癫痫患者动态脑血流自动调节功能研究
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摘要
目的探究癫痫患者的dCA功能。方法研究纳入100例癫痫患者和100例年龄、性别相匹配的健康志愿者作为对照组,分别测定其dCA功能。采用TCD联合无创指尖血压监测法分别连续采集受试者双侧MCA脑血流速度(cerebral blood flow velocity,CBFV)和动脉血压(arterial blood pressure,ABP)信号。将采集的CBFV和ABP信号经过传递函数法(transfer function analysis,TFA)分析,得出dCA参数(相位差和增益)。结果癫痫患者的总体相位差显著低于正常对照组(P=0.046),提示其dCA功能受损。此外,合并发作间期慢波的患者其相位差更低(P=0.012),dCA功能受损更明显。EEG表现为局灶性放电的患者与表现为多灶性放电的患者的相位差无显著性差异。同样,在EEG表现为单侧放电的患者中,其放电侧大脑半球与放电对侧大脑半球的相位差也无显著性差异。通过单因素和多因素回归模型分析临床因素与dCA参数的关系,发现发作间期慢波与相位差受损独立相关(P=0.016)。结论癫痫患者的dCA功能受损,而痫样放电合并发作间期慢波患者dCA受损更明显。dCA功能与癫痫患者的放电类型、放电部位无关。发作间期慢波是癫痫患者dCA功能受损的独立预测因素。临床研究注册号NCT02775682
Objective The aim of this study is to analyze dCA in patients with epilepsy.Methods One hundred patients with epilepsy and 100 age-and sex-matched healthy controls were recruited. Noninvasive continuous cerebral blood flow velocity of the bilateral middle artery and arterial blood pressure were recorded. Transfer function analyses were used to analyze the autoregulatory parameters(phase difference and gain).Results The overall phase difference of patients with epilepsy was significantly lower than that of the healthy control group(P=0.046). Furthermore, patients with interictal slow wave had significant lower phase difference than the slow-wave-free patients(P=0.012). There was no difference in overall phase between focal discharges and multifocal discharges in patients with epilepsy. Simultaneously,there was no difference in mean phase between the affected and unaffected hemispheres in patients with unilateral discharges. In particular, interictal slow wave was an independent factor that influenced phase difference in patients with epilepsy(P=0.016).Conclusions Our study documented that dCA is impaired in patients with epilepsy, especially in those with interictal slow wave. The impairment of dCA occurs irrespective of the discharge location and type. Interictal slow wave is an independent factor to predict impaired dCA in patients with epilepsy.Clinical Trial Identifier This trial is registered with NCT02775682.
Objective The aim of this study is to analyze dCA in patients with epilepsy.Methods One hundred patients with epilepsy and 100 age-and sex-matched healthy controls were recruited. Noninvasive continuous cerebral blood flow velocity of the bilateral middle artery and arterial blood pressure were recorded. Transfer function analyses were used to analyze the autoregulatory parameters(phase difference and gain).Results The overall phase difference of patients with epilepsy was significantly lower than that of the healthy control group(P=0.046). Furthermore, patients with interictal slow wave had significant lower phase difference than the slow-wave-free patients(P=0.012). There was no difference in overall phase between focal discharges and multifocal discharges in patients with epilepsy. Simultaneously,there was no difference in mean phase between the affected and unaffected hemispheres in patients with unilateral discharges. In particular, interictal slow wave was an independent factor that influenced phase difference in patients with epilepsy(P=0.016).Conclusions Our study documented that dCA is impaired in patients with epilepsy, especially in those with interictal slow wave. The impairment of dCA occurs irrespective of the discharge location and type. Interictal slow wave is an independent factor to predict impaired dCA in patients with epilepsy.Clinical Trial Identifier This trial is registered with NCT02775682.
引文
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[10]REINHARD M,RUTSCH S,LAMBECK J,et al.Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke[J].Acta Neurol Scand,2012,125(3):156-162.
