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1 원저 한국인자발하방안진의임상특성 : 218 예의분석 김기태 a 정일억 b 김지수 a,b 서울대학교의과대학 a 분당서울대학교병원 b 신경과 Clinical Characteristics of Spontaneous Downbeat Nystagmus in Koreans: Analysis of 218 Cases Ki Tae Kim, MD a, Ileok Jung, MD b, Ji-Soo Kim, MD, PhD a,b Department of Neurology, Seoul National University College of Medicine, Seoul, Korea a Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea b Background: Downbeat nystagmus is the most-common type of central nystagmus. However, no published study has attempted to analyze the etiology and clinical features of downbeat nystagmus in a large sample of Korean patients. Methods: We analyzed the demographic and clinical features of spontaneous downbeat nystagmus in 218 Korean patients who had been evaluated at the Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to Results: All patients were aged from 15 to 92 years (mean±sd: 58.7±18.0 years), and they included 117 (53.7%) men. Underlying causes were found in 162 patients (74.3%, secondary group), while no etiology was identified in the remaining patients (idiopathic group). The age and sex distributions did not differ between the idiopathic and secondary groups. The underlying etiology included hereditary disorders (n=48, 22.0%), vascular diseases (n=46, 21.1%), and inflammatory diseases (n=19, 8.7%). Infarctions (n=34, 15.6%) and episodic ataxia (n=32, 14.7%) were the most-frequent underlying disorders. The most-common site of lesions identified by MRI was the cerebellum (68.9%), followed by the brainstem (28.6%). Among the 74 patients with lesions confirmed by MRI, 25 (33.7%) showed an isolated cerebellar involvement, while 35 (47.6%) had lesions in multiple areas. Conclusions: This study extends the clinical features of spontaneous downbeat nystagmus to Korean patients. Cerebellum is the most-common lesion site, which is consistent with the results of previous studies. The prevalence of Arnold-Chiari malformation is relatively low, which may be a distinct finding relative to those of previous studies involving other ethnic populations. J Korean Neurol Assoc 34(1):27-32, 2016 Key Words: Downbeat nystagmus, Dizziness, Vertigo, Cerebellum, Brainstem 서 론 하방안진 (downbeat nystagmus) 은가장흔한중추안진으로양안이서서히위로치우쳤다가교정신속보기 (corrective saccades) 에의해제일안위 (primary position) 로되돌아오는형태의안진 Received September 12, 2015 Revised November 11, 2015 Accepted November 11, 2015 Address for correspondence: Ji-Soo Kim, MD Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: Fax: jisookim@snu.ac.kr 이다. 1 상방안진 (upbeat nystagmus) 과달리하방안진은지속적인경우가대부분이다. 