원저 서울의료원신경과, 중앙대학교의과대학신경과학교실 a, 심장내과 b 박태환이은희 a 윤영철 a 김상욱 b Differences in Reactivity of Middle and Posterior Cerebral Artery in with Neurocardiogenic Syncope Tai Hwan Park, M.D., Eun Hee Lee, M.D. a, Young-Chul Yoon, M.D. a, Sang Wook Kim, M.D. b Department of Neurology, Seoul Medical Center; Department of Neurology a and Cardiology b, Chungang University College of Medicine, Seoul, Korea Background: Neurocardiogenic syncope (NCS) is the most common type of neurally mediated syncopes. Though presyncopal symptoms may represent hypoperfusion in posterior circulation, studies for evaluating the cerebrovascular response of posterior circulation in patients with NCS were scanty. We evaluated the cerebrovascular response of the posterior circulation using transcranial Doppler monitoring in patients with NCS. Methods: We measured the blood flow velocity (BFV) of the middle cerebral artery (MCA) and contralateral posterior cerebral artery (PCA) simultaneously in 11 patients with a diagnosis of NCS both at rest and during the head-up tilt test (HUT) for 5 minutes. The mean arterial pressure (MAP), pulse rate (PR), and end-tidal pco 2 (EtCO 2) were also monitored. The obtained data were compared with those of 17 normal control subjects. Results: The syncope patients showed a significantly larger decline in BFV of PCA (P<0.05) and a larger increase in pulsatility indexes of MCA and PCA during HUT compared to those of control subjects. In control subjects BFV of PCA decreased less than those of MCA. On the contrary, in patients with NCS, those of PCA decreased more. These different regional cerebrovascular responses to HUT were accompanied with neither presyncopal symptoms nor decrease in MBP. Conclusions: The regional cerebrovascular response to HUT in NCS patients was different in the PCA flow. Impairment of autonomic neural control of posterior circulation may play an important role in the pathophysiology of NCS. J Korean Neurol Assoc 26(1):28-34, 2008 Key Words: Syncope, Transcranial Doppler, Posterior cerebral artery 서론 실신은일시적으로뇌관류가저하되어나타나는갑작스런의식소실과자세의긴장도소실을가리킨다. 임상의가흔히접하는증상이지만, 약 40% 의경우에서는정확한원인을찾을수없고환자의약 1/3 은실신재발을겪는다. 1 다른신경학적 Received August 9, 2007 Accepted September 6, 2007 *Tai Hwan Park, M.D. Department of Neurology, Seoul Medical Center, Samsung-dong 171-1, Gangnam-gu, Seoul, 135-740, Korea Tel: +82-2-3430-0643 Fax: +82-2-562-9883 E-mail: strokezero@gmail.com 이상이나심혈관계의이상징후등이동반되지않을경우신경심장성실신 (neurocardiogenic syncope, 이하 NCS) 이가장흔한데, 혈관미주신경성실신 (vasovagal syncope) 이라고도하며신경매개성실신 (neurally mediated syncope) 의범주에속한다. 2 유발조건에따라서중추성 (central), 자세성 (postural), 상황성 (situational) 실신으로구분할수있으며 3 이중자세성실신이가장흔하고기전을밝히는연구들의주대상이되어왔다. 기립시발생하는심장으로의정맥혈액량의유입감소는정상적인반사작용으로서교감신경을활성화시키는데, 실신환자들은이때과도한심실수축이발생하고이로인해좌심실의기계수용체 (mechanoreceptor) 가자극받아구심성신경이 28
