대의미미한병변만관찰되다가 3일후에증상의악화와함께전형적인영상소견이관찰되었던메트로니다졸에의한뇌병증을경험하였기에보고하는바이다. 증례 83세여자가왼팔의어둔함과구음장애로응급실을방문하였다. 환자는오전 7시에왼팔로수저질을하는데평소와다르게잘되지않았고발음도어둔하였다. 최근에세균성척추염으로진단되어메트로니다졸을하루에 1 g씩총 44일간복용하고있었고고혈압, 당뇨병, 협심증및 C 형간염으로약물치료를받고있었다. 응급실내원하여심방세동이처음으로발견되었다. 활력징후는혈압 134/87 mmhg, 맥박 127회 / 분, 체온 36.5 C, 호흡 18회 / 분이었다. 환자는왼손잡이고신경학적진찰에서의식장애는없었으나왼쪽손가락코검사 (finger-to-nose test) 에서겨냥이상과구음장애가관찰되었다. 하지는운동실조가관찰 16 Copyright 2016 The Korean Neurocritical Care Society

2 Metronidazole-Induced Encephalopathy Cho J, et al. A B C Figure 1. Initial brain magnetic resonance image. Diffusion-weighted image (A) shows subtle high signal intensity in the splenium of corpus callosum. Apparent diffusion coefficient map (B) shows no significant changes in the splenium. Fluid attenuated inversion recovery image (C) shows subtle high signal intensity in the splenium of corpus callosum and severe white matter change. 되지않았다. 안구운동장애와안진은없었으며나머지신경학적검사에도이상소견은없었다. MRI의확산강조영상 (diffusion-weighted image, DWI) 과액체감쇠역전회복 (fluid attenuated inversion recovery, FLAIR) 영상에서뇌량팽대에미미한고신호강도가관찰되었으나겉보기확산계수 (apparent diffusion coefficient, ADC) 지도에서는정상이었으며고령에의한백질변성이광범위하게관찰되었다 (Fig. 1). 응급실에서환자가자의로퇴원하였다가 3일후인지기능저하로다시내원하였다. 신경학적진찰에서의식은명료하였으나지남력저하와착란을보였다. 안구운동은정상이었으며자발안진도관찰되지않았다. 하지만구음장애는 3일전보다악화되었으며착란으로운동실조검사와한국판간이정신상태검사 (Korean mini mental status examination, K-MMSE) 는시행할수없었다. 추적 MRI의 DWI와 FLAIR영상에서처음에관찰되었던뇌량 팽대부의신호강도는현저히증가되었으며이전에보이지않았던고신호강도병변이소뇌의치상핵, 섬엽및피질하백질에좌우대칭으로관찰되었으며 ADC 지도에서는저신호강도가관찰되었다 (Fig. 2). 뇌척수액검사에서단백이 mg/dl로증가되어있었고뇌파에서는후두부우세리듬 (posterior dominant rhythm) 이느려져있었다. 환자는메트로니다졸을장기간복용하였고추적 MRI에서뇌량팽대부, 소뇌의치상핵, 섬엽및피질하백질에병변이관찰되었기때문에메트로니다졸에의한뇌병증으로판단되어메트로니다졸을중단하고보존적치료를하였다. 메트로니다졸을중단하고 5일이지나면서환자의착란이호전되기시작하였고왼쪽상지의운동실조도호전되었다. 입원 7일째에는이름과나이를정확하게대답하고간단한대화가가능하여퇴원하였다. 퇴원 16일후에는천천히독립보행이가능하였고구음장애도호전되었으며 K-MMSE는 18점이었다. 퇴원 4개월후에는독립 17