하방안진은아래쪽을쳐다볼때심해지고, 2 대부분의일상생활이하방주시상태에서이루어지므로환자들은상방안진에비해불편을호소하는경우가많다. 상방안진이주로뇌간의국소병변에의해발생하는데비해, 3 하방안진은원인이밝혀지지않는경우도흔하며 ( 원발성, idiopathic), 원인이확인되는경우는주로소뇌나뇌간부위의국소병변이나독성 / 대사성질환, 4,5 소뇌변성등과같은미만성 (diffuse) 질환에의한경우가많다. 현재까지하방안진에대한국내연구는제한적이며, 6-8 많은수의환자를대상으로원인및인구학적특성을분석한경우는없었다. 외국에서도대규모환자들을대상으로인구학적이나임 J Korean Neurol Assoc Volume 34 No. 1,

2 김기태정일억김지수 상적특성을분석한논문은소수에지나지않는다. 1,9-11 본연구에서는일개대학병원에서진단된 218명의자발하방안진환자를대상으로한국인하방안진의임상적, 인구학적특성을규명하고, 기존의외국보고들 1,9-11 과비교함으로써인종간의차이가있는지확인하고자하였다. 대상과방법 1. 대상 2003년부터 2014년까지분당서울대학교병원뇌신경센터에서자발하방안진으로진단된 218명의환자를대상으로하였다. 환자검색은뇌신경센터신경이안과클리닉에등록된환자를대상으로하였으며, 자발하방안진없이특정자세나유발행위에의해서만하방안진이유발된경우는제외하였다. 모든환자는신경학적진찰과더불어하방안진에대한신경이안과적검사를해당전문의로부터받았다. 2. 방법 of view: mm. 급성뇌경색환자의경우확산강조영상 (diffusion-weighted imaging) 이추가적으로시행되었고, 사용되었던매개변수값은다음과같다 : b=1000, 4119/89, 단면두께 : 3 mm, matrix 값 : ( 보정값 : ), a field of view: 220 mm. 모든환자의원인질환을진단명과병변부위로분류하였다. 원인질환은전자의무기록에서등록된진단명중하방안진과가장관련깊은질환으로하였다. 뚜렷한원인질환이발견되지않은경우는원발성으로분류하였다. 유전자이상이알려진조화운동불능 (ataxia) 은유전성 (hereditary), 소뇌위축 (cerebellar atrophy) 만이확인된경우는퇴행성 (degenerative) 질환으로분류하였다. 뇌경색 (infarction), 뇌출혈 (hemorrhage), 혈관기형 (vascular anomaly) 등의질환들은혈관성으로, 림프종 (lymphoma), 수막종 (meningioma), 뇌실막세포종 (ependymoma), 표피유사 (epidermoid), 부신생물증후군 (paraneoplastic syndrome) 등의질환들은종양성 (neoplasm) 으로분류하였다. 뇌병변부위는 MRI 판독을기준으로하방안진과관련이있는부위를기록하였다. 하방안진과관련된부위가여러부분일경우에는관련병변을모두포함시켰다. 안진을검사하기전환자의두위에이상이있는지를확인하였다. 이후시력, 시야, 색각, 입체시력등을측정하고검안경으로안저검사를하였다. 동공과눈꺼풀의이상, 사시유무와눈운동의제한여부도확인하였다. 안진을검사할때는안진의방향, 속도, 크기, 주시방향에따른변화등을관찰하였다. 제일안위, 좌우상하주시, 눈모음 (convergence) 상태에서안진의양상이양안에서차이가있는지도확인하였다. 앞서기술한안진검사외에, 비디오안구운동기록 (video-oculography) 을이용하여안구운동을측정하였다. 시고정 (visual fixation) 을없앨필요가있거나암시야가필요한경우에는적외선카메라를장착한프렌젤고글을이용하여안진을관찰하였다. 수평과수직안구운동은동공의변연부와중심점을계산하여중심점의이동을추적기록하였고, 회선 (torsional) 운동은홍채의특성을촬영한영상을분석하여측정하였다. 모든환자에서 1.5-T 또는 3.0T MRI 기기 (Intera; Philips Medical Systems, Best, The Netherlands) 를사용하여뇌영상검사를진행하였다. 표준영상프로토콜로 axial turbo spin-echo T2-강조영상 (weighted imaging), axial spin-echo T1-강조영상, 경사에코영상 (gradient-echo imaging) 을얻었다. 각각의영상에서사용된매개변수값은다음과같다 : T2 강조영상 : 4,800/100 [ 반복시간 (ms)/ 에코시간 (ms)], T1 강조영상 : 500/11, 단면두께 : 3 mm, 경사에코영상 : 700/23, matrix 값 : ( 보정값 : ), a field 3. 통계처리두집단의이분형변수들은카이제곱검정, 연속형변수들을비교할때에는독립검정 t-검정을하였다. 세집단이상의비교에서는비모수적검정법 (Kruskall-Wallis test) 을이용하였다. SPSS 프로그램 (18.0 Version; SPSS Inc., Chicago, IL, USA) 을통해통계처리를하였고, 통계적유의수준은 p값 0.05 이하로하였다. 결과 1. 인구학적특성 본연구에선별된총 218명의환자중, 남자는 117명 (53.7%), 여자는 101명 (46.3%) 이었으며, 연령은 15세에서 92세까지분포하였다. 전체환자나이의중앙값은 60세, 평균은 58.7세, 표준편차는 17.9였다 (Table 1). 원발성그룹의환자는 56명 (25.7%) 이었고, 그중남자가 34명 (60.7%), 이차성자발하방안진환자 162명 (74.3%) 중남자는 83 명 (51.2%) 이었다 (Table 1). 기존의논문들과비교해보았을때전체환자군의연령은본연구에서유의하게높았다 (p<0.0001, Table 1). 또한본연구와 Wagner 등 11 의논문에서는남성의비가더높았지만다른연구에서는여성이상대적으로많았다. 본 28 대한신경과학회지제 34 권제 1 호, 2016

3 한국인자발하방안진의임상특성 : 218 예의분석 Table 1. Demographic characteristics compared with previous studies Our study (n=218) Yee, et al. 1 (n=91) Bronstein, et al. 10 (n=24) Wagner, et al. 11 (n=117) Halmagyi, et al. 9 (n=62) p value Sex NA Men (%) 117 (53.7) 35 (38.5) 6 (25.0) 64 (54.7) a Women (%) 101 (46.3) 56 (61.5) 18 (75.0) 53 (45.3) Etiology < a Idiopathic (%) 56 (25.7) 5 (5.5) 5 (20.8) 45 (38.5) 27 (43.6) Secondary (%) 162 (74.3) 86 (95.4) 19 (79.2) 72 (61.5) 35 (56.4) Age (mean±sd) 58.7± ± ±18.1 NA NA < b Men 62.3± ± ±22.8 <0.05 b Women 54.6± ± ± b Idiopathic 59.8± ± ±18.0 < b Secondary 58.4± ± ±17.0 < b a χ 2 (p) : Chi-square test, SD: standard deviation, NA: not available. b Kruskal Wallis test (p<0.05) 연구와기존 4개의연구모두에서원발성의비중은 % 까지폭넓게분포하였다. 본연구에서는 25.7% 의환자에서원인을찾을수없었는데, 원발성의분율을다른연구들과비교했을때중간값에해당하였다. 2. 뇌 MRI 결과와임상양상 218명의환자중 MRI로병변부위를알수있었던환자는 74명 (33.9%) 이었다. 가장흔한병변부위는소뇌 (51/74, 68.9%) 였다. 이중에서는소뇌단독병변이 25명 (25/74, 33.8%) 이었다. 소뇌다음으로는교뇌 (15/74, 20.3%) 가가장흔하였다. 교뇌에병변이있었던경우교뇌와연수부위를동시에침범한경우 (7/74 9.5%) 가가장많았고, 교뇌만단독으로침범된경우 (6/74, 8.1%) 가그다음으로많았다 (Table 2). 3. 원인질환원인이밝혀진이차성환자 162명 (162/218, 74.3%) 중유전성 (48/218, 22.0%) 질환이가장흔하였고, 혈관성 (48/218, 21.1%) 과염증성 (19/218, 8.7%) 질환이다음을차지하였다. 유전성질환 48명에서는제2형간헐실조 (episodic ataxia 2) 와제 6형척수소뇌실조 (spinocerebellar ataxia 6) 가 2:1의비율 (32:16) 을차지하고있었다. 혈관성질환에서는뇌경색이 15.6% (34/218) 로많은원인을차지했다. 뇌경색에서는후하소뇌동맥 (posterior inferior cerebellar artery, n=5) 공급부위, 연수 (medulla, n=4, 가쪽 3개, 안쪽 1개 ), 교뇌 (pons, n=3) 가단독으로침범되었고, 7명에서는대뇌백색질 (cerebral white matter) 에서다발경색 (multiple ischemia) Table 2. Lesion location in our patients Number (%) Cerebellum 51 (68.9) Cerebellum alone 25 (33.8) Plus pons 3 (4.0) Plus medulla 1 (1.3) Plus other site 5 (6.8) Plus pons, medulla, and other site 17 (23) Pons 19 (25.7) Pons alone 6 (8.1) Plus medulla 7 (9.5) Plus cerebellum 3 (4.0) Plus other site 3 (4.0) Medulla 15 (20.3) Medulla alone 5 (6.8) Plus cerebellum 1 (1.3) Plus pons 7 (9.5) Plus other site 2 (2.7) Midbrain 2 (2.7) Others (temporal, parietal and occipital cortex) 10 (13.5) Total 74 (100%) 이동반되었다 (Table 3). 4. 다른신경이안과적소견주시유발안진 (gaze-evoked nystagmus) 이 83명 (38.1%) 에서동반되었고, 두진후안진은 107명 (49.1%) 에관찰되었다. J Korean Neurol Assoc Volume 34 No. 1,

4 김기태정일억김지수 Table 3. Etiology of downbeat nystagmus compared with previous studies Our study (n=218) Yee et al. 1 (n=91) Bronstein et al. 10 (n=24) Wagner et al. 11 (n=117) Halmagyi et al. 9 (n=62) Idiopathic 56 (25.7) 5 (5.5) 6 (25) 29 (24.8) 27 (42.2) Hereditary 48 (22.0) 1 (1.0) 17 (14.5) 6 (9.7) Episodic ataxia2 32 (14.7) 4 (3.4) Spino-cerebellar ataxia6 16 (7.3) 13 (11.1) Vascular 46 (21.1) 25 (27.5) 1 (4.2) 10 (8.5) Infarction 34 (15.6) VBI 7 (3.2) Hemorrhage 4 (1.8) RVAS 1 (0.4) Inflammation/infection 19 (8.7) 1 (1.0) 4 (3.4) Demyelination 3 (1.3) 12 (13.2) 2 (8.3) Migraine 13 (6.0) Arnold-Chiari malformation 9 (4.1) 11 (12.1) 6 (25) 8 (6.8) 17 (27.4) Degenerative 8 (3.7) 24 (26.4) 6 (25) 23 (19.6) 9 (14.5) Neoplasm 7 (3.2) 3 (3.3) 1 (4.2) 10 (8.5) 1 (1.6) Cerebellar lymphoma 2 (0.9) Meningioma 2 (0.9) Cerebellar ependymoma 1 (0.4) Pontine epidermoid 1 (0.4) Paraneoplastic 1 (0.4) Toxic 8 (3.7) 1 (4.2) 5 (4.3) 1 (1.6) Medication 1 (0.4) 4 (4.4) Others 5 (5.5) 11 (9.4) 1 (1.6) Values are n (%) RVAS; rotational vertebral artery syndrome, VBI; vertebrobasilar insufficiency. 고찰 본연구는하방안진환자를대상으로한국내최초의대규모연구이며, 외국에서진행되었던기존의연구들과비교해볼때도가장많은수의환자를대상으로원인과인구학적특성을분석한논문이다. 본연구는기존의외국연구들과비교해볼때원인질환과인구학적특성에있어몇가지주목할만한유사점과차이점들을보여주고있다. 우선본연구에서환자군의평균연령은 50대후반으로기존의연구에비해서높았다 (Table 1). 그러나연령을원발성과이차성으로나누어다른두연구와 1,10 비교했을때원발성그룹간평균연령이통계적으로유의한차이를보였고 (p<0.0001), 이차성그룹간에도통계적으로유의미한차이가있었다 (p<0.0001). 10 이러한이유는확실하지않으나진단기술의발달에따른원인질환의재분류가중요한요인이되었을가능성이있다. 즉기존에원발성으로분류되었던고령의경미한소뇌변성환자들이 영상기술과유전자진단법의발달로퇴행이나유전질환으로분류되었을수있기때문이다. 두번째로하방안진의원인질환에있어기존연구와차이를보였다 (Table 3). 보고마다차이가있으나일반적으로하방안진의중요한원인으로는원발성, 소뇌변성, 아놀드 -키아리기형, 뇌경색등이제기되어왔다. 1,9,12-14 Bronstein 등 10 은 24명의하방안진환자에대한분석을통해하방안진의원인은원발성, 소뇌변성, 아놀드-키아리기형그리고나머지원인들이각각 1/4을차지한다고주장한바있다. 이러한주장은 62명의환자를분석했던이전의논문에서원발성이 40% 를차지하고소뇌이소증 (cerebellar ectopia) 과소뇌변성이각각 25% 를차지하며, 기타원인이나머지 10% 를차지한다는결과와도어느정도일치한다고볼수있다. 9 그러나이후 91명의환자를대상으로했던또다른연구에서는소뇌변성과함께뇌경색이각각 25% 정도로가장흔했으며다발경화증 (multiple sclerosis) 도 13% 를차지했던반면, 소뇌이소증과원발성은 12% 과 5% 에불과하였다. 1 또한비교적최근에 30 대한신경과학회지제 34 권제 1 호, 2016

5 한국인자발하방안진의임상특성 : 218 예의분석 진행되었던연구에서는원발성이 38% 를차지하였고, 이차성원인중에서는소뇌변성, 뇌혈관질환, 아놀드- 키아리기형이가장흔하였다. 11 본연구에서하방안진의원인은원발성 (25.7%), 유전성 (22.0%), 혈관성 (21.1%), 염증성 (8.7%) 순이었다 (Table 3). 특히소뇌변성을포함한퇴행질환의비중은 3.7% 로낮았고아놀드- 키아리기형또한 4.1% 로낮게조사되었다. 반면유전질환과혈관질환의비중이높았고, 기존에는중요하게생각되지않았던염증질환의비중이높은것을알수있다. 특히유전질환중에서는간헐실조의비중이높은것이특징이었다. 본연구에서기존연구에비해퇴행질환의비중이낮았던것은유전자검사법의발달로기존에단순소뇌변성으로분류되었던많은질환들에서유전자이상이확인됨으로써유전질환으로분류되었기때문으로생각된다. 실제유전질환으로분류된질환중에소뇌변성을주로하는간헐실조와척수소뇌실조질환들을함께묶을경우전체원인중 22% (48/218) 를차지함을알수있다. 아놀드 -키아리기형의빈도가낮은이유는분명하지않다. 아놀드-키아리의발병률에있어서인종이중요한요소로알려져있는데본연구는한국인만을대상으로한것이하나의요인으로추정할수있다. 15 그러나본연구에서아놀드 -키아리기형으로진단된대부분의환자들이어지럼과자세불안으로신경이안과클리닉을직접방문했던경우이고, 신경외과에서수술전신경안과적평가를위해의뢰했던경우는거의없었던것으로미루어우리나라의의료행태도중요한요인으로판단된다. 본연구에서원인질환에대한또다른특징으로는간헐실조와염증질환의비중이높았다는것이다. 기존의보고중간헐실조가원인으로분류되었던것은비교적최근에진행되었던 Wagner 등 11 의연구에서였고, 전체 117명의환자중 4명에불과하였다. 따라서본연구에서총 218명의환자중간헐실조가 32명 (14.7%) 을차지한것은매우이례적으로볼수있다. 이러한이유에대한설명으로는간헐실조의임상진단과유전자적확인이 2000년도이후에일반화되었다는점을들수있다. 또한본연구가진행되었던신경이안과클리닉이주로진단이어려운환자들이의뢰되는의료기관에속했던점도하나의요인이될수있을것으로보인다. 본연구에서다발경화증을제외한염증질환의비중이높았던이유는감염원인이뚜렷하지않지만뇌척수액검사에서백혈구증가가있는경우나뇌 MRI에서염증을시사하는소견을보이는경우염증질환으로분류하였기때문으로보인다. 하나더언급할점은선천안진에서는자발하방안진이거의없다고알려져온것처럼 9 본연구에서도전체 218명의환자중선천안진은없었다는것이다. 하방안진의기전은몇가지가설들로설명되고있다. 그중에서가장중요한것은 1) 수직전정안반사의불균형, 16 2) 하방 원활추종운동 (smooth pursuit) 의장애, 12 3) 이석전정안반사의불균형, 4) 뇌간방정중신경로세포군 (paramedian tract cell group) 의손상이다. 9,17 소뇌타래엽 (flocculus) 의푸르킨예세포 (Purkinje cell) 는전반고리관 (anterior semicircular canal) 으로부터의신호를주로억제하기때문에 17 소뇌병변에서는전반고리관신경로가탈억제 (disinhibition) 상태가되어눈이위로치우치고결과적으로하방안진이발생이된다는것이수직전정안반사의불균형기전에대한설명이다. 12,13 실제로기존연구에서는소뇌타래를절제할때하방안진이발생하였다. 12,18 또한소뇌타래- 소절엽의푸르킨예세포활성도가상방보다하방원활추종운동시에더높다는것이동물실험을통해알려졌다. 19 따라서이부위에병변이생기면하방원활추종운동에장애가생겨눈이위로향하고하방안진이발생된다는설명이다. 실제로원발성하방안진환자에서하방원활추종운동시에곁타래 (paraflocculus) 와교뇌- 연수부위에서뇌활성도가감소되었음이보고된바있다. 20 반면뇌간에서눈움직임관련정보를소뇌로전달하는방정중신경로세포군의손상이하방안진을유발한다는주장도있다. 실제로원숭이에서교뇌의방정중신경로세포군을불활성화시켰을때하방안진이유발된바있다. 17 이모든주장과연구결과들이하방안진의원인병변부위로소뇌와뇌간을지목하고있다. 본연구에서도 MRI를통하여원인부위를알수있었던환자중가장흔한병변부위는소뇌였고 (68.9%), 그중에서는소뇌가단독으로침범된경우가가장많았다 (49.0%, Table 2). 기존연구에서도소뇌가가장많이침범된부위였고, 그중에서도소뇌단독병변인경우가가장많았던것으로보아, 1 본논문의결과가기존연구와일치함을알수있다. 본연구의제한점으로연구대상이일개대학병원신경이안과클리닉에국한되었다는점을들수있다. 일반적으로진단이잘되지않거나난치성환자들이본클리닉으로의뢰되는점을고려할때본연구의대상이비교적드물거나치료가힘들었던질환들로선택치우침이있었을가능성이있다. 실제로본연구에서하방안진의원인질환으로간헐실조의비중이높았던것은이러한가능성을시사한다고볼수있다. 본연구의이러한제한점은향후국내다기관연구를통해극복되어야할것이다. REFERENCES 1. Yee RD. Downbeat nystagmus: characteristics and localization of lesions. Trans Am Ophthalmol Soc 1989;87: Kim JS. Nystagmus. J Korean Neurol Assoc 2004;22: Choi JH, Jung NY, Kim MJ, Choi KD, Kim JS, Jung DS. Pure upbeat nystagmus in association with bilateral internuclear ophthalmoplegia. J Neurol Sci 2012;317: J Korean Neurol Assoc Volume 34 No. 1,

6 김기태정일억김지수 4. Corbett JJ, Jacobson DM, Thompson HS, Hart MN, Albert DW. Downbeating nystagmus and other ocular motor defects caused by lithium toxicity. Neurology 1989;39: Oh SY, Kim JS, Lee YH, Lee AY, Kim J, Kim JM. Downbeat, positional, and perverted head-shaking nystagmus associated with lamotrigine toxicity. J Clin Neurol 2006;2: Shin HJ, Oh SY. Treatment of Downbeat Nystagmus in Arnold-Chiari Malformation using 3,4-Diaminopyridine. J Korean Neurol Assoc 2014;32: Choi JH, Yang TI, Cha SY, Lee TH, Choi KD, Kim JS. Ictal downbeat nystagmus in cardiogenic vertigo. Neurology 2010;75: Moon KH, Ahn JS, Kwun BD. Downbeat Nystagmus Associated With Brainstem Compression by Vertebral Artery. J Korean Neurosurg Soc 2007;41: Halmagyi GM, Rudge P, Gresty MA, Sanders MD. Downbeating nystagmus. A review of 62 cases. Arch Neurol 1983;40: Bronstein AM, Miller DH, Rudge P, Kendall BE. Down beating nystagmus: magnetic resonance imaging and neuro-otological findings. J Neurol Sci 1987;81: Wagner JN, Glaser M, Brandt T, Strupp M. Downbeat nystagmus: aetiology and comorbidity in 117 patients. J Neurol Neurosurg Psychiatry 2008;79: Zee DS, Friendlich AR, Robinson DA. The mechanism of downbeat nystagmus. Arch Neurol 1974;30: Marti S, Straumann D, Glasauer S. The origin of downbeat nystagmus: an asymmetry in the distribution of on-directions of vertical gaze-velocity Purkinje cells. Ann N Y Acad Sci 2005;1039: Cogan DG. Down-beat nystagmus. Arch Ophthalmol 1968;80: Caetano de Barros M, Farias W, Ataide L, Lins S. Basilar impression and Arnold-Chiari malformation. A study of 66 cases. J Neurol Neurosurg Psychiatry 1968;31: Baloh RW, Spooner JW. Downbeat nystagmus: a type of central vestibular nystagmus. Neurology 1981;31: Nakamagoe K, Iwamoto Y, Yoshida K. Evidence for brainstem structures participating in oculomotor integration. Science 2000;288: Bohmer A, Straumann D. Pathomechanism of mammalian downbeat nystagmus due to cerebellar lesion: a simple hypothesis. Neurosci Lett 1998;250: Marti S, Straumann D, Buttner U, Glasauer S. A model-based theory on the origin of downbeat nystagmus. Exp Brain Res 2008;188: Hufner K, Stephan T, Kalla R, Deutschländer A, Wagner J, Holtmannspötter M, et al. Structural and functional MRIs disclose cerebellar pathologies in idiopathic downbeat nystagmus. Neurology 2007;69: 대한신경과학회지제 34 권제 1 호, 2016

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