뇌간을거쳐교감신경의억제와부교감신경의활성화를통해서맥과심박출량의감소를일으키는것으로추정하고있다. 3-5 뇌혈류초음파검사 (TCD) 를이용해 NCS 환자에서기립후증상발생전후에나타나는뇌혈류의변화를관찰하는연구들이있어왔으며, 6-13 실신환자들에서뇌혈관조절능의이상이있다는주장이있었지만, 8 아직까지일차적인뇌혈관의조절이상이 NCS 환자에서존재하는지여부는밝혀지지않았다. 한편과거에진행된연구는모두중대뇌동맥에서의변화만관찰한것으로상대적으로혈류속도가느리고전방순환계에비해교감신경원의수용기가부족하다고알려져있는추골기저혈관계를함께관찰한연구는없었다. 저자들은실신전증상 (presyncopal symptoms) 중일부가후방순환계의혈류저하를시사하는점과자율신경의반사를담당하는중요한신경핵들이대부분뇌간에위치하는점을고려할때, NCS 환자에서후방순환계의혈관운동반응성이상유무를조사해볼필요가있다고생각하였다. 이에저자들은기립검사동안뇌혈류초음파를이용해중대뇌동맥과후대뇌동맥을동시에모니터링하여기절환자들이정상인과다른반응을보이는지조사해보았다. 대상과방법 1. 대상 2006 년 1월부터 7개월간실신을주소로신경과및심장내과외래를방문한환자중 NCS 으로진단되고최근 2년간 2차례이상실신의병력이있었던 11명의환자 ( 남자 5명, 평균연령 27±10세 ) 를대상으로하였다. 자세한병력청취를통해자세성이외의실신양상을보이는환자들은배제하였으며이학적, 신경학적검사소견상정상인환자만을포함하였다. 모든환자들에서일반혈액검사를포함하는혈액검사와 12극심전도, 기립혈압검사, 24시간심박동감시기, 경흉심장초음파, 기립경사침대검사 (tilt-table test) 와자율신경기능검사를실시하여진단을내리는데보조자료로활용하였다. 정상대조군은모두 17명으로병원직원중건강한자원자로서실신의병력이없고최근 2년간자세유발성실신전증상도없었던자로하였다. 환자및대조군모두에게뇌자기공명혈관촬영을실시하여뇌혈관이상유무확인및내경동맥으로부터기원하는후대뇌동맥의검사가능성을배제하였다. 2. 방법기립경사침대검사는모두피검자의동의하에실시하였으며, 가벼운점심식사후최소 4시간이상경과한오후 5시경에실시하였다. 흡연자는 24 시간이상금연하도록하였고, 12시간이내에커피를포함하여혈압및혈관반응에영향을줄수있는모든약제를금지한상태에서실시하였다. 환자는기립경사침대에앙와위자세로편하게누워 10분간휴식후 1분간격으로 2차례생체활력징후및중대뇌동맥과후대뇌동맥의혈류속도를측정하여평균값으로서안정시기준을구하였다. 환자의복부와대퇴부에는압력을느끼지않을정도로만지지대를고정하여기립해있는동안에사고가일어나지않도록하였다. 혈압및심박동수는우측상완에혈압측정띠를감고환자감시장치 (PAMO II, MEK ) 를이용해측정하였으며, 호기말이산화탄소분압측정기 (Microstream ) 를통해호기말이산화탄소분압 (EtCO 2) 을측정하고과호흡여부를관찰하였다. 혈류속도의평가는 TCD (Nicolet Companion III) 를이용하였으며, 탐지자고정장치를사용하여 2 MHz 탐지자중하나는측두창을이용해깊이 55-60 mm 에서중대뇌동맥의결흐름 (laminar flow) 이가장잘관찰되는위치에고정시키고, 다른하나는반대편측두창에서깊이 65-70 mm 에서후대뇌동맥의결흐름이가장잘관찰되는곳에고정하여연속적으로측정하였다. 측정장치들로부터의안정시값을구한후바로기립경사침대를 70도로세워 5분간환자의활력징후및혈류속도의변화를관찰하였다. 기립경사침대검사중환자가실신전증상을느끼거나불편을호소하면검사를즉시중단하는것을원칙으로하였다. 자료의분석을위해기립후 30초, 2분, 5분째의측정치들을환자군과대조군사이에비교하였으며각군내에서기준값과비교하여차이가있는지조사하였다. 혈류속도는수축기, 이완기, 평균혈류속도로구분하여비교하였고기록된 spectrum 내의 pulsatility index (P.I.) 도조사하였다. 환자군과대조군사이의연속형자료의비교분석은 Mann-Whitney U test 를이용하였으며, 각기록시점들에서측정된값들과기준값의비교는 paired t-test 를사용하였다. 빈도분석은 chisquare 검정을하였다. P 값은 0.05 미만이면통계적유의성이있는것으로판단하였고, 모든통계분석은 SPSS for Window version 11.0 을이용하였다. 결과 환자군의평균연령 (27 세, 18-49) 이대조군보다 (34 세, 19-53) 약간낮았으나통계적차이는없었고, 성별분포의차이도없었다. 안정시평균혈압, 심박동수, EtCO 2 는대조군과차이가없었으나안정시평균혈류속도가중대뇌동맥과후대뇌동맥모두환자군에서약간높았으며특히후대뇌동맥에서의차 J Korean Neurol Assoc Volume 26 No. 1, 2008 29
