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대한임상신경생리학회지 16(1):27-31, 2014 eissn 2288-1026 pissn 1229-6414 http://dx.doi.org/10.14253/kjcn.2014.16.1.27 Case Report 급성양측손목처짐으로발현한베르니케뇌병증 1 예 전북대학교의학전문대학원신경과학교실 1, 전북대학교병원신경과, 임상의학연구소 2 김도형 2 오선영 1,2 A Case of Wernicke's Encephalopathy Presenting as Acute Bilateral Wrist Drop Do-Hyung Kim 2, Sun-Young Oh 1,2 1 Department of Neurology, Chonbuk National University College of Medicine, Jeonju; 2 Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea Thiamine deficiency can cause peripheral polyneuropathy and Wernicke s encephalopathy. Wernicke s encephalopathy is characterized by ataxia, ophthalmoplegia, nystagmus, and confusion, and typically presents acute and rapidly progressive course, whereas peripheral neuropathy associated with thiamine deficiency manifests chronic and slowly progressive one. However, acute and rapidly progressive axonal polyneuropathy combined with Wernicke s encephalopathy is quite rare and unusual. Here, we describe a patient with Wernicke s encephalopathy who presented with acute bilateral axonal neuropathy. (Korean J Clin Neurophysiol 2014;16:27-31) Key Words: Wernicke's encephalopathy, Acute axonal polyneuropathy, Thiamine Received 18 September 2013; received in revised form 10 February 2014; accepted 14 May 2014. 베르니케뇌병증 (Wernicke's encephalopathy) 은티아민 (thiamine) 의결핍으로나타나는의식혼돈, 안구운동장애, 실조증을특징으로하는급성신경정신행동질환 (neuropsychiatric disorder) 이다. 티아민은수용성비타민으로서건강한성인에서하루 1-2 mg 정도필요로하며, 30-50 mg 정도가체내에저장되어혈액-뇌장벽 (blood-brain barrier) 을 Address for correspondence; Sun-Young Oh Department of Neurology, Chonbuk National University Hospital, Chonbuk National University College of Medicine, 20 Geonji-ro, Deokjin-gu, Jeonju 561-712, Korea Tel: +82-63-250-1590 Fax: +82-63-251-9363 E-mail: ohsun@jbnu.ac.kr * This study was supported by a Fund of Biomedical Research Institute, Chonbuk National University Hospital, and by research funds of Chonbuk National University. 지나뇌조직이나신경세포에도달후신경세포내의사립체 (mitochondria) 와핵으로전달된다. 1 티아민이전혀공급되지않는상태가약 4-6주정도지속되면티아민결핍으로인한증상이나타날수있는데가장흔한티아민결핍질환이각기병 (beriberi) 과베르니케뇌병증이다. 1 티아민결핍은말초신경병을흔히동반할수있는데, 사지의근위부보다원위부의운동, 감각신경의전도속도를대칭적으로저하시키는말초신경병이특징인 dry beriberi와, 부종 (edema), 빈맥 (tachycardia), 심장비대 (cardiomegaly) 가말초신경병에동반되는 wet beriberi가있다. 베르니케뇌병증에서도만성다발말초신경병이동반할수있으나, 2,3 첫증상으로급성대칭축삭신경병 (acute axonal neuropathy) 으로발현한경우는국내에서보고된바가없다. 4 저자들은갑작스런양측손목처짐 (wrist drop) 의급성대칭축삭신경병으로발현된베르니케뇌병증환자를경험하였기에문헌고찰과함께 Copyright 2014 by The Korean Society of Clinical Neurophysiology 27

