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1 Journal of Movement Disorders ORIGINAL ARTICLE Journal of Movement Disorders Vol. 1, No. 2, October 2008 Received September 26, 2008 Accepted October 13, 2008 특발성파킨슨병과다계통위축증의진단에있어서혈청항갑상선항체의신뢰도 성균관대학교의과대학삼성서울병원신경과학교실 이택준신희영윤원태이원용 Reliability of Serum Anti-thyroid Antibody Screening in the Diagnosis of Parkinson s Disease and Multiple System Atrophy Taek-Jun Lee, MD, Hee-Young Shin, MD, Won Tae Yoon, MD, Won Yong Lee, MD, PhD Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine Backgrounds: Ataxia associated with Hashimoto s thyroiditis autoantibodies has been reported as acquired cerebellar ataxia. However, relationship between anti-thyroid antibodies and cerebellar ataxia has not been clarified yet. Objectives: W e aim ed to analysis the relibility of serum anti-thyroid antibodies screening in the diagnosis of Parkinson s disease (PD) and multiple system atrophy (MSA). Method: We enrolled 105 patients with clinically diagnosed PD and 75 patients with probable M SA. Patients with PD were classified into 70 patients with early PD (Hoehn & Yahr stage I to II) and 35 patients with late PD (Hoehn & Yahr stage III to IV). In M SA, 28 patients were classified as MSA-p (parkinsonism predominant) and 47 MSA-c (cerebellar predominant). For analysis of thyroid function, serum free triiodothyronine (T3), free thyroxine (T4), anti-thyroglobuline (TG) antibodies and anti-m icrosomal antibodies were m easured. Cut-off level for abnormal titers of anti-thyroid antibodies were defiend as above 100 U/ml. Results: Abnormally high titer of serum anti-tg antibodies and anti-microsomal antibodies was more frequently observed in MSA than in PD (p=0.001 and 0.003, respectively). However, there was no significant difference in the frequency of abnormal titer either between M SA-c and M SA-p (p>0.05) nor between early PD and late PD (p>0.05). Am ong clinical param eters, only ataxia was correlated with both titer of anti-tg antibody and anti-microsomal antibody (p=0.007 and 0.002, respectively). Conclusion: These results suggest that high titer of anti-thyroid antibodies may be associated with M SA rather than PD and screening of serum anti-thyroid antibodies may be helpful for discrimiation of PD from MSA. However, anti-thyroid antibodies screening may not be helpful to differentiate M SA-c from M SA-p. Journal of Movement Disorders 1(2):75-81, 2008 Key Words: Anti-thyroid antibody, Cerebellar ataxia, Parkinson s disease, M ultiple system atrophy 서론 비가족성성인기발병소뇌퇴행 (non-familial adult onset cerebellar degeneration) 을일으키는원인은영양결핍, 부 종양증후군 (paraneoplastic syndrome), 저산소증, 중독, 고체온증등이잘알려져왔다. 그외에도갑상선기능저하증이소뇌퇴행을일으키는원인중하나로알려지고있다. Selim 등은 2001년에하시모토갑상선염 (Hashimoto s thy- Address for correspondence: Won Yong Lee, MD, PhD Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, , Korea Tel: , Fax: , neurolwy@skku.edu 75

2 Journal of Movement Disorders Vol. 1, No. 2, 2008 roditis) 에서소뇌기능의이상을보인 6명의환자를보고하면서갑상선호르몬의투여에도소뇌기능이상이호전이없음을기술하였다.[1] 따라서항갑상선항체가높은환자들에서의소뇌기능이상이면역매개성으로설명될수있음을지적하였다. 당시 6명의환자중한명은소뇌기능의장애이외에자율신경계이상을보였고, 추체로장애및파킨슨증을보여다계통위축증 (multiple system atrophy; MSA) 과유사한증상을보였다.[1] 또한 Mantu 는항갑상선항체가높은다계통위축증환자의경우, 항갑성선항체의상승과다계통위축증발병이연관성이있을것이라고하였으나아직명확하지는않다.[2] 신경계장애를보인환자들을대상으로항신경세포성 (antineuronal) 자가항체를조사한연구에서다계통위축증환자 10명중한명의환자에서조롱박세포 (Purkinje cell) 세포질반응성을발견하였다.[3] 이러한연구결과들을통해면역매개성병인론이자가면역성갑상선염뿐만아니라다계통위축증에도관여하며두질환에서모두나타날수있는소뇌기능이상을유발할수있을것으로추측할수있다. 그러나자가면역에관계하는다양한항체들을조사하여면역매개성병인론이다계통위축증발생에관여하는지에대한연구는현재까지없다. 한편, 파킨슨병 (Parkinson s disease; PD) 은다계통위축증과감별이어려울뿐아니라, 임상적으로갑상선기능저하증가진환자와유사한증상을보여서로감별하기힘든경우가있다.[4-6] 파킨슨병에서갑상선기능저하증이부수적으로병발할수있다는보고는있으나 [7] 자가항체와연관된면역매개성병인론과의관계는알려진바가없다. 따라서본연구는, 임상적으로진단된파킨슨병환자와다계통위축증환자에서항갑상선항체를포함한갑상선기능검사를시행하고, 항갑상선항체의이상이각환자군간에어떻게다른지, 또한다양한임상지표와항갑상선항체의이상소견사이에상관관계가있는지조사하여, 파킨슨병과다계통위축증에서면역매개성병인론과의연관성및항갑상선항체측정의타당성을알아보고자하였다. 대상과방법 1. 대상 본연구는운동질환자료등록 (Movement Disorder Registry) 을이용하여전향적으로조사하였다. 먼저, 2005년 1월부터 2005년 8월까지신경과외래를방문한환자들중널리알려진 파킨슨병과다계통위축증진단기준에따라 [8,9] 각각 probable PD, 및 probable MSA 를만족하는환자를대상으로하였다. 파킨슨병은 Hoehn & Yahr (H-Y) stage I, II인환자들을초기파킨슨병환자군 (early PD) 으로, H-Y stage III, IV인환자들을진행된파킨슨병환자군 (late PD) 으로, 다계통위축증의경우소뇌기능장애가주된증상인군 (MSA-c) 과, 파킨슨증상이주된군 (MSA-p) 으로정하였다. 이들중소뇌기능장애를유발할수있는감염성질환, 종양성, 부종양성질환, 혈관성질환, 영양겹핍, 과다한음주력및과거력상갑상선질환으로진단받거나치료받았던환자는연구대상에서제외하였고갑상선기능검사와항갑상선항체검사를시행하지않은환자도제외하였다. 이결과 180명 ( 평균연령 62±10, 남자 85명 ) 이선정되었는데각군별로는 early PD 70명 ( 평균연령 60±10, 남자 31명 ), late PD 35명 ( 평균연령 64±11, 남자 16명 ), MSA-c 47명 ( 평균연령 60±11, 남자 24명 ), MSA-p 28명 ( 평균연령 68±8.5, 남자 14명 ) 이조사되었다. 2. 방법 1) 임상지표의정의임상지표로추체로증후는족저반사혹은심건반사이상항진을동반하는경우로하였고, 소뇌기능장애는사지의운동실조, 의도진전, 보행실조등의증상이동반된경우로정의하였다. 자율신경계장애는반복되는기립시실신, 요실금, 대변실금, 도뇨를필요로하는요저류, 혹은지속적인발기부전의 5가지증상중최소한한가지이상인경우로정의하였다. 2) 갑상선기능및항갑상선항체평가대상환자에서혈중 triiodothyronine (T3), tetraiodothyronine (T4), thyroid-stimulating hormone (TSH), 및 thyroglobulin antibody (anti-tg antibody), anti-microsomal antibody검사를시행하였다. T3, T4, TSH 의기준범위는 T3 는 ng/dl, T4는 ng/dl, TSH는 uiu/ml이며, Thyroglobulin antibody (anti-tg antibody), anti-microsomal antibody 의분기값 (cut-off value) 은 100 U/mL로정의하였다. TSH, T4 수치가정상인환자는정상갑상선기능 (euthyroidism), 높은 TSH 수치와낮은 T4 수치를보인경우는임상적갑상선기능저하증 (clinical hypothyroidism), 낮은 TSH 수치와높은 T4 수치를보일때임상적갑상선기능항진증 (clinical hyperthyroidism), 높은 TSH 수치와정상 T4 수치일때무증상갑상선기능저하증 (sub- 76