3 J Neurocrit Care 2016;9(1):16-20 A B C Figure 2. Follow-up brain magnetic resonance image. Diffusion-weighted imaging (A) shows symmetric high signal intensities in the dentate nuclei of the cerebellum, splenium of corpus callosum, insula, and extensive subcortical white matter. Apparent diffusion coefficient mapping (B) shows low signal intensities and fluid attenuated inversion recovery imaging (C) shows high signal intensities in the same area of (A). 적인일상생활이가능할정도로호전되었다. 고찰 현재까지의보고에의하면메트로니다졸에의한뇌병증은 g을복용한후에발생하였으며 (Table 1) 1-8 특히하루 2 g 이상복용하면위험성이높은것으로알려져있다. 2 메트로니다졸복용기간도 7-90일까지다양하게나타났으며메트로니다졸중단후증상이회복되기시작할때까지걸린시간은 5-10일정도이다. 2 대부분의환자들은메트로니다졸을중단한후에회복되었지만 10주동안 132 g을정맥주사한후에사망하였다는보고도 9 있으므로메트로니다졸에의한뇌병증으로판단되면즉시약물투여를중단하여야한다. 본증례에서는하루 1 g씩 44일동안메트로니다졸을복용하였고약물중단후 5일째부터증상이회복되기시작하였다. 메트로니다졸에의한뇌병증의발생기전에대해서는아직명확하게밝혀지지않았지만메트로니다졸유도체의산화반응으로독성라디칼이생성되고이로인하여축삭부종 (axonal swelling) 이발생하는것으로설명된다. 4,10,11 메트로니다졸을중단하면 5-10일이내에증상이호전되기시작하고 MRI의병변도사라지는데이또한부종과같은가역적인변화를시사하는소견이다. 1,3,12 따라서메트로니다졸에의한뇌병증으로진단된환자에서추적 MRI를시행하여뇌병변이사라지는것을확인한다면진단의정확성을높일수있을것이다. 본증례에서는보호자가추적 MRI 촬영을거부하여시행하지못하였다. 메트로니다졸에의한뇌병변은양측대칭으로발생하는데소뇌의치상핵이가장흔히침범되고뇌량팽대및뇌간에도병변이흔히관찰되는것으로보고되었다. 2,3,13 병변은종괴효과없이 T2강조영상, FLAIR 영상및 DWI에서고신호강도를보이며조영증강은되지않는다. 2,3,12-14 ADC지도에서는다양한신호강도 18

4 Metronidazole-Induced Encephalopathy Cho J, et al. Table 1. Summary of reported cases of metronidazole-induced encephalopathy Cases Age/ gender Total dose (g)/ duration of metronidazole (days) Duration of metronidazole before development of symptoms (days) Interval between symptom onset and MRI (days) Our patient 83/F 48/ Kwon et al. 5 56/M 45/ Splenium Kwon et al. 5 72/M 110/ Brain MRI lesions Splenium Dentate nuclei, insula, splenium, subcortical WM Splenium Brainstem, splenium Bahn et al. 6 52/F 48/ Brainstem, dentate nuclei, periventricular WM, splenium Kim et al. 8 71/M 45.5/ Dentate nuclei, splenium Huang et al. 3 56/F 24/ Brainstem Huang et al. 3 70/F 41.25/ Brainstem, dentate nuclei Kim et al. 2 71/M 66/ Brainstem, dentate nuclei Kim et al. 2 55/M 21/ Brainstem, dentate nuclei, splenium Kim et al. 2 61/F 40.5/ Brainstem, dentate nuclei Choi et al. 4 60/M 120/ Dentate nuclei Kim et al. 2 70/M 57/ Brainstem, dentate nuclei, splenium Ahmed et al. 1 45/F 35/ Dentate nuclei, splenium, subcortical WM Kim et al. 2 64/M 37.5/ Brainstem, dentate nuclei, splenium, subcortical WM Kim et al. 2 54/M 49.5/ Brainstem, dentate nuclei, splenium Kim et al. 2 49/M 155/ Brainstem, dentate nuclei Seok et al. 7 74/F 180/ Basal ganglia, brainstem, cerebellar WM, splenium, subcortical WM MRI, magnetic resonance imaging; WM, white matter. 로나타나는것으로보고되어있지만증상발생후 7일이내에촬영하였던 8예가운데저신호강도가 7예, 고신호강도가 1예로저신호강도를보이는경우가대부분이었다. 2,5,6,13 메트로니다졸에의한뇌병증환자들가운데증상발현후 24 시간이내에촬영하였던 MRI에는대부분의환자에서뇌량팽대에병변이관찰되었고치상핵과뇌간에도병변이발견되었다 (Table 1). 1-8 일주일이내에촬영하였던 MRI에서는치상핵, 뇌간, 뇌량팽대의빈도로병변이관찰되었고시간이경과하면서대뇌백질에도병변이발견되었다 (Table 1). 1-8 본증례에서도증상발생 6시간후에촬영한 MRI에서는뇌량팽대부위에미미한병변만관찰되었고 3일후에촬영한 MRI에서는소뇌의치상핵, 섬엽및피질하백질에도병변이관찰되었다. 증상발현후 24시간이내에 MRI를촬영하면뇌량팽대에만병변이관찰되는경우가많으므로조기진단이힘든경우가있을것으로사료된다. 5 그러므로메트로니다졸을장기간복용하고있는환자에서갑작스런신경계증상이발생하면메트로니다졸에의한뇌병증의가능성을염두에두어야하고, 초기에특징적인 MRI 병변이관찰되지않더라도추적 MRI를시행하는것이바람직하다. 본환자는심방세동이처음으로발견되었기때문에뇌경색을의심하였지만 MRI에서환자의증상과일치하는병변이발견되지않았기때문에뇌경색은아닌것으로판단하였다. 증상이악화되어 3일후촬영한추적 MRI에서특징적인소견이관찰되어메트로니다졸에의한뇌병증으로진단하고메트로니다졸을중단하였으며이후에증상은서서히호전되었다. 성인에서메트로니다졸에의한뇌병증과감별할질환으로는베르니케뇌병증, 메틸브로마이드중독, enterovirus 뇌염등이있다. 베르니케뇌병증은만성알코올중독혹은영양결핍환자에서의식장애, 안구운동장애및운동실조가발생하고 MRI 에서유두체, 시상, 제4뇌실의바닥및뇌수도관주위에서양측대칭적인고신호강도를보이는것이특징적이다. 2 본환자에서는베르니케뇌병증을일으키는병력이없었고 MRI 소견도일치하지않았기때문에베르니케뇌병증은배제하였고혈중티아민농도는검사하지않았다. 메틸브로마이드는훈증소독제나 19