김도형 오선영 보고한다. 증례수개월전부터지속되는심한식욕부진, 구토와전신위약으로내과에입원중인 57세남자가입원후발생한양측손목처짐과손저림, 의식변화를보여신경과로의뢰되었다. 환자는과거복부전산단층촬영에사용한조영제로유발된신장병 (nephropathy) 으로혈액투석을받고있었으며, 입원 4개월전원위부총담관종양으로날문보존이자샘창자절제술 (pylorus-preserving pancreaticoduodenectomy) 을받은기왕력이있으며, 다른수술이나외상의과거력은없었다. 입원당시혈액검사에서경미한간수치의상승 (AST: 41 IU/L, ALT: 44 IU/L) 과신장기능부전 (BUN: 42 mg/dl, Cr: 4.10 mg/dl) 외에는특이소견이보이지않아보존적치료중이었다. 입원 7일째부터, 양측손저림을호소하기시작했으 며다음날부터양손의처짐, 위약과함께가끔씩질문에적절하게대답하지못하고상황에맞지않는이야기를하였다. 신경학적검사에서기면상태의의식수준과시간과장소에대한지남력장애, 전향성기억상실증을보이는중등도인지능력저하가관찰되었다. 자발안진은없었으며, 외안근운동은정상이었고신속보기운동 (saccades) 과부드러운따라보기운동 (smooth pursuit) 도잘수행하였으나양안에서수평주시유발안진 (gaze-evoked nystagmus) 이관찰되었다. 운동검사에서하지및상지근위부힘은정상이었으나양측손목의신전이전혀되지않았고전완의내회전위약 (MRC grade II), 엄지손가락의외전위약 (MRC grade II) 이양측에서관찰되었다. 첫째등쪽뼈사이근 (first dorsal interosseous) 이나새끼벌림근 (abductor digiti minimi) 의운동은정상이었다. 감각검사에서양손등과손바닥에저린느낌과감각저하를호소하였으며, 4, 5번째손가락과이와연결된손바닥, 손등에서는정상이었다. 소뇌기능검사에서 Table 1. Result of nerve conduction study of bilateral upper and lower extremities Latency (msec) Conduction velocity (m/sec) Amplitude (m; mv/ s; uv) RT LT NL RT LT NL RT LT NL Motor nerve Median nerve NR NR 4.4 NR NR 49.96 NR NR 5 Ulnar nerve Wrist 2.7 2.8 3.3 7.2 5.7 5 Elbow 6.8 7.1 59 65 50.61 5.3 4.6 Axilla 8.5 9.7 52 51 5.1 4.7 Radial nerve NR NR 2.9 NR NR 57.2 NR NR 2 Peroneal nerve EDB Ankle 5.9 3.8 6.5 1.8 6.0 4 B Fib 13.0 10.6 42 47 41.85 1.6 4.8 Poplit 14.4 12.1 41 45 40.0 1.9 4.7 TA Fib head 4.6 4.2 6.7 40.5 5.0 5.3 5.0 Poplit 6.4 6.1 44 45 5.0 5.1 Tibial nerve Ankle 3.7 4.5 5.8 11.5 7.1 5.0 Knee 11.6 11.9 48 51 40.63 9.4 5.1 Sensory nerve Median nerve NR NR 3.5 NR NR 41.26 NR NR 10 Ulnar nerve 2.7 2.7 3.1 38 35 39.26 40.5 45.6 10 Radial nerve 2.7 NR 3.1 37 NR 44.31 3.8 NR 10 Peroneal nerve 1.8 2.2 4.4 56 64 40.5 4.1 4.8 4.0 Sural nerve 2.6 2.3 4.4 46 52 34.68 8.2 13.4 6.0 RT; right, LT; left, NL; normal range, NR; no response, m; motor, s;sensory, EDB; extensor digitoriumbrevis, TA; tibialis anterior, B Fib; below fibular head, Poplit; popliteal fossa, Fib head; fibular head. 28 Korean J Clin Neurophysiol / Volume 16 / June 2014

A Case of Wernicke's Encephalopathy presenting as Acute Bilateral Wrist Drop 사지의경미한겨냥이상과스스로걷기힘들정도의실조증을보였다. 심부건반사검사에서양상지의상완요골근반사와무릎반사는유발되지않았으며, 다른관절에서는약간감소되었다. 신경전도검사에서양측정중신경과요골신경에복합근육활동전위 (compound muscle action potential, CMAP) 와양측정중신경과좌측요골신경에감각신경활동전위 (sensory nerve action potential, SNAP) 가나타나지않고우측요골신경의감각신경활동전위의진폭감소를보여상지정중신경과요골신경의심한축삭신경병증 (axonal neuropathy) 을시사하였다. 그러나양쪽내측, 가측전상완피부신경 (medial-, lateral antebrachialcutaneous nerve) 신경전도검사는정상이었다. 하지신경전도검사에서우측짧은발가락폄근 (extensor digitorum brevis) 의복합근육활동전위진폭은감소하였으나앞정강근 (tibialis anterior) 진폭은정상범위의하한에해당하였다. 정강신경복합근육활동전위, 종아리감각신경활동전위의진폭역시정상범위하한이었으나, 장딴지신경 (sural nerve) 신경전도검사는정상이었다 (Table 1). 