3 Reliability of Serum Anti-thyroid Antibodies Screening in the Diagnosis of Parkinson s Disease and Multiple System Atrophy Taek-Jun Lee, et al. Table 1. Thyroid function test among the groups Early PD (n=70) PD Late PD (n=35) Euthyroidism 66 (94.3) 33 (94.3) 44 (93.6) 28 (100) NS a Sub hypot 2 (2.9) 0 (0) 3 (6.4) 0 (0) NS a Sub hypert 2 (2.9) 1 (2.9) 0 (0) 0 (0) NS a Clin hypot 0 (0) 0 (0) 0 (0) 0 (0) NS a Clin hypert 0 (0) 1 (2.9) 0 (0) 0 (0) NS a Value are number (percentage) of patients. Early PD; Hoehn & Yahr stage I, II, late PD; Hoehn & Yahr stage III, IV, MSA-c; multiple system atrophy, predominantly cerebellar, MSA-p; multiple system atrophy, predominantly parkinsonism, hypot; hypothyroidism, hypert; hyperthyroidism, a by Chi-square test, NS; not significant. MSA-c (n=47) MSA MSA-p (n=28) clinical hypothyroidism), 낮은 TSH 수치와정상 T4 수치를보인경우무증상갑상선기능항진증 (subclinical hyperthyroidism) 으로정의하였다. 3) 통계분석통계분석은 SPSS 11.01을이용하여성별, H-Y stage, 추체로증후, 소뇌기능이상, 자율신경계이상증상, 자율신경기능검사이상과같은범주형변수의분석은 Chi-square 검정을이용하였고, 나이, 증상발생나이, 질병경과시간과같은연속변수는 Student t 검정을이용하였다. 모든분석에서 p value가 0.05 미만일경우통계적으로유의한것으로판정하였다. 결 과 1. PD군 (early PD와 late PD) 과 MSA군 (MSA-c와 MSA-p) 에서갑상선기능비교 Table 2. Serum thyroglobulin and microsomal antibody abnormality in PD and MSA patients PD (n=105) MSA (n=75) TG ab 14 (13.3) 25 (33.3) a Micro ab 6 (5.7) 15 (20.0) a Value are number (percentage) of patients. PD; Parkinson disease, MSA; multiple system atrophy, TG ab; thyroglobulin antibody abnormality, Micro ab; microsomal antibody abnormality, a by Chi-square test. Table 3. Serum thyroglobulin and microsomal antibody abnormality in Early PD and Late PD patients early PD late PD (n=70) (n=35) TG ab 12 (17.1) 2 (5.7) NS a Micro ab 4 (5.7) 2 (5.7) NS a Value are number (percentage) of patients. early PD; Hoehn & Yahr stage I, II, late PD Hoehn & Yahr stage III, IV, TG ab; thyroglobulin antibody abnormality, Micro ab; microsomal antibody abnormality, a by Chi-square test, NS; not significant. 전체 180명의환자에서정상갑상선기능을보인환자는 171명 (95%), 임상적갑상선기능항진증을보인환자는 1명 (0.5%), 무증상갑상선기능저하증은 5명 (2.8%), 무증상갑상선기능항진증을보인환자는 3명 (1.7%) 이었으나임상적갑상선기능저하증을보인환자는없었다. 임상적갑상선기능항진증은 late PD에서보였고, 무증상갑상선기능저하증을보인환자들 5명중 2명은 early PD군에속하였고 3명은 MSA-c 군에속하였다. 무증상갑상선기능항진증을보인 3명의환자들은모두파킨슨병에속하였고그중 2명은 early PD였으며 1명은 late PD에속하였다 (Table 1). 2. PD군 (early PD와 late PD) 과 MSA군 (MSA-c와 MSA-p) 에서항갑상선항체비교전체환자 180명중 anti-tg antibody 의이상을보인환자는 39명 (21.7%) 이며 anti-microsomal antibody의이상을보인환자는 21명 (11.7%) 이었다. PD군에서 anti-tg antibody의이상을보인환자는 14명 (13.3%), MSA군에서는 25명 (33.3%) 으로, MSA군에서 anti-tg antibody의이상을보인환자가유의하게높았다 (p=0.001, Table 2). 또한 PD군에서 anti-microsomal antibody 의이상을보인환자는 6명 (5.7%), MSA군에서는 15명 (20.0%) 으로 anti-microsomal antibody의이상을보인환자가 MSA군에서유의하게높았다 (p=0.003, Table 2). Early PD군과 late PD군에서항갑상선항체를비교한결과에서는 early PD군에서 anti-tg antibody의이상을보인환자는 12명 (17.1%), Late PD군에서는 2명 (5.7%) 으로, 두군간에유의한차이는없었다 (Table 3). 또한 anti-microsomal antibody의이상을보인환자는 early PD에서 4명 (5.7%), late PD군에서 2명 (5.7%) 로두군간에유의한차이는없었다 (Table 3). MSA-c군과 MSA-p군에서항갑상선항체비교한결과에 77

4 Journal of Movement Disorders Vol. 1, No. 2, 2008 Table 4. Serum thyroglobulin and microsomal antibody abnormality in MSA-c and MSA-p patients MSA-c MSA-p (n=47) (n=28) TG ab 17 (36.2) 8 (28.6) NS a Micro ab 11 (23.4) 4 (14.3) NS a Value are number (percentage) of patients. MSA-c; multiple system atrophy, predominantly cerebellar, MSA-p; multiple system atrophy, predominantly parkinsonism, TGab; thyroglobulin antibody abnormality, Micro ab; microsomal antibody abnormality, a by Chi-square test, NS; not significant. 서는 MSA-c군에서 anti-tg antibody의이상을보인환자는 17명 (36.2%), late PD군에서는 8명 (28.6%) 으로, 두군간에유의한차이는없었다 (Table 4). 또한 anti-microsomal antibody의이상을보인환자는 MSA-c 군에서 11명 (23.4%), MSA-p군에서 4명 (14.3%) 으로두군간에유의한차이는없었다 (Table 4). 3. 항갑상선항체이상과임상지표와의관계 전체 180명의환자에서 anti-tg antibody 이상을보인 39명환자의나이 (62.59±9.97세), 발병연령 (58.20±13.99세), 이환기간 (20.58±18.29개월) 과정상을보인 141명환자의나이 (61.79±10.90세), 발병연령 (58.38±11.24세), 이환기간 (27.76± 33.60개월 ) 을비교해볼때유의한차이가없었다. 또한 antimicrosomal antibody 이상을보인 21명환자의나이 (62.38± 12.62세 ), 발병연령 (59.57±12.96세), 이환기간 (20.71±21.57 개월 ) 와, 정상을보인 159명환자의나이 (61.91±10.45세), 발병연령 (58.18±11.73세), 이환기간 (26.93±32.05개월) 을비교해볼때유의한차이가없었다. 또한, anti-tg antibody 및 anti-microsomal antibody 의이상유무에따라성별, 추체로증상및자율신경이상증상을비교분석해볼때양군간에유의한차이는없었다. 소뇌기능장애와비교분석해보면, 소뇌기능장애가있는 환자중 anti-tg antibody 이상이있는환자는 18명 (46.2%) 이고, anti-tg antibody가환자는 34명 (24.1%) 으로소뇌기능장애가있는환자에서 anti-tg antibody 이상이있을가능성이유의하게높았다 (p=0.007). 또한, 소뇌기능장애가있는환자중 anti-microsomal antibody 이상이있는환자는 12명 (57.1%) 이고, anti-microsomal antibody가정상인환자는 40명 (25.2%) 으로소뇌기능장애가있는환자에서 antimicrosomal antibody 이상이있을가능성이유의하게높았다 (p=0.002)(table 5). 고찰 본연구에서대다수의환자들은정상갑상선기능을가지고있었고, MSA 환자군에서 PD 환자군에비해항갑상선항체의높은수치를보이고있었다. 그러나 MSA를세분하여 MSA-c군과 MSA-p군에서비교하면유의한차이를발견할수없었다. 몇몇논문에서는 PD를가진환자들에서갑상선기능저하가간과될수있으므로 PD 환자들에서갑상선기능검사를하도록제안하고있다.[6,10-12] 본연구결과에서도임상적으로무증상이지만검사상갑상선기능저하를가지는 5명중 2명은 PD였고 3명은 MSA군에속하였다. MSA와갑상선질환의연관성을언급한외국의예를보면, 소뇌성운동실조를보인갑상선기능저하증환자의부검소견에서소뇌벌레 (vermis) 의전상부의퇴행성변화와교뇌배측, 가로교뇌섬유 (transverse pontine fibers), 중간및위소뇌각의위축소견이관찰되었다.[13] 환자의소견은 MSA에부합하는소견으로갑상선기능저하와 MSA와관련이있을수있음을보여주었으나, 이러한해부학적인변화와소뇌성운동실조와의관계에대하여는명확히제시할수는없었다.[13] 병리학적으로입증된 MSA환자에서위암과갑상선기능저하가있는환자가보고된예가있으며, 이러한예들은아직명확 Table 5. Clinical parameters of each antithyroid antibodies (+) and antithyroid antibodies (-) patients TG ab (+) TG ab (-) Micro ab (+) Micro ab (-) (n=39) (n=141) (n=21) (n=159) Age, year 62.59± ±10.90 NS b 62.38± ±10.45 NS b Onset, year 58.20± ±11.24 NS b 59.57± ±11.73 NS b Duration 20.58± ±33.60 NS b 20.71± ±32.05 NS b Male 15 (38.5) 70 (49.6) NS a 7 (33.3) 78 (49.1) NS a Pyramidal (+) 3 (7.7) 15 (10.6) NS a 3 (14.3) 15 (9.4) NS a Cbll (+) 18 (46.2) 34 (24.1) a 12 (57.1) 40 (25.2) a dysautonomia (+) 23 (59.0) 87 (61.7) NS a 15 (71.4) 95 (59.7) NS a Values are number (percentage) or mean±sd of patients. TG ab; thyroglobulin antibody, Micro ab; microsomal antibody, Onset; Onset of age, Pyramidal; pyramidal tract sign, Cbll; cerebellar sign, NS; not significant, a by Chi-square test, b by student t test. 78

5 Reliability of Serum Anti-thyroid Antibodies Screening in the Diagnosis of Parkinson s Disease and Multiple System Atrophy Taek-Jun Lee, et al. 하지않는 MSA와갑상선기능저하의관련을보여주는예들이다.[14] MSA의병인론에관하여는명확히알려진바는없는데, 상염색체우성으로유전하는양상의올리브교소뇌위축우세형인성인기발병하는척수소뇌실조증 (spinocerebellar ataxia) 의경우, 백혈구와배양된섬유아세포에서글루탐산탈수소효소 (glutamic acid dehydrogenase) 의결핍이확인된바있었다.[15] Gahring 등의연구에서는비가족성올리브교소뇌위축환자에서 AMPA형의글루탐산수용체에대한고역가의면역글로빈M 의존재를발견하였고, 이항체가배양된피질신경세포에의해발현된글루탐산수용체의아집단을직접적으로활성화한다는것을보여주었다. 이것은일부 MSA 환자에있어서글루탐산수용체에대한자가면역이신경세포의진행적이며, 선택적인소실에중요한역할을할수있음을보여주었다.[16] Polinsky 등의연구에서는 MSA 환자에서얻어낸뇌척수액의항체가쥐의청반 (locus ceruleus) 에서특이적반응을일으켰으며, MSA에서의퇴행성과정들이청반의신경에대한항체형성을일으키는항원의방출에의한것일수있음을보여주었으며, MSA의병인론적기전의하나로면역반응의가능성을제시하였다.[17] 신경퇴행성질환환자의뇌척수액에서항체의발견은지속적으로보고되고있는데, 저자의연구는이러한연구들을뒷받침하는추가적인연구로생각된다. 저자의연구에서파킨슨병과다계통위축증의임상지표중항갑상선항체이상과연관있는임상적지표는소뇌성운동실조증이었다. 이점은점액부종이나하시모토갑상선염과소뇌기능부전이연관있다는기존의보고에 [1,18] 부합하는소견으로생각되는데점액부종의환자의약 3분의 1에서소뇌기능장애가보고된바있으며, 이것은심박출량, 뇌혈류량, 뇌산소및당소비의저하등과같은뇌혈관성역동학과뇌대사의변화가주요한이유로생각된다. 또한이러한변화들은갑상선호르몬의투여에정상으로회복될수있다고알려져왔다.[18] 반면 Selim 등 [1] 은하시모토갑상선염환자에서갑상선호르몬투여에반응없는소뇌성운동실조를보고하면서, 소뇌기능이상의원인으로자가면역에의해일어남을제시한바있다.[1] 하시모토갑상선염과연관된자가면역이소뇌기능을일으키는기전은몇가지가제시되었는데, 하시모토갑상선염환자에서광범위한자가면역성반응이관찰되며, 소뇌의퇴행은확인되지않은항조롱박세포항체에의하여매개될수있다는것이다. 이러한경우자가면역성갑상선염은소뇌를침범할수있는전신적인자가면역질환의 존재를알리는하나의표지자역할을한다고할수있다. 또하나의가설은갑상선과소뇌의항원사이에면역학적교차반응이존재한다면, 항갑상선항체가특이적으로소뇌에영향을줄수있다는것이다. 아직하시모토갑상선염에서소뇌세포에대한항체의존재는알려지지않았으나, 가능성있는항체로글루탐산탈카르복실효소항체 (GAD-Ab) 가있다. 이효소의이상이올리브교소뇌위축환자의조직에서증명된바있었으며, GAD-Ab 가소뇌피질위축이있는일부환자에서발견된바있다.[1] Honnorat 등은높은수준의혈청 GAD-Ab과소뇌성운동실조와연관이있으며, 특히인슐린의존성당뇨병인여성인경우더욱관련이있음을보였다.[19] 마지막으로하시모토갑상선염과연관된소뇌성운동실조에관한가설은자가면역매개성의칼슘채널병증 (channelopathy) 이병인이라는것이다. 전압의존성칼슘통로를가진조롱박세포의조절이상이조롱박세포의퇴행과이에따른운동실조를야기하게되며, 갑상선중독성주기성마비, 칼슘통로질환및척수소뇌성실조증에서도자가면역성갑상선질환과조롱박세포형칼슘채널병의연관성이밝혀진바있다.