余叶蓉,
Email: yerongyu@scu.edu.cn
内分泌激素和神经系统一起调节着机体的各种生命活动,癫痫和内分泌激素有着密切而复杂的关联,癫痫的发作可能影响体内激素水平,反之,体内激素水平的变化尤其是神经类固醇激素可影响癫痫的发作频率和严重程度,激素还可以间接通过药物代谢动力作用改变抗癫痫药物(AEDs)的浓度从而对癫痫产生影响。癫痫与内分泌激素之间关系复杂,给临床治疗带来一定的挑战。目前随着人们对于下丘脑-垂体-肾上腺(Hypothalamus pituitary adrenal, HPA)轴、下丘脑-垂体-甲状腺((Hypothalamic pituitary thyroid axis, HPT)轴及下丘脑-垂体-性腺(卵巢/睾丸)(Hypothalamo pituitary ovarian, HPO)轴在癫痫中的表现和作用研究的逐渐深入,给临床治疗和控制癫痫带来一丝曙光。如何发现癫痫患者发作规律,揭示诱发癫痫和内分泌紊乱的病因机制和危险因素,对早期进行干预和指导医师临床诊疗具有重大的临床意义,对于癫痫患者生活质量的提高也有所裨益。现围绕癫痫与内分泌激素的相互作用和相关研究进展进行分析阐述。
Citation： 谭惠文, 余叶蓉. 癫痫与内分泌激素关系的研究进展. Journal of Epilepsy, 2016, 2(6): 509-514. doi: 10.7507/2096-0247.20160090 Copy
| 1. | Pack M, Reddy DS, Duncan S,et al. Neuroendocrinological aspects of epilepsy:important issues and trends in future research. Epilepsy Behav, 2011, 22(7):94-102. |
| 2. | Reddy DS. Role of hormones and neurosteroids in eplileptogenesis. Front Cell Neurosci, 2013, 7(3):115. |
| 3. | Biagini G,Panuccio G, Avoli M. Neruosteroids and epilepsy. Curr Opin Neurol, 2010, 23(2):170-176. |
| 4. | Svalheim S, Sveberg L, Mochol M,et al.Interactions between antiepileptic drugs and hormones. Seizure, 2015, 28(2):12-17. |
| 5. | Luef G.Hormonal alterations following seizures. Epilepsy Behav, 2010, 19(2):131-133. |
| 6. | Maguire J, Salpekar JA. Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.Epilepsy Behav, 2013,26(3):352-362. |
| 7. | Wulsin AC, Solomon MB, Privitera MD,et al.Hypothalamic-pituitary-adrenocortical axis dysfunction in epilepsy.Physiol Behav, 2016,166(1):22-31. |
| 8. | Joshi S, Rajasekaran K, Kapur J.GABAergic transmission in temporal lobe epilepsy:the role of neurosteroids.Exp Neurol, 2013, 244(2):36-42. |
| 9. | Danzer SC.Depression, stress, epilepsy and adult neurogenesis.Exp Neurol, 2012, 233(1):22-32. |
| 10. | van Campen JS, Valentijn FA, Jansen FE. Seizure occurrence and the circadian rhythm of cortisol:a systematic review.Epilepsy Behav, 2015, 47(3):132-137. |
| 11. | Badawy RA, Freestone DR, Lai A. Epilepsy:Ever-changing states of cortical excitability.Neuroscience, 2012, 222(11):89-99. |
| 12. | 胡琳, 张华丹,陈亚天,等. 不同药物诱导的小鼠癫痫模型的差异性研究.浙江大学学报(医学版), 2013, 42(6):609-610. |
| 13. | Jones NC.Potentiating the strength of extrasynaptic currents by neurosteroid hormones.Epilepsy Curr, 2016, 16(4):261-262. |
| 14. | De Leon J.The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part I:A summary of the current state for clinicians.Rev Psiquiatr Salud Ment, 2015, 8(2):97-115. |
| 15. | Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab, 2007, 3(1):249-259. |
| 16. | Hamed SA.The effect of antiepileptic drugs on thyroid hormonal function:causes and implications. Expert Rev Clin Pharmacol, 2015, 8(6):741-750. |
| 17. | Kaya M, Becker AJ, Gürses C.Blood-brain barrier, epileptogenesis, and treatment strategies in cortical dysplasia.Epilepsia, 2012, 53(Suppl 6):31-36. |
| 18. | Hamed SA, Hamed EA, Kandil MR.Serum thyroid hormone balance and lipid profile in patients with epilepsy.Epilepsy Res, 2005,66(1-3):173-183. |
| 19. | Mehran L, Amouzegar A, Tohidi M.Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects. Thyroid, 2014, 24(11):1566-1574. |
| 20. | El-Khayat HA, Aly GS, Tomoum HY, et al.Growth hormone levels in children and adolescents with epilepsy.Eur J Paediatr Neurolm, 2010, 14(6):508-512. |
