13-09이성재

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1 대한응급의학회지제 23 권제 4 호 Volume 23, Number 4, August, 2012 원 저 응급실에내원한벨마비환자의스테로이드및항바이러스치료에대한임상적고찰 서울아산병원응급의학과 이성재 김형주 서동우 손창환 이재호 오범진 임경수 김원영 Analysis of Clinical Outcome and Effectiveness of Steroid and Antiviral Treatment in Patients with Bell s Palsy in the Emergency Department Sung Jae Lee, M.D., Hyung Ju Kim, M.D., Dong Woo Seo, M.D., Chang Hwan Sohn, M.D., Jae Ho Lee, M.D., Byum Jin Oh, M.D., Kyung Soo Lim, M.D., Won Young Kim, M.D. patients with initial HB grade III/IV (85.2% vs. 92.7%, p<0.01), and age over 40 years (85.72% vs. 95.2%, p=0.04). Conclusion: The satisfactory recovery rate of patients with Bell s palsy treated with steroid and antiviral agents was 77.9% at three months, and 88.3% at 12 months, and initial severity was found to be an important factor in predicting the long term prognosis of Bell s palsy. Purpose: This study was conducted for investigation of the recovery rate and prognostic factors of Bell s palsy treated with steroid and antiviral agents in the emergency department (ED). Methods: A retrospective review of electronic medical records of patients with acute, unilateral Bell s palsy within 72 hrs of onset who were admitted from the ED between March 2008 and February 2010 was conducted. All patients were treated uniformly with high-dose steroid and valaciclovir. The House-Brackmann (HB) grading system was used for evaluation of the severity of facial palsy. Satisfactory recovery was defined as facial palsy that recovered to Grade I on the HB grading scale. Results: During the three-year period, 231 patients (age, 51±15) with confirmed Bell s palsy were included in this study. Initial grade of paralysis was as follows: 43 patients (18.6%) were HB grade II, 107 patients (46.3%) were grade III, 72 patients (31.2%) were grade IV, and nine patients (3.9%) were grade V. The satisfactory recovery rate was 77.9% at three months, and 88.3% at 12 months from diagnosis. Satisfactory recovery rate was significantly lower in 책임저자 : 김원영서울특별시송파구풍납동 울산대학교의과대학서울아산병원응급의학과 Tel: 02) , Fax: 02) wonpia@yahoo.co.kr 접수일 : 2012년 5월 30일, 1차교정일 : 2012년 6월 10일게재승인일 : 2012년 7월 20일 531 Key Words: Bell s palsy, facial nerve, Prognosis, Emergency department Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 서 안면신경마비는응급실에서드물지않게접하는급성질환이다. 그원인으로는이성대상포진, 외상성마비, 청신경종양, 이하선종양등이알려져있으나대부분은원인이될만한질환이나외상없이한쪽의안면근에완전또는부분적으로말초성마비를보이는특발성안면신경마비 ( 벨마비, Bell s palsy) 가 75% 이상을차지하는가장흔한형태로보고되고있다 1-3). 발생원인에대한가설로는바이러스감염설, 모세혈관확장과투과성증가로여출액이생성되면서국소적허혈을일으킨다는설, 당뇨에의한혈관장애, 한랭노출등여러가설이존재하며아직까지도논란의대상이다 1,2). 최근에헤르페스바이러스와관련된얼굴신경의감염이벨마비의주요한요인으로주목받고있다 4-9). 이에대해다양한임상적, 실험적, 자기공명영상촬영및병리학적인결과들이보고되고있다 7-12). 벨마비의치료는스테로이드치료가근간을이루나최근헤르페스감염이주요인으로알려진이후초기벨마비의치료에항바이러스제를사용하는것이일반화되었다 13-15). 벨마비의예후는일반적으로나쁘지않다고알려져있으나안면신경마비증세로인한얼굴표정근육의마비증상은환자에게있어매우심각한사회적문제를야기하며 론