[20] 이러한결과들은소뇌운동기능부전과자가면역이많은연관성을가진다는것을시사해주고있으며본연구의 MSA 에서나타난소뇌성운동실조가항갑상선항체이상과유의한관계를보이는결과를설명할수있다. 그러나 Polinsky 등의연구에서 MSA 환자 43명중뇌척수액쥐의신경조직에대한항체의반응성이청반에서 35명, 복측피개 (dorsal tegmentum) 에서 8명인데반해, 소뇌에서는단지 1명만반응했던점은 MSA를일으키는자가면역성반응이일어나는부위가소뇌보다는다른부위일수있는가능성을시사한다.[17] 그러나첫째, 소뇌성운동실조증상이없는 PD 환자들의항갑상선항체수치가 MSA 환자들보다낮았다는점과둘째, PD와 MSA의또다른증상의차이점인추체외로증상이있는군과없는군간의항갑상선항체유무의의미있는차이가없었다는점들은 MSA의소뇌성운동실조가다른변수들보다항갑상선항체증가와서로연관되어있음을말해준다. MSA 자체는소뇌성, 추체로성, 추체외로성, 및자율신경계이상질환들의조합이다.[21,22] 따라서 MSA 환자들의일부에서는초기에파킨슨증상이먼저나타나고후에자율신경계증상또는소뇌성운동실조가따로또는함께동반되고나머지일부에선소뇌성실조증또는자율신경계증상이먼저나타난뒤파킨슨증상이나중에나타날수있다.[23] 또한자율신경계증상과추체외로증상만발생한환자들도 79

6 Journal of Movement Disorders Vol. 1, No. 2, 2008 신경병리학적검사에서결국뇌간및소뇌의퇴행성변화가관찰된다는보고가있다.[24,25] 이러한사실들은 MSA-p 환자로분류된환자들도질병후기에는소뇌성운동실조증이나타날수있음을말해주며 MSA-p와 MSA-c간의항갑상선항체유무에서차이가없는이유로설명할수있다. 항갑상선항체가어떻게선택적으로소뇌성운동실조를일으키는지는명확하지않다. 항갑상선항체의이상은단지신경계에대한복합적인면역반응을반영하는지표일가능성이높다. Saiz 등은 GAD-Ab가높으면서소뇌성운동실조를보인환자에서는인슐린의존성당뇨병, 자가면역성갑상선염, 악성빈혈과같은자가면역질환의과거력혹은가족력등을확인할수있었으나, 소뇌성운동실조를가졌으면서근강직증후군 (stiffman syndrome) 과자가면역질환의증거가없는환자에서는 GAD-Ab를전혀발견할수없었다는사실은이를뒷받침해준다.[26] 결론적으로 PD에비해 MSA에서보다높은항갑상선항체이상은 MSA가면역매개성질환과더가까이연관되어있음을시사해준다. 이는 MSA의진단에있어항갑상선항체를포함한갑상선기능검사를하는것이타당하다는근거가될수있을뿐만아니라파킨슨병과의감별에도영향을줄수있다. 그러나, MSA-c 와 MSA-p를감별함에있어항갑상선항체는의의가없는것으로생각된다. 추가로소뇌성운동실조환자에서항갑상선항체검사뿐아니라, 소뇌성운동실조와연관이있다고알려진 GAD-Ab, 혈청 Ig A antigliadin antibodies[19] 등의자가면역항체에대한체계적인연구는향후신경퇴행성질환에서의자가면역기전을밝히는데도움이될것이다. REFERENCES 1. Selim M, Drachman DA. Ataxia associated with Hashimoto s disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis. J Neurol Neurosurg Psychiatry 2001;71: Mantu MU. Hashimoto s associated ataxia. J Neurol Neurosurg Psychiatry 2002;72: Vianello M, Vitaliani R, Pezzani R, Nicolao P, Betterle C, Keir G, et al. The spectrum of antineuronal autoantibodies in a series of neurological patients. J Neurol Sci 2004;15; 220: Wartofsky L, Ingbar SH. Diseases of the thyroid. In: Wilson JD, Braunwald E, Isselbacher KJ, et al, eds. Harrison s principles of internal medicine. 12th ed. New York: McGraw- Hill, 1991: Tandeter HB, Shvartzman P. Parkinson s disease camouflaging early signs of hypothyroidism. Postgrad Med 1993;94: Johannessen AC, Boye A, Pakkenber H. Thyroid function in patients with PD. Acta Neurol Scand 1987;75: Berger JR, Kelley RE. Thyroid function in Parkinson disease. Neurology 1981;31: Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol 1999;56: Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, et al. Consensus statement on the diagnosis of multiple system atrophy. J Auton Nerv Syst 1998;74: Francis T, Wartofsky L. Common thyroid disorders in the elderly. Postgrad