원저 당뇨병환자에게동반된손목굴증후군의임상적특징 울산대학교의과대학신경과학교실, 경북대학교의과대학신경과학교실 a 김선영고민수권지현서정규 a Clinical Characteristics of Carpal Tunnel Syndrome in Patients With Diabetes Sun-Young Kim, MD, Min-Soo Ko, MD, Jee-Hyun Kwon, MD, Chung-Kyu Suh, MD a Department of Neurology, University of Ulsan College of Medicine, Ulsan, Korea Department of Neurology a, Kyungpook National University School of Medicine, Daegu, Korea Background: The clinical symptoms and signs of carpal tunnel syndrome (CTS) were investigated in patients with diabetes. Methods: The nondominant hands of 105 consecutive patients with diabetes or CTS were divided into three groups: diabetic CTS, diabetic non CTS, and nondiabetic CTS. The symptoms of CTS (pain, paresthesias, numbness, awakening, weakness, and clumsiness) were scored using the Global Symptom Score. The following signs of CTS were evaluated: Tinel s sign, Phalen s sign, thenar atrophy, and weakness of the abductor pollicis brevis (APB). The severity of the diabetic neuropathy was evaluated using the Michigan Diabetic Neuropathy Score. The score on the neuropathy scale, number of nerves involved, and the score for each CTS symptom and sign were compared among the groups. Results: The duration of diabetes was longer (p=0.000) and diabetic polyneuropathy was more severe (p=0.014) in the diabetic CTS group than in the diabetic non CTS group. The mean scores for pain and paresthesias were lower in the diabetic CTS group than in the nondiabetic CTS group (p=0.047 and p=0.049, respectively), whereas the mean scores for numbness and weakness did not differ significantly between these two groups (p=0.528 and p=0.638, respectively). In addition, APB weakness was more frequent whereas Phalen s sign was less frequent in the diabetic CTS group than in the nondiabetic CTS group (p=0.002 and p=0.02, respectively). Conclusions: Patients with diabetic CTS complained less of pain and paresthesias, but their intrinsic hand function did not differ significantly from that of patients with nondiabetic CTS. J Korean Neurol Assoc 28(4):277-282, 2010 Key Words: Carpal tunnel syndrome, Diabetic polyneuropathy, Neuropathy scale, Tinel s sign, Phalen s sign, Paresthesias 서론 손저림증상은당뇨병성다발신경병증및손목굴증후군환자모두에게나타날수있는증상으로신경전도검사를시행하는가장흔한이유중하나이다. Received April 30, 2010 Revised July 13, 2010 Accepted July 13, 2010 *Sun-Young Kim, MD Department of Neurology, Ulsan University Hospital, Jeonha 1-dong, Dong-gu, Ulsan 682-060, Korea Tel: +82-52-250-8860 Fax: 82-52-250-7080 E-mail: biggirl77@medimail.co.kr 손목굴증후군은정중신경의압박성신경염으로손에운동및감각장애를일으킬수있는질환이다. 모든형태의압박성신경염중가장흔하게발생하며당뇨병환자에게발생할수있는단일신경병중에서도가장흔하다. 1-3 손목굴증후군의위험인자는외부적원인, 내부적원인그리고신경자체의원인으로나눌수있다. 외부적원인으로는손목굴내압력을증가시킬수있는관절염, 염증, 건막염및지방종을비롯한섬유종, 혈우병, 백혈병또는항응고제에의한출혈등이있으며, 내부적원인으로는신경내에발생하는종양등이있다. 신경자체의원인으로는당뇨, 알코올중독, 비타민결핍그리고독성노출등을그원인으로들수있다. 3 J Korean Neurol Assoc Volume 28 No. 4, 2010 277
김선영고민수권지현서정규 당뇨병과손목굴증후군의연관성에대해서는아직까지논란이많은상태이나당뇨병환자들에게, 특히당뇨병성다발신경병증이있을경우손목굴증후군이흔히동반된다고알려져있으며, 당뇨병자체가손목굴증후군을일으키는중요한위험인자라고주장하는학자도있다. 4 일반적으로손목굴증후군의유병률은약 2~3% 인반면, 5,6 당뇨병환자에서손목굴증후군의유병률은전세계적으로 1.3~33.7% 까지다양하며, 7,8 국내연구에서는각각 16.2%, 44.0% 로보고된바있다. 9,10 당뇨병환자가일반인에비해손목굴증후군의유병률이높은것으로알려져있으나, 이를임상적으로나전기생리학적으로구분하는뚜렷한진단기준은없다. 11,12 당뇨병성다발신경병증에동반된손목굴증후군을진단하기위한여러전기진단학적검사방법들이제시되고그유용성이강조되고있다. 12,13 그러나 Perkins 등 11 은당뇨병성다발신경병증이동반된손목굴증후군환자들과일반손목굴증후군환자들, 그리고다발신경병증이동반되지않은손목굴증후군을가진당뇨병환자등각각의군에서전기생리학적인감별점을찾기는어려웠다고하였고, 손목굴증후군을진단하는데쓰이는여러가지전기생리학적인결과가손목굴증후군보다는다발신경병증의상태를더민감하게반영하므로치료할때전기생리학적결과에의존해서는안된다고주장하였다. 앞서언급한대부분의연구들 4,9-11,13,14 이당뇨병환자에서임상적으로손목굴증후군을진단하고전기생리학적결과를비교분석하였으나전기생리학적으로확진된손목굴증후군환자들의임상적특징을세부적으로분석한연구는드물었다. 따라서저자들은당뇨병이있으면서전기진단검사를통하여손목굴증후군으로진단한환자들의임상적특징및징후를분석하고, 이를일반손목굴증후군환자들과비교하고자하였다. 또한당뇨병환자에게서손목굴증후군이발병한군과그렇지않은군사이의당뇨병성다발신경병증의정도및유병기간에차이가있는지알아보았다. 대상과방법대상 본연구는 2007 년 8월부터 2008 년 12월까지손저림으로전기생리학적검사를받은환자중당뇨가있는환자들을연속적으로모아진행하였다. 대상군은당뇨병환자중전기진단법으로손목굴증후군으로진단한군 (Diabetic-CTS group) 과손목굴증후군으로진단하지않은군 (Diabetic-non CTS group) 으로나누었다. 또한당뇨병없이손목굴증후군으로진단한환자들 (Non-diabetic CTS group) 을대조군으로하였다. 모든환 자에게손목굴증후군의가장흔한위험인자인반복적인작업으로인한미세한손목손상의원인을배제하기위해비우세손만을대상으로하였으며, 당뇨이외의다른원인으로생각되는다발신경병증이있거나, 목신경뿌리병증또는허리신경뿌리병증이있는경우는본연구에서제외되었다. 또한, 당뇨병환자중신경전도검사상정중감각또는운동신경의전위가전혀나오지않는경우는아주심한손목굴증후군에의한것인지아니면당뇨병성말초신경병증에의한것인지감별이어려워제외하였다. 각군마다 35명이모집되어총 105 명의환자를대상으로각각문진, 이학적검사및전기진단학적검사를시행하였다. 전기진단학적검사장비는 Medelec Synergy (VIASYS/London /UK) 기기를이용하였고, 검사실의실내온도는 20 에서 24 사이로유지하였다. 손목굴증후군은정중신경말단부에간헐적또는지속적인무감각이나작열통또는근력및감각이상을호소하는사람으로서, 다음두가지중하나를만족하는경우로하였다. 첫째, 정중신경에대한신경전도검사시종말잠복기가운동신경은 4.2 msec 이상, 감각신경은 3.3 msec 이상인경우모두를만족할때, 둘째, 정중신경 -척골신경종말잠복기를비교했을때잠복기의차이가당뇨병이없는군은 0.5 ms 이상, 15 당뇨병이있는군은 0.4 ms 이상 14 인경우로정하였다. 첫번째기준은본근전도실에서 30명의정상인을기준으로시행한신경전도검사상평균치와표준편차를기준으로하였다. 통상적인방법외에종말잠복기비교방법 (comparison study) 을추가하여이를통해앞서제시한두가지진단기준모두를만족시키지는못하나손저림이있었던환자들에서경증또는잠복기손목굴증후군을감별하고자하였다. 자극은통상적인신경전도검사법에따라시행하였으며감각신경은역방향으로자극하였고잠복기차이는네번째손가락에고리전극을사용하여정중신경및척골신경각각의주행경로에따라활성전극에서 14 cm 떨어진근위부를자극하여구하였다. 당뇨병환자의경우다발신경병증을진단하기위해사지에대한신경전도검사와문진및신경학적검사를시행하였다. 당뇨병환자들의다발신경병증을좀더객관적으로진단하고그중증도를평가하기위해 Michigan Diabetic Neuropathy Score (MDNS) 16 를적용하였다. 이는양하지에서진동감각과통각, 양측상하지의근력및심부건반사를포함하는신경학적검사점수와신경전도검사 ( 장딴지신경, 종아리신경, 정중운동및감각신경, 척골감각신경 ) 에서이상소견을보이는신경의개수에따라신경병증의정도를구분한다. 신경학적검사항목은좌측, 우측각각감각증상 ( 진동각, 10 g filament test, 엄지발가락 Pin prick test) 과근력측정 ( 손가락뻗히기, 엄지발가락뻗히 278 대한신경과학회지제 28 권제 4 호, 2010
당뇨병환자에서동반된손목굴증후군의임상적특징 기, 발목굽히기 ), 심부건반사 ( 두갈래근반사, 세갈래근반사, 무릎반사, 아킬레스반사 ) 등을시행하여정상 0, 감소 1, 비정상 2, 완전이상 3점으로점수를매기고총 46점을만점으로한다. MDNS score 및신경전도검사상이상소견을보이는신경의개수에따라다발신경병증의정도를 0기 ( 다발신경병증이없는경우 ), 1기 ( 경미한다발신경병증 ), 2기 ( 중등도의다발신경병증 ), 3기 ( 심한다발신경병증 ) 로분류하였다. 모든환자의손저림증상정도를객관적으로평가하기위해손목굴증후군의증상에민감하다고알려진 Global Symptom Score (GSS) 17 를사용하였다. 이는통증, 저린감, 무딘감등을강도, 빈도및지속시간등으로세분화하여각 10점, 수면중깨어나는빈도에따라 10점, 손근력약화, 미세한조작시둔함을각 5점만점으로하여총 6개항목, 50점만점으로한다. GSS 는손목굴증후군환자의증상을객관적으로측정하는데쓰이는도구이며주로수술후경과관찰에자주이용되고있다. 손목굴증후군환자의특징적징후인티넬징후, 팔렌징후, 엄지두덩위축및단무지외전근의근력약화를한사람의신경과전문의가신경학적진찰을통해확인하였다. 통계적검증은 SPSS 15.0 (SPSS Inc., Chicago, Illinois, USA) 프로그램을사용하여, 각군간나이, 성별및유병기간, 비만지수의차이점을 t-검정, 카이제곱검정또는일원배치분산분석검정등을통해분석하였다. 당뇨환자군간의신경병증척도의차이를검증하기위해교차분석을사용하였다. 세군에서나타나는손목굴증후군의임상증상및징후를비교하는데있어범주형자료인경우교차분석을, 연속형자료인경우나이와성별을보정한단변량분산분석 (ANCOVA) 을시행하였다. 최 종적으로손목굴증후군에서관찰되는임상증상에대한세군각각의차이를비교하기위해사후검정 (post hoc comparison) 을시행하였다. 통계적유의수준은 P<0.05 로하였다. 결과 일반손목굴증후군환자군과손목굴증후군이동반된당뇨환자군그리고일반당뇨환자군사이에성비및비만도의차이는없었으며, 평균연령은각각 53세, 59세, 59세로당뇨병이있는두군에서나이가더많았으나 (p=0.032), 손목굴증후군이동반된당뇨군과동반되지않은당뇨군사이의차이는없었다. 당뇨이환기간은손목굴증후군이동반된당뇨병환자군이 12.23 년으로일반당뇨병환자군의 5.54 년에비해훨씬길었다 (p=0.000) (Table 1). 손목굴증후군이동반된당뇨병환자군이손목굴증후군이동반되지않은당뇨병환자군에비해전기진단검사로손상이확인된신경의평균개수가더많았으며 (p=0.031) 신경병증의정도도더심하였다 (p=0.014) (Table 1). 세군각각의임상징후를비교한결과, 팔렌징후및단무지외전근위약이통계적으로유의한차이가있었다 (p=0.023, p=0.002). 손목굴증후군이동반된당뇨환자들은팔렌징후양성을보이는빈도가일반수근관증후군환자들에비해적었으나일반당뇨환자들에비해서는많았으며, 단무지외전근위약빈도는일반손목굴증후군환자및일반당뇨환자들에비해더많았다. 엄지두덩의위축을보이는빈도는두그룹에서각각 1 명, 4명으로차이가있었으나대조군과비교시통계적인차이 Table 1. Demographics and neuropathy status among 3 groups Non-diabetic CTS Diabetic CTS Diabetic non CTS Demographic Data Age, yr, mean (SD) 53.17 (9.83) 59.23 (12.03) a 59.03 (10.37) a 0.032 Sex, %, female 34.3 40 57 0.321 DM duration, yr, mean (SD) 12.23 (8.29) b 5.54 (6.41) 0.000 BMI 24.03 (3.06) 23.78 (2.65) 22.89 (2.65) 0.254 Number of nerve involvement 0, number (%) 5 (14.3) a 16 (45.7) 0.031 1, number (%) 5 (14.3) a 6 (17.1) 2, number (%) 9 (25.7) a 8 (22.9) 3, number (%) 5 (14.3) a 2 (5.7) 4, number (%) 5 (14.3) a 2 (5.7) Neuropathy scale Stage 0, number (%) 10 (28.6) a 22 (62.9) 0.014 Stage 1, number (%) 9 (25.7) a 8 (22.9) Stage 2, number (%) 10 (28.6) a 3 (8.6) Stage 3, number (%) 6 (17.1) a 2 (5.7) Significant difference between patients and controls by t test, a p<0.05, b p<0.01. p J Korean Neurol Assoc Volume 28 No. 4, 2010 279
김선영고민수권지현서정규 Table 2. Comparison of clinical symptoms and signs among 3 groups Clinical signs Non-diabetic CTS Diabetic CTS Diabetic non CTS p Tinel sign, frequency 11 12 6 0.247 Phalen sign, frequency 11 7 a 2 0.023 a Thenar atrophy, frequency 1 4 1 0.361 APB weakness, frequency 11 13 a 4 0.002 a Clinical symptoms Pain, mean (SD) 3.40 (3.90) 2.03 (3.54) 1.09 (2.42) 0.009 b Paresthesia, mean (SD) 5.91 (2.83) 4.86 (3.07) 3.20 (2.71) 0.000 b Numbness, mean (SD) 2.91 (3.61) 2.94 (3.74) 1.26 (2.55) 0.013 a Awakening, mean (SD) 2.57 (2.97) 1.97 (3.09) 0.91 (2.44) 0.038 a Weakness, mean (SD) 1.09 (1.67) 1.06 (1.55) 0.29 (0.98) 0.012 a Clumsiness, mean (SD) 1.11 (1.62) 0.94 (1.61) 0.71 (1.81) 0.277 Total GSS, mean (SD) 17.00 (12.58) 13.80 (12.91) 7.29 (9.26) 0.000 b Significant difference between patients and controls by χ 2 or ANCOVA test, a p<0.05, b p<0.01. 3.4 * * 2.03 1.09 * * 5.91 4.86 3.2 Non-diabetic CTS Diabetic CTS Diabetic non-cts 2.91 2.94 * * 1.26 2.57 1.97 0.91 * 1.09 1.06 1.11 0.94 0.71 0.29 17 13.8 * Pain Paresthesia Numbness Awakening Weakness Clumsiness Total GSS 7.29 Figure. Comparison of clinical symptoms of CTS among three groups (post hoc comparison). Significant difference between three groups by post hoc comparison p<0.05, p<0.01. 는없었다 (Table 2). 세군에서 GSS 각항목의점수를분석한결과를 Figure 에도표로나타내었다. 손목굴증후군이동반된당뇨병환자군에서관찰된손의통증및저린감점수는각각평균 2.03 점, 4.86 점으로일반손목굴증후군환자들에게관찰된 3.4 점, 5.91 점에비해서낮았다 (p=0.047, p=0.049). 두군간의무감각, 밤에깸, 근력약화, 둔함및총 GSS 점수에는차이가없었다 (Fig.). 손목굴증후군이동반된당뇨환자들은손저림, 무감각, 근력약화및총 GSS 항목에서일반당뇨환자에비해높은점수를보였다 (p=0.014, p=0.023, p=0.018, p=0.014) (Fig.). 고찰 당뇨병환자에게손목굴증후군은다발신경병증다음으로가장흔한신경계합병증으로, 18 당뇨병자체가손목굴증후군의위험성을증가시킨다고주장하는학자들은첫째, 당뇨병환자 는흔히비만, 노화, 높은체질량지수등대사문제를동반할가능성이높은점, 19 둘째, 당뇨병환자에서듀파이렌구축, 굴곡건건초염, 관절운동제한같은결체조직의변화가흔히동반되는점, 8,20 셋째, 당뇨병환자의신경자체가압박및신경외부압력에취약한점 21 등을근거로제시하고있다. 당뇨병환자에서손목굴증후군은당뇨병의유병기간이길수록, 여성, 고령, 22 체질량지수가높을수록, 23 다발성신경병증이심할수록 4 발생이증가한다. 당뇨병성말초신경병증이손목굴증후군의위험성을증가시키는기전으로는첫째, 당뇨성다발신경병증은원위부에서부터시작되는특징 (length-dependent axonopathy) 이있어정중신경원위부가초기에침범될가능성이높고둘째, 고혈당에의한신경내솔비톨 (sorbitol) 의축적때문에신경내단백질의당화 (glycosylation) 와폴리올경로활성화등에의한대사장애, 신경으로유입되는혈류감소및신경내혈류저항의증가에의한신경내허혈 (endoneural ischemia) 등이정중신경에영향 280 대한신경과학회지제 28 권제 4 호, 2010
당뇨병환자에서동반된손목굴증후군의임상적특징 을미치는점등을들수있다. 11 본연구에서는손목굴증후군이동반된당뇨병환자는손목굴증후군이동반되지않은당뇨병환자들에비해당뇨병의이환기간이길었으며, 전기진단검사로확인한손상된신경의개수및신경염의척도가높았다. 이는당뇨병성다발신경병증이손목굴증후군의위험성을증가시키는위험인자라고주장한연구들과일치하는결과이다. 그러나나이, 체질량지수및성비에따른차이는없었다. 손저림증상은있으나전기진단검사에서정중신경에이상이없었던당뇨병환자들은이것이초기의당뇨병성신경병증또는임상적으로정의된당뇨병성신경병증 (clinically defined diabetic polyneuroapthy) 으로생각하는데, 이를뒷받침하는근거로실제로이들의당뇨병성말초신경병증의정도가정중신경에이상이있었던군에비해경미하며, 유병기간이짧았음을들수있다. 이는당뇨병초기에일어날수있는 임상소견-전기생리학적해리 (clinic-electrophysiological dissociation) 를반영하는결과라할수있다. 해부학적으로정중신경은손목굽힘인대와함께횡수근인대밑을통과하며, 손목굽힘에의해약 9.6 mm 정도그리고손목펼침에의해그보다덜움직이며, 24 신경섬유내의결체조직을둘러싼막은이러한신경의움직임에중요한역할을한다. 만성적인압박에의한결체조직의섬유화및 mesoneurium 손상에의한신경과주위조직간의유착은이러한신경의매끄러운마찰을방해하고이를통해손목굴증후군의여러증상이나타나게된다. 25 Mackinnon 25 이제시한신경압박의단계에따른임상증상및전기생리학적소견을요약하면, 1단계신경손상 (neuropraxia) 은전기생리학적으로전도차단 (conduction block) 과함께분절탈수초 (segmental demyelination) 가일어나는시기로축삭 (axon) 은손상되지않는다. 이시기에손목굽힘팔렌징후검사와같은유발검사를통해손목굴내압력을증가시키면손저림증상이악화되며진동및촉각변화등주로굵은감각신경의손상을시사하는증상들이나타난다. 손목굴증후군의대표적유발검사인팔렌검사의민감도및특이도는각각 68%, 73% 정도로알려져있으며, 주로경증및중등도신경손상시잘관찰되며심한손상에는오히려적게관찰된다. 3 2단계신경손상즉, 축삭절단 (axonotmesis) 은주로축삭손상을동반하고, 신경섬유의재생이관찰되며, 티넬시험양성, 근전도검사상세동 (fibrillation) 및두점식별능력변화등이주로관찰된다. 정중신경에물리적인자극을가하여전기쇼크가오는듯한통증을유발하는티넬징후시험은민감도보다는특이도가높은검사법으로 (50% 대 77%), 재생신경섬유 (regenerating nerve fiber) 가있을때주로양성반응을보이 기때문에, 중등도이상의손목굴증후군환자들에게자주동반된다. 26-28 1단계에서 2단계로신경손상이진행되면환자는평상또는유발검사시나타나는저린감은줄어들면서, 무감각이오히려심해지고, 간간이손근력의약화를보이기도한다. 3단계신경절단 (neurotmesis) 은축삭손상및내신경막 (endoneurium) 의손상에의한것으로이시기에환자는지속적인무감각을호소하며, 엄지두덩의위축을동반하기도한다. 이신경손상은매우심해완전회복이어려울수도있다. 엄지두덩위축은아주심한손목굴증후군상태를반영하는소견으로, 한연구에따르면전체손목굴증후군전체환자의 12% 정도에서만관찰할수있을정도로민감도는떨어지나, 특이도는 94% 정도로높다. 3 본연구에서는당뇨병에동반된손목굴증후군환자들이일반손목굴증후군환자들에비해손의통증및저린감을비교적덜호소하였으며, 팔렌징후가적은빈도로나타났다. 그러나손의무감각, 밤중에깸, 근력약화및둔함등의점수는두군간에의미있는차이가없었고, 단무지외전근의근력약화빈도는당뇨병에동반된손목굴증후군환자들에게서많이나타났다. 따라서당뇨병에동반된손목굴증후군은병태생리학적으로주로 2단계이상의신경손상에가깝다고판단하였다. 이에대한근거로이들이일반적당뇨병환자들에비해당뇨병유병기간이길고당뇨병성말초신경병증의정도가심해서감각역치 (sensory threshold) 가증가되어같은정도의신경손상에도통증이나저린감이비교적덜한것을제시할수있겠다. 이는 streptozocin 을이용한당뇨병쥐모델을통한연구에서, 당뇨병유병기간이짧은쥐들은통증이동반된신경염 (painful neuropathy) 이나타나지만, 유병기간이긴쥐들은오히려감각둔마 (insensate neuropathy) 신경염을보이는것과일치하는결과이다. 29 Sorensen 등도당뇨병성감각둔마신경염은당뇨병유병기간이길수록당뇨병성다발신경병증의정도가심할수록위험도가증가한다고하였다. 30 위결과들로미루어보아당뇨병에동반된손목굴증후군에서관찰되는정중신경의병태생리는포착성신경염초기에관찰되는물리적압박에의한분절탈수초 (segmental demyelination) 와당뇨병에의한축삭변성 (axonal degeneration) 이함께존재하는것이라하겠다. 본연구의제한점은첫째, 연구에포함된환자수가적어전체당뇨병환자를대변하기에한계가있으며, 둘째, 당뇨병이손목굴증후군에미치는영향을알기위해우세손을배제함으로써오히려증상이경하거나잠복기 (preclinical or dynamic) 단계의환자들이연구에주로참여하게되었다. 따라서손목굴 J Korean Neurol Assoc Volume 28 No. 4, 2010 281
김선영고민수권지현서정규 증후군에특징적인징후들이나타나는빈도가낮았으며, 총 GSS 점수또한다른연구에서제시한평균점수인 20-30 점에비해낮았다. 향후더많은수의당뇨병환자들을대상으로한연구가필요하겠다. 결론적으로, 당뇨병이동반된환자들은대사또는혈류역학적장애로인해여러신경에이상또는기능적장애가동반되며이로인해감각역치가높아져서일반손목굴증후군환자들에비해통증및저린감은덜하다. 그러나손의위약감및근력저하는일반손목굴증후군환자들과차이가없었으며일반당뇨병환자보다뚜렷하였다. 따라서당뇨병에동반된손목굴증후군환자들의치료에있어통증보다는손의기능에초점을맞추어야하겠다. 손의통증이나저림은손목굴증후군에상관없이당뇨병자체에의해서도나타날수있으므로손저림을호소하는당뇨환자들을진료할때자세한병력청취및신경학적검사를통해손목굴증후군을조기진단하여신경기능회복에도움을줄수있어야겠다. REFERENCES 1. Stamboulis E, Vassilopoulos D, Kalfakis N. Symptomatic focal mononeuropathies in diabetic patients: increased or not? J Neurol 2005;252:448-452. 2. de Krom MC, Kester AD, Knipschild PG, Spaans F. Risk factors for carpal tunnel syndrome. Am J Epidemiol 1990;132:1102-1110. 3. MacDermid JC, Doherty T. Clinical and electrodiagnostic testing of carpal tunnel syndrome: a narrative review. J Orthop Sports Phys Ther 2004;34:565-588. 4. Comi G, Lozza L, Galardi G, Ghilardi MF, Medaglini S, Canal N. 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