Pediatric Neurology
Volume 26, Issue 1 , Pages 9-17 , January 2002

Thyrotropin-releasing hormone in the treatment of intractable epilepsy

  • Michael J Kubek, PhD

      Affiliations

    • Corresponding Author InformationCommunications should be addressed to: Dr. Kubek; Department of Anatomy and Cell Biology, MS 5035; Indiana University School of Medicine; 635 Barnhill Drive; Indianapolis, IN, USA 46202-5120
    • Departments of Anatomy and Cell Biology and the Department of Psychiatry; Indiana University School of Medicine; Indianapolis, IN 46202-5120, USA
  • ,
  • Bhuwan P Garg, MB, BS

      Affiliations

    • Section of Pediatric Neurology; Department of Neurology; Indiana University School of Medicine; Indianapolis, IN 46202-5120, USA

Received 26 February 2001 ,Accepted 24 May 2001.

References 

  1. Kubek MJ, Lorincz MA, Wilber JF. The identification of thyrotropin releasing hormone (TRH) in hypothalamic and extrahypothalamic loci of the human nervous system. Brain Res. 1977;126:196–200
  2. Burt DR, Snyder SH. Thyrotropin releasing hormone (TRH) (Apparent receptor binding in rat brain membranes). Brain Res. 1975;93:309–328
  3. Nillni EA, Sevarino KA. The biology of pro-TRH-derived peptides. Endocrine Rev. 1999;20:599–648
  4. Kubek MJ, Low WC, Sattin A, Morzorati SL, Meyerhoff JL, Larsen SH. Role of TRH in seizure modulation. Ann NY Acad Sci. 1989;553:286–303
  5. Inanaga K, Kumashiro H, Fukuyama Y, Ohtahara S, Shirouzu M. Clinical study