Med 1992;92: Garcia-Moreno JM, Chacon-Pena J. Hypothyroidism and Parkinson s disease and the issue of diagnostic confusion. Mov disord 2003;18: Munhoz RP, Teive HA, Troiano AR, Hauck PR, Herdoiza Leiva MH, Graff H, et al. Pakrinson s disease and thyroid dysfunction. Parkinsonism Relat Disord 2004;10: Barnard RO, Campbell MJ, McDonald WI. Pathological findings in a case of hypothyroidism with ataxia. J Neurol Neurosurg Psychiat 1971;34: Quinn N, Barnard RO, Kelly RE. Cerebellar syndrome in myxoedema revisited: a published case with carcinomatosis and multiple system atrophy at necropsy. J Neurol Neurosurg Psychiat 1992;55: Durr A, Chneiweiss H, Khati C, Stevanin G, Cancel G, Feingold J, et al. Phenotypic variability in autosomal dominant cerebellar ataxia type I is unrelated to genetic heterogeneity. Brain 1993;116: Gahring LC, Rogers SW, Twyman RE. Autoantibodies to glutamate receptor subunit GluR2 in nonfamilial olivopontocerebellar degeneration. Neurology 1997;48: Polinsky RJ, McRae A, Baser SM, Dahlstrom A. Antibody in the CSF of patients with multiple system atrophy reacts specifically with rat locus ceruleus. J Neurol Sci 1991;106: Cremer GM, Goldstein NP, Paris J. Myxedema and ataxia. Neurology 1969;19: Honnorat J, Saiz A, Giometto B, Vincent A, Brieva L, de Andres C, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 2001;58: Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 1997;15: Graham JG, Oppenheimer DR. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 1969;32: Quinn N. Multiple system atrophy: the nature of the beast. J Neurol Neurosurg Psychiatry 1989;(suppl): Gilman S, Quinn NP. The relationship of the multiple system atrophy to sporadic olivopontocerebellar atrophy and other forms of idiopathic late onset cerebellar atrophy. Neurology 1996;46:

7 Reliability of Serum Anti-thyroid Antibodies Screening in the Diagnosis of Parkinson s Disease and Multiple System Atrophy Taek-Jun Lee, et al. 24. Kume A, Takahashi A, Hashizume Y, Asai J. A histometrical and comparative study on Purkinje cell loss and olivary nucleus cell loss in multiple system atrophy. J Neurol Sci 1991;101: Wenning GK, Tison F, Elliott L, Quinn NP, Daniel SE. Olivopontocerebellar pathology in multiple system atrophy. Mov Disord in press. 26. Saiz A, Arpa J, Sagasta A, Casamitjana R, Zarranz JJ, Tolosa E, et al. Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulindependent diabetes mellitus, and polyendocrine autoimmunity. Neurology 1997;49:

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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