2 532 / 대한응급의학회지 : 제 23 권제 4 호 2012 현대인에게있어서질병자체가주는문제점뿐만이아니라미용적측면과정신적측면에서심대한영향을미칠수있으므로, 치료에따른회복률과치료예후에영향을미치는인자를파악하는것은응급실에내원한급성안면신경마비환자의진료에있어서매우중요하다고할수있다 1,16). 이에저자들은응급의료센터에증상발현 3일이내의급성안면신경마비를주증상으로내원하여이비인후과진료후벨마비로진단된환자를대상으로하여스테로이드제와항바이러스제치료를받은뒤안면신경마비회복률을알아보고자하였고안면신경마비회복과관련된인자를확인하고자본연구를시행하였다. 한용법의경구스테로이드와항바이러스제치료를받았다. 경구스테로이드는 methylprednisolone을아침, 저녁으로투여하였다. 처음 9일동안에는 48 mg/ 일을경구투여, 10, 11병일에는 32 mg/ 일, 12, 13병일에는 16 mg/ 일, 14병일에는 8 mg/ 일순으로점진적으로감량하였고, 항바이러스제는 valaciclovir 3000 mg을 8시간간격으로세번에나누어투여하였다. 대상환자중 16세이하의소아환자, 타원에서치료가시작되었던환자, 경구스테로이드와항바이러스제치료를받지못하였던환자, 그리고추적기간이 12개월미만인환자의경우는본연구에서제외하였다. 대상과방법 1. 연구대상 2008년 3월부터 2011년 2월까지 3년간 2800 병상의 3차의료기관응급의료센터에증상발현 3일이내의급성안면신경마비를주증상으로내원하여이비인후과진료후벨마비로진단된환자를대상으로하였다. 연구대상이되었던환자는진단받은날부터모두다음과같이동일 2. 자료조사전자의무기록을바탕으로응급실내원시환자의나이, 성별등인구학적특징과기본적인임상정보를수집하였다. 급성안면신경마비의평가는응급실내원시평가된 House-Brackmann (HB) 의분류체계를이용하였다 17) (Table 1). 마비호전정도는 3개월이경과한시점과 12 개월이경과한시점에서외래추적관찰자료를통하여확인하였으며만족할만한회복은 HB Grade I으로호전된것으로정의하였다 13-15,17). Table 1. House-Brackmann classification of facial nerve dysfunction Grade Characteristics I Normal Normal facial function in all areas II Mild Gross Slight weakness noticeable on close inspection May have slight synkinesis At rest, normal symmetry and tone Motion Forehead - Moderate-to-good function Eye - Complete closure with minimal effort Mouth - Slight asymmetry III Moderate Gross Obvious but not disfiguring difference between the two sides Noticeable but not severe synkinesis, contracture, or hemifacial spasm At rest, normal symmetry and tone Motion Forehead - Slight-to-moderate movement Eye - Complete closure with effort Mouth - Slightly weak with maximum effort IV Moderately severe Gross Obvious weakness and/or disfiguring asymmetry At rest, normal symmetry and tone Motion Forehead - None Eye - Incomplete closure Mouth - Asymmetric with maximum effort V Severe Gross Only barely perceptible motion At rest, asymmetry Motion Forehead - None Eye - Incomplete closure Mouth - Slight movement VI Total paralysis No movement

3 이성재외 : 응급실에내원한벨마비환자의스테로이드및항바이러스치료에대한임상적고찰 / 자료분석및통계성별, 연령군, 초기안면신경마비정도, 안면신경마비후스테로이드치료시작시기및항바이러스제치료시작등에따른치료예후인자를조사하였다. 모든수치는평균 ± 표준편차의형식으로표시하였으며소수점한자리까지반올림한수치로표시하였다. 통계분석은윈도우용 SPSS version 12.0(SPSS Inc., Chicago, IL, USA) 를사용하였으며, 서로다른두군간의평균값은독립표본 t 검정을이용하였으며, 범주형자료는카이제곱검정 (Chisquare test) 이나피셔의정확한검정 (Fisher s exact test) 를사용하여분석하였다. p값이 0.05 미만인경우통계적으로유의한차이가있다고판정하였다. 결과 1. 대상환자의특성연구기간동안벨마비로진단되었던환자 268명중추적관찰할수없었던환자 35명, 항바이러스제치료를받을수없었던환자 2명을제외한총 231명의환자를대상으로하였다. 총 231명의환자중남자가 118명 (51.1%) 이었으며평균나이는 50.5±15.0세이었다. 