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1 대한안과학회지 2016 년제 57 권제 6 호 J Korean Ophthalmol Soc 2016;57(6): ISSN (Print) ISSN (Online) Case Report 톨로사 - 헌트증후군에서속발한경막동맥해면정맥굴샛길 1 예 A Case of Cavernous Sinus Dural Arteriovenous Fistula Following Tolosa-Hunt Syndrome 박아람 김승우 정승아 Aram Park, MD, Seung Woo Kim, MD, Seung Ah Chung, MD, PhD 아주대학교의과대학안과학교실 Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea Purpose: To report a case of cavernous sinus dural arteriovenous fistula following Tolosa-Hunt syndrome. Case summary: A 64-year-old female with a history of hypertension, presented with blepharoptosis and periorbital pain in the right eye and diplopia. Her right pupil was dilated. She had right exotropia and right hypertropia with inability to elevate, depress, and adduct the right eye. Magnetic resonance imaging including angiography, revealed hyperintensities in the right cavernous sinus consistent with inflammation and no vascular abnormalities. Three days after oral corticosteroid therapy, the pain disappeared. A presumptive diagnosis was Tolosa-Hunt syndrome presenting as a form of complete oculomotor nerve palsy. Two months later, she experienced severe pain in the right periocular area, even though blepharoptosis was resolved and ocular motility was improved. A rapid response to high-dose intravenous corticosteroids was consistent with recurrence of Tolosa-Hunt syndrome. Three months later, she had normal ocular motility, but developed a conjunctival injection, pulsatile orbital bruits, and exophthalmos in the right eye. Cerebral angiography showed a cavernous sinus dural arteriovenous fistula. She received a transvenous coil embolization and her symptoms markedly improved over 2 months. Conclusions: Tolosa-Hunt syndrome, a granulomatous inflammation in the cavernous sinus may be followed by cavernous sinus dural arteriovenous fistula and should be considered during follow-up. J Korean Ophthalmol Soc 2016;57(6): Keywords: Cavernous sinus, Dural arteriovenous fistula, Tolosa-Hunt syndrome 톨로사-헌트증후군 (Tolosa-Hunt syndrome) 은한쪽안구주위통증이외안근마비와함께혹은 2주이내에선행하여나타나는질환으로, 자기공명영상이나조직검사에서해면 Received: Revised: Accepted: Address reprint requests to Seung Ah Chung, MD, PhD Department of Ophthalmology, Ajou University Hospital, #164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea Tel: , Fax: * This study was presented as a poster at the 113th Annual Meeting of the Korean Ophthalmological Society 정맥굴, 위안와틈새, 또는안와꼭지부위에육아종성염증이관찰되고다른전신적인원인을찾을수없을때진단할수있다. 1-3 이러한톨로사-헌트증후군은스테로이드치료에빠르고좋은반응을보이는특징이있으며이를진단기준으로사용하기도하였다. 2 경막동맥해면정맥굴샛길은내경동맥혹은외경동맥의뇌막동맥분지와해면정맥굴사이에비정상적인연결을보이는혈관질환으로, 결막출혈, 안구돌출, 박동성잡음이나타날수있다. 3-6 또한톨로사-헌트증후군과유사하게안구주위통증과외안근마비가발생할수있다. 3-6 이러한톨로사-헌트증후군과경막동맥해면정맥굴샛길이드물게는함께혹은순차적으로발생할수있다고알려 c2016 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 977

2 - 대한안과학회지 2016 년제 57 권제 6 호 - A B C D Figure 1. Clinical findings and imaging at initial presentation. (A) Gaze photographs showing severe limitation on supraduction, adduction, and infraduction in the right eye. (B) Photographs showing blepharoptosis, and dilated pupil in the right eye. (C) Brain magnetic resonance angiography (MRA) not showing any abnormality such as aneurysmal dilatation or compressed lesion. (D) Gadolinium enhanced T1-weighted brain magnetic resonance image (MRI) showing increased signal intensity in the right cavernous sinus, indicated by red circle. P = posterior aspect; A = anterior aspect. 978

3 - 박아람외 : 톨로사 - 헌트증후군후동정맥샛길 - Figure 2. Gaze photographs 2 months after initial presentation when she suffered from severe periocular pain and headache, showing resolution of blepharoptosis and improvement in ocular motility in the right eye. 져있으나, 3,7-9 국내에서는신경과에서보고한한증례이외에는보고된적이없다. 3 이에저자들은톨로사-헌트증후군으로치료받은눈에서발생한경막동맥해면정맥굴샛길증례를경험하여문헌고찰과함께국내에서는두번째로이를보고하고자한다. 증례보고 64세여자환자가 5일전부터발생한우안위눈꺼풀주변의통증과두통, 3일전부터발생한우안눈꺼풀처짐, 대각선복시를주소로내원하였다. 7년전우측얼굴신경마비가있었고, 5년된고혈압으로약을복용하고있었으며, 6 개월전양안백내장수술을받은과거력이있었다. 양안나안시력 1.0이었고, 안압은우안 11 mmhg, 좌안 13 mmhg로정상이었다. 시축을가리는우안눈꺼풀처짐이있었고, 정면주시에서 35 프리즘디옵터 (prism diopter, PD) 우안외사시와 8PD 우안상사시가있었으며상전, 하전, 내전의심한안구운동장애 (-4) 가있었다. 우안동공이 6.5 mm 로산대된채빛자극에거의반응하지않았다 (Fig. 1A, B). 우안에익상편이있는것을제외하고는전안부나안저에는특이소견이없었다. 면역학적검사를포함한혈청학적검사와뇌척수액검사는모두정상이었다. 뇌 / 뇌혈관자기공 명영상에서오래된다발성열공성뇌경색이있었지만뇌혈관이상이나압박성뇌병변은관찰되지않았다 (Fig. 1C). 하지만우측해면정맥굴에염증성고신호강도가관찰되어 (Fig. 1D), 신경과에서경구스테로이드치료 (prednisolone, 20 mg) 를시작하였고 3일뒤모든통증과두통이소실되어우안완전동안신경마비로나타난톨로사-헌트증후군으로생각되었다. 경구스테로이드는 2주간복용후자의로중단하였다. 2개월뒤 1일전부터발생한시각통증척도 (visual analogue scale, VAS) 10점의극심한우안주변통증, 즉우측삼차신경의제1가지 (V 1, 눈신경 ) 와제2가지 (V 2, 위턱신경 ) 영역의통증과두통으로통증클리닉에내원하였다. 우안눈꺼풀처짐은소실되었고안구운동장애도호전되어경도의내전과하전장애 (-1) 가있었고, 25PD 우안외사시와 14PD 우안상사시가있었다 (Fig. 2). 우안동공산대도 4.3 mm로호전되었다. 비용문제로자기공명영상을다시시행하지못하였지만, 톨로사-헌트증후군의재발로생각되어고용량스테로이드주사치료 (methylprednisolone, 1 g/day) 를시작하였고, 3일뒤우안주변통증과두통이 VAS 2점으로감소하여이에합당하였다. 이후경구스테로이드 (prednisolone, 1 mg/kg/day) 로바꾸어 1주간격으로 10 mg 씩 5주에걸쳐감량하였다. 979

4 - 대한안과학회지 2016 년제 57 권제 6 호 - A B Figure 3. Clinical findings and imaging 5 months after initial presentation. (A) Gaze photographs showing resolution of the right oculomotor nerve palsy, but severe redness in the right eye. Slit lamp photographs showing engorged vessels on the conjunctiva of right eye. (B) Cerebral angiography showing arteriovenous shunt from the right middle meningeal artery and ascending pharyngeal artery, supplied from the right external carotid artery to the cavernous sinus (type C in Barrow classification, 10 red arrow, left column), and no more shunt after coil embolization (right column). 3개월뒤 10일전부터발생한우안충혈로내원하였다. 우안동공산대는여전하였으나, 안구운동장애는모두소실되어복시를호소하지는않았다 (Fig. 3A). 양안시력은모두 1.0이었으나, 안압은우안 21 mmhg, 좌안 19 mmhg로이전보다높았다. 우측귀주변의박동성잡음을호소하였고, 안구돌출계검사상우안 19.0 mm, 좌안 15.0 mm로우안이 4.0 mm 돌출되어있었다. 조영제를사용한안와전산화단층촬영과뇌혈관촬영술에서우측외경동맥에서분지 하는중간뇌막동맥 (middle meningeal artery) 과오름인두동맥 (ascending pharyngeal artery) 이해면정맥굴로연결되는 Barrow type C 경막동맥해면정맥굴샛길이확인되었다 (Fig. 3B). 10 신경외과에서경정맥접근법 (transvenous approach) 으로코일색전술을시행하였고, 2개월뒤동공산대를제외한모든증상과임상소견이소실되었다. 색전술후 6개월에시행한뇌혈관자기공명영상에서잔여동정맥샛길이나재발은관찰되지않았다. 980

5 - 박아람외 : 톨로사 - 헌트증후군후동정맥샛길 - 고찰 본증례는우측얼굴신경마비의과거력이있는중년여자환자에서, 통증을동반한우안완전동안신경마비로발현한톨로사-헌트증후군과우안결막충혈과안구돌출을주증상으로한우측경막동맥해면정맥굴샛길이순차적으로발생한경우였다. 톨로사-헌트증후군은염증질환이고, 경막동맥해면정맥굴샛길은혈관질환이지만, 이들의공통된병변부위는우측해면정맥굴로생각할수있다. 3,7-9 또한경막동맥해면정맥굴샛길도톨로사- 헌트증후군의주된임상소견인통증을동반한외안근마비로나타날수있다. 3-6 경막동맥해면정맥굴샛길에대한국내연구들에서도 % 의환자에서두통이나안구통증, % 에서복시를주증상으로하였다고보고하였다. 4-6 같은증상과임상소견을나타낼수있어이둘을감별하는것이필요하지만, 드물게는이들이함께혹은순차적으로발생하는경우들도보고되었다. 3,7-9 현재까지보고된 4 증례모두통증을동반한외안근마비로처음나타나스테로이드로증상이호전되었고, 이후동정맥샛길이발견되었다. Itokawa et al 7 은 71세여자환자에서통증은즉시호전되었으나 6개월이지나도지속된외향신경마비에대한평가를위해시행한뇌혈관조영술에서동정맥샛길을발견하였다. Sugano et al 8 의증례는 48 세여자환자가 4개월이지나도동안신경마비가완전히회복되지않았고, 이때결막충혈등전안부소견이나타나뇌혈관조영술로동정맥샛길을발견하였다. Brazis et al 9 은 73 세남자환자에서통증을동반한안구운동장애가스테로이드에좋은반응을보였지만, 이전영상을다시확인한결과동정맥샛길이있었다고하였다. Kim et al 3 이보고한국내증례는 47세여자환자에서통증을동반한외향신경마비가고용량스테로이드로호전되었으나, 17개월후경막동맥해면정맥굴샛길이발견되었다. 하지만모든이전증례는신경과에서보고하여안과적인임상소견이제한적으로기술되어있었다. 이러한병의경과를보인데에는 2가지설명이가능할수있다. 첫째로, 다양한임상양상을보일수있는경막동맥해면정맥굴샛길의특징으로설명할수있다. 3 경막동맥해면정맥굴샛길은외상성목동맥해면정맥굴샛길과달리대부분저절로발생하며, 그증상과임상소견이뚜렷하지않아진단이지연되는경우가많다. 3-6 아직명확한발생기전이밝혀져있지는않지만, 해면정맥굴내에정맥혈전이형성된후경막동맥의얇은벽이파열되어동정맥샛길이형성된다는의견이많은지지를얻고있다. 4,11 경막동맥해면정맥굴샛길의증상과예후는정맥혈의배액형태에따라달라지는것으로알려져있다. 3,12 정상적인아래바위정맥굴 (inferior petrosal sinus) 로의배액이유지되는경우에는해면정맥굴의압력이증가하여뇌신경을압박하거나뇌신경으로향하는혈류의스틸현상이발생하여뇌신경이마비되면서복시, 눈꺼풀처짐, 동공산대등의증상이주로나타난다. 반면에위눈정맥으로역류가발생하면결막충혈, 안구돌출, 안구주위통증, 눈꺼풀부종등의증상이주로발생하게된다. 12 따라서본증례는아래바위정맥굴로의정상적인혈류배액이유지되다가역류가시작되는시기에는외안근마비가발생하였고, 이후아래바위정맥굴이막히면서결막충혈, 안구돌출이발생하였을것으로추정할수있다. 3 하지만, 일반적으로동정맥샛길은본증례와같이스테로이드에빠르고좋은반응을보이지않는다. 8 더욱이본증례는심한우안주변통증의재발에서도스테로이드에좋은빠른반응을보였다. 또한처음통증을동반한우안완전동안신경마비가발생하였을때의영상소견은혈관성병변이아닌염증성조영증강임을다시확인하였다. 즉 2013 년국제두통학회 (International Headache Society, IHS) 에서제시한톨로사-헌트증후군진단기준인해면정맥굴의육아종성염증병변에합당하였다. 1 하지만본증례에서는첫증상이발현하였을때동정맥샛길에대한임상소견이명확하지않고검사의침습성때문에동정맥샛길에대하여가장정확한진단을할수있는뇌혈관조영술을시행하지않은제한점이있다. 두번째로, 톨로사- 헌트증후군의염증성변화로인해경막동정맥샛길이발생했을수있다. 7,8,11,13,14 경막동맥해면정맥굴샛길의발생기전을연구한동물실험에서정맥굴폐쇄와정맥고혈압에의해혈류공급이원활하지않으면서허혈에의한혈관신생이보고되었고, 또염증에의한혈관신생물질이동정맥샛길을생성하는가능성도제시되었다 이때염증과정에서분비가증가하는혈관신생물질로는혈관내피세포성장인자 (vascular endothelial growth factor, VEGF) 와염기성섬유모세포성장인자 (basic fibroblast growth factor, bfgf) 가확인되었다. 14,15 즉해면정맥굴의염증성변화로인하여신생혈관형성이촉진되고해면정맥굴과경막동맥사이에동정맥샛길이형성되었을수있다. 7,8 톨로사-헌트증후군은저절로호전되거나스테로이드에 72시간이내에반응하는특징을보이지만, 수일에서수주에걸쳐증상의악화와호전을반복하며, 일부에서는수차례재발하거나영구적인안구운동장애가남을수있어서장기간의추적관찰이필요한것으로알려져있다. 2 또톨로사-헌트증후군의스테로이드치료용량에대해서는아직확립된바가없지만, 많은연구자들은의미있는치료효과를얻기위해서는고용량 (1 mg/kg) 의스테로이드가필요하다고하였다. 2,3 본증례에서톨로사- 헌트증후군의재발이한차례있 981

6 - 대한안과학회지 2016 년제 57 권제 6 호 - 었는데, 첫증상때충분한스테로이드치료가이루어지지않아서 2개월뒤재발하였을가능성이있다. 또한불충분한치료로염증이지속되어혈관신생물질이증가하고이로인해동정맥샛길발생위험이함께증가하였을것으로생각된다. 완전히치료가되었다고하더라도적어도 2년이상의장기간의추적관찰기간이필요하다는보고도있듯이, 2 비교적좋은경과를가지는것으로알려져있는톨로사-헌트증후군이지만재발을염두에둔주의깊은경과관찰이필요함을본증례를통해확인할수있었다. 또한톨로사-헌트증후군환자에서드물게경막동맥해면정맥굴샛길이발생할수있으므로추적관찰기간동안이에대한고려도필요하겠다. REFERENCES 1) Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33: ) Lee HK, Lee SG. Clinical observations on Tolosa-Hunt syndrome. J Korean Ophthalmol Soc 2009;50: ) Kim I, Yang S, Lee H, et al. Cavernous sinus dural arteriovenous fistula mimicking Tolosa-Hunt syndrome. J Korean Neurol Assoc 2014;32: ) Ahn JH, Jung JH, Choi KD, Choi HY. The clinical characteristics and endovascular management outcomes of dural carotid cavernous fistulas. J Korean Ophthalmol Soc 2011;52: ) Kim C, Khwarg SI, Han MH. The clinical characteristics and treatment outcomes of dural carotid-cavernous sinus fistula. J Korean Ophthalmol Soc 2003;44: ) Jang JW, Lee SY, Kim SJ. Clinical characteristics of dural cavernous sinus fistula. J Korean Ophthalmol Soc 2000;41: ) Itokawa K, Fukui M, Yamamoto T, et al. Dural arteriovenous fistula as a possible cause of Tolosa-Hunt syndrome: a case report. J Neurol 2010;257: ) Sugano H, Iizuka Y, Arai H, Sato K. Progression of Tolosa-Hunt syndrome to a cavernous dural arteriovenous fistula: a case report. Headache 2003;43: ) Brazis PW, Capobianco DJ, Chang FL, et al. Low flow dural arteriovenous shunt: another cause of sinister Tolosa-Hunt syndrome. Headache 1994;34: ) Barrow DL, Spector RH, Braun IF, et al. Classification and treatment of spontaneous carotid-cavernous sinus fistulas. J Neurosurg 1985;62: ) Houser OW, Campbell JK, Campbell RJ, Sundt TM Jr. Arteriovenous malformation affecting the transverse dural venous sinus-an acquired lesion. Mayo Clin Proc 1979;54: ) Suh DC, Lee JH, Kim SJ, et al. New concept in cavernous sinus dural arteriovenous fistula: correlation with presenting symptom and venous drainage patterns. Stroke 2005;36: ) Lawton MT, Jacobowitz R, Spetzler RF. Redefined role of angiogenesis in the pathogenesis of dural arteriovenous malformations. J Neurosurg 1997;87: ) Sundt TM Jr, Piepgras DG. The surgical approach to arteriovenous malformations of the lateral and sigmoid dural sinuses. J Neurosurg 1983;59: ) Uranishi R, Nakase H, Sakaki T. Expression of angiogenic growth factors in dural arteriovenous fistula. J Neurosurg 1999;91: = 국문초록 = 톨로사 - 헌트증후군에서속발한경막동맥해면정맥굴샛길 1 예 목적 : 톨로사 - 헌트증후군이었던눈에서발생한경막동맥해면정맥굴샛길증례를경험하여이를보고하고자한다. 증례요약 : 고혈압이있는 64 세여자환자가우안주변의통증, 우안눈꺼풀처짐, 복시를주소로내원하였다. 우안동공산대와함께, 우안외사시와상사시, 그리고심한상전, 하전, 내전장애가있었다. 뇌 / 뇌혈관자기공명영상에서뇌혈관이상은없었으나우측해면정맥굴에염증소견이있어서경구스테로이드로치료하였고 3 일뒤통증이소실되어완전동안신경마비로발현한톨로사 - 헌트증후군으로생각되었다. 2 개월뒤우안눈꺼풀처짐은소실되고안구운동장애도호전되었으나, 심한우안주변통증이다시발생하였다. 톨로사 - 헌트증후군의재발로생각되어고용량스테로이드주사치료를시행하였고, 빠른호전을보였다. 3 개월뒤안구운동장애도소실되었으나, 우안결막충혈, 박동성잡음, 안구돌출이있어시행한뇌혈관조영술에서우측경막동맥해면정맥굴샛길이확인되었다. 경정맥코일색전술 2 개월후증상은소실되었다. 결론 : 해면정맥굴에발생하는육아종성염증질환인톨로사 - 헌트증후군에서경막동맥해면정맥굴샛길이뒤이어발생할수있으므로경과관찰시주의해야한다. < 대한안과학회지 2016;57(6): > 982

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