5 J Neurocrit Care 2016;9(1):16-20 살충제로사용되는데본환자에서메틸브로마이드중독을의심 할만한과거력은없었다. 발열이없었고응급실에서시행한뇌 척수액검사에서이상소견이없었으므로 enterovirus 뇌염은배 제할수있었다. 메트로니다졸을장기간복용하면뇌병증이발생할수있으며 초기 MRI 에서는주로뇌량팽대, 소뇌치상핵또는뇌간에병변 이관찰된다. 메트로니다졸에의한뇌병증이의심되는환자에 서증상과일치하는병변이초기에발견되지않으면추적 MRI 를시행하여확인하는것이바람직하다. REFERENCES 1. Ahmed A, Loes DJ, Bressler EL. Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy. Neurology 1995;45(3 Pt 1): Kim E, Na DG, Kim EY, Kim JH, Son KR, Chang KH. MR imaging of metronidazole-induced encephalopathy: lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 2007;28: Huang YT, Chen LA, Cheng SJ. Metronidazole-induced encephalopathy: case report and review literature. Acta Neurol Taiwan 2012;21: Choi HC, Oh SY, Shin BS, Seo MW, Kim YH. Metronidazole-induced reversible cerebellopathy. Res Vestibul Sci 2009;8: Kwon KY, Lee DK, Lee KH, Cho KH, Lee E, Chung SJ. Two cases of metronidazole-induced encephalopathy lacking of clinico-radiological correlation. J Korean Neurol Assoc 2006;24: Bahn Y, Kim E, Park C, Park HC. Metronidazole induced encephalopathy in a patient with brain abscess. J Korean Neurosurg Soc 2010;48: Seok JI, Yi H, Song YM, Lee WY. Metronidazole-induced encephalopathy and inferior olivary hypertrophy: lesion analysis with diffusion-weighted imaging and apparent diffusion coefficient maps. Arch Neurol 2003;60: Kim H, Kim YW, Kim SR, Park IS, Jo KW. Metronidazoleinduced encephalopathy in a patient with infectious colitis: a case report. J Med Case Rep 2011;5: Groothoff MV, Hofmeijer J, Sikma MA, Meulenbelt J. Irreversible encephalopathy after treatment with high-dose intravenous metronidazole. Clin Ther 2010;32: Bradley WG, Karlsson IJ, Rassol CG. Metronidazole neuropathy. Br Med J 1977;2: Rao DN, Mason RP. Generation of nitro radical anions of some 5-nitrofurans, 2- and 5-nitroimidazoles by norepinephrine, dopamine, and serotonin. A possible mechanism for encephalopathy caused by nitroheterocyclic drugs. J Biol Chem 1987;262: Kim DS, Jung JW, Kim JY, Kim JH, Kim EK, Kim SE. Reversible MRI findings in metronidazole-induced cerebellar dysfunction. J Korean Neurol Assoc 1999;17: Lee SS, Cha SH, Lee SY, Song CJ. Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging. J Comput Assist Tomogr 2009;33: Heaney CJ, Campeau NG, Lindell EP. MR imaging and diffusion-weighted imaging changes in metronidazole (Flagyl)-induced cerebellar toxicity. AJNR Am J Neuroradiol 2003;24:

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical