305 Symposium J Korean Orthop Assoc 2017; 52: 305-309 https://doi.org/10.4055/jkoa.2017.52.4.305 www.jkoa.org Neurogenic Pain Disorder in the Foot and Ankle pissn : 1226-2102, eissn : 2005-8918 족부족관절주위의신경병성통증질환 : 말초신경병 김학준 박영환 김수현 고려대학교구로병원정형외과 Neurogenic Pain Disorder in the Foot and Ankle: Peripheral Neuropathy Hak Jun Kim, M.D., Ph.D., Young Hwan Park., M.D., and Soo Hyun Kim, M.D. Department of Orthopedic Surgery, Korea University Guro Hospital, Seoul, Korea Most common peripheral neuropathy around foot and ankle is diabetic neuropathy, but there are another cause of peripheral neuropathy, such as rheumatoid arthritis, metabolic disease, genetic disease, toxic material, and so on. The main symptom of peripheral neuropathy is pain. The disturbance of sensory and balancing, weakness of muscle, deformity of foot and neuropathic arthropathy are also the symptoms of the peripheral neuropathy. History taking is most important to identify the cause of peripheral neuropathy. Neurological exam have to include the pin prick test, vibration test, 10 g-monofilamant test and ankle reflex test. Simple radiography is essential to observe the deformities or neuropathic arthropathy at foot and ankle. The presence of peripheral neuropathy, involvement and severity can be identified from nerve conduction study. The study of occlusive arteritis is essential for diabetic neuropathy. The medical treatment of associated disease is important but the pain of peripheral neuropathy should be controlled simultaneously. Medicine include the antidepressants, anticonvulsants, opioids and topical agents. The surgical treatment of peripheral neuropathy include lengthening of Achilles tendon, correction of deformity, the total contact cast and arthrodesis. Surgical decompression of specific nerve might helpful in pain control of peripheral neuropathy. Key words: ankle, foot, peripheral neuropathies, diagnosis, treatment 서론 말초신경병은하나의독립된질환또는전신질환의합병증으로 발생하며노화에의한정상적인변화와병적인변화가혼재되어 있는경우가흔하다. 1,2) 말초신경병은단일신경을침범하는포착 성신경병 (entrapment neuropathy) 뿐만아니라면역매개질환으로 발생하는만성염증탈수초다발신경병 (chronic inflammatory demyelinating polyneuropathy), 급성염증다발신경뿌리신경병 (acute inflammatory demyelinating polyradiculoneuropathy, Guillain- Received May 8, 2017 Revised June 5, 2017 Accepted June 27, 2017 Correspondence to: Hak Jun Kim, M.D., Ph.D. Department of Orthopedic Surgery, Korea University Guro Hospital, 148 Gurodongro, Guro-gu, Seoul 08308, Korea TEL: +82-2-2626-3090 FAX: +82-2-2626-1163 E-mail: dakjul@korea.ac.kr Barré syndrome), 다초점운동신경병 (multifocal motor neuropathy) 이있으며, 유전자의결함으로발생하는유전운동감각다발신경병인샤르코-마리-투스병 (Charcot-Marie-Tooth disease) 이있다. 기타후전척으로발생하는신경병으로는당뇨병성신경병, 혈관염신경병, 나병신경병, 알코올성신경병, 암성신경병, 영양결핍성신경병등이알려져있다. 3,4) 족부및족관절분야에서의접하는가장흔한말초신경병은당뇨병으로인해발생하는당뇨병성말초신경병으로알려져있으나다발성신경병의 25% 에서는그원인을알수없는경우가있다고한다. 5) 최근의연구에서는류마티스관절염와같이병발된신경병의중요성을강조하기도한다. 6) 족부및족관절에발생한말초신경병은통증이나저린감을호소하는신경증상만있는경미한경우에서부터궤양이나신경병 The Journal of the Korean Orthopaedic Association Volume 52 Number 4 2017 Copyright 2017 by The Korean Orthopaedic Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
306 Hak Jun Kim, et al. 성관절병 (Charcot arthropathy) 이발생하는심각한상태에이르기까지다양한양상을나타내지만치료방법은당뇨병성신경병의단계적인치료를이용할수있다. 그러나당뇨병이동반되지않은말초신경병의경우는신경병의심각성을쉽게간과할수있어서주의를요한다. 류마티스관절염이나원인미상의말초신경병에서신경병성관절병이동반된최근의연구결과가 6-8) 있으므로더욱주의를기울여야한다. 말초신경병의증상및진단 말초신경병의증상은주로무감각, 화끈거린다거나뻣뻣하다는이상감각, 미세한움직임이잘되지않는둔감, 균형감의소실및근력저하등이다. 샤르코-마리-투스병의경우는족부의요족변형을주로호소하기도한다. 진단은우선정확한증상에대한자세한묘사와증상의발현기간및변화정도를알아야하며가족력을파악하여야하고독성물질에노출되었는지또는흡연이나알코올의섭취여부및기간을파악해야한다. 신체검사로는족배동맥과후경골동맥을촉지하여혈액순환의정도를파악하고하지거상이나기립시의발의피부색깔의변화를관찰하며감각및운동신경의이상을측정하여야하고자율신경계의이상에의한이영양성변화 (dystrophic change) 인발바닥의피부건조나발톱의깨짐도관찰하여야한다. 9-11) 특히당뇨병성말초신경병의경우는다발성신경을침범하는경우가많으므로특정한신경과관련이있는신경분절 (dermatome) 에증상이있기보다는양말을신은것과같이 (glove type) 증상이여러신경분절에광범위하게나타난다. 신경이상에대한직접적인검사는침통각검사 (pin prick test), 진동지각 (vibration perception), 10 g 단섬유압각검사 (monofilament test) 및발목반사검사 (ankle reflex) 가있으며원인이명확하지않은경우는전기생리학적검사를시행할수있다. 4,5,12,13) 혈액순환의장애를측정하기위해발목-상완지수검사 (anklebrachial index test) 를시행하고 14) 필요하다면경피내혈액산소분압 (transcutaneous oxygen pressure, TcPo2) 을측정할수있다. 추가적으로혈액학적검사를시행하여후천성면역결핍증이나매독등의감염성질환및비타민 B12 결핍증, 경구당부하검사, 당화혈색소검사 (HgA1C), 갑상선기능검사, 혈청면역검사등을시행할수있다. 15) 족부의변형정도를파악하고신경병성관절증의감별진단을위해단순방사선검사가필요하고추가적으로골주사검사나자기공명영상등의영상의학적검사는족부의신경종이나신경을누르는공간점유병소 (space occupying lesion) 가있는경우제한적으로시행할수있다. 16) 신경전도검사를시행하여말초신경병의존재여부, 침범범위와중증도를객관적으로평가할수있으며주된병리기전이 축삭성 (axonal) 인지탈수초성 (demyelinating) 인지를알수있다. 그러나신경전도검사는수초가잘형성된굵은신경섬유의기능만관찰할수있기때문에가는신경이선택적으로손상된경우에는아무리증상이심해도신경전도검사에서는정상소견을보인다. 1) 가는신경만손상된경우에는 C-신경섬유의기능을평가할수있는땀분비축삭반응검사 (quantitative sudomotor axon reflex test) 를포함한자율신경기능검사가도움을줄수있다. 17) 치료 말초신경병의가장흔한증상은통증으로알려져있으며 1,10,18) 일차적으로는통증을조절하는약물을사용한다. 신경병통증은말초나중추통각전달체계의감작화, 손상된신경말단에서의이소성방전, 척수내에서통각과촉각을매개하는신경분포의재배치, 내인성진통조절의억제등그원인이다양하므로원인질환에따라서약제를선택하기보다는증상을초래하는기전에따라약물을선택하는것이효과적이다. 19) 신경병통증은매우치료가어려운증상이므로치료전환자에게치료효과, 약물과관련된부작용을충분히설명하여야한다. 우울증이나수면장애가동반된경우에는항우울제를우선고려할수있고불안장애가있는경우에는 pregabalin이효과적이고녹내장, 자율신경계이상, 심장질환이있는경우는삼환계항우울제 (tricyclic antidepressant, TCA) 는피하는것이좋고경련성질환이있는경우에는 tramadol은주의하여야한다. 1,19) Amitriptyline을포함한 TCA는지속적인통증이나작열통에모두효과적이어서가장널리처방되지만입마름, 졸림, 변비, 안압상승, 요로폐색등의항콜린작용에의한부작용이있어서 65세이상노인, 갑상선기능항진증, 녹내장증, 전립선비대증환자에게서는신중히투여하여야한다. 당뇨병성신경병통증을비롯하여대상포진후통증과중추성통증등거의모든신경병성통증에효과적이다. 사용방법은 10 mg을자기전에투여하는방법으로서서히증량하는것이좋으며필요에따라서 20-150 mg/d로유지한다. 심각한심장부정맥이발생할수있으므로급성심근경색의회복기이거나 monoamine oxidase를복용중인환자에게는투여하지말아야하며 nortriptyline은비교적부작용이적어안전하게사용할수있다. 1,19-21) 세로토닌-노르에피네프린재흡수억제제 (serotonin norepine-phrine reuptake inhibitor) 는 TCA에비해안전하게사용할수있다. Venlafaxine, duloxetine, milacipran이여기에해당하며, 당뇨병신경병통증에는 duloxetine이보험급여가가능하다. 1) 항경련제중 gabapentine과 pregabalin이신경병통증에주로사용되며지속적인자발통과이질통에모두효과적이다. Gabapentine의일반적인투여용량은 900-3,600 mg/d로투여개시약 2주째부터효과가나타나며반감기가짧아 3회분복이필요하
307 Neurogenic Pain Disorder in the Foot and Ankle: Peripheral Neuropathy 고약물상호작용이나심각한부작용이적으나졸음, 현기증, 무기력감, 말초부종이약물을빠르게증량한경우나타날수있다. Pregabalin은 gabpetine과비교하여생체이용률이약 6배정도높아빨리목표농도에도달하는장점이있으며일반적으로 75-150 mg/d로시작하여증량하는데최대허용용량은 600 mg/d이다. 10,20) 국내에서는당뇨병신경병통증, 대상포진후신경통, 복합부위통증증후군, 섬유근육통, 암성통증, 척추수술후통증에보험인정을받았으며최근당뇨병환자에서 thioctic acid와병용처방하는경우에도보험인정을받게되었다. 1) 아편유사제 (opioids) 는아편유사제수용체를통해통증경감효과를나타내며이질통에특히효과를보인다. 변비, 오심, 구토, 어지럼증, 졸림, 약물의존성이발생할수있으며, oxycodone controlled release은당뇨병성신경통증과대상포진후통증에효과적이고 10-100 mg 하루 2회복용하며 tramadol은다른약물에비해의존성이적으며 50-400 mg/d 사용한다. Acetaminophen과 tramadol 병용투여할수있다. 1,19-21) 국소도포제로는캡사이신이있으며피부의캡사이신수용체를지속적으로자극하여신경전달물질을고갈시켜서진통효과를나타내고작열통, 감각부전, 칼로베는듯한통증등의전형적인 C 섬유신경병증에주로사용한다. 19-21) 말초신경병으로인해발생하는족부의변형, 궤양및샤르코씨관절증은치료는통증치료와병행하여치료하여야하며수술적인변형의교정, 아킬레스연장술을통한전족부의압력의감소를통해궤양의발생을예방할수있다. 16,22,23) 샤르코씨관절증이병발한경우에는초기에는전접촉석고고정을이용하여변형의진행을막을수있으며관절고정술을시행하여안정적이고발바닥으로지면보행이가능하게할수있다. 6-8,24) 또한, 약물로잘반응하지않는말초신경병의경우에는선택적으로침범된신경의감압술을시행할수있다. 25,26) 결론 족부및족관절에서가장흔히볼수있는말초신경병은당뇨병과연관이있는경우가가장많으나류마티스관절염, 유전적질환, 대사질환, 독성물질, 혈관염등다양한원인에의해일어날수있으므로말초신경병의원인에대한검사를시행한후환자의통증을치료하기위한약물치료를시행하고동반된변형이나궤양, 샤르코씨관절증에대한수술적인치료를병행하는것이환자의삶을향상시킬수있을것으로생각된다. CONFLICTS OF INTEREST The authors have nothing to disclose. REFERENCES 1. Oh J. Peripheral neuropathy. Korean J Med. 2016;90:394-401. 2. Kim BJ, Park KW. Peripheral neuropathy in the elderly. J Korean Geriatr Soc. 2001;5:9-17. 3. Moon J, Kim SB. Ultrasonographic findings in peripheral neuropathy. Korean J Med. 2015;89:644-53. 4. Smith AG, Bromberg MB. A rational diagnostic approach to peripheral neuropathy. J Clin Neuromuscul Dis. 2003;4:190-8. 5. Johannsen L, Smith T, Havsager AM, et al. Evaluation of patients with symptoms suggestive of chronic polyneuropathy. J Clin Neuromuscul Dis. 2001;3:47-52. 6. Grear BJ, Rabinovich A, Brodsky JW. Charcot arthropathy of the foot and ankle associated with rheumatoid arthritis. Foot Ankle Int. 2013;34:1541-7. 7. Bariteau JT, Tenenbaum S, Rabinovich A, Brodsky JW. Charcot arthropathy of the foot and ankle in patients with idiopathic neuropathy. Foot Ankle Int. 2014;35:996-1001. 8. Myers TG, Lowery NJ, Frykberg RG, Wukich DK. Ankle and hindfoot fusions: comparison of outcomes in patients with and without diabetes. Foot Ankle Int. 2012;33:20-8. 9. Mold JW, Vesely SK, Keyl BA, Schenk JB, Roberts M. The prevalence, predictors, and consequences of peripheral sensory neuropathy in older patients. J Am Board Fam Pract. 2004;17:309-18. 10. Klein SE, Chu J, McCormick JJ, Johnson JE. Evaluation of peripheral neuropathy of unknown origin in an outpatient foot and ankle practice. Foot Ankle Int. 2015;36:1058-63. 11. James JS, Page JC. Painful diabetic peripheral neuropathy. A stepwise approach to treatment. J Am Podiatr Med Assoc. 1994;84:439-47. 12. Won JC, Park TS. Recent advances in diagnostic strategies for diabetic peripheral neuropathy. Endocrinol Metab (Seoul) 2016;31:230-8. 13. Dros J, Wewerinke A, Bindels PJ, van Weert HC. Accuracy of monofilament testing to diagnose peripheral neuropathy: a systematic review. Ann Fam Med. 2009;7:555-8. 14. Ha BK, Kim BG, Kim DH, et al. Relationships between Brachial-ankle pulse wave velocity and peripheral neuropathy in type 2 diabetes. Diabetes Metab J. 2012;36:443-51. 15. England JD, Gronseth GS, Franklin G, et al. Evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review). Muscle Nerve. 2009;39:116-25.
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309 pissn : 1226-2102, eissn : 2005-8918 Symposium J Korean Orthop Assoc 2017; 52: 305-309 https://doi.org/10.4055/jkoa.2017.52.4.305 www.jkoa.org 족부족관절에서신경성통증이상 족부족관절주위의신경병성통증질환 : 말초신경병 김학준 박영환 김수현 고려대학교구로병원정형외과 족부및족관절에흔히관찰되는말초신경병은당뇨병과관련이있는경우가가장흔하지만류마티스관절염, 대사성질환, 유전질환, 독성물질등다양한원인이존재한다. 말초신경병의주된증상은통증이지만감각이상, 균형감각이상, 근력저하등의신경학적증상이외에도족부의변형이나신경병성관절증이나타나기도한다. 말초신경병의원인을알아내기위해서는환자의병력청취가가장중요하며일반적인신경학적검사에추가적으로침통각검사, 진동지각, 10 g 단섬유압각검사및발목반사검사를시행하여야한다. 특히족부에서는관절의변화와족부의변형정도를관찰하기위한방사선사진이필수적이다. 말초신경병의존재유무, 침범정도, 중증도등을평가하기위한신경전도검사가필요하다. 당뇨병성신경병의경우는혈관의폐색에대한검사가필요하다. 말초신경병의치료는원인이되는질환의내과적치료가선행되어야하겠지만원인을알수없는경우가있으므로주로통증에대한약물치료가우선적으로고려되어야한다. 약물치료는항우울제, 항경련제, 마약성진통제, 도포제등이있으며증상을초래하는기전에따라서약제를사용하여야한다. 족부의변형이나신경병성관절증이동반된경우에는변형교정, 전접촉석고고정, 관절유합술등의수술적인치료가필요할수있으며선택적으로침범된신경의감압술을시행하기도한다. 색인단어 : 족관절, 족부, 말초신경병, 진단, 치료 접수일 2017 년 5 월 8 일수정일 2017 년 6 월 5 일게재확정일 2017 년 6 월 27 일책임저자김학준 08308, 서울시구로구구로동로 148, 고려대학교구로병원정형외과 TEL 02-2626-3090, FAX 02-2626-1163, E-mail dakjul@korea.ac.kr 대한정형외과학회지 : 제 52 권제 4 호 2017 Copyright 2017 by The Korean Orthopaedic Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.