[11]CLOZEL M,DAVAL J L,MONIN P,et al.Regional cerebral blood flow during bicucullineinduced seizures in the newborn piglet:effect of phenobarbital[J].Dev Pharmacol Ther,1985,8(3):189-199.
[12]HASCOET J M,MONIN P,VERT P.Persistence of impaired autoregulation of cerebral blood flow in the postictal period in piglets[J].Epilepsia,1988,29(6):743-747.
[13]MEEL-VAN DEN ABEELEN A S,VAN BEEK AH,SLUMP C H,et al.Transfer function analysis for the assessment of cerebral autoregulation using spontaneous oscillations in blood pressure and cerebral blood flow[J].Med Eng Phys,2014,36(5):563-575.
[14]FISHER R S,ACEVEDO C,ARZIMANOGLOUA,et al.ILAE official report:a practical clinical definition of epilepsy[J].Epilepsia,2014,55(4):475-482.
[15]WONG K S,LI H,CHAN Y L,et al.Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease[J].Stroke,2000,31(11):2641-2647.
[16]CLAASSEN J A,MEEL-VAN DEN ABEELEN A S,SIMPSON D M,et al.Transfer function analysis of dynamic cerebral autoregulation:a white paper from the International Cerebral Autoregulation Research Network[J].J Cereb Blood Flow Metab,2016,36(4):665-680.
[17]GILLER C A.The frequency-dependent behavior of cerebral autoregulation[J].Neurosurgery,1990,27(3):362-368.
[18]VAN BEEK A H,CLAASSEN J A,RIKKERT MG,et al.Cerebral autoregulation:an overview of current concepts and methodology with special focus on the elderly[J].J Cereb Blood Flow Metab,2008,28(6):1071-1085.
[19]KUO T B,CHERN C M,SHENG W Y,et al.Frequency domain analysis of cerebral blood flow velocity and its correlation with arterial blood pressure[J].J Cereb Blood Flow Metab,1998,18(3):311-318.
[20]SILLANPAA M,ANTTINEN A,RINNE J O,et al.Childhood-onset epilepsy five decades later.A prospective population-based cohort study[J].,,Epilepsia,2015,56(11):1774-1783.
[21]JIN J,CHEN R,XIAO Z.Post-epilepsy stroke:Areview[J].Expert Rev Neurother,2016,16(3):341-349.
[22]OLESEN J B,ABILDSTROM S Z,ERDAL J,et al.Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction,stroke,and death in patients with or without previous stroke:a nationwide cohort study[J].Pharmacoepidemiol Drug Saf,2011,20(9):964-971.
[23]ZHAO M,SUH M,MA H,et al.Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy[J].Epilepsia,2007,48(11):2059-2067.
[24]ANDERSEN A R,WALDEMAR G,DAM M,et al.SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report[J/OL].Acta Neurochir Suppl(Wien),1990,50:80-83.https://doi.org/10.1586/14737175.2016.1151355.
[25]SZIRMAI I,MOLNAR M,CZOPF J,et al.Spreading epileptiform discharges and cortical regional blood flow in rabbits[J].Electroencephalogr Clin Neurophysiol,1977,42(2):238-247.
[26]ZHAO M,NGUYEN J,MA H,et al.Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus[J].J Neurosci,2011,31(37):13 292-13 300.
[27]VAN PAESSCHEN W,DUPONT P,VAN DRIELG,et al.SPECT perfusion changes during complex partial seizures in patients with hippocampal sclerosis[J].Brain,2003,126(Pt 5):1103-1111.
[28]RABINOWICZ A L,SALAS E,BESERRA F,et al.Changes in regional cerebral blood flow beyond the temporal lobe in unilateral temporal lobe epilepsy[J].Epilepsia,1997,38(9):1011-1014.
[29]DUTSCH M,DEVINSKY O,DOYLE W,et al.Cerebral autoregulation improves in epilepsy patients after temporal lobe surgery[J].J Neurosci,2004,251(10):1190-1197.
[30]GOMEZ-GONZALO M,LOSI G,BRONDI M,et al.Ictal but not interictal epileptic discharges activate astrocyte endfeet and elicit cerebral arteriole responses[J/OL].Front Cell Neurosci,2011,5:8.https://doi.org/10.3389/fncel.2011.00008.
