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新生儿惊厥的治疗

Author
Renee Shellhaas, MD, MS
Section Editors
Douglas R Nordli, Jr, MD
Joseph A Garcia-Prats, MD
Deputy Editor
April F Eichler, MD, MPH
Translators
朱长连, 主任医师，教授

引言

新生儿惊厥可能是新生儿中枢神经系统(central nervous system, CNS)疾病中最早及可能唯一出现的临床体征。惊厥的出现提示可能存在潜在可治疗的病因，提示应当立刻进行评估，以明确病因并采取病因特异性治疗。此外，惊厥本身可能需要紧急治疗，因为该情况会对新生儿稳态造成不良影响或可能促进进一步的脑损伤。新生儿惊厥的某些类型具有相对较高的早期死亡率，并且生存者的神经功能缺损、发育迟滞和新生儿期后癫痫的发生率较高。

新生儿惊厥的处理包括准确诊断惊厥、快速评估其病因并进行针对性治疗，以及给予药物消除脑电图(electroencephalogram, EEG)惊厥。本专题将讨论新生儿惊厥的治疗方法。新生儿惊厥的病因、临床特征和诊断将单独讨论。 (参见“新生儿癫痫发作的病因和预后”和“新生儿癫痫综合征”和“新生儿癫痫发作的临床特征、评估和诊断”)

稳定患者

惊厥及其随后的治疗可能会改变呼吸、心率和血压。因此，治疗早期就必须确保气道足够通畅和循环系统通路的建立。

病因治疗

针对新生儿惊厥病因的治疗至关重要，因为这可防止进一步的脑损伤。在一些代谢紊乱(如，低血糖、低钙血症和低镁血症)、CNS感染或全身感染引起的惊厥中，这尤其重要。另外，如果基础病因没有得到治疗，抗癫痫药可能无法有效控制新生儿惊厥。

新生儿惊厥的最常见病因如表所示(表 1)。

                       

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Literature review current through: 2017-07 . | This topic last updated: 2017-03-06.
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References
Top
  1. Glass HC, Wusthoff CJ, Shellhaas RA, et al. Risk factors for EEG seizures in neonates treated with hypothermia: a multicenter cohort study. Neurology 2014; 82:1239.
  2. Nicolai J, van Kranen-Mastenbroek VH, Wevers RA, et al. Folinic acid-responsive seizures initially responsive to pyridoxine. Pediatr Neurol 2006; 34:164.
  3. Bok LA, Maurits NM, Willemsen MA, et al. The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy. Epilepsia 2010; 51:2406.
  4. Segal EB, Grinspan ZM, Mandel AM, Gospe SM Jr. Biomarkers aiding diagnosis of atypical presentation of pyridoxine-dependent epilepsy. Pediatr Neurol 2011; 44:289.
  5. Stockler S, Plecko B, Gospe SM Jr, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 2011; 104:48.
  6. Mills PB, Struys E, Jakobs C, et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 2006; 12:307.
  7. Mills PB, Footitt EJ, Mills KA, et al. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain 2010; 133:2148.
  8. Gallagher RC, Van Hove JL, Scharer G, et al. Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol 2009; 65:550.
  9. van Karnebeek CD, Hartmann H, Jaggumantri S, et al. Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials. Mol Genet Metab 2012; 107:335.
  10. Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev 2004; :CD004218.
  11. Slaughter LA, Patel AD, Slaughter JL. Pharmacological treatment of neonatal seizures: a systematic review. J Child Neurol 2013; 28:351.
  12. Srinivasakumar P, Zempel J, Trivedi S, et al. Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial. Pediatrics 2015; 136:e1302.
  13. Bartha AI, Shen J, Katz KH, et al. Neonatal seizures: multicenter variability in current treatment practices. Pediatr Neurol 2007; 37:85.
  14. Glass HC, Kan J, Bonifacio SL, Ferriero DM. Neonatal seizures: treatment practices among term and preterm infants. Pediatr Neurol 2012; 46:111.
  15. Hellström-Westas L, Boylan G, Ågren J. Systematic review of neonatal seizure management strategies provides guidance on anti-epileptic treatment. Acta Paediatr 2015; 104:123.
  16. Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med 1999; 341:485.
  17. Antiepileptic Drugs, 4th, Levy, RA, Mattson, RH, Meldrum, BS, Perucca, E (Eds), Raven Press, New York 1995.
  18. DeLorenzo, RJ. Phenytoin. Mechanisms of Action. In: Antiepileptic Drugs, 4th, Levy, RH, Mattson, RH, Meldrum, BS (Eds), Raven Press, New York 1995. p.271.
  19. Macdonald, RL. Benzodiazepines. In: Antiepileptic Drugs, 4th, Levy, RH, Mattson, RH, Meldrum, BS (Eds), Raven Press, New York 1995. p.695.
  20. Painter, MJ, Gaus, LM.. Phenobarbital: Clinical Use. In: Antiepileptic Drugs, 4th, Levy, H, Mattson, RH, Meldrum, BS (Eds), Raven Press, New York 1995. p.401.
  21. Shellhaas RA, Ng CM, Dillon CH, et al. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia. Pediatr Crit Care Med 2013; 14:194.
  22. Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology 1987; 37:1837.
  23. Mizrahi, EM, Kellaway, P. The response of electroclinical neonatal seizures to antiepileptic drug therapy. Epilepsia 1992; 33:114.
  24. Shellhaas RA, Chang T, Tsuchida T, et al. The American Clinical Neurophysiology Society's Guideline on Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol 2011; 28:611.
  25. Boylan GB, Rennie JM, Chorley G, et al. Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study. Neurology 2004; 62:486.
  26. Glass HC, Wirrell E. Controversies in neonatal seizure management. J Child Neurol 2009; 24:591.
  27. Silverstein FS, Ferriero DM. Off-label use of antiepileptic drugs for the treatment of neonatal seizures. Pediatr Neurol 2008; 39:77.
  28. Kilicdag H, Daglıoglu K, Erdogan S, et al. The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury. Early Hum Dev 2013; 89:355.
  29. Komur M, Okuyaz C, Celik Y, et al. Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats. Childs Nerv Syst 2014; 30:1001.
  30. Talos DM, Chang M, Kosaras B, et al. Antiepileptic effects of levetiracetam in a rodent neonatal seizure model. Pediatr Res 2013; 73:24.
  31. Khan O, Chang E, Cipriani C, et al. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol 2011; 44:265.
  32. Abend NS, Gutierrez-Colina AM, Monk HM, et al. Levetiracetam for treatment of neonatal seizures. J Child Neurol 2011; 26:465.
  33. Sharpe CM, Capparelli EV, Mower A, et al. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res 2012; 72:43.
  34. Merhar SL, Schibler KR, Sherwin CM, et al. Pharmacokinetics of levetiracetam in neonates with seizures. J Pediatr 2011; 159:152.
  35. Castro Conde JR, Hernández Borges AA, Doménech Martínez E, et al. Midazolam in neonatal seizures with no response to phenobarbital. Neurology 2005; 64:876.
  36. Painter MJ, Pippenger C, MacDonald H, Pitlick W. Phenobarbital and diphenylhydantoin levels in neonates with seizures. J Pediatr 1978; 92:315.
  37. Gal P, Toback J, Boer HR, et al. Efficacy of phenobarbital monotherapy in treatment of neonatal seizures -- relationship to blood levels. Neurology 1982; 32:1401.
  38. Donn SM, Grasela TH, Goldstein GW. Safety of a higher loading dose of phenobarbital in the term newborn. Pediatrics 1985; 75:1061.
  39. Dzhala VI, Talos DM, Sdrulla DA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med 2005; 11:1205.
  40. Galanopoulou AS. Developmental patterns in the regulation of chloride homeostasis and GABA(A) receptor signaling by seizures. Epilepsia 2007; 48 Suppl 5:14.
  41. Dzhala VI, Brumback AC, Staley KJ. Bumetanide enhances phenobarbital efficacy in a neonatal seizure model. Ann Neurol 2008; 63:222.
  42. Cleary RT, Sun H, Huynh T, et al. Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures. PLoS One 2013; 8:e57148.
  43. Kahle KT, Barnett SM, Sassower KC, Staley KJ. Decreased seizure activity in a human neonate treated with bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1. J Child Neurol 2009; 24:572.
  44. Pressler RM, Boylan GB, Marlow N, et al. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2 trial. Lancet Neurol 2015; 14:469.
  45. Bourgeois BF, Dodson WE. Phenytoin elimination in newborns. Neurology 1983; 33:173.
  46. Dodson WE. Antiepileptic drug utilization in pediatric patients. Epilepsia 1984; 25 Suppl 2:S132.
  47. Malingré MM, Van Rooij LG, Rademaker CM, et al. Development of an optimal lidocaine infusion strategy for neonatal seizures. Eur J Pediatr 2006; 165:598.
  48. van den Broek MP, Rademaker CM, van Straaten HL, et al. Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine: efficacy, safety and dosing. Arch Dis Child Fetal Neonatal Ed 2013; 98:F341.
  49. van Rooij LG, Toet MC, Rademaker KM, et al. Cardiac arrhythmias in neonates receiving lidocaine as anticonvulsive treatment. Eur J Pediatr 2004; 163:637.
  50. Guillet R, Kwon J. Seizure recurrence and developmental disabilities after neonatal seizures: outcomes are unrelated to use of phenobarbital prophylaxis. J Child Neurol 2007; 22:389.
  51. Boer HR, Gal P. Neonatal seizures: a survey of current practice. Clin Pediatr (Phila) 1982; 21:453.
  52. Fenichel, GM. Paroxysmal disorders. In: Clinical Pediatric Neurology, 3rd, WB Saunders (Ed), Philadelphia 1997. p.1.