胎兒酒精譜系障礙綜合征與癲癇_Journal of Epilepsy

Authors：

王克玲 ,  施榮富

海南省兒童醫院神經內科（海口 ?570206）;

Corresponding?author：

施榮富, Email: srf.111@126.com

Keywords：

酒精; 胎兒酒精譜系障礙; 癲癇

DOI：

10.7507/2096-0247.20180012

Video：

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以往研究資料顯示胎兒酒精譜系障礙（Fetal alcohol spectrum disorders，FASD）合并有較高的癲癇發生率，FASD 高發癲癇的機制尚不十分清楚，現有的研究認為其機制有下面幾個方面原因：① 酒精作用于胎兒腦組織引起代謝和形態學改變，而導致功能改變，誘發癲癇；② 酒精降低了神經元的興奮閾值；③ 通過突觸機制；④ 或非突觸路徑引發癲癇。研究資料還顯示酒精暴露對胎兒腦組織的損傷具有時效性，不同時間暴露酒精，損害的部位不一樣，造成的不良事件也不一樣；癲癇也是 FASD 常見的不良事件之一。快速發育中的腦組織對酒精尤其敏感。目前對 FASD 及合并的癲癇還沒有安全有效的治療方法，有學者在動物實驗中嘗試用雷帕霉素和神經干細胞注射治療 FASD 合并的癲癇和其它神經功能障礙，并顯示了一定效果，但安全性和有效性有待進一步認證。FASD 合并癲癇在我國的研究較少，現將相關研究進行綜述分析。

Citation： 王克玲, 施榮富. 胎兒酒精譜系障礙綜合征與癲癇. Journal of Epilepsy, 2018, 4(1): 49-52. doi: 10.7507/2096-0247.20180012 Copy