근전도검사에서양측고유시지신근 (extensor indicis proprius), 자쪽손목폄근 (extensor carpi ulnaris), 상완요골근 (brachioradialis), 긴엄지굽힘근 (flexor pollicis longus), 긴노쪽손목폄근 (extensor carpi radialis, long head), 원엎침근 (pronator teres), 짧은엄지벌림근 (abductor pollicis bervis) 에이상자발전위 (abnormal spontaneous activities) 를볼수있었으나첫째등뼈사이근 (first dorsal interosseus), 새끼벌림근 (abductor digitiminimi), 4, 5번깊은손가락굽힘근 (flexor digitorumprofundus to digits 4, 5), 위팔세갈래근 (triceps brachii), 위팔두갈래근 (biceps brachii) 과위팔신경얼기병증 (brachial plexopathy) 을확인하기위해추가로검사한다른근육및척추주위근 (paraspinal muscle), 우측긴종아리근 (peroneus longus) 를제 외한양하지근육들은정상이었다. 증상발생이틀째촬영한뇌자기공명영상의 FLAIR (fluid attenuated inversion recovery) 영상에서시상내측 (medial thalamus), 중뇌수도관주위영역 (periaqueductal area of the midbrain) 과뇌교의제4 뇌실바닥에양측으로대칭적인고신호강도가확인되었다 (Fig. 1). 환자의입원전병력, 임상증상, 신경학적검사, 뇌자기공명영상및신경전도, 근전도검사소견으로미루어베르니케뇌병증과함께동반된양측정중신경및요골신경의축삭신경병으로진단할수있었다. 일반혈액검사, 갑상선기능검사, 당화혈색소, 공복혈당, 자가항체 (autoimmune antibody, anti-ro (SS-A) and anti-la (SS-B), anti-rnp, anti-dsdna, anti-sm, anti-tm antibody, rheumatoid factor, Anti-TSH receptor antibody, anti-histone antibody, anti-rib-p antibody, anti-cardiolipinantibody, anti SCL antibody anti Jo-1 antibody, c-anca, p-anca, anti-phospholipid antibody), 항핵항체 (antinuclear antibody), 루푸스항응고인자 (Lupus anticoagulant), 매독검사, 인간면역결핍바이러스 (Human immunodeficiency virus) 및비타민 B12 (500 pg/ml, normal range 200-950 pg/ml) 검사는정상이었다. 혈중티아민 (thiamine) 혈중농도가감소되어있었으며 (24.0 μg/ml, normal range 59-213 μg/ml), 하루 200 mg의티아민정주 (intravenous injection) 치료를시작하였다. 티아민치료시작후환자의이상신경학적증상은현저하게호전되었으나최근일에대한기억력저하, 양측손목처짐은지속되었다. 티아민을경구약제로전환후환자는퇴원하였으며 6주후실시한뇌자기공명영상추적검사에서입원당시뇌병변은관찰되지않았으나기억력저하및양측손목처짐의뚜렷한호전은없었다. 3개월후외래진료에서기억력저하및양측손목처짐은거 A B C D Figure 1. Coronal fluid attenuated inversion recovery (FLAIR) MR images. These FLAIR images show signal intensity alterations of medial thalamus (white arrows, A) and periaqueductal area of the midbrain (white arrow, B) in an acute period of disease. After six weeks of treatment, follow-up FLAIR MR images (C and D) showed a normalized signal change in same area (A and B level) that affected by Wernicke's encephalopathy. Korean J Clin Neurophysiol / Volume 16 / June 2014 29

김도형 오선영 의정상으로회복하였다. 고찰베르니케뇌병증의원인인티아민결핍을유발하는가장흔한원인은잘못된방식의음주이지만알콜과관련없이도티아민의공급저하또는흡수감소를유발하는후천성면역겹핍증, 악성종양, 영양소이상흡수, 신경성식욕부진, 임신에인한입덧, 지속적인정맥영양공급, 특히위절제술 (gastrectormy) 후에도유발가능하다. 1,2,5 일반적으로티아민은뇌세포안으로들어가당대사과정에관여하는데에탄올이티아민의이러한작용을억제하고신경세포손상을야기한다. 3 베르니케뇌병증환자는뇌자기공명영상이나컴퓨터단층촬영에서내측시상 (medial thalamus) 과제 3뇌실주변의백질 (periventricular regions of the third ventricle) 에선택적으로병변이나타나는데, 그외소뇌나그주변구조물, 뇌신경핵 (cranial nerve nuclei), 적색핵 (red nuclei), 치아핵 (dentate nuclei), 꼬리핵 (caudate nuclei), 뇌들보팽대 (splenium) 등에도나타난다. 6 베르니케뇌병증과코르사코프증후군 (Korsakoff syndrome) 이함께나타난환자의약 80% 에서만성축삭다발신경병을동반하는데, 베르니케뇌병증만있는환자에서도이러한만성말초신경병이동반된보고가있다. 4,7 베르니케뇌병증과동반하여나타나는다발신경병환자의신경전도검사와조직검사는대부분축삭형신경병증을보이며수개월에걸쳐상지보다하지에, 근위부보다는원위부에주로나타난다. 5 티아민결핍이심하거나빠르게진행되는경우중추신경계손상확률이높은반면, 결핍이오랜기간동안서서히진행되는경우말초신경계손상이주로발생하지만위성형술 (gastroplasty) 후급속한티아민결핍으로베르니케- 코르사코프증후군환자에서급성다발신경병이동반된보고가있으며이는주로비만치료방법인위절제술 (gastrectomy) 과루와이문합술 (Roux-en-Y) 에서많이보고되었다. 5,7,8 이는위성형술을받은환자에서만성적인티아민흡수장애뿐만아니라수술후나타난구토가빠른속도로티아민결핍상태를유발하여베르니케뇌병증환자에서급성다발신경병이함께발생하는것으로생각된다. 7 본증례의환자도원위부총담관종양으로날문보존이자샘창자절제술을받은후만성적인흡수장애상태에서반복적인구토와식욕부진으로인해티아민결핍이가속되어베르니케뇌병증과함께급성축삭다발신경병이발병한것으로생각할수있겠다. 이전의보고와다르게주로상지에국한된축삭신경 병을보이고있지만신경전도검사에서척골신경과정강신경복합근육활동전위, 종아리신경의복합근육활동전위와감각신경활동전위진폭이정상범위지만하한수준으로감소를확인할수있다 (Table 1). 본환자에서처럼만성티아민감소상태에서급속하게신경병을악화시킬수있는원인으로는, 티아민결핍으로인해당대사과정에작용하는 pyruvate dehydrogenase (PDH) 의활성감소로인해삼인산아데노신 (Adenosine Triphosphate, ATP) 생성감소로유추할수있다. 이는말초신경의탈분극과축삭의흥분조절에중요한역할을하는신경세포표면의랑비에결절의 Na + -K + -ATPase의활성을감소시킨다. 우아바인 (ouabain) 을이용해 Na + -K + -ATPase 를억제시키는실험에서유수신경과무수신경의신경전도속도변화는저명하지않지만복합신경활동전위진폭은감소하였다. 7 따라서본환자의급성양손목처짐은장기간의티아민결핍과지속적이고반복적인구토로인한급속한티아민결핍의초래로말초신경의축삭변성이급격하게악화된것으로추정할수있다. 베르니케뇌병증에대한최근의치료지침은진단후가급적빨리티아민투여를시작해야하는데, 하루 200 mg의티아민을세차례나눠당투여전에정주 (intravenous injection) 해야하며식이섭취가가능해지면경구투여로전환하여유지한다. 9 위절제술이나위성형술을실시한환자는최소 6개월이상지속적으로혈중티아민농도를추적관찰한다. 9 결론적으로, 베르니케뇌병증은중추신경계이상증상뿐아니라티아민결핍이오래지속되면말초신경병을동반할수있지만, 본증례와같이급성축삭형말초신경병을동반할수있다는점을유의해야하며, 의심환자에게말초신경병동반여부를확인하는것이불필요한검사를막고빠른치료방법결정에중요하다. REFERENCES 1. Thomson AD, Guerrini I, Marshall EJ. Wernicke s encephalopathy: role of thiamine. Practical Gastroenterol 2009;75:21-30. 2. Donnino MW, Vega J, Miller J, Walsh M. Myths and misconceptions of Wernicke s encephalopathy: what every emergency physician should know. Ann Emerg Med 2007;50:715-721. 3. Butterworth RF. Thiamin deficiency and brain disorders. Nutr. Res. Rev. 2003;16:277-283. 4. Lehmann HC, Lindenberg R, Arendt G, Ploner M. Acute axonal neuropathy and Wernicke s encephalopathy. J Neurol 2006; 253:1516-1517. 5. Koike H, Misu K, Hattori N, Ito S, Ichimura M, Ito H, et al. 30 Korean J Clin Neurophysiol / Volume 16 / June 2014

A Case of Wernicke's Encephalopathy presenting as Acute Bilateral Wrist Drop Postgastrectomy polyneuropathy with thiamine deficiency. J Neurol Neurosurg Psychiatry 2001;71:357-362. 6. Zuccoli G, Pipitone N. Neuroimaging findings in acute Wernicke s encephalopathy: review of the literature. AJR Am J Roentgenol 2009;192:501-508. 7. Ishibashi S, Yokota T, Shiojiri T, Matunaga T, Tanaka H, Nishina K, et al. Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency? J Neurol Neurosurg Psychiatry 2003;74:674-676. 8. Thaisetthawatkul P, Collazo-Clavell ML, Sarr MG, Norell JE, Dyck PJ. A controlled study of peripheral neuropathy after bariatric surgery. Neurology 2004;63:1462-1470. 9. Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol 2010;17: 1408-1418. Korean J Clin Neurophysiol / Volume 16 / June 2014 31