박태환이은희윤영철김상욱 Table 1. Demographic and baseline characteristics of subjects Parameter Syncopal patients Control subjects p n 11 17 Male, n (%) 5 (46) 7 (41) 0.57 Age, y 27±10 (18-49) 34±10 (19-53) 0.07 Mean BP, mm Hg 82±9 (66-96) 85±10 (77-118) 0.71 Heart rate, bpm 67±12 (45-90) 71±11 (49-89) 0.55 EtCO 2, mm Hg 39±3 (35-47) 38±3 (32-43) 0.35 Systolic BFV of MCA, cm/s 101±19 (72-139) 90±19 (61-137) 0.13 Diastolic BFV of MCA, cm/s 53±10 (38-68) 46±10 (29-69) 0.18 Mean BFV of MCA, cm/s 72±12 (51-92) 65±14 (42-99) 0.11 a Systolic BFV of PCA, cm/s 69±14 (47-88) 53±10 (36-70) 0.005 a Diastolic BFV of PCA, cm/s 36±8 (23-49) 27±6 (16-34) 0.002 a Mean BFV of PCA, cm/s 50±10 (33-61) 38±7 (27-47) 0.005 P.I. of MCA 0.67±0.14 0.68±0.09 0.7 P.I. of PCA 0.67±0.19 0.68±0.12 0.6 BP; indicates blood pressure, BFV; blood flow velocity, MCA; middle cerebral artery, PCA; posterior cerebral artery, P.I.; pulsatility index. Values are mean±sd (range). a Significant difference between patients and control (p<0.05). 이는통계적으로의미가있었다. 하지만안정시 P.I. 의차이는없었다. 환자군과대조군의안정시측정값들은표 1에요약하였다. 5분간의기립검사동안의미있는실신전증상이나불편감을호소하여검사가중단된피검자는없었으며환자군중한명이머리가저리다고하였으나평소느꼈던실신전증상은아니었다. 안정시평균혈압은환자군과정상군이각각 82±9, 85±1 mmhg 로비슷했으며, 양군모두 30 초측정값이안정시측정치에비해비슷한정도로증가하는양상 (+3.9, +5.9 mmhg; 환자, 대조군 ) 을보였으나 2분과 5분측정치에서정상대조군은증가된상태가유지된반면에환자군은약간감소하는양상을보였다 (Table 2). 하지만안정시혈압이하로떨어지는변화는 Table 2. Changes of cardiovascular and TCD parameters in the syncopal patients and control subjects during HUT Mean BP, mm Hg Heart rate, bpm EtCO 2, mm Hg P.I. of MCA P.I. of PCA Baseline 30 sec. 2 min. 5min. 82±9 85±10 67±12 71±11 39±3 38±3 0.67±0.14 0.68±0.09 0.67±0.19 0.68±0.12 89±11 a 84±8 82±10 87±10 a 90±11 a 90±12 a 82±13 a 85±14 a 87±13 a 77±10 a 80±12 a 81±12 a 37±4 a 36±4 a 36±3 a 36±3 0.71±0.18 0.7±0.1 0.74±0.26 0.7±0.11 0.81±0.24 0.69±0.1 0.8±0.24 0.68±0.13 37±4 a 36±3 0.89±0.42 0.68±0.12 0.93±0.55 0.7±0.13 Values are mean±sd. a Significant difference from baseline (p<0.05, paired t-test). 아니었다. 심박동수는양군모두안정시보다의미있는증가를보였는데특히첫 30초동안의변화가가장컸다. 심박동수가기립해있는 5분간증가하는양상은양군에서비슷하였으나첫 30초동안의증가폭은환자군에서더컸다 (Fig. 1). EtCO 2 는안정시환자군과정상군이 39±3, 38±3 mmhg 에서기립후 30초에각각 37±4, 36±3 mmhg 로평균 2 mmhg 정도씩감소했으나 (Table 2), 이후의기립동안추가적인감소는관찰되지않았다 (Fig. 1). 중대뇌동맥과후대뇌동맥의 P.I. 는정상대조군에서는기립동안변화가관찰되지않았으며, 환자들은시간이지남에따라약간씩증가하는양상이었으나대조군과비교해통계적유의성은없었다 (Table 2). 혈류속도는환자와대조군모두에서두혈관의수축기, 이완기, 평균혈류속도가모두안정시보다의미있게감소하였으며 (Table 3), 이는활력징후의변화와마찬가지로초기 30 초간의변화폭이가장컸다. 안정시혈류속도에대한기립후혈류속도의변화를보면중대뇌동맥의경우평균혈류속도가첫 30 초동안환자군과대조군이각각 18.1±14.1%, 15.9±8.5% 감소하여차이가없었으나 (P=0.963), 후대뇌동맥의경우환자들은평균속도가첫 30 초동안 21.7±12.6% 감소한반면대조군은 12.4± 9.5% 만감소하여유의한차이를보였고 (P=0.047), 이러한차이는 2분과 5분에측정한감소율에서도정상대조군과차이를보였다 (Table 3, Fig. 2). 또한정상대조군의혈류속도가기립후 30초에감소했다가 2분, 5분째에약간씩다시증가하는양상을취하는반면, 환자군에서는 2분째에비록감소폭은줄었지만계속감소하는양상이중대뇌동맥및후대뇌동맥모두에서관찰되었다. 대조군과달리환자군의경우에는기립해있는동안의혈류속도감소정도가통계적으로유의한차이는없었지만, 후대뇌동맥이중대뇌동맥보다컸다 (Table 3). 고찰 실신전증상을포함하는실신증상대부분은뇌관류압저하로인해나타나게된다. 하지만뇌는관류압변화에도불구하고일정한뇌혈류량을유지하는뇌혈관자율조절능 (cerebral autoregulation) 을가지고있다. 14 따라서이전의 NCS 에관한연구에서는 6-13 실신환자들이뇌혈관자율조절능이상을가지고있는지를주로조사하였고, 급격한뇌혈류변화를실시간으로평가하기위해서 TCD 가사용되었다. Grubb 등 8 은 NCS 환자에서관류압저하에도불구하고역설적혈관수축이발생한다고주장하였다. 하지만이러한현상이기립시동반된저탄산혈증에의한 30
Figure 1. Changes of cardiovascular parameters for patient group (solid line) and control group (dotted line) during 5-minute head-up tilt; error bars represent mean±sd. Table 3. Rate of changes in blood flow velocity of the middle cerebral artery and the posterior cerebral artery Rate of interval change from baseline value Systolic BFV of MCA, % Diastolic BFV of MCA, % Mean BFV of MCA, % Systolic BFV of PCA, % Diastolic BFV of PCA, % Mean BFV of PCA, % 30 sec. P b 2 min. P b 5 min. P b -17±10 a 0.264-21±19 a 0.047-21±13 a 0.073-13±7 a -11±9 a -11±9 a -14±15 a 0.926-27±26 a 0.053-27±24 a 0.073-13±9 a -10±12 a -9±13 a -18±14 a 0.963-27±22 a 0.042-26±19 a 0.147-16±9 a -12±11 a -13±11 a -19±7 a 0.003-25±15 a -9±9 a -17±16 a 0.111-29±21 a -8±10 a -5±10-22±13 a -12±9 a 0.047-31±17 a Values are mean±sd. a Significant difference from baseline (p<0.05, paired t-test). b P value represents difference between the patients and normal control subjects. -7±8 a 0.000-23±9 a 0.000-31±26 a -6±10 a 0.000-7±13 0.004-8±9 a 0.000-28±15 a -11±10 a 0.002 J Korean Neurol Assoc Volume 26 No. 1, 2008 31
박태환이은희윤영철김상욱 Figure 2. Systolic (SFV), diastolic (DFV), and mean flow velocity (MFV) changes of MCA and PCA for patient group (solid line) and control group (dotted line) during 5-minute head-up tilt; error bars represent mean±sd. 혈관수축반응이라는반론과 15 함께이완기혈류속도의감소내지는소실이선행하는혈압저하에따른이차적인변화, 즉뇌혈관폐쇄압력 (closing pressure of cerebral vessel) 이하로이완기혈압이떨어지면서발생한종말혈관의허탈 (collapse of downstream vessel) 때문이라는연구결과도있다. 12 실신환자의기립검사시측정된역동적뇌혈관조절능이정상인과다르지않다는연구 16 도있었지만, Dan 등 10 은혈압감소전에실신전증상과중대뇌동맥혈류속도의감소가선행되는것을발견 32
하였고, 따라서뇌혈관조절능의변화가실신의발생에기여한다고주장하였다. 이렇듯아직까지 NCS 의발생기전으로서뇌혈관조절능이상에대한논란은계속되고있는상태이다. 현재까지의관련연구들은혈류변화를중대뇌동맥에서만관찰하였는데, 6-13,17 실신환자들의전구증상중시야장애, 동공산대, 복시, 안면감각이상등일부증상은중대뇌동맥이담당하는전방순환계보다는후방순환계가담당하는뇌간이나후두엽의혈류저하때문일가능성이있다. 아울러기립에따른자율신경반사를담당하는신경핵들이대부분연수를포함하는뇌간에위치하고있기때문에실신환자의뇌혈관조절능의평가는중대뇌동맥뿐만아니라기저혈관이나후대뇌동맥에서시행될필요가있다. 한편일반인구집단과비교하여실신과기립못견딤증의유병률이높다고알려진편두통의경우 18 기저혈관의고탄산혈증에대한혈관반응성이중대뇌동맥에비해떨어진다는연구결과도 19 있어실신환자의후방순환계역시이상이있을가능성이높다고여겨진다. 하지만본연구대상중편두통환자는 NCS 환자군과대조군에각각 3명이포함되었으며, 전조가동반된편두통환자는대조군에만 1명이있어 NCS 와혈관반응성의관계분석에는영향을주지않았을것으로생각한다. NCS 에서전방순환계와함께후방순환계를조사해야하는또다른이론적근거는조직화학적연구결과에있는데, 추골기저혈관계가경동맥순환계에비해교감신경원의수용체밀도가낮다고보고되었다. 20 뇌혈관자율조절능에교감신경계가중요한역할을하고있기때문에이러한조직화학적소견은임신중독증이나고혈압성뇌병증에서관찰되는비가역적후대뇌백질의변성을일부설명하는배경이되기도한다. 21 즉과도한혈압상승시나타나는뇌저항혈관의수축반응이상대적으로교감신경원수용체가적은뇌뒷부분에서부족하여혈액-뇌장벽의손상이생기고혈관성부종이발생한다고여겨지고있다. 본연구의결과, 정상대조군과비교하여 NCS 환자들은중대뇌동맥보다후대뇌동맥에서더큰혈류속도의감소가나타났으며, 특히이러한혈류속도의변화는기립후 30초까지의구간에서가장컸다. 정상적으로기립을하게되면가슴안정맥혈약 800 ml 가신체하부로이동하게되며이를보상하기위한정상적인심혈관반응으로교감신경흥분도가증가하여심박동수의증가와말초저항혈관의수축이발생한다고알려져있다. 22 본연구의피검자들또한첫 30초간평균혈압및심박동수가빠르게증가했고, 이는교감신경활성도의증가를시사한다고생각한다. 따라서기립경사침대검사동안관찰된혈류속도의감소도교감신경활성화에의한뇌저항혈관의수축에동반된혈류량감소때문일가능성이있다. 하지만혈류속도감소의원인이단지항진된교감신경활성도때문이라는해석은 위험하다. 실신환자의혈류속도감소및 PI의증가가혈압감소없이동반된과호흡과저탄산혈증때문이라는이전연구가있었고 17 본연구에서도환자군과대조군모두기립초기 EtCO 2 의감소를보였기때문에저탄산혈증이혈류속도의감소에일정부분기여했을가능성이있다. 하지만양군이거의비슷한정도의 EtCO 2 감소를보였기때문에환자군에서후대뇌동맥혈류속도감소가더큰것을저탄산혈증으로설명할수없다. 또한정상대조군의 P.I. 는기립해있는동안증가하지않았지만, 실신환자들은작은폭이지만증가하는양상을보였기때문에역시저탄산혈증으로양군의차이를설명하기에는부족하다. 본연구는개인별교감신경활성도의차이를정량화하지못했고, 연속적인혈압측정이불가능하여자의적으로측정시점을고정하였기때문에기록외구간에서나타날수있는변화를알지못하는단점이있다. 하지만저자들의연구가이전연구들과다른중요한차이점은연구의목적이기립경사침대검사를통해실신을유발하여동반된혈류변화를관찰하는것이아니라, 실신의증상이아직나타나지않는 5분간의기립경사침대검사동안초기의혈류변화를관찰하여혈관반응성의이상이실신의일차적인원인이되는지를확인하고자한점이다. 또한중대뇌동맥과반대편후대뇌동맥을동시에비교함으로써 NCS 환자들에서후방순환계의혈관반응성이정상인과다를가능성을확인하였다. 본연구결과를토대로 NCS 환자들의후대뇌동맥영역이정상인에비해어떠한원인에서건기립초기교감신경자극에대한혈관반응도가높다고추정할수있으며, 이러한현상이정상인과달리수용체밀도가높아서인지또는민감도의차이가있어서인지등에대해서는추후더많은연구를통해밝혀져야할것으로생각한다. REFERENCES 1. Savage DD, Corwin L, McGee DL, Kannel WB, Wolf PA. Epidemiologic features of isolated syncope: the Framingham Study. Stroke 1985;16:626-629. 2. Grubb BP, Karas B. Clinical disorders of the autonomic nervous system associated with orthostatic intolerance: an overview of classification, clinical evaluation, and management. Pacing Clin Electrophysiol 1999;22:798-810. 3. Mosqueda-Garcia R, Furlan R, Tank J, Fernandez-Violante R. The elusive pathophysiology of neurally mediated syncope. Circulation 2000;102:2898-2906. 4. Milstein S, Buetikofer J, Dunnigan A, Benditt DG, Gornick C, Reyes WJ. Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia. Am J Cardiol 1990;65:1339-1344. 5. Wallin BG, Sundlof G. Sympathetic outflow to muscles during vasovagal syncope. J Auton Nerv Syst 1982;6:287-291. J Korean Neurol Assoc Volume 26 No. 1, 2008 33
박태환이은희윤영철김상욱 6. Albina G, Fernandez Cisneros L, Laino R, Nobo UL, Ortega D, Schwarz E, et al. Transcranial doppler monitoring during head upright tilt table testing in patients with suspected neurocardiogenic syncope. Europace 2004;6:63-69. 7. Carey BJ, Manktelow BN, Panerai RB, Potter JF. Cerebral autoregulatory responses to head-up tilt in normal subjects and patients with recurrent vasovagal syncope. Circulation 2001;104:898-902. 8. Grubb BP, Gerard G, Roush K, Temesy-Armos P, Montford P, Elliott L, et al. Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope. A paradoxic and unexpected response. Circulation 1991;84:1157-1164. 9. Brooks DJ, Redmond S, Mathias CJ, Bannister R, Symon L. The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of ephedrine. J Neurol Neurosurg Psychiatry 1989;52:962-966. 10. Dan D, Hoag JB, Ellenbogen KA, Wood MA, Eckberg DL, Gilligan DM. Cerebral blood flow velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope. J Am Coll Cardiol 2002;39:1039-1045. 11. Novak V, Spies JM, Novak P, McPhee BR, Rummans TA, Low PA. Hypocapnia and cerebral hypoperfusion in orthostatic intolerance. Stroke 1998;29:1876-1881. 12. Schondorf R, Benoit J, Wein T. Cerebrovascular and cardiovascular measurements during neurally mediated syncope induced by headup tilt. Stroke 1997;28:1564-1568. 13. Soo-Jin Cho, June Soo Kim, Kwang Ho Lee, Chin-Sang Chung, Hee-Jung Song, Sang-Chol Lee, et al. Changes of cerebral blood flow during head-up tilt test in patients with recurrent syncope and presyncope. J Korean Neurol Assoc 1999;17:376-383. 14. Aaslid R, Lindegaard KF, Sorteberg W, Nornes H. Cerebral autoregulation dynamics in humans. Stroke 1989;20:45-52. 15. Carey BJ, Eames PJ, Panerai RB, Potter JF. Carbon dioxide, critical closing pressure and cerebral haemodynamics prior to vasovagal syncope in humans. Clin Sci (Lond) 2001;101:351-358. 16. Schondorf R, Stein R, Roberts R, Benoit J, Cupples W. Dynamic cerebral autoregulation is preserved in neurally mediated syncope. J Appl Physiol 2001;91:2493-2502. 17. Lagi A, Cencetti S, Corsoni V, Georgiadis D, Bacalli S. Cerebral vasoconstriction in vasovagal syncope: Any link with symptoms? A transcranial doppler study. Circulation 2001;104:2694-2698. 18. Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG. Syncope in migraine: the population-based CAMERA study. Neurology 2006;66:1034-1037. 19. Silvestrini M, Baruffaldi R, Bartolini M, Vernieri F, Lanciotti C, Matteis M, et al. Basilar and middle cerebral artery reactivity in patients with migraine. Headache 2004;44:29-34. 20. Edvinsson L, Owman C, Sjoberg NO. Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study. Brain Res 1976;115:377-393. 21. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494-500. 22. Cooke WH, Hoag JB, Crossman AA, Kuusela TA, Tahvanainen KU, Eckberg DL. Human responses to upright tilt: a window on central autonomic integration. J Physiol 1999;517:617-628. 34