| 21. | Devinsky O, Emoto S, Goldstein DS, et al. Cerebrospinal fluid and serum levels of dopa, catechols, and monoamine metabolites in patients with epilepsy.Epilepsia, 1992, 33(2):263-270. |
| 22. | Martinez A, Finegersh A, Cannon DM.The 5-HT1A receptor and 5-HT transporter in temporal lobe epilepsy. Neurology, 2013, 80(16):1465-1471. |
| 23. | Kurian MA, Gissen P, Smith M.The monoamine neurotransmitter disorders:an expanding range of neurological syndromes.Lancet Neurol, 2011, 10(8):721-733. |
| 24. | Recio MV, Gallagher MJ, McLean MJ. Clinical features of epilepsy in patients with cerebellar structural abnormalities in a referral center.Epilepsy Res, 2007, 76(1):1-5. |
| 25. | Scharfman HE. The neurobiology of epilepsy.Curr Neurol Neurosci Rep, 2007, 7(4):348-354. |
| 26. | Bauer J.Epilepsy and prolactin in adults:a clinical review.Epilepsy Res, 1996, 24(1):1-7. |
| 27. | Luef G, Madersbacher H.Sexual dysfunction in patients with epilepsy. Handb Clin Neurol, 2015, 130(2):383-394. |
| 28. | Schmidt D, Schachter SC. Drug treatment of epilepsy in adults.BMJ, 2014, 348(28):254. |
| 29. | Sundararajan T, Tesar GE, Jimenez XF.Biomarkers in the diagnosis and study of psychogenic nonepileptic seizures:a systematic review.Seizure, 2016, 35(3):11-22. |
| 30. | Du Y, Kemper T, Qiu J, Jiang J. Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus. Expert Rev Neurother, 2016,16(2):123-130. |
| 31. | Onaka T, Takayanagi Y, Leng G. Metabolic and stress-related roles of prolactin-releasing peptide. Trends Endocrinol Meta, 2010, 21(5):287-293. |
| 32. | Trimble MR. Serum prolactin in epilepsy and hysteria. Br Med J, 1978, 2(6153):1682. |
| 33. | Kanasaki H, Oride A, Mijiddorj T.Role of thyrotropin-releasing hormone in prolactin-producing cell models.Neuropeptides, 2015, 54(1):73-77. |
| 34. | 陈柳静, 周列民,周珏倩,等. 育龄女性癫痫患者的生殖内分泌紊乱相关危险因素分析. 中山大学学报(医学科学版), 2010, 31(2):302-305. |
| 35. | Maguire J, Salpekar JA.Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.Epilepsy Behav, 2013, 26(3):352-362. |
| 36. | Frye CA. Hormonal influences on seizures:basic neurobiology.Int Rev Neurobiol, 2008, 83(3):27-77. |
| 37. | Mehta V, Ferrie CD, Cross JH. Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms. Cochrane Database Syst Rev, 2015, 15(6):CD005222. |
| 38. | Xiong F, Zhang L. Role of the hypothalamic-pituitary-adrenal axis in developmental programming of health and disease.Front Neuroendocrinol, 2013,34(1):27-46. |
| 39. | Fekete C, Lechan RM.Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions.Endocr Rev, 2014, 35(2):159-194. |
| 40. | Woodbury DM, Hurley RE.Effect of thyroxin, thyroidectomy and 6-n-propyl-2-thiouracil on brain function. J Pharmacol Exp Ther, 1952, 106(3):331-340. |
| 41. | Jabbari B, Huott AD.Seizures in thyrotoxicosis. Epilepsia, 1980, 21(1):91-96. |
| 42. | Taubøll E, Sveberg L, Svalheim S.Interactions between hormones and epilepsy.Seizure, 2015, 28(5):3-11. |
| 43. | Jeurissen B, Leemans A, Tournier JD, et al. Investigating theprevalence of complex fiber configurations in white matter tissue withdiffusion magnetic resonance imaging. Hum Brain Mapp, 2013, 34(5):2747-2766. |
| 44. | Shultz SR, Zheng P, Wright DK, et al. Tractography and magneticresonance spectroscopy in acquired epilepsy models. WONOEP XⅡmeeting planner, 2013, QC, Canada. |
| 45. | Jones DK, Knosche TR, Turner R. White matter integrity, fiber count,and other fallacies:the do's and dont's of diffusion MRI. Neuroimage, 2013, 73(12):239-254. |
| 46. | Ogawa S, Lee TM, Nayak AS, et al. Oxygenation-sensitive contrast inmagnetic resonance image of rodent brain at high magnetic fields.Magn Reson Med, 1990, 14(7):68-78. |
| 47. | Smith G, Wagner JL, Edwards JC. Epilepsy Update, Part 1:refining our understanding of a complex disease.Am J Nurs, 2015, 115(5):40-47. |
| 48. | Galimberti CA, Magri F, Copello F. Changes in sex steroid levels in women with epilepsy on treatment:relationship with antiepileptic therapies and seizure frequency. Epilepsia, 2009,50 (Suppl 1):28-32. |
| 49. | Herzog AG.Menstrual disorders in women with epilepsy.Neurology, 2006, 66(Suppl 3):23-28. |
| 50. | van Luijtelaar G, Onat FY, Gallagher MJ.Animal models of absence epilepsies:what do they model and do sex and sex hormones matter?. Neurobiol Dis, 2014,72(Pt B):167-179. |
| 51. | Chiu AW, Daniel S, Khosravani H.Prediction of seizure onset in an in-vitro hippocampal slice model of epilepsy using Gaussian-based and wavelet-based artificial neural networks.Ann Biomed Eng, 2005,33(6):798-810. |
| 52. | Mejías-Aponte CA, Jiménez-Rivera CA, Segarra AC.Sex differences in models of temporal lobe epilepsy:role of testosterone.Brain Res, 2002,944(1-2):210-218. |
| 53. | Bauer J, Blumenthal S, Reuber M.Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy.Neurology, 2004,62(2):243-246. |
| 54. | Herzog AG, Fowler KM.Sexual hormones and epilepsy:threat and opportunities.Curr Opin Neurol, 2005, 18(2):167-172. |
| 55. | Hamed SA.Neuroendocrine hormonal conditions in epilepsy:relationship to reproductive and sexual functions. Neurologist, 2008, 14(3):157-169. |
| 56. | R, Wainwright SR, Galea LA.Sex hormones and adult hippocampal neurogenesis:Regulation, implications, and potential mechanisms.Front Neuroendocrinol. 2016,41:129-52. |
| 57. | Alam MN, Ahmad A, Al-Abbasi FA, Ahmad A.Female ovarian steroids in epilepsy:a cause or remedy.Pharmacol Rep, 2013,65(4):802-12. |
| 58. | Herzog AG.Catamenial epilepsy:Update on prevalence, pathophysiology and treatment from the findings of the NIH progesterone treatment trial. Seizure, 2015, 28(5):18-25. |
- 1. Pack M, Reddy DS, Duncan S,et al. Neuroendocrinological aspects of epilepsy:important issues and trends in future research. Epilepsy Behav, 2011, 22(7):94-102.
- 2. Reddy DS. Role of hormones and neurosteroids in eplileptogenesis. Front Cell Neurosci, 2013, 7(3):115.
- 3. Biagini G,Panuccio G, Avoli M. Neruosteroids and epilepsy. Curr Opin Neurol, 2010, 23(2):170-176.
- 4. Svalheim S, Sveberg L, Mochol M,et al.Interactions between antiepileptic drugs and hormones. Seizure, 2015, 28(2):12-17.
- 5. Luef G.Hormonal alterations following seizures. Epilepsy Behav, 2010, 19(2):131-133.
- 6. Maguire J, Salpekar JA. Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.Epilepsy Behav, 2013,26(3):352-362.
- 7. Wulsin AC, Solomon MB, Privitera MD,et al.Hypothalamic-pituitary-adrenocortical axis dysfunction in epilepsy.Physiol Behav, 2016,166(1):22-31.
- 8. Joshi S, Rajasekaran K, Kapur J.GABAergic transmission in temporal lobe epilepsy:the role of neurosteroids.Exp Neurol, 2013, 244(2):36-42.
- 9. Danzer SC.Depression, stress, epilepsy and adult neurogenesis.Exp Neurol, 2012, 233(1):22-32.
- 10. van Campen JS, Valentijn FA, Jansen FE. Seizure occurrence and the circadian rhythm of cortisol:a systematic review.Epilepsy Behav, 2015, 47(3):132-137.
- 11. Badawy RA, Freestone DR, Lai A. Epilepsy:Ever-changing states of cortical excitability.Neuroscience, 2012, 222(11):89-99.
- 12. 胡琳, 张华丹,陈亚天,等. 不同药物诱导的小鼠癫痫模型的差异性研究.浙江大学学报(医学版), 2013, 42(6):609-610.
- 13. Jones NC.Potentiating the strength of extrasynaptic currents by neurosteroid hormones.Epilepsy Curr, 2016, 16(4):261-262.
- 14. De Leon J.The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part I:A summary of the current state for clinicians.Rev Psiquiatr Salud Ment, 2015, 8(2):97-115.
- 15. Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab, 2007, 3(1):249-259.
- 16. Hamed SA.The effect of antiepileptic drugs on thyroid hormonal function:causes and implications. Expert Rev Clin Pharmacol, 2015, 8(6):741-750.
- 17. Kaya M, Becker AJ, Gürses C.Blood-brain barrier, epileptogenesis, and treatment strategies in cortical dysplasia.Epilepsia, 2012, 53(Suppl 6):31-36.
- 18. Hamed SA, Hamed EA, Kandil MR.Serum thyroid hormone balance and lipid profile in patients with epilepsy.Epilepsy Res, 2005,66(1-3):173-183.
- 19. Mehran L, Amouzegar A, Tohidi M.Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects. Thyroid, 2014, 24(11):1566-1574.
- 20. El-Khayat HA, Aly GS, Tomoum HY, et al.Growth hormone levels in children and adolescents with epilepsy.Eur J Paediatr Neurolm, 2010, 14(6):508-512.
- 21. Devinsky O, Emoto S, Goldstein DS, et al. Cerebrospinal fluid and serum levels of dopa, catechols, and monoamine metabolites in patients with epilepsy.Epilepsia, 1992, 33(2):263-270.
- 22. Martinez A, Finegersh A, Cannon DM.The 5-HT1A receptor and 5-HT transporter in temporal lobe epilepsy. Neurology, 2013, 80(16):1465-1471.
- 23. Kurian MA, Gissen P, Smith M.The monoamine neurotransmitter disorders:an expanding range of neurological syndromes.Lancet Neurol, 2011, 10(8):721-733.
- 24. Recio MV, Gallagher MJ, McLean MJ. Clinical features of epilepsy in patients with cerebellar structural abnormalities in a referral center.Epilepsy Res, 2007, 76(1):1-5.
- 25. Scharfman HE. The neurobiology of epilepsy.Curr Neurol Neurosci Rep, 2007, 7(4):348-354.
- 26. Bauer J.Epilepsy and prolactin in adults:a clinical review.Epilepsy Res, 1996, 24(1):1-7.
- 27. Luef G, Madersbacher H.Sexual dysfunction in patients with epilepsy. Handb Clin Neurol, 2015, 130(2):383-394.
- 28. Schmidt D, Schachter SC. Drug treatment of epilepsy in adults.BMJ, 2014, 348(28):254.
- 29. Sundararajan T, Tesar GE, Jimenez XF.Biomarkers in the diagnosis and study of psychogenic nonepileptic seizures:a systematic review.Seizure, 2016, 35(3):11-22.
- 30. Du Y, Kemper T, Qiu J, Jiang J. Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus. Expert Rev Neurother, 2016,16(2):123-130.
- 31. Onaka T, Takayanagi Y, Leng G. Metabolic and stress-related roles of prolactin-releasing peptide. Trends Endocrinol Meta, 2010, 21(5):287-293.
- 32. Trimble MR. Serum prolactin in epilepsy and hysteria. Br Med J, 1978, 2(6153):1682.
- 33. Kanasaki H, Oride A, Mijiddorj T.Role of thyrotropin-releasing hormone in prolactin-producing cell models.Neuropeptides, 2015, 54(1):73-77.
- 34. 陈柳静, 周列民,周珏倩,等. 育龄女性癫痫患者的生殖内分泌紊乱相关危险因素分析. 中山大学学报(医学科学版), 2010, 31(2):302-305.
- 35. Maguire J, Salpekar JA.Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.Epilepsy Behav, 2013, 26(3):352-362.
- 36. Frye CA. Hormonal influences on seizures:basic neurobiology.Int Rev Neurobiol, 2008, 83(3):27-77.
- 37. Mehta V, Ferrie CD, Cross JH. Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms. Cochrane Database Syst Rev, 2015, 15(6):CD005222.
- 38. Xiong F, Zhang L. Role of the hypothalamic-pituitary-adrenal axis in developmental programming of health and disease.Front Neuroendocrinol, 2013,34(1):27-46.
- 39. Fekete C, Lechan RM.Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions.Endocr Rev, 2014, 35(2):159-194.
- 40. Woodbury DM, Hurley RE.Effect of thyroxin, thyroidectomy and 6-n-propyl-2-thiouracil on brain function. J Pharmacol Exp Ther, 1952, 106(3):331-340.
- 41. Jabbari B, Huott AD.Seizures in thyrotoxicosis. Epilepsia, 1980, 21(1):91-96.
- 42. Taubøll E, Sveberg L, Svalheim S.Interactions between hormones and epilepsy.Seizure, 2015, 28(5):3-11.
- 43. Jeurissen B, Leemans A, Tournier JD, et al. Investigating theprevalence of complex fiber configurations in white matter tissue withdiffusion magnetic resonance imaging. Hum Brain Mapp, 2013, 34(5):2747-2766.
- 44. Shultz SR, Zheng P, Wright DK, et al. Tractography and magneticresonance spectroscopy in acquired epilepsy models. WONOEP XⅡmeeting planner, 2013, QC, Canada.
- 45. Jones DK, Knosche TR, Turner R. White matter integrity, fiber count,and other fallacies:the do's and dont's of diffusion MRI. Neuroimage, 2013, 73(12):239-254.
- 46. Ogawa S, Lee TM, Nayak AS, et al. Oxygenation-sensitive contrast inmagnetic resonance image of rodent brain at high magnetic fields.Magn Reson Med, 1990, 14(7):68-78.
- 47. Smith G, Wagner JL, Edwards JC. Epilepsy Update, Part 1:refining our understanding of a complex disease.Am J Nurs, 2015, 115(5):40-47.
- 48. Galimberti CA, Magri F, Copello F. Changes in sex steroid levels in women with epilepsy on treatment:relationship with antiepileptic therapies and seizure frequency. Epilepsia, 2009,50 (Suppl 1):28-32.
- 49. Herzog AG.Menstrual disorders in women with epilepsy.Neurology, 2006, 66(Suppl 3):23-28.
- 50. van Luijtelaar G, Onat FY, Gallagher MJ.Animal models of absence epilepsies:what do they model and do sex and sex hormones matter?. Neurobiol Dis, 2014,72(Pt B):167-179.
- 51. Chiu AW, Daniel S, Khosravani H.Prediction of seizure onset in an in-vitro hippocampal slice model of epilepsy using Gaussian-based and wavelet-based artificial neural networks.Ann Biomed Eng, 2005,33(6):798-810.
- 52. Mejías-Aponte CA, Jiménez-Rivera CA, Segarra AC.Sex differences in models of temporal lobe epilepsy:role of testosterone.Brain Res, 2002,944(1-2):210-218.
- 53. Bauer J, Blumenthal S, Reuber M.Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy.Neurology, 2004,62(2):243-246.
- 54. Herzog AG, Fowler KM.Sexual hormones and epilepsy:threat and opportunities.Curr Opin Neurol, 2005, 18(2):167-172.
- 55. Hamed SA.Neuroendocrine hormonal conditions in epilepsy:relationship to reproductive and sexual functions. Neurologist, 2008, 14(3):157-169.
- 56. R, Wainwright SR, Galea LA.Sex hormones and adult hippocampal neurogenesis:Regulation, implications, and potential mechanisms.Front Neuroendocrinol. 2016,41:129-52.
- 57. Alam MN, Ahmad A, Al-Abbasi FA, Ahmad A.Female ovarian steroids in epilepsy:a cause or remedy.Pharmacol Rep, 2013,65(4):802-12.
- 58. Herzog AG.Catamenial epilepsy:Update on prevalence, pathophysiology and treatment from the findings of the NIH progesterone treatment trial. Seizure, 2015, 28(5):18-25.