1.	Waja T, Ebrahim J, Yohannis Z, et al. Prevalence of alcohol use disorders and associated factors among people with epilepsy attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. Neuropsychiatr Dis Treat, 2016, 12: 2989-2996.
2.	Johnson JL, Leff M. Children of substance abusers: overview of research findings. Pediatrics, 1999,103(5 Pt 2): 1085-1099.
3.	Bell SH, Stade B, Reynolds JN, et al.The remarkably high prevalence of epilepsy and seizure history in fetal alcohol spectrum disorders. Alcohol Clin Exp Res, 2010, 34(6): 1084-1089.
4.	O'Malley KD, Rich SD. Clinical implications of a link between fetal alcohol spectrum disorders (FASD) and autism or asperger's disorder - a neurodevelopmental frame for helping understanding and management. edn. 2013, INTECH Open Access Publisher.
5.	Sampson PD, Bookstein FL, Barr HM, et al. Prenatal alcohol exposure, birthweight, and measures of child size from birth to age 14 years. Am J Public Health, 1994, 84(9): 1421-1428.
6.	Sampson PD, Streissguth AP, Bookstein FL,et al.Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology, 1997, 56(5):317-326.
7.	Sokol RJ, Delaney-Black V, Nordstrom B. Fetal alcohol spectrum disorder. JAMA , 2003, 290(22):2996-2999.
8.	Chudley AE, Conry J, Cook JL, et al. Fetal alcohol spectrum disorder: canadian guidelines for diagnosis. CMAJ, 2005, 3(1): 172.
9.	May PA, Gossage JP, Kalberg WO, et al. Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies. Dev Disabil Res Rev, 2009, 15(3): 176-192.
10.	Iosub S, Fuchs M, Bingol N, et al. Fetal alcohol syndrome revisited. Pediatrics, 1981, 68(4): 475-497.
11.	O’Malley K, Barr H. Fetal Alcohol syndrome and seizure disorder. Can J Psychol, 1998, 43(10): 1051.
12.	Spohr H, Steinhausen H. Follow-up studies of children with fetal alcohol syndrome. Neuropediatrics, 1987, 18(1): 13-17.
13.	Liang J, Shen Y, Shao XM, et al. Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescence. Neurochem Res, 2014, 39(6): 1147-1161.
14.	Bonthius DJ, Pantazis NJ, Karacay B, et al. Alcohol exposure during the brain growth spurt promotes hippocampal seizures, rapid kindling, and spreading depression. Alcohol Clin Exp Res, 2001, 25(5): 734-745.
15.	Fernandes Y, Gerlai R. Long-term behavioral changes in response to early developmental exposure to ethanol in zebrafish. Alcohol Clin Exp Res, 2009, 33(4): 601-609.
16.	Tanguay RL, Reimers MJ. Analysis of ethanol developmental toxicity in zebrafish. Methods Mol Biol, 2008, 447: 63-74.
17.	Carvan MJ, Loucks E, Weber DN, et al. Ethanol effects on the developing zebrafish: neurobehavior and skeletal morphogenesis. Neurotoxicol Teratol, 2004, 26(6): 757-768.
18.	Str?mland K, Pinazo-Durán MD. Ophthalmic involvement in the fetal alcoholsyndrome: clinical and animal model studies. Alcohol Alcohol, 2002, 37(1): 2-8.
19.	Kashyap B, Pegorsch L, Frey RA, et al. Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1. Reprod Toxicol, 2014, 43: 111-124.
20.	Boronat S, Vicente M, Lainez E, et al. Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders. Eur J Med Genet, 2017, 60(1): 72-78.
21.	Church MW, Holloway JA. Audiogenic seizure susceptibility in mature rats with fetal alcohol syndrome. Alcohol Clin Exp Res, 1981, 5: 145.
22.	胡建, 楊德森. 酒精中毒所致大腦損害的病因與神經生化研究. 國外醫學精神病分冊, 1998, 25(1): 31-34.
23.	Hirai K, Yoshioka H, Kihara M, et al. Effects of ethanol on neuronal migration and neural cell adhesion molecules in the embryonic rat cerebral cortex: A tissue culture study. Dev Brain Res,1999, 118(1-2): 205-210.
24.	Ikonomidou C, Bittigan P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science, 2000, 287(5455): 1056-1060.
25.	West JR, Hodges CA, Black AC. Prenatal exposure to ethanol alters the organization of hippocampal mossy fibers in rats. Science, 1981, 211(4485): 957-959.
26.	Bouilleret V, Ridoux V, Depaulis A, et al. Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice. Electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience, 1999, 89(3): 717-729.
27.	Chen WJA, Parnell SE, West JR. Effects of alcohol and nicotine on developing olfactory bulb: Loss of mitral cells and alterations in neurotransmitter levels. Alcohol Clin Exp Res, 1999, 23(1): 18-25.
28.	Bailey CD, Brien JF, Reynolds JN. Altered GABA(A)-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure. Alcohol Clin Exp Res, 1999, 23(11): 1816-1824.
29.	Baulac M, Laplane D. Alcohol and epilepsy. Rev Prat, 1990,40(4): 307-311.
30.	Bonthius DJ, Woodhouse J, Bonthius NE, et al. Reduced seizure threshold and hippocampal cell loss in rats exposed to alcohol during the brain growth spurt. Alcohol Clin Exp Res, 2001, 25(1): 70-81.
31.	Thomas JD, Goodlett CR, West JR. Alcohol-induced Purkinje cell loss depends on developmental timing of alcohol exposure and correlates with motor performance. Dev Brain Res, 1998, 105(2): 159-166.
32.	董志霞, 陸倫根. 酒精戒斷綜合征的機制、臨床特點及治療進展. 現代醫藥衛生, 2017, 33(1): 12-14.
33.	Carlson SL, O'Buckley TK, Thomas R, et al. Altered GABAA receptor expression and seizure threshold following acute ethanol challenge in mice lacking the RIIβ subunit of PKA. Neurochem Res, 2014, 39(6): 1079-1087.
34.	Fox JE, Bikson M, Jefferys JG. Tissue resistance changes and the profile of synchronized neuronal activity during ictal events in the low calcium model of epilepsy. J Neurophysiol, 2004, 92(1): 181-188.
35.	Santos LE, da Silveira GA, Costa VD,et al.Alcohol abuse promotes changes in non-synaptic epileptiform activity with concomitant expression changes in cotransporters and glial cells. PLoS ONE, 2000, 8(11): e78854.
36.	Anton RF, Randall CL. Central nervous system prostaglandins and ethanol. Alcohol Clin Exp Res, 2006, 11(1): 10-18.
37.	Morales-Aza BM, Chilingworth NL, Payne JA, et al. Inflammation alters cation chloride cotransporter expression in sensory neurons. Neurobiol Dis, 2004, 17(1): 62-69.
38.	de Almeida AC, Rodrigues AM, Scorza FA, et al. Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state: computational simulation. Epilepsia, 2008, 49(11): 1-17.
39.	Goodlett CR, Eilers AT. Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: a stereological study of temporal windows of vulnerability. Alcohol Clin Exp Res, 1997, 21(4): 738-744.
40.	Maier SE, Miller JA, Blackwell JM, et al. Fetal alcohol exposure and temporal vulnerability: Regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development. Alcohol Clin Exp Res, 1999, 23(4): 726-734.
41.	Cartwright MM, Smith SM. Stage dependent effects of ethanol on cranial neural crest cell development: partial basis for the phenotypic variations observed in fetal alcohol syndrome. Alcohol Clin Exp Res, 1995, 19(6): 1454-1462.
42.	Kotch LE, Sulik KK. Experimental fetal alcohol syndrome: Proposed pathogenic basis for a variety of associated focal and brain anomalies. Am J Med Genet, 1992, 44(2): 168-176.
43.	Goodlett CR, Johnson TB. Neonatal binge ethanol exposure using intubation: timing and dose effects on place learning. Neurotoxicol Teratol, 1997, 19(6): 435-446.
44.	Fu X, Guo Z, Gao C, et al. Long-term alcohol-Induced activation of mammalian target of rapamycin is a key risk factor of epilepsy. Med Sci Monit, 2016, 25(22): 3975-3980.
45.	Yoshinaga T, Hashimoto E, Ukai W, et al. Neural stem cell transplantation in a model of fetal alcohol effects. Neural Transm Suppl, 2007, 72: 331-337.
46.	Shirasaka T, Ukai W, Yoshinaga T, et al. Promising therapy of neural stem cell transplantation for FASD model-neural network reconstruction and behavior recovery. Nihon Arukoru Yakubutsu Igakkai Zasshi, 2011, 46(6): 576-584.
47.	Lippert T, Gelineau L, Napoli E, et al. Harnessing neural stem cells for treating psychiatric symptoms associated with fetal alcohol spectrum disorder and epilepsy. Prog Neuropsychopharmacol Biol Psychiatry, 2018, 3(80):10-22.

1. Waja T, Ebrahim J, Yohannis Z, et al. Prevalence of alcohol use disorders and associated factors among people with epilepsy attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. Neuropsychiatr Dis Treat, 2016, 12: 2989-2996.
2. Johnson JL, Leff M. Children of substance abusers: overview of research findings. Pediatrics, 1999,103(5 Pt 2): 1085-1099.
3. Bell SH, Stade B, Reynolds JN, et al.The remarkably high prevalence of epilepsy and seizure history in fetal alcohol spectrum disorders. Alcohol Clin Exp Res, 2010, 34(6): 1084-1089.
4. O'Malley KD, Rich SD. Clinical implications of a link between fetal alcohol spectrum disorders (FASD) and autism or asperger's disorder - a neurodevelopmental frame for helping understanding and management. edn. 2013, INTECH Open Access Publisher.
5. Sampson PD, Bookstein FL, Barr HM, et al. Prenatal alcohol exposure, birthweight, and measures of child size from birth to age 14 years. Am J Public Health, 1994, 84(9): 1421-1428.
6. Sampson PD, Streissguth AP, Bookstein FL,et al.Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology, 1997, 56(5):317-326.
7. Sokol RJ, Delaney-Black V, Nordstrom B. Fetal alcohol spectrum disorder. JAMA , 2003, 290(22):2996-2999.
8. Chudley AE, Conry J, Cook JL, et al. Fetal alcohol spectrum disorder: canadian guidelines for diagnosis. CMAJ, 2005, 3(1): 172.
9. May PA, Gossage JP, Kalberg WO, et al. Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies. Dev Disabil Res Rev, 2009, 15(3): 176-192.
10. Iosub S, Fuchs M, Bingol N, et al. Fetal alcohol syndrome revisited. Pediatrics, 1981, 68(4): 475-497.
11. O’Malley K, Barr H. Fetal Alcohol syndrome and seizure disorder. Can J Psychol, 1998, 43(10): 1051.
12. Spohr H, Steinhausen H. Follow-up studies of children with fetal alcohol syndrome. Neuropediatrics, 1987, 18(1): 13-17.
13. Liang J, Shen Y, Shao XM, et al. Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescence. Neurochem Res, 2014, 39(6): 1147-1161.
14. Bonthius DJ, Pantazis NJ, Karacay B, et al. Alcohol exposure during the brain growth spurt promotes hippocampal seizures, rapid kindling, and spreading depression. Alcohol Clin Exp Res, 2001, 25(5): 734-745.
15. Fernandes Y, Gerlai R. Long-term behavioral changes in response to early developmental exposure to ethanol in zebrafish. Alcohol Clin Exp Res, 2009, 33(4): 601-609.
16. Tanguay RL, Reimers MJ. Analysis of ethanol developmental toxicity in zebrafish. Methods Mol Biol, 2008, 447: 63-74.
17. Carvan MJ, Loucks E, Weber DN, et al. Ethanol effects on the developing zebrafish: neurobehavior and skeletal morphogenesis. Neurotoxicol Teratol, 2004, 26(6): 757-768.
18. Str?mland K, Pinazo-Durán MD. Ophthalmic involvement in the fetal alcoholsyndrome: clinical and animal model studies. Alcohol Alcohol, 2002, 37(1): 2-8.
19. Kashyap B, Pegorsch L, Frey RA, et al. Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1. Reprod Toxicol, 2014, 43: 111-124.
20. Boronat S, Vicente M, Lainez E, et al. Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders. Eur J Med Genet, 2017, 60(1): 72-78.
21. Church MW, Holloway JA. Audiogenic seizure susceptibility in mature rats with fetal alcohol syndrome. Alcohol Clin Exp Res, 1981, 5: 145.
22. 胡建, 楊德森. 酒精中毒所致大腦損害的病因與神經生化研究. 國外醫學精神病分冊, 1998, 25(1): 31-34.
23. Hirai K, Yoshioka H, Kihara M, et al. Effects of ethanol on neuronal migration and neural cell adhesion molecules in the embryonic rat cerebral cortex: A tissue culture study. Dev Brain Res,1999, 118(1-2): 205-210.
24. Ikonomidou C, Bittigan P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science, 2000, 287(5455): 1056-1060.
25. West JR, Hodges CA, Black AC. Prenatal exposure to ethanol alters the organization of hippocampal mossy fibers in rats. Science, 1981, 211(4485): 957-959.
26. Bouilleret V, Ridoux V, Depaulis A, et al. Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice. Electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience, 1999, 89(3): 717-729.
27. Chen WJA, Parnell SE, West JR. Effects of alcohol and nicotine on developing olfactory bulb: Loss of mitral cells and alterations in neurotransmitter levels. Alcohol Clin Exp Res, 1999, 23(1): 18-25.
28. Bailey CD, Brien JF, Reynolds JN. Altered GABA(A)-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure. Alcohol Clin Exp Res, 1999, 23(11): 1816-1824.
29. Baulac M, Laplane D. Alcohol and epilepsy. Rev Prat, 1990,40(4): 307-311.
30. Bonthius DJ, Woodhouse J, Bonthius NE, et al. Reduced seizure threshold and hippocampal cell loss in rats exposed to alcohol during the brain growth spurt. Alcohol Clin Exp Res, 2001, 25(1): 70-81.
31. Thomas JD, Goodlett CR, West JR. Alcohol-induced Purkinje cell loss depends on developmental timing of alcohol exposure and correlates with motor performance. Dev Brain Res, 1998, 105(2): 159-166.
32. 董志霞, 陸倫根. 酒精戒斷綜合征的機制、臨床特點及治療進展. 現代醫藥衛生, 2017, 33(1): 12-14.
33. Carlson SL, O'Buckley TK, Thomas R, et al. Altered GABAA receptor expression and seizure threshold following acute ethanol challenge in mice lacking the RIIβ subunit of PKA. Neurochem Res, 2014, 39(6): 1079-1087.
34. Fox JE, Bikson M, Jefferys JG. Tissue resistance changes and the profile of synchronized neuronal activity during ictal events in the low calcium model of epilepsy. J Neurophysiol, 2004, 92(1): 181-188.
35. Santos LE, da Silveira GA, Costa VD,et al.Alcohol abuse promotes changes in non-synaptic epileptiform activity with concomitant expression changes in cotransporters and glial cells. PLoS ONE, 2000, 8(11): e78854.
36. Anton RF, Randall CL. Central nervous system prostaglandins and ethanol. Alcohol Clin Exp Res, 2006, 11(1): 10-18.
37. Morales-Aza BM, Chilingworth NL, Payne JA, et al. Inflammation alters cation chloride cotransporter expression in sensory neurons. Neurobiol Dis, 2004, 17(1): 62-69.
38. de Almeida AC, Rodrigues AM, Scorza FA, et al. Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state: computational simulation. Epilepsia, 2008, 49(11): 1-17.
39. Goodlett CR, Eilers AT. Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: a stereological study of temporal windows of vulnerability. Alcohol Clin Exp Res, 1997, 21(4): 738-744.
40. Maier SE, Miller JA, Blackwell JM, et al. Fetal alcohol exposure and temporal vulnerability: Regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development. Alcohol Clin Exp Res, 1999, 23(4): 726-734.
41. Cartwright MM, Smith SM. Stage dependent effects of ethanol on cranial neural crest cell development: partial basis for the phenotypic variations observed in fetal alcohol syndrome. Alcohol Clin Exp Res, 1995, 19(6): 1454-1462.
42. Kotch LE, Sulik KK. Experimental fetal alcohol syndrome: Proposed pathogenic basis for a variety of associated focal and brain anomalies. Am J Med Genet, 1992, 44(2): 168-176.
43. Goodlett CR, Johnson TB. Neonatal binge ethanol exposure using intubation: timing and dose effects on place learning. Neurotoxicol Teratol, 1997, 19(6): 435-446.
44. Fu X, Guo Z, Gao C, et al. Long-term alcohol-Induced activation of mammalian target of rapamycin is a key risk factor of epilepsy. Med Sci Monit, 2016, 25(22): 3975-3980.
45. Yoshinaga T, Hashimoto E, Ukai W, et al. Neural stem cell transplantation in a model of fetal alcohol effects. Neural Transm Suppl, 2007, 72: 331-337.
46. Shirasaka T, Ukai W, Yoshinaga T, et al. Promising therapy of neural stem cell transplantation for FASD model-neural network reconstruction and behavior recovery. Nihon Arukoru Yakubutsu Igakkai Zasshi, 2011, 46(6): 576-584.
47. Lippert T, Gelineau L, Napoli E, et al. Harnessing neural stem cells for treating psychiatric symptoms associated with fetal alcohol spectrum disorder and epilepsy. Prog Neuropsychopharmacol Biol Psychiatry, 2018, 3(80):10-22.

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