안면신경마비의위치는우측이 126명 (54.5%) 로더흔하였고초기마비정도는 3.2±0.8 HB Grade 이었으며평균적으로증 상발현 1.1±0.9 일에내원하였다. 증상부터스테로이드치료시작까지의시간은평균 30.4±21.0 시간이었고항바이러스제치료시작까지의시간은평균 30.7±21.4 시간이었다. Ramsay Hunt 증후군이동반된경우는 16명 (6.9%) 였다. 2. 전체적인회복률벨마비의초기마비정도는 HB Grade II가 II가 43명 (18.6%), Grade III가 107명 (46.3%), Grade IV가 72명 (31.2%), Grade V가 9명 (3.9%) 이었다. 3개월추적관찰시 HB Grade I으로회복되었던환자는 180명으로그회복률은 77.9% 이었고, 12개월추적관찰시 HB Grade I으로회복되었던환자는 204명으로그회복률은 88.3% 로관찰되었다. 3. 회복률에영향을미치는요인최종적으로회복되었던 204명의환자군과회복되지못하였던 27명의환자군사이의나이, 성별, 증상발현후내원시까지시간, 스테로이드치료시작까지의시간및항바이러스제치료시작까지의시간에있어서는유의한차이는없었다 (Table 2). 또한 Ramsay-Hunt 증후군이동반되었던군의회복률은 86.5% 로동반되지않았던군의회복률 87.5% 와유의한차이가없었다 (p=0.83). 그러나전체대상환자를연령군 (20대이하, 30대, 40대, 50대, 60대, Table 2. Demographic features and clinical characteristics in patients with Bell s palsy Satisfactory recovery (n=204) Non-satisfactory recovery (n=27) p value Demographic features Age, years 50.0± ± Sex, n (%) Male 106 (52.0) 12 (44.4) Female 098 (48.0) 15 (55.6) Clinical characteristics Onset, days 1.1± ± mpd time to treatment, hours 30.5± ± antiviral time to treatment, hours 30.9± ± Side of facial palsy, n (%) Left 089 (43.6) 16 (59.3) Right 115 (56.4) 11 (40.7) HB grade on arrival, n (%) Grade (20.1) 02 (07.4) Grade (48.0) 09 (33.3) Grade (28.9) 13 (48.1) Grade (02.9) 03 (11.1) Associated with RH, n (%) 016 (07.8) 0 (0) Values are mean±standard deviation mpd: methylprednisolone, HB: House-Brackmann classification, RH: Ramsay-Hunt syndrome

4 534 / 대한응급의학회지 : 제 23 권제 4 호 대이상 ) 으로나누어회복률을비교하면 20대이하는 96.0%, 30대는 94.7%, 40대는 83.3%, 50대는 87.5%, 60대는 81.5%, 70대이상은 85.0% 로 40대이상부터회복률이감소하는것을관찰할수있었다. 전체대상환자를 40세미만과 40세이상두군으로나누어회복률을비교하면 40세이상인군에서통계적으로유의하게회복률이낮음을확인할수있었다 (95.2% vs. 85.7%, p=0.04). 또한전체대상환자를초기안면신경마비정도에따라 HB Grade II/III군과 HB Grade IV/V군으로나누어회복률을비교하였더니 HB Grade IV/V군에서회복률이 80.2% 로 HB Grade II/III군회복률 92.7% 에비해통계적으로유의하게낮음을확인할수있었다 (p<0.01)(table 3). 회복률과관련된독립적인예측인자를확인하기위하여다변량로지스틱회귀분석을시행하였고 HB Grade IV/V 이 Odds ratio 3.05(confidence interval ) 로회복률과관련된유의한예측인자였다 (p<0.01)(table 4). 고찰본연구에서저자들은벨마비환자에서스테로이드제와항바이러스제치료를받은후안면신경마비회복률을알아보고자하였고치료 3개월째회복률은 77.9%, 12개월째회복률은 88.3% 의회복률을확인할수있었다. 또한내원시안면신경마비정도가심할수록 (HB Grade IV/V) 회복률이낮다는것을확인하였다. 19세기초영국의신경해부학자인찰스벨의이름을따벨마비라고불리는특발성안면신경마비는급성안면신경마비중가장흔하지만아직까지명확한발생원인이밝 혀지지않았기에보고자마다다른치료법과다양한회복률을보고하고있다 1,2). 현재벨마비의치료법으로가장우선적으로사용되고있는것은경구스테로이드제이다 13,15). 그러나최근수년간벨마비의병인중에바이러스감염설의이론적근거하에스테로이드제와항바이러스제의병합요법이대두되었고, 병합투여의효과에대해서몇몇연구결과가발표되었으나항바이러스제의효과에서는아직까지논쟁중이다 7,18). 최근발표된한무작위이중-맹검, 위약-조절연구에서스테로이드제와항바이러스제모두투여하지않은이중위약군환자에서 3개월추적관찰시 54.0% 의회복률을그리고 12개월추척관찰시 65.0% 의회복률을보였었고, 스테로이드제와항바이러스제모두투여한환자에서는 3개월, 12개월회복률이각각 65.0%, 80.0% 임을보고하였다 15). 이는벨마비환자를대상으로회복률을확인할수있는가장대규모연구로서두가지약제의동시투여시회복률은 80.0% 로본연구결과와큰차이가없음을확일할수있었다. 그러나 2011년에그리스에서보고된연구에서는 2년회복률이 73.0% 로, 같은해일본에서보고된연구에서는 1년째회복률이 86.0% 로지역과환자군에따라벨마비환자의회복률에차이가있음을알수있었다 19,20). 벨마비는질병자체의신체적영향뿐만아니라미용적, 정신적측면, 나아가환자가사회생활을영위함에있어심대한영향을미칠수있으므로그예후인자를파악하는것은응급실에내원한급성안면신경마비환자의진료에있어서매우중요할것이다. 즉예후가좋지않을것으로예상되는환자에서는조기에보다적극적인치료방법을선택할수있는기회를제공받을수있을것이다. 본연구에서는치료후벨마비회복률에영향을미치는요인을알아보고자회복되었던군과회복되지못하였던군간의성별, Table 3. Satisfactory recovery related with age and HB grade Satisfactory recovery (n=204) Non-satisfactory recovery (n=27) p value Age grade, n (%) <0.04 < 40 years 060 (29.4) 03 (11.1) > 40 years 144 (70.6) 24 (88.9) HB grade, n (%) <0.01 mild (II/III) 139 (68.1) 11 (40.7) severe (IV/V) 065 (31.9) 16 (59.3) HB: House-Brackmann classification Table 4. Factors associated with satisfactory recovery OR 95% confidence interval p value Age grade HB grade OR: odd ratio, HB: House-Brackmann classification

5 이성재외 : 응급실에내원한벨마비환자의스테로이드및항바이러스치료에대한임상적고찰 / 535 연령군, 초기안면신경마비정도, 동반증상및동반질환유무, 증상발현부터스테로이드투약까지의시간및항바이러스제투약까지의시간에서차이점을조사하였다. 본연구결과연령의차이에따른회복률의차이를확인할수있었는데 40대이하인군에서 40대이상군보다통계적으로유의하게안면신경마비회복률이더높았었다. 이는 Peitersen 1) 의연구결과에서환자의연령이많을수록예후가나쁘다는보고하였던것과유사한결과이다. 그러나연령대는다변량분석에서는독립된예측인자가아니었다. 이는본연구가치료시작까지시점이 30시간으로다른문헌들에비해매우빠름으로인해연령에상관없이좀더좋은예후를갖게되어연령에따른영향이희석되지않았을까생각된다. 치료시작시점이안면신경마비회복률에영향을줄수있는또하나의요소라고알려져있고이전연구에서스테로이드제나항바이러스제치료시작까지의시간이 72시간이내일때가회복률이더좋았다고보고되었다 21). 그러나본연구결과에서는증상발현부터투약까지시간은안면신경마비회복률에영향을미치지않았는데이는본연구가증상발현 72시간내에환자들을대상으로하여평균치료시작시간이 30시간으로매우빠른시기에치료를시작하여치료시기에따른회복률의차이가없었을것으로생각된다. 초기안면신경마비정도가회복률에영향를미친다는몇몇보고들이있었다. 본연구에서도 HB Grade IV/V군에서회복률이 80.2% 로 HB Grade II/III군회복률 92.7% 에비해통계적으로유의하게낮음을확인할수있었고, HB Grade IV/V는 Odds ratio 3.05(CI ) 로회복률과관련된유의한예측인자임을확인할수있었다. 그러므로응급실내원시안면신경마비가 HB Grade IV/V로심할경우에는약물치료에도불구하고회복이되지않을가능성이높기에약물요법뿐만아니라지속적인물리치료등회복률을조금이라도더높이기위한병합치료를시행하여야할것이다. 본연구는전향적으로자료를수집한후향적분석연구이기에후향적연구에따른한계가있을것이며대상환자군을일정하게하기위해 3일이내에, 이전에치료받은적없이응급실로내원한환자들만을대상으로진행하였기에다른외국문헌에비해많지않은환자수를대상으로진행된것은연구의제한점일것이다. 또한진행된연구기간동안모든환자에서스테로이드와항바이러스제병합요법이사용되었기에최근논란이되고있는스테로이드단독사용군과항바이러스제병합치료에따른벨마비회복률을비교할수없었다는점또한연구의제한점일것이다. 결론스테로이드제와항바이러스제의병합치료를받은급성 벨마비환자들의회복률은 3개월째 77.9%, 12개월째 87.9% 였으며, 내원시안면신경마비정도가심할수록 (HB Grade IV/V) 회복률이낮았다. 참고문헌 01. Peitersen E. Bell s palsy: the spontaneous course of 2,500 peripheral facial nerve palsies of different etiologies. Acta Otolaryngol Suppl 2002: Peitersen E. The natural history of Bell s palsy. Am J Otol 1982;4: Devriese PP, Schumacher T, Scheide A, de Jongh RH, Houtkooper JM. Incidence, prognosis and recovery of Bell's palsy. A survey of about 1000 patients ( ). Clin Otolaryngol Allied Sci 1990;15: Adour KK, Bell DN, Hilsinger RL. Herpes simplex virus in idiopathic facial paralysis (Bell palsy). JAMA 1975; 233: Furuta Y, Fukuda S, Suzuki S, Takasu T, Inuyama Y, Nagashima K. Detection of varicella-zoster virus DNA in patients with