目的 探讨亚低温治疗新生儿胆红素脑病的临床疗效及18-氟脱氧葡萄糖(18F-FDG)正电子发射断层(PET)/CT和振幅整合脑电图(aEEG)的诊断和疗效判断价值。方法 2013年5月至2014年12月,29例胆红素脑病患儿分为常规组(n=15)和亚低温组(n=14)。常规组采用常规治疗,亚低温组加用选择性头部亚低温治疗。观察两组患儿治疗前后aEEG、神经烯醇化酶(NSE)及治疗后的18F-FDG PET/CT脑葡萄糖代谢率。结果 两组NSE治疗后均显著降低(t>9.670, P<0.001),亚低温组治疗后NSE显著低于常规组(F=46.146, P<0.001)。两组治疗后aEEG的睡眠觉醒周期(SWC)、癫痫样活动及异常程度均有改善(P<0.05),亚低温组治疗后的SWC、癫痫样活动及异常程度恢复更好(P<0.05)。亚低温组治疗后各脑区脑葡萄糖代谢改善明显优于常规组(Z>2.943, P<0.01)。脑葡萄糖代谢率与aEEG及NSE改变呈负相关(r>0.640, P<0.05)。结论 亚低温治疗新生儿急性胆红素脑病,可更好地促进脑细胞能量代谢恢复;18F-FDG PET/CT和aEEG可用于胆红素脑病的早期诊断及疗效判断,具有一定临床价值。
Objective To investigate the clinical effect of mild hypothermia on neonatal bilirubin encephalopathy, and the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT and amplitude integrated electroencephalogram (aEEG) for diagnosis and evaluation of curative effect. Methods From May, 2013 to December, 2014, 29 newborns with bilirubin encephalopathy were divided into conventional group (n=15) and mild hypothermia group (n=14). The conventional group received conventional therapy, and the other group received mild hypothermia in addition. The aEEG and neuron-specific enolase (NSE) were measured before and after treatment, as well as the glucose metabolism rate with 18F-FDG PET/CT after treatment. Results The NSE was lower after treatment in both groups (t>9.670, P<0.001), and was lower in the mild hypothermia group than in the conventional group (F=46.146, P<0.001). After treatment, sleep-wake cycle (SWC), epileptiform activity and the degree of abnormality were obviously improved (P<0.05), and were better in the mild hypothermia group than in the conventional group (P<0.05). The cerebral glucose metabolism rate was significantly better in the mild hypothermia group than in the conventional group (t>2.943, P<0.01). The cerebral glucose metabolism rate was negatively correlated with aEEG and NSE (r>0.640, P<0.05). Conclusion Mild hypothermia therapy could further promote the energy metabolism of brain cells in neonatal bilirubin encephalopathy. 18F-FDG PET/CT and aEEG can be used for early diagnosis and therapeutic evaluation.
[1] 中华医学会儿科学分会新生儿学组,中国新生儿胆红素脑病研究协作组. 中国新生儿胆红素脑病的多中心流行病学调查研究[J]. 中华儿科杂志, 2012, 50(5): 331-335.
[2] Manning D, Todd P, Maxwell M, et al. Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland [J]. Arch Dis Child Fetal Ed, 2007, 92(5): F342-346.
[3] Sgro M, Campbell DM, Kandasamy S, et al. Incidence of chronicbilirubin encephalopathy in Canada, 2007-2008 [J]. Pediatrics, 2012, 130(4): e886-890.
[4] Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND) [J]. J Perinatol, 2005, 25(1): 54-59.
[5] Kaplan M, Hammerman C. Understanding severe hyperbilirubinemia and preventing kernicterus: adjuncts in the interpretation of neonatal serum bilirubin [J]. Clin Chim Acta, 2005, 356(1-2): 9-21.
[6] Katar S, Akay HO, Taskesen M, et al. Clinical and cranial magnetic resonance imaging (MRI) findings of 21 patients with serious hyperbilirubinemia [J]. Child Neurol, 2008, 23(4): 415-417.
[7] 邵肖梅. 亚低温治疗新生儿缺氧缺血性脑病方案[J]. 中国循证儿科杂志, 2011, 6(5): 337-339.
[8] Hellstrom-Westas L, Rosen I. Continuous brain-function monitoring: state of the art in clinical practice [J]. Semin Fetal Neonatal Med, 2006, 11(6):503-511.
[9] Van Rooij LG, Toet MC, van Huffelen AC, et al. Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial [J]. Pediatrics, 2010, 125(2): 358-366.
[10] Ruotsalainen U, Suhonen-Polvi H, Eronen E, et al. Estimated radiation does to the newborn in FDG-PET studies [J]. J Nucl Med, 1996, 37(2): 387-393.
[11] Bhutani VK, Donn SM, Johnson LH. Risk management of severe neonatal hyperbilirubinemia to prevent kernicterus [J]. Clin Perinatol, 2005, 32(1): 125-139.
[12] Grojean S, Koziel V, Vert P, et al. Bilirubin induced apoptosis via activation of NMDA in developing rat neurons [J]. Exp Neurol, 2000, 166(2): 334-341.
[13] Binda S, Mammoliti A, Primache V, et al. P65 antigenemia, plasma real-time PCR and DBS test in aymptomatic and asymptomatic cytomagelovirus congenitally infected newborns [J]. BMC Infect Dis, 2010, 10: 24.
[14] Wu W, Zhang P, Wang X, et al. Usefulness of (1) H-MRS in differentiating bilirubin encephalopathy from severe hyperbilirubinemia in neonates [J]. J Magn Reson Imaging, 2013, 38(3): 634-640.
[15] 史源,金榕兵,赵锦宁,等. 18 F-FDG PET/CT在新生儿缺氧缺血性脑病中的临床应用[J]. 第三军医大学学报, 2010, 32(1): 51-53.
[16] Luo M, LI QP, Dong WB, et al. Evaluation of mild hypothermia therapy neonatal hypoxic-ischaemic encephalopathy on brain energy metabolism using 18 F-fluorodeoxyglucose positron emission computed tomography [J]. Exp Ther Med, 2014, 8(4): 1219-1224.
[17] Chierichetti F, Pizzolato G. 18 F-FDG-PET/CT [J]. Q J Nucl Med Mol Imaging, 2012, 56(2): 138-150.
[18] Berger RP, Adelson PD, Richichi R, et al. Serum biomarkers after traumatic and hypoxemic brain injuries: insight into the biochemical response of the pediatric brain to inflicted brain injury [J]. Dev Neurosci, 2006, 28(4/5): 327-335.
[19] Pinton F, Ducot B, Motte J, et al. Cognitive functions in children with benign childhood epilepsy with centrotemporal spikes (BECTS) [J]. Epileptic Disord, 2006, 8(1):11-23.
[20] 丁香平,吴秀珍,唐文燕,等. 不同胆红素水平对脑干听觉诱发电位的影响及临床意义[J].实用临床医学, 2013, 14(9): 82-83.
[21] Sharma P, Chhangani NP, Meena KR, et al. Brainstem evoked response audiometry (BAER) in neonates with hyperbilirubinemia [J]. Indian J Pediatr, 2006, 73(5): 413-416.
[22] 罗芳,林慧佳,鲍毓,等. 新生儿胆红素脑病急性期脑功能监测[J].中华儿科杂志, 2013, 51(3): 221-226.
[23] 李金玲,李林,李翠玲,等. 亚低温对胆红素脑病仔鼠脑保护作用的实验研究[J]. 中国康复理论与实践, 2007, 13(10): 928-930.
[24] 王丽梅,马艳辉,金翊思. 局部亚低温治疗胆红素脑病仔兔脑组织的病理变化[J]. 中国康复, 2010, 25(3): 167-169.
[25] Shankaran S, Pappas A, Laptook AR, et al. Outcomes of safety and effectiveness in a multicenter randomized, controlled trim of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy [J]. Pediatrics, 2008, 122(4): e791-e798.
[26] Rutherford M, Ramenghi LA, Edwards AD, et al. Assessment of brain tissue injure after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy a nested substudy of a randomised controlled trial [J]. Lancet Neurol, 2010, 9(1):39-45.
[27] 曹长青,李宇宁,杨雪梅,等. 亚低温治疗新生儿缺氧缺血性脑病远期临床效果的Meta分析[J]. 中国当代儿科, 2015, 17(2): 122-127.
[28] Kilani RA. The safety and practicality of selective head cooling in asphyxiated human newborn infant, a retrospective study [J]. J Med Liban, 2002, 50(1-2): 17-22.
[29] Shankaran S. Neonatal encephalopathy: treatment with hypothermia [J]. J Neurotrauma, 2009, 26(3): 437-443.