[31]ROSENGARTEN B,HUWENDIEK O,KAPS M.Neurovascular coupling and cerebral autoregulation can be described in terms of a control system[J].Ultrasound Med Biol,2001,27(2):189-193.
[32]DRUSCHKY A,HILZ M J,HOPP P,et al.Interictal cardiac autonomic dysfunction in temporal lobe epilepsy demonstrated by[(123)I]metaiodobenzylguanidine-SPECT[J].Brain,2001,124(Pt 12):2372-2382.
[33]DIEHL B,DIEHL R R,STODIECK S R,et al.Spontaneous oscillations in cerebral blood flow velocities in middle cerebral arteries in control subjects and patients with epilepsy[J].Stroke,1997,28(12):2457-2459.
[34]BLABER A P,BONDAR R L,STEIN F,et al.Transfer function analysis of cerebral autoregulation dynamics in autonomic failure patients[J].Stroke,1997,28(9):1686-1692.
[35]CASTRO P M,SANTOS R,FREITAS J,et al.Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva maneuver:comparison between healthy and autonomic dysfunction subjects[J].J Appl Physiol(1985).,2014,117(3):205-213.
[36]PERSSON H,ERICSON M,TOMSON T.Heart rate variability in patients with untreated epilepsy[J].Seizure,2007,16(6):504-508.
[37]CSERCSA R,DOMBOVARI B,FABO D,et al.Laminar analysis of slow wave activity in humans[J].Brain,2010,133(9):2814-2829.
[38]PELLEGRINO G,TOMBINI M,CURCIO G,et al.Slow Activity in Focal Epilepsy During Sleep and Wakefulness[J].Clin EEG Neurosci,2016,48(3):200-208.,,
[39]GLOOR P,BALL G,SCHAUL N.Brain lesions that produce delta waves in the EEG[J].Neurology,1977,27(4):326-333.
[40]GAMBARDELLA A,GOTMAN J,CENDES F,et al.Focal intermittent delta activity in patients with mesiotemporal atrophy:a reliable marker of the epileptogenic focus[J].Epilepsia,1995,36(2):122-129.
[41]KELLER C J,TRUCCOLO W,GALE J T,et al.Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex[J].Brain,2010,133(Pt 6):1668-1681.
[42]ALTAFULLAH I,HALGREN E,STAPLETONJ M,et al.Interictal spike-wave complexes in the human medial temporal lobe:typical topography and comparisons with cognitive potentials[J].Electroencephalogr Clin Neurophysiol,1986,63(6):503-516.
[43]TOTH P,TARANTINI S,CSISZAR A,et al.Functional vascular contributions to cognitive impairment and dementia:mechanisms and consequences of cerebral autoregulatory dysfunction,endothelial impairment,and neurovascular uncoupling in aging[J/OL].Am J Physiol Heart Circ Physiol,2017,312(1):H1-H20.https://doi.org/10.1152/ajpheart.00581.2016.
[2]SILVERMAN I E,RESTREPO L,MATHEWS GC.Poststroke seizures[J].Arch Neurol,2002,59(2):195-201.
[3]BAROLIN G S.The cerebrovascular epilepsies[J].Electroencephalogr Clin Neurophysiol Suppl,1982,35:287-295.
[4]CLEARY P,SHORVON S,TALLIS R.Late-onset seizures as a predictor of subsequent stroke[J].Lancet,2004,363(9416):1184-1186.
[5]TELLEZ-ZENTENO J F,MATIJEVIC S,WIEBES.Somatic comorbidity of epilepsy in the general population in Canada[J].Epilepsia,2005,46(12):1955-1962.
[6]BRIGO F,TEZZON F,NARDONE R.Late-onset seizures and risk of subsequent stroke:a systematic review[J/OL].Epilepsy behav,2014,31:9-12.https://doi.org/10.1016/j.yebeh.2013.11.003.
[7]SCHWARTZ T H.Neurovascular coupling and epilepsy:hemodynamic markers for localizing and predicting seizure onset[J].Epilepsy Curr,2007,7(4):91-94.
[8]HARRIS S,BOORMAN L,BRUYNS-HAYLETTM,et al.Contralateral dissociation between neural activity and cerebral blood volume during recurrent acute focal neocortical seizures[J].Epilepsia,2014,55(9):1423-1430.
[9]REINHARD M,GERDS T A,GRABIAK D,et al.Cerebral dysautoregulation and the risk of ischemic events in occlusive carotid artery disease[J].J Neurol,2008,255(8):1182-1189.
[10]REINHARD M,RUTSCH S,LAMBECK J,et al.Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke[J].Acta Neurol Scand,2012,125(3):156-162.
[11]CLOZEL M,DAVAL J L,MONIN P,et al.Regional cerebral blood flow during bicucullineinduced seizures in the newborn piglet:effect of phenobarbital[J].Dev Pharmacol Ther,1985,8(3):189-199.
[12]HASCOET J M,MONIN P,VERT P.Persistence of impaired autoregulation of cerebral blood flow in the postictal period in piglets[J].Epilepsia,1988,29(6):743-747.
[13]MEEL-VAN DEN ABEELEN A S,VAN BEEK AH,SLUMP C H,et al.Transfer function analysis for the assessment of cerebral autoregulation using spontaneous oscillations in blood pressure and cerebral blood flow[J].Med Eng Phys,2014,36(5):563-575.
[14]FISHER R S,ACEVEDO C,ARZIMANOGLOUA,et al.ILAE official report:a practical clinical definition of epilepsy[J].Epilepsia,2014,55(4):475-482.
[15]WONG K S,LI H,CHAN Y L,et al.Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease[J].Stroke,2000,31(11):2641-2647.
[16]CLAASSEN J A,MEEL-VAN DEN ABEELEN A S,SIMPSON D M,et al.Transfer function analysis of dynamic cerebral autoregulation:a white paper from the International Cerebral Autoregulation Research Network[J].J Cereb Blood Flow Metab,2016,36(4):665-680.
[17]GILLER C A.The frequency-dependent behavior of cerebral autoregulation[J].Neurosurgery,1990,27(3):362-368.
[18]VAN BEEK A H,CLAASSEN J A,RIKKERT MG,et al.Cerebral autoregulation:an overview of current concepts and methodology with special focus on the elderly[J].J Cereb Blood Flow Metab,2008,28(6):1071-1085.
[19]KUO T B,CHERN C M,SHENG W Y,et al.Frequency domain analysis of cerebral blood flow velocity and its correlation with arterial blood pressure[J].J Cereb Blood Flow Metab,1998,18(3):311-318.
[20]SILLANPAA M,ANTTINEN A,RINNE J O,et al.Childhood-onset epilepsy five decades later.A prospective population-based cohort study[J].,,Epilepsia,2015,56(11):1774-1783.
[21]JIN J,CHEN R,XIAO Z.Post-epilepsy stroke:Areview[J].Expert Rev Neurother,2016,16(3):341-349.
[22]OLESEN J B,ABILDSTROM S Z,ERDAL J,et al.Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction,stroke,and death in patients with or without previous stroke:a nationwide cohort study[J].Pharmacoepidemiol Drug Saf,2011,20(9):964-971.
[23]ZHAO M,SUH M,MA H,et al.Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy[J].Epilepsia,2007,48(11):2059-2067.
[24]ANDERSEN A R,WALDEMAR G,DAM M,et al.SPECT in the presurgical evaluation of patients with temporal lobe epilepsy--a preliminary report[J/OL].Acta Neurochir Suppl(Wien),1990,50:80-83.https://doi.org/10.1586/14737175.2016.1151355.
[25]SZIRMAI I,MOLNAR M,CZOPF J,et al.Spreading epileptiform discharges and cortical regional blood flow in rabbits[J].Electroencephalogr Clin Neurophysiol,1977,42(2):238-247.
[26]ZHAO M,NGUYEN J,MA H,et al.Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus[J].J Neurosci,2011,31(37):13 292-13 300.
[27]VAN PAESSCHEN W,DUPONT P,VAN DRIELG,et al.SPECT perfusion changes during complex partial seizures in patients with hippocampal sclerosis[J].Brain,2003,126(Pt 5):1103-1111.
[28]RABINOWICZ A L,SALAS E,BESERRA F,et al.Changes in regional cerebral blood flow beyond the temporal lobe in unilateral temporal lobe epilepsy[J].Epilepsia,1997,38(9):1011-1014.
[29]DUTSCH M,DEVINSKY O,DOYLE W,et al.Cerebral autoregulation improves in epilepsy patients after temporal lobe surgery[J].J Neurosci,2004,251(10):1190-1197.
[30]GOMEZ-GONZALO M,LOSI G,BRONDI M,et al.Ictal but not interictal epileptic discharges activate astrocyte endfeet and elicit cerebral arteriole responses[J/OL].Front Cell Neurosci,2011,5:8.https://doi.org/10.3389/fncel.2011.00008.
[31]ROSENGARTEN B,HUWENDIEK O,KAPS M.Neurovascular coupling and cerebral autoregulation can be described in terms of a control system[J].Ultrasound Med Biol,2001,27(2):189-193.
[32]DRUSCHKY A,HILZ M J,HOPP P,et al.Interictal cardiac autonomic dysfunction in temporal lobe epilepsy demonstrated by[(123)I]metaiodobenzylguanidine-SPECT[J].Brain,2001,124(Pt 12):2372-2382.
[33]DIEHL B,DIEHL R R,STODIECK S R,et al.Spontaneous oscillations in cerebral blood flow velocities in middle cerebral arteries in control subjects and patients with epilepsy[J].Stroke,1997,28(12):2457-2459.
[34]BLABER A P,BONDAR R L,STEIN F,et al.Transfer function analysis of cerebral autoregulation dynamics in autonomic failure patients[J].Stroke,1997,28(9):1686-1692.
[35]CASTRO P M,SANTOS R,FREITAS J,et al.Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva maneuver:comparison between healthy and autonomic dysfunction subjects[J].J Appl Physiol(1985).,2014,117(3):205-213.
[36]PERSSON H,ERICSON M,TOMSON T.Heart rate variability in patients with untreated epilepsy[J].Seizure,2007,16(6):504-508.
[37]CSERCSA R,DOMBOVARI B,FABO D,et al.Laminar analysis of slow wave activity in humans[J].Brain,2010,133(9):2814-2829.
[38]PELLEGRINO G,TOMBINI M,CURCIO G,et al.Slow Activity in Focal Epilepsy During Sleep and Wakefulness[J].Clin EEG Neurosci,2016,48(3):200-208.,,
[39]GLOOR P,BALL G,SCHAUL N.Brain lesions that produce delta waves in the EEG[J].Neurology,1977,27(4):326-333.
[40]GAMBARDELLA A,GOTMAN J,CENDES F,et al.Focal intermittent delta activity in patients with mesiotemporal atrophy:a reliable marker of the epileptogenic focus[J].Epilepsia,1995,36(2):122-129.
[41]KELLER C J,TRUCCOLO W,GALE J T,et al.Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex[J].Brain,2010,133(Pt 6):1668-1681.
[42]ALTAFULLAH I,HALGREN E,STAPLETONJ M,et al.Interictal spike-wave complexes in the human medial temporal lobe:typical topography and comparisons with cognitive potentials[J].Electroencephalogr Clin Neurophysiol,1986,63(6):503-516.
[43]TOTH P,TARANTINI S,CSISZAR A,et al.Functional vascular contributions to cognitive impairment and dementia:mechanisms and consequences of cerebral autoregulatory dysfunction,endothelial impairment,and neurovascular uncoupling in aging[J/OL].Am J Physiol Heart Circ Physiol,2017,312(1):H1-H20.https://doi.org/10.1152/ajpheart.00581.2016.