acute peripheral facial palsy by the polymerase chain reaction, and its use for early diagnosis of zoster sine herpete. J Med Virol 1997;52: McCormick DP. Herpes-simplex virus as a cause of Bell s palsy. Lancet 1972;1: Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med 1996;124: Stjernquist-Desatnik A, Skoog E, Aurelius E. Detection of herpes simplex and varicella-zoster viruses in patients with Bell s palsy by the polymerase chain reaction technique. Ann Otol Rhinol Laryngol 2006;115: Theil D, Arbusow V, Derfuss T, Strupp M, Pfeiffer M, Mascolo A, et al. Prevalence of HSV-1 LAT in human trigeminal, geniculate, and vestibular ganglia and its implication for cranial nerve syndromes. Brain Pathol 2001;11: Cathorne T. The surgery of otosclerosis. Proc R Soc Med 1950;43: Fisch U, Esslen E. Total intratemporal exposure of the facial nerve. Pathologic findings in Bell s palsy. Arch Otolaryngol 1972;95: Kim IS, Shin SH, Kim J, Lee WS, Lee HK. Correlation between MRI and operative findings in Bell s palsy and Ramsay Hunt syndrome. Yonsei Med J 2007;48: Sullivan FM, Swan IR, Donnan PT, Morrison JM, Smith BH, McKinstry B, et al. Early treatment with prednisolone or acyclovir in Bell s palsy. N Engl J Med 2007;357:1598-

6 536 / 대한응급의학회지 : 제 23 권제 4 호 Hato N, Yamada H, Kohno H, Matsumoto S, Honda N, Gyo K, et al. Valacyclovir and prednisolone treatment for Bell s palsy: a multicenter, randomized, placebo-controlled study. Otol Neurotol 2007;28: Engstrom M, Berg T, Stjernquist-Desatnik A, Axelsson S, Pitkaranta A, Hultcrantz M, et al. Prednisolone and valaciclovir in Bell s palsy: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet Neurol 2008;7: Neely JG, Neufeld PS. Defining functional limitation, disability, and societal limitations in patients with facial paresis: initial pilot questionnaire. Am J Otol 1996;17: Peitersen E. Natural history of Bell s palsy. Acta Otolaryngol Suppl 1992;492: Linder T, Bossart W, Bodmer D. Bell s palsy and Herpes simplex virus: fact or mystery? Otol Neurotol 2005;26: Mantsopoulos K, Psillas G, Psychogios G, Brase C, Iro H, Constantinidis J. Predicting the long-term outcome after idiopathic facial nerve paralysis. Otol Neurotol 2011;32: Takemoto N, Horii A, Sakata Y, Inohara H. Prognostic factors of peripheral facial palsy: multivariate analysis followed by receiver operating characteristic and Kaplan- Meier analyses. Otol Neurotol 2011;32: de Almeida JR, Al Khabori M, Guyatt GH, Witterick IJ, Lin VY, Nedzelski JM, et al. Combined corticosteroid and antiviral treatment for Bell palsy: a systematic review and meta-analysis. JAMA 2009;302:

012임수진

012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar