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1 원저접수번호 :09-029(2 차 -0710) 전남대학교의과대학신경과학교실, 영상의학과학교실 a 박명호김병채최성민김동은최강호김준태윤웅 a 남태승이승한박만석김명규조기현 Relationship Between Findings on Brain MRI and Prognosis in Patients With Spontaneous Intracranial Hypotension Myung-Ho Park, MD, Byeong C. Kim, MD, Seong-Min Choi, MD, Dong-Eun Kim, MD, Kang-Ho Choi, MD, Joon-Tae Kim, MD, Woong Yoon, MD a, Tai-Seung Nam, MD, Seung-Han Lee, MD, Man-Seok Park, MD, Myeong-Kyu Kim, MD, Ki-Hyun Cho, MD Department of Neurology and Radiology a, Chonnam National University Medical School, Gwangju, Korea Background: The outcome of spontaneous intracranial hypotension (SIH) is unpredictable and some patients have persistent and often incapacitating symptoms. This study was aimed to investigate whether abnormalities on initial magnetic resonance imaging (MRI) can predict the outcome in patients with SIH. Methods: We retrospectively included 44 patients with SIH. Brain MRI was available for all patients. Treatment consisted of conservative treatment and/or high-volume epidural blood patching. Patients were divided into two groups: favorable or non-favorable group. Favorable group was defined as clinical improvement by conservative therapy or one trial of autologous epidural blood patching; non-favorable group as more than two week of admission, two or more trials of autologous epidural blood patching, or relapse of orthostatic headache. Results: Twenty-one (48%) of 44 patients were classified as the favorable group. The non-favorable group had several abnormal findings on brain MRI (16 cases vs. 5 cases in favorable group, p<0.003), including platybasia (1), skull base tumor (1), Chiari I malformation (1), diffuse mild thickening and enhancement of dural and epidural layer of thoracic spine (1), pituitary enlargement (3), sagging brain (3) and subdural hemorrhage (4). In the non-favorable group, 13 out of 23 patients (57%) showed pachymeningeal enhancement in brain MRI (2 patients in favorable group, p<0.001). Conclusions: Brain MRI abnormalities were more frequently related with non-favorable outcomes in SIH. Pachymeningeal enhancement in particular could suggest an unfortunate prognosis. J Korean Neurol Assoc 32(1):14-18, 2014 Key Words: Spontaneous intracranial hypotension, Pachymeningeal enhancement, Epidural blood patch 서 론 자발두개내압저하 (spontaneous intracranial hypotension, SIH) 는만성지속성두통의중요한원인중의하나이다. 1 SIH는뇌척수액누출을일으킬만한시술이나사고등의병력없이뇌척 Received April 15, 2013 Revised September 27, 2013 Accepted September 27, 2013 *Byeong C. Kim, MD Department of Neurology, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju , Korea Tel: Fax: byeong.kim@chonnam.ac.kr 수액압이저하되는질환으로, 기저의전반적인결합조직질환과연관된자발적인뇌척수액소실이그원인으로알려져있다. 2 SIH는기립 15분이내에유발되거나악화되고눕고난후 30 분이내에소실되거나호전되는기립두통이특징적이며 3,4 오심과구토, 경부강직, 복시, 현훈, 이명, 눈부심, 시야장애등이두통과동반된다. SIH의발생기전은낮은뇌척수액압으로인한뇌하향전위, 보상적인수막혈관확장그리고미로내압의변화등으로추정된다. 5 SIH는척추천자를이용하여뇌척수액압측정으로진단하였으나최근에는임상경과초기에뇌 MRI를이용하여진단한다. 6 SIH 환자들의뇌 MRI에서경수막의뚜렷한조영증강, 7 뇌하방전위, 경막하수종이나혈종등이특징적이 14 대한신경과학회지제 32 권제 1 호, 2014

다. 5,6 하지만뇌 MRI의특징과예후와의관련성에대한연구는많지않다. SIH는일차적으로침상안정과수액공급위주의보존치료를한다. 하지만보존치료이후에도증상이지속되어경막외혈액첩포술 (epidural blood patch clamp) 이나뇌척수액소실에대한수술적교정같은추가치료를필요로한다. 7,8 이와같은치료결과는비교적좋은것으로알려져있으나일부에서는증상이지속되기도한다.

대상 2005년 1월부터 2011년 12월까지 7년동안기립두통으로전남대학교병원에입원한 67명의환자중 SIH로진단된환자를대상으로병원기반후향연구를하였다. 포함기준 (Inclusion criteria) 인 SIH로인한기립두통은 Schievink 등 9 이제안한진단기 Table.

486 Sex, female (%) 25 (57) 15 (71) 10 (44) 0.058 Time to first MRI (Mean±SD, day) 7.57±6.21 5.71±3.73 9.26±7.51 0.063 Associated symptoms Nausea, vomiting, n (%) 28 (64) 17 (81) 11 (48) 0.

2 다. 5,6 하지만뇌 MRI의특징과예후와의관련성에대한연구는많지않다. SIH는일차적으로침상안정과수액공급위주의보존치료를한다. 하지만보존치료이후에도증상이지속되어경막외혈액첩포술 (epidural blood patch clamp) 이나뇌척수액소실에대한수술적교정같은추가치료를필요로한다. 7,8 이와같은치료결과는비교적좋은것으로알려져있으나일부에서는증상이지속되기도한다. 지금까지 SIH에대한연구는주로전형적인임상증상이나징후, 방사선특징에대하여이루어져왔으나치료결과를예측하는인자에대한연구는미비한상태이다. 본연구는 SIH 환자를대상으로뇌 MRI에서확인가능한이상이 두통의임상양상에미치는영향을조사하고치료예후와관련성이있는지알아보았다. 대상과방법 1. 대상 2005년 1월부터 2011년 12월까지 7년동안기립두통으로전남대학교병원에입원한 67명의환자중 SIH로진단된환자를대상으로병원기반후향연구를하였다. 포함기준 (Inclusion criteria) 인 SIH로인한기립두통은 Schievink 등 9 이제안한진단기 Table. Characteristics of 44 patients with spontaneous intracranial hypotension Total Favorable group Non-favorable group (n=44) (n=21) (n=23) p value Age (Mean±SD, yr) 37.8± ± ± Sex, female (%) 25 (57) 15 (71) 10 (44) Time to first MRI (Mean±SD, day) 7.57± ± ± Associated symptoms Nausea, vomiting, n (%) 28 (64) 17 (81) 11 (48) Neck stiffness, n (%) 11 (25) 4 (19) 7 (30) Blurred vision, n (%) 1 (2) 0 (0) 1 (4) Dizziness, n (%) 2 (4) 2 (9) 0 (0) Tinnitus, n (%) 2 (4) 1 (5) 1 (4) Photophobia, n (%) 1 (2) 0 (0) 1 (4) Mental change, n (%) 1 (2) 0 (0) 1 (4) Abnormal MRI findings, n (%) 21 (48) 5 (24) 16 (70) Diffuse meningeal enhancement, n (%) 15 (34) 2 (10) 13 (57) Downward displacement, n (%) 4 (9) 1 (5) 3 (13) Subdural fluid collection, n (%) 4 (9) 1 (5) 3 (13) Subdural hemorrhage, n (%) 4 (9) 0 (0) 4 (17) Pitutary hyperemia, n (%) 4 (9) 1 (5) 3 (13) A B C Figure. The abnormal findings of brain MRI in patients with SIH. (A) Diffuse pachymeningeal enhancement is shown on coronal enhanced T1-weighted MRI, and (B) bilateral subdural hygroma along both cerebral hemispheres are shown on axial T2-weighted MRI. (C) Lines drawn to measure displacement of the iter (black arrow) and the cerebellar tonsils (white arrow) on sagittal T1-weighted MRI. J Korean Neurol Assoc Volume 32 No. 1,

3 박명호김병채최성민김동은최강호김준태윤웅남태승이승한박만석김명규조기현 준에따라정하였다. Schievink 등 9 이제안한진단기준은 A. 기립두통, B. 다음중한가지이상이있을때 : 1) 뇌척수액검사에서낮은개방압력 ( 60 mmh 20), 2) 경막외혈액첩포술을통한증상의호전, 3) 뇌 MRI에서경수막의전반적인조영증강, 4) 뇌척수액의누출, C. 최근요추천자기왕력이없을때, 그리고 D. 유발할수있는다른질환이없을때로정의하였다. 9 기립두통환자 67명중에서원인이될만한외상, 감염, 수술과거력이있는 21명과추적관찰이안된 2명을제외한 44명을최종연구대상으로선정하여분석하였다. 2. 방법뇌 MRI는 T2강조영상, T1강조영상, 액체감쇄역전회복영상 (fluid attenuated inversion recovery imaging, FLAIR) 을기본으로촬영하였고 gadolinium diethylenetriamine pentaacetic acid (DTPA, Gadovist, Bayer) 0.1 mmol/kg를주사하여조영증강영상을얻었다. 뇌 MRI 이상의기준은경수막의조영증강, 뇌하향전위, 경막하삼출과출혈, 뇌하수체혹은정맥충혈이있는경우로정의하였다 (Fig.). 10 뇌 MRI의관상면영상에서대뇌와소뇌경막과반구간틈새에대칭적으로광범위하고연속적인조영증강이나타날때의미있는조영증강으로판단하였으며 7 뇌하향전위의측정은뇌 MRI 시상면영상에서패임선 (incisural line) 과큰구멍선 (foramen magnum line) 을기준으로대뇌수고관의통로 (iter of cerebral aqueduct) 나소뇌편도의하향전위여부로판단하였다 (Fig.). 11 영상은신경과의사두명이분석하였고결과가다를경우는동의를이루어해결하였다. 대상환자의나이, 성별같은기본자료와두통양상, 위치, 동반증상은의무기록을통해조사하였다. 치료는침상안정, 수액공급같은보존치료와경막외혈액첩포술, 수술치료가시행되었으며예후에대한평가는마지막치료로부터최소 3달이내의추적관찰을통하여평가하였으며두통정도는시각통증등급 (visual analog scale score) 을이용하였다. 12 보존치료혹은한번의경막외혈액첩포술시행이후호전을보인경우를좋은예후 (favorable group) 두차례이상의경막외혈액첩포술시행, 기립두통이재발한경우를나쁜예후 (non-favorable group) 로정의하였다. 3. 자료처리와분석방법뇌 MRI 이상유무와예후에따라두군으로나누어각각두통의특징과영상결과의차이를비교 분석하였다. 범주형변수는카이제곱 (Chi-square) 검정이나교차분석표분석을이용하였 고연속변수는 t-검정 (t-test) 을이용하였다. 통계적유의수준은 p 값 0.05 미만을기준으로하였고통계분석은 SPSS (statistical package for the social science) 18.0 버전을이용하였다. 결과 최종적으로연구에포함된환자는 44명 ( 남자 19명, 여자 25 명 ) 이고평균연령은 37.8세 (20-71세) 였다. 예후에따라분류한결과, favorable group 21명 (48%), non-favorable group 23명 (52%) 이었고평균연령은 favorable group은 36.7세 (20-52세), non-favorable group는 38.8세 (20-71세) 로유의한차이는없었고남녀비에서도차이가없었다. 두통의임상양상은주로지속적인양상 (n=36, 82%) 으로, 박동성 (n=22, 50%), 조이는듯한양상 (n=9, 21%) 이많았으며위치는두피전체 (n=20, 46%), 후두부 (n=15, 34%), 전두부 (n=6, 14%) 순이었다. 두통과동반되는증상에는오심과구토가 28명 (64%) 으로가장흔했고경부강직이 11명 (25%), 시야장애, 어지럼, 이명, 눈부심, 의식변화등이일부환자에서있었다. 상기증상은오심과구토증상이 favorable group에서통계적으로의미있게높았지만 (favorable group 81% vs non-favorable group 48%, p=0.024), 다른증상은두군간에유의한차이가없었다 (Table). 임상증상발현부터뇌 MRI 시행까지의걸린시간은총 7.57 일이었으며, favorable group은 5.71±3.73일, non-favorable group은 9.26 ±7.51일로, non-favorable group에서증상발현부터뇌 MRI 촬영까지의시간이지연되어있었다. 뇌 MRI 이상이있는환자비율은 favorable group에서 5명 (24%), non-favorable group에서 16명 (70%) 으로, non-favorable group에서뇌 MRI 이상이있는환자의빈도가 favorable group에비해통계적으로높았다 (p=0.003) (Table). SIH 진단과정에서뇌 MRI가정상이었던환자의뇌척수액누출을확인하기위하여방사성동위원소뇌수조조영술 (radioisotope cisternography) 을하였다. favorable group에서는흉추에서 1명, non-favorable group에서는경추 1명, 흉추 4명, 상부요추 2명, 총 7명의환자에서뇌척수액누출을확인하였다. 치료는침상안정, 경구수액요법같은보존치료를우선적으로하였으며 1주일정도보존치료를해도호전되지않으면경막외혈액첩포술같은추가처치를하였다. 전체 44명중 15명 (34%) 이경막외혈액첩포술을받았고 favorable group은 1명 (5%), non-favorable group은 14명 (61%) 이었다. 이들중경막외혈액첩포술을반복한경우는 10명 (44%) 이였고 5회까지반복한경우도있었다. 16 대한신경과학회지제 32 권제 1 호, 2014

4 고찰 현재까지 SIH의여러가지임상증상과영상에대한연구는많았으나예후와관련된연구는적었고이역시환자의수가적어서인과관계를규명하기어려웠다. 본연구는 SIH에서초기뇌 MRI 이상이치료에대한예후를예측하는인자임을보여주었다. 뇌 MRI 이상이있는경우치료에대한반응도좋지않았고입원기간도길었다. 특히경막조영증강이있는경우는예후가나쁜것으로예측할수있었다. SIH는 1938년 Schaltenbrand에의하여처음기술되었고이후다양한증례와연구가있었으나현재까지발생률도명확하지않다. 한지역사회기반연구에의하면성인에서 50,000명중의 1 명정도발생한다고하였고남성보다여성에서흔하며 40대에서발생률이높다고하였다. 7 실제임상진단은잠재적인뇌척수액누출을의심하지않으면진단하지못하는경우가많다. 1 SIH 발병은경막위약이나이상이자발적인뇌척수액누출의위험을높이므로마르팡증후군 (Marfan syndrome), 13,14 Ehlers-danlos syndrome, 15 보통염색체우성다낭신장병같은결합조직질환에서위험성이높다. 두통은대부분자연혹은보존치료만으로호전되나증상이지속또는악화되면보다적극적인치료로경막외혈액첩포술, 경막외강식염수주입, 경구카페인투여, 경구또는정맥내수액공급, 부신피질호르몬투여를고려할수있다. 9,16 비교적진단과치료가용이한양성질환으로예후는양호하지만증상호전이없으며뇌척수액의지속적누출이교정되지않으면두통의만성화혹은다양한신경계합병증이나타날수있다. 17 따라서 SIH의예후를예측하는것은치료방향을결정하는데중요하다. 최근 Ferrante 등 18 은 SIH 환자 42명을대상으로트렌델렌부르크자세 (Trendelenburg position) 로경막외혈액첩포술을할경우 42명전원이 3회의시술로완치되었다. 하지만현재까지 SIH의일차적인치료는보존치료이기때문에모든환자에게경막외혈액첩포술을시행하기에는무리가있다. 증상발생초기에보존치료로충분한지경막외혈액첩포술이필요한지를결정할수있는요소가필요하다. 뇌 MRI에서확인할수있는이상에는광범위한수막조영증강, 6,15 뇌경막하삼출과출혈그리고뇌의하향전위에따른 iter 와소뇌편도의전위, 경사대를따른교뇌의평탄화, 시신경교차부압박이있다. 수막조영증강은 SIH의가장대표적인영상이상으로, Gadolinium조영증강뇌 MRI 촬영의약 83% 이상에서나타난다 이는염증에의한것이아니라연수막의섬유야교증식에따른이차적변화의결과로알려져있다. 6,22 경막하수종은 SIH 환자의 17-60% 에서나타나며 20,22 치료하지않은 SIH 의후기에잘나타난다. 23,24 이는뇌척수액의용적이줄면서거미막하, 경막하공간이확장되어나타나는현상이다. 25 그밖에도뇌하수체의비대나정맥충혈도 SIH에서나타날수있으며 5,6,15 이는뇌척수액누출에따른 Monroe-kellie 기전에따른보상의결과이다. 26 뇌 MRI 도입이전까지대부분환자에서척추천자를통한뇌척수액압의확인이필수적이었다. 27 하지만일부 SIH 환자에서뇌척수액압이정상인경우가있으므로 28 뇌 MRI를일차진단도구로활용하면서뇌 MRI진단가치가강조되고있다. 6 일차진단도구로서뇌 MRI의용도외에도예후예측인자로서활용하는연구도있다. Yoon 등 29 은 SIH 환자 30명의뇌 MRI 를분석하였고예후와관련된진단또는치료방법의차이를분석하였으나숫자가적어서의미있는차이를발견하지못했다. 실제로 SIH 환자의예후를확인한연구로는 Schievink 등 12 의보고가있다. SIH 환자 33명을대상으로뇌 MRI 이상이있으면예후가나쁜것을확인하였다. 이와같은결과는뇌 MRI가정상이면초기진단이늦어지고적극적인치료가이루어지지않은점을이유로생각하였다. 하지만 Schievink 등 12 의연구는영상이상에대한개별분석이이루어지지않았으며정확한기전에대한평가역시제한적이었다. 하지만본연구에서는 SIH 환자의초기뇌 MRI에서이상이있는군은나쁜예후를이상이없는군은좋은예후를예측할수있음을확인하였다. SIH에서뇌 MRI 특징이병태생리학적으로두통과신경계이상을초래하는기전임을시사한다. 일반적으로뇌 MRI 이상이 SIH가진행된후기에나타나는점을고려하면 뇌 MRI 이상군이예후가나쁠것을예측할수있다. 따라서 SIH에서신경계이상과뇌 MRI에이상이있을경우예후가나쁠가능성이높으므로보다적극적인치료가필요하다고생각한다. 본연구는환자수가적은소규모후향연구라는제한점이있어서분석결과를일반화하는데한계가있다. 또한 3개월이내의단기예후만을분석하여장기적인예후를알수는없었다. 마지막으로전반적인 SIH의임상경과또는발생기전에대한분석이부족하였다. 본연구는 SIH의예후인자를분석한연구이며특히뇌 MRI 이상이 SIH의나쁜예후를예측할수있다는것을입증한첫번째연구이다. 앞으로대단위의연구가체계적으로진행된다면 SIH 환자의초기뇌 MRI 분석을통해예후예측에더객관적인정보를얻을수있을것으로기대한다. REFERENCES 1. Schievink WI. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol 2003;60: J Korean Neurol Assoc Volume 32 No. 1,

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Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical