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1 Research in Vestibular Science Vol. 8, No. 1 June 2009 Review ISSN 소뇌경색의신경이과적고찰 계명대학교의과대학신경과학교실 이형 Neurotological Aspect of Cerebellar Infarction Hyung Lee, MD, PhD Department of Neurology, Keimyung University School of Medicine, Daegu, Korea 서 론 허혈성소뇌뇌졸중증후군 소뇌는대뇌의약 1/10 크기에해당하며뇌기능에미치는영향은대뇌에비해경미하여 little brain 으로불리어진다. 어지럼 ( 현훈 ) 은소뇌경색의가장흔한증상으로대개다른증상및징후들을동반하지만때때로어지럼단독만으로나타나는경우가있으며이경우말초성어지럼과의감별이용이하지않을수도있다. 소뇌경색에의한어지럼은그치료방침및예후가말초성어지럼과는다르며, 또한소뇌경색은전방에있는뇌간을압박하여환자가사망에이를수있으므로의심되는경우에는반드시 MRI를통한정확한진단및적절한치료가요구된다. 정확한진단및치료를위해서는각각의소뇌경색증후군의임상적양상에대한정확한이해가중요하므로저자는소뇌를지배하는각각의혈관들에서발생한소뇌경색의임상적특징을주로신경이과적관점에서살펴보고자한다. Received May 10, 2009 Accepted May 31, 2009 Corresponding Author: Hyung Lee, MD, PhD Department of Neurology, Keimyung University School of Medicine, 194 Dongsan-dong, Daegu , Korea Tel: Fax: hlee@dsmc.or.kr Copyrightc 2009 by The Korean Balance Society. All rights reserved. 소뇌에분포된혈관은크게세가지로후하소뇌동맥 (posterior inferior cerebellar artery, PICA), 전하소뇌동맥 (anterior inferior cerebellar artery, AICA) 및상소뇌동맥 (superior cerebellar artery, SCA) 이있다. 이들은모두뇌간의특정부위에혈액공급을한후각각그이름에따라소뇌의특정부위에대한혈액공급을담당한다 (Figure 1). 1. AICA 영역의소뇌경색에따른급성전정증후군 1) 임상적관점에서의해부 AICA는말초성및중추성전정계의혈액공급을담당하는가장중요한혈관이다. 약 75% 에서는기저동맥 (basilar artery) 의미측 1/3 (caudal third) 에서기원하며때때로중간 1/3에서나타나기도하며정상인에서도약 4% 에서는보이지않을수있다. 이경우에는발달된 PICA에서그혈관공급을대신할수있다. MRA상약 51% 에서관찰되며 PICA 에비해굵기가가는관계로소뇌반구의일부 ( 앞및내측 ) 와편엽 (flocculus), 중소뇌각 (middle cerebellar peduncle), 하뇌교 (lower pons) 의외측부위에있는 5번, 7번뇌신경핵, 위및내측전정핵 (superior and medial vestibular nucleus), 와우핵 (cochlear nucleus) 과 7번및 8번뇌신경및그근위부 (root portion) 의혈액공급을담당하며내이 (inner ear) 에분포되어있는주된혈관인내와우혈관 (internal auditory artery, IAA) 의주공급원이되기도한다. 1,2 AICA는혈관해부학적특징상말초성전정계인내이와중추성전정계를함 3

2 Res Vestibul Sci Vol. 8, No. 1 June ) AICA 영역의뇌경색의진단을위한중요한징후로서의미로경색 IAA의폐색은청각및전정기능의소실을초래하여급성청력소실및어지럼이나타난다 ( 미로경색, 즉내이경색 ). 대개뇌간및소뇌경색이동반되어나타나는경우가흔하지만드물게내이경색만단독으로나타나는경우도있다 ( 비록 MRI에서 AICA 영역의급성뇌경색이보이지만 ). 6 청력소실은신경과영역에서뇌졸중의증상으로덜알려져있다. 이러한이유로는첫째로, 환자들은어지럼및구토가심할때경한일측성청력손실을알지못하는경우가흔히있으며, 둘째로신경과의사들은전통적으로 AICA 경색의진단을위해순음청력검사 (pure tone audiogram, PTA) 과같은각종청력검사들을잘이용하지않는다는점이다. 하지만최근연구에따르면 AICA 영역의뇌경색환자의약 92% 에서 PTA에서급성청력소실이확인되었으며이들은모두온도안진검사에서일측성반고리관마비 (canal paresis) 를보였다. 3 이후여러연구들을종합해볼때미로경색은 AICA 영역의뇌경색의진단에중요한징후이다. 7-9 청력소실은대개영구적인것으로알려져있지만최근연구에따르면어지럼과함께청력소실도시간이경과되면서부분적혹은완전히회복된다. 10 A B Figure 1. Anatomic drawing of the territory of cerebellar arteries and their branches. M, medial; L, lateral. 께혈관공급하므로중추성전정이상소견뿐만아니라말초성전정이상소견에따른임상양상이함께나타날수있다. 3 IAA는약 90% 가량에서 AICA로부터기원하나일부에서는기저동맥에서직접나올수있다. 4,5 3) AICA 영역의뇌경색의전구증상으로서의고립성미로경색내이의혈액공급을담당하는혈관인 IAA는대개 AICA 에서기원하므로, 이론적으로부분적인 IAA 허혈성손상은급성와우전정기능의소실을초래한다. 기존의증례보고들과함께 최근연구에따르면 AICA 영역의뇌경색환자의약 8% (4/43) 에서 AICA 영역의뇌경색진단전 1주일사이에급성와우전정기능의소실만단독으로보였다 ( 즉미로경색 ). 15 상기연구들을종합해볼때뇌졸중의위험인자가있는노령층에서말초성안진과함께급성청력소실이나타날때비록전형적인뇌간및소뇌증상및징후가나타나지않더라도반드시허혈성손상의가능성을의심해보아야한다. 내이는 MRI에서잘보이지않으므로병리소견이없는한내이경색을확진할수는없다. 따라서급성와우전정증후군 (acute audio-vestibular syndrome) 의원인을규명하려고할때 MRI보다는여러임상양상을더중요시하여야한다. 16 4) AICA 영역의뇌경색에서전정장애의유형 AICA 영역의뇌경색에서나타나는전정장애의가장흔한유형은말초성및중추성전정장애의혼합이다. 즉환자는말초성전정장애의대표적인징후인반고리관마비와함께, 주시유발성안진, 원활추적성안구운동장애 (asymmetrically impaired smooth pursuit), 시각정보를이용한전정반응의조절이상 (impaired modulation of the vestibular responses using visual input) 등과같은중추성전정및안구운동장애가동시에나타난다 (Table 1). 이는 AICA가내이를포함한말초성전정계뿐만아니라중추성전정계에도혈액공급을한다는혈관해부학적사실에의해잘설명된다. 2,3 AICA에의해혈액공급을받는어느구조물의손상에서도어지럼이발생할수있으므로어지럼을일으키는확실한부위를밝힐수는없다. 하지만대부분의경우에서반고리관마비가동반되므로적어도이런환자에서는말초성전정계의이상에의해서어지럼이나타남을알수있다. 반 4

3 이형. 소뇌경색의신경이과적고찰 Table 1. Frequencies of audiovestibular dysfunctions in 82 patients with AICA territory infarction. Frequency (n=82) Vertigo as a presenting or main symptom at the time of AICA infarction 98% (80/82) Central ocular motor or vestibular signs* 96% (79/82) Vestibular labyrinth infarction 65% (53/82) Cochlear infarction 63% (52/82) Combined vestibulo-cochlear infarction 60% (49/82) No auditory or vestibular infarction 32% (26/82) Isolated vestibular infarction without cochlear involvement 5% (4/82) Isolated cochlear infarction without vestibular involvement 3% (3/82) Non-vertigo symptom as a presenting or main symptom at the time of AICA infarction 2% (2/82) Isolated audiovestibular loss without central symptoms or signs 1% (1/82) *Asymmetrical abnormalities of pursuit or optokinetic nystamus, gaze-evoked bidirectional nystagmus, or impaired modulation of the vestibular response using visual input. AICA, anterior inferior cerebellar artery. Table 2. Patterns of audiovestibular loss in 82 patients with AICA territory infarction. Group 1 (n=35) Group 2 (n=13) Group 3 (n=3) Group 4 (n=4) Group 5 (n=24) Group 6 (n=1) Presented with vertigo Yes Yes Yes Yes Yes Yes No Combined audiovestibular loss Yes Yes No No No Yes No Isolated auditory loss No No Yes No No No No Isolated vestibular loss No No No Yes No No No No audiovestibular loss No No No No Yes No Yes Associated with ocular motor dysfunction Yes Yes Yes Yes Yes No No Associated with other neurological symptoms or signs Yes Yes Yes Yes Yes No Yes Prodromal audiovestibular disturbance No Yes No No No No No AICA, anterior inferior cerebellar artery. Group 7 (n=2) 대로일부환자에서는온도안진검사에서정상적인소견을보이므로이경우에는어지럼은중추성전정계의손상에의함을알수있다. 결론적으로 AICA 영역의뇌경색에서어지럼은말초성및중추성전정계모두의손상이그원인으로생각된다 (Table 2). 5) AICA 영역의뇌경색에서이석기능이상눈기울임반응 (ocular tilt reaction, OTR) 은관상회전면 (roll plane) 에서의전정안구반사이상에의해발생하며, 머리기울임 (head tilt), 스큐편위 (skew deviation) 및안구회선 (cyclotorsion) 의 3가지반응으로이루어진다. 17 OTR은대개뇌간병변에의해흔히나타나나 AICA 영역의경색또한부분적인 OTR을초래하여머리기울임없이안구회선및스큐편위만나타날수있다. 18,19 이경우모든환자에서주 관적수직축 (subjective visual vertical, SVV) 의이상 ( 즉 SVV의 tilting) 도함께나타난다. 병변측을향한공액성안구회선은스큐편위를동반하며감각신경성청력소실및반고리관마비가동반되었지만, 청력소실및반고리관마비가없는환자에는사편위의동반없이반대측으로향하는안구회선만관찰되었다. 19 두군간의 MRI 소견에서는경색부위의차이는보이지않았으며이러한결과는내이를포함한말초성전정계가 AICA 영역의뇌경색에서안구회선의방향을결정짓는주된인자라는사실을의미한다 PICA 영역의소뇌경색에따른급성전정증후군 1) 임상적관점에서의해부 PICA는추골동맥 (vertebral artery) 에서분지되는혈관 5

4 Res Vestibul Sci Vol. 8, No. 1 June 2009 중가장굵은혈관이나정상인에서도그개인차가심하여서약 15~25% 가량에서는선천적으로보이지않으며 5% 에서는혈관발육이부진 (hypoplastic) 할수있다. 이와같이정상인에서그개인차가심하므로이경우잘발달된 AICA가혈액공급을대신할수있다. 이처럼정상인에서도 AICA 와 PICA는서로풍부한측부순환 (collateral circulation) 을통해소뇌의정상적인혈관공급을유지한다. PICA의내측분지 (medial branch) 는연수 (medulla) 의배측부위 (dorsal part) 와함께미측소뇌 (caudal cerebellum) 의혈액공급을담당한다. PICA는소뇌반구의미측 (caudal) 대부분과소절 (nodulus), 목젓 (uvula), 추체 (pyramid), 결절 (tuber) 및비스듬틀 (clivus) 을포함하는하충부 (inferior vermis) 와편도 (tonsil) 의혈액공급을담당하며혈관폐색시어지럼이주증상으로나타난다. 20 외측분지 (lateral branch) 는내측분지가지배하는부위를제외한하외측소뇌반구 (hemisphere) 에분포되어있으며이부위의경색은때때로증상이없을수가있다. MRA상약 89% 에서 PICA를관찰할수있다. 소절은전정안반사를조절하는데있어중요한부위로알려져있으며내측 PICA에의해혈액공급을받으므로내측 PICA에국한된뇌경색은심한어지럼, 구토및자세불안과같은순수한전정증후군으로나타날있다. 20 외측 PICA 는외측소뇌반구에분포되어있고사지의조화로운운동조절에관여하므로외측 PICA에국한된경색은어지럼, 구토등의증상없이, 상하지조화운동불능증 (limb ataxia), 보행장애, 근긴장도감소 (hypotonia) 등이나타날수있다. 21 2) 내측 PICA 영역의소뇌경색에의한가성-말초성전정장애내측 PICA 영역의허혈성뇌경색의전형적인증상들은심한어지럼, 구토, 측방돌진 ((body lateropulsion), 구음장애, 사지실조증등이있다. 어지럼과연관된부위로는소절로서동측의전정신경핵과서로연결되어있으며또한미로로부터직접적인연결을받는다. 22,23 기능적으로소절에서전정신경핵으로가는풀킨예세포는동측의전정신경핵에대한억제성신호를보내는것으로알려져있다. 22,23 내측 PICA 소뇌경색은경색의크기가적은경우에상하지조화운동불능증이나타나지않거나그정도가경할수있으므로 24,25 그임상양상이급성말초성전정장애 (acute peripheral vestibulopathy, APV) 와유사할수있다. 응급실에급성어지럼, 안진및보행장애를주소로오는환자의약 25% 에서내측 PICA 영역의경색이원인이다. 26 PICA 내측분지에국한된 소뇌경색에서는말초성안진과유사하게병변쪽을향한수평및회전성분을가진안진을보였고환자는일관되게병변반대쪽으로넘어지는경향을보일수있다. 27,28 이에대한정확한기전은알수없지만침범된소절로부터전정핵으로가는억제성신경섬유인풀킨예세포의차단으로인한내이의상측 하측 외측반고리관에서의전정자극이유입되는상측 (superior) 및내측 (medial) 전정핵의탈억제 (disinhibition) 현상이일어나고이로인해병변쪽으로향하는안진이나타나고내이질환에서는안진의방향 ( 즉주변사물의돌아가는방향 ) 반대방향으로환자가기울어지는원리로환자의측방돌진을설명할수있다. 즉전정핵에가해지는기능적이상 (functional but not structural vestibular nuclei lesion) 으로인해마치내이질환에서볼수있는현상이나타난다고할수있겠다. 최근연구에따르면 240명의고립성소뇌경색환자의약 11% (25/240) 에서어지럼단독만을증상으로보였으며대부분 (24/25: 96%) 에서소절을포함한내측 PICA 영역의경색을보였다 (Figure 2, 3). 29 Head thrust 및온도안진검사에서정상소견을보인다는점에서 APV와감별될수있다 (Table 3). 특히 Head thrust 검사는특별한장치없이간단히할수있으므로뇌졸중환자를진단하고치료하는임상가는반드시두부충돌검사의방법및결과해석에대한정확한이해를하여야한다. 이외에도심한자세불안 ( 즉측방돌진 ), 주시유발성안진등도약 71% 및 54% 에서관찰되므로중추성어지럼을시사하는중요한소견이다. 소뇌경색과 APV를감별하는데있어두부충돌검사의임상적의의는최근다른연구에의해서도확인되었다. 30 비록내측 PICA 영역의작은소뇌경색은대개그예후가양호하지만고립성소뇌경색은심장혹은혈관에서기원한색전 (emboli) 이그원인이되므로 31 재발성색전은추후치명적인뇌간경색을초래할수있으므로반드시치료되어야한다. 또한소뇌경색의약 25% 에서부종에의한뇌압상승을일으킬수있으며특히 PICA영역의경색에서상소뇌동맥 (superior cerebellar artery, SCA) 영역의경색보다더흔히뇌압이상승되어뇌수두증, 뇌간압박, 심폐기능정지등과같은심각한합병증을초래할수도있다. 31,32 3) PICA 영역의소뇌경색에서이석기능이상앞에서도언급하였듯이, OTR은말초전정계의타원낭 (utricle) 에서부터중뇌- 간뇌접합부의 Cajal 사이핵 (interstitial nucleus of Cajal) 에이르는모든병변에서발생할수있 6

5 이형. 소뇌경색의신경이과적고찰 Figure 2. Topographic distribution of isolated cerebellar infarction in the territory of either the medial branch of the posterior inferior cerebellar artery (patients 1-24) or the anterior inferior cerebellar artery (patient 25). Patients 1-24, A, section at upper medulla level; B, section at midsagittal level. Patient 25, A: section at middle pontine level. 다. 따라서이론적으로는소뇌병변에서는 OTR이나타날수없지만 1997년 Halmagyi 등은소절 (nodulus) 을포함한 PICA의내측분지가지배하는영역에뇌졸중 ( 소뇌경색 1 예및소뇌출혈 1예 ) 이발생한 2명의환자에서병변반대측을향하는공액성안구회선 (contraversive conjugate ocular torsion) 이유일한신경학적이상소견임을보고하였다. 33 비록머리기울어짐은없었지만안구회선은관상회전면에 서의전정안구반사의이상을의미하므로 OTR 진단에있어서필수적인징후이다. 소뇌병변에서 OTR의발생기전은정확하게밝혀져있지는않지만손상된소절에서전정핵으로가는억제성신경섬유인풀킨예세포의손상과이로인한전정핵의이차성이석신경원 (secondary otholithic neurons) 의신경흥분이과도하게일어나서병변반대편으로향하는안구회선이나타나는것으로설명할수있다. 하지만, 7

6 Res Vestibul Sci Vol. 8, No. 1 June 2009 Figure 3. Frequency of cerebellar infarction subtypes simulating vestibular neuritis. PICA, posterior inferior cerebellar artery; AICA, anterior inferior cerebellar artery; SCA, superior cerebellar artery. 내측 PICA 질환은비교적흔히볼수있는뇌졸중인데반해이러한현상이매우드물게볼수있으므로이러한가설이외에다른기전들을생각해볼수도있다. 4) Non-AICA (mostly PICA) 영역의소뇌경색과연관된급성청력소실뇌졸중에의한급성청력소실은대부분 AICA영역의뇌경색과동반되어나타나지만, 드물게 IAA는드물게는 PICA에서기원될수있으므로 PICA 영역의소뇌경색도급성청력소실을일으킬수있다. 34 Mazzoni는관자뼈해부 (temporal bone dissection) 소견상 100명중에서약 3명에서 IAA가 PICA에서분지됨을보고하였다. 35 최근연구에따르면 685명의후방순환계뇌졸중환자중 7명 ( 약 1%) 에서 AICA 영역이아닌뇌경색과연관되어청력소실이나타났으며이중 5명 (71%) 에서 PICA 영역의소뇌경색이보였다 (Figure 4). 36 이는기존의 Mazzoni의연구결과와일치하며병리소견없이청력장애의정확한부위를알수는없지만각종청각신경생리검사를통해서청력소실은내이기원으로생각할수있다. 36 결론적으로급성청력소실이 AICA 영역이아닌후방순환계뇌경색과연관되어나타날때대부분 PICA 영역의뇌경색과함께나타나며이는 IAA 가일부에서는 PICA에서분지됨을의미한다. 3. SCA 영역의소뇌경색에따른급성전정증후군 1) 임상적관점에서의해부 소뇌에분포된혈관들중그굵기및분지되는부위가 Table 3. Vestibular findings and imbalance in 24 patients with pseudo-apv associated with medial PICA territory cerebellar infarction. Patients Head thrust test normal SN 15 GEN Typical* 13 Unidirectional 4 Gaze to only lesion side 7 Asymmetrical pursuit 6 Asymmetrical OKN 4 Canal paresis none Imbalance Grade Direction Lesion side 17 Healthy side 7 APV, acute peripheral vestibulopathy; PICA, posterior inferior cerebellar artery; SN, spontaneous nystagmus; GEN, gaze evoked nystagmus; OKN, optokinectic nystagmus. *Direction-changed bidirectional gaze- evoked nystagmus that the intensity was maximal when gaze to the lesion side. Direction-fixed unidirectional gaze- evoked nystagmus beating toward the side of lesion. Ipsilateral impairment of smooth pursuit with frequent corrective saccade. Canal paresis defined as side differences more than 25% at bithermal caloric stimulation. 가장일정한혈관으로서후대뇌동맥 (posterior cerebral artery) 이분지되는지점의바로아래쪽에서기저동맥으로부터기원하며 MRA상약 98% 에서 SCA를볼수있다. SCA 경색환자는 AICA 및 PICA의병변보다현훈을호소하는경우가드물다. 소뇌반구및충부 (vermis) 의문측부위 (rostral part) 와치상핵 (dentate nucleus) 및꼭지핵 (fastigal nucleus) 에분포되어있으며문측뇌교의외측부위에있는상소뇌각 (superior cerebellar peduncle), 제 4뇌신경및각종신경계에혈액공급을담당한다. 37,38 충부중안구운동과밀접한연관이있는부위 (oculomotor vermis- layer Ⅵ and Ⅶ) 의혈액공급은 PICA의내측분지와 SCA가서로겹쳐서분포되어있다. 문측외측소뇌반구는주로사지조절과연관되어있는 8

7 이형. 소뇌경색의신경이과적고찰 반면에문측충부는보행및자세조절기능을담당한다. 문측충부의 central lobule은 fmri에서발의움직임과연관되어활성화되는부분으로알려져있으며이부분은내측 SCA에의해혈액공급을받고있다. 39 2) SCA 영역경색의전형적인증상전형적인 SCA 증후군은문측뇌교의외측침범에따른편측사지겨냥이상 (dysmetria), Horner 증후군, 병변반대측활차신경 (trochlear nerve) 마비및사지감각마비 ( 온도각및통각 ) 등의증상을가지지만대부분의경우첨부기저동맥증후군 (top of basilar syndrome) 에동반되어나타나므로 SCA 경색에의한안구운동장애는주로동반된뇌간, 시상 (thalamus) 및후두엽병변에의한경우가많으며소뇌단독의 SCA 경색은드문것으로알려져있다. 40 SCA 경색에의한전형적인안구운동장애는 saccadic lateroplusion 으로병변반대쪽으로의 saccades는겨낭과다 (overshooting), 병변쪽으로의 saccades는겨냥부족 (undershooting) 을보이며수직방향의 saccades는비스듬하게병변쪽에서멀 어지는현상즉 saccades의 contrapulsion 이다. 41 Contrapulsion은상소뇌각 (superior cerebellar peduncle) 과인접한꼭지핵유출로 (uncinate fasciculus) 의손상으로설명할수있다. 중추성전정계에대한직접적인손상이적은관계로 AICA와 PICA 병변에비해환자들은심한어지럼을호소하는경우가드물다. 3) 측방돌진이주증상인내측 SCA 영역의소뇌경색 SCA 영역의뇌경색의여러임상양상중가장흔한유형은외측 SCA 영역의경색으로서전체 SCA 영역의경색중약 50% 를차지하며 38,42 주위가돌아가지않는어지럼, 오심, 비틀거림, 및심한상하지조화운동불능증을주된증상으로한다. 내측 SCA 영역의경색은임상양상이잘알려있지않았는데최근연구에따르면 14명의내측 SCA영역의고립성경색환자중약 76% (11명) 에서서있지못할정도의심한자세불안을보였으며이는문측충부가보행, 근육긴장도, 자세조절등에관여한다는기존의연구결과들과일치하는소견이다. 43 따라서심한측방돌진은어지럼과보행장애를호소하는환자에서내측 SCA 영역의경색과외측 SCA 영역의경색을감별하는데도움이되는임상적지표로사용될수있다. Table 4에서각종소뇌경색에서나타나는임상소견들을신경이과적관점에서요약하였다. 결 론 Figure 4. Frequency of VBIS subtypes associated with sudden deafness. VBIS, vertebrobasilar ischemic stroke; PICA, posterior inferior cerebellar artery; AICA, anterior inferior cerebellar artely. 각각의소뇌경색은특징적인증상및징후를가지므로각소뇌경색의특징적인임상양상을이해하는것은적절한진단및효과적인치료를위해매우중요하다. 두부충돌검사는내이기원의어지럼과소뇌경색과의감별에중요한검사로서모든어지럼환자에서반드시시행되어야한다. Table 4. Differentiating among common cerebellar ischemic stroke syndromes focused on neuro-otological aspects. AICA CI Vertigo/related structure CP/related structure Hearing loss/related structure Gait ataxia ++/inner ear, 8 th nerve, VN, flocculus ++/inner ear, 8 th nerve, VN ++/ inner ear, 8 th nerve, cochlear nucleus medial PICA CI ++/nodulus none rare ++ lateral PICA CI none none none none medial SCA CI rare none rare/lateral lemniscus ++ lateral SCA CI none none none + CP, canal paresis; VN, vestibular nucleus; AICA, anterior inferior cerebellar artery; PICA, posterior inferior cerebellar artery; SCA, superior cerebellar artery; CI, cerebellar infarction. + 9

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untitled J Korean Balance Soc 2006;5(2):224-228 계명대학교의과대학신경과학교실 1,2, 원광대학교의과대학생리학교실 3,4 김현아 1,2, 이형 1,2, 박병림 3,4 Body Lateropulsion as an Isolated or Predominant Symptom of a Pontine Infarction Hyun-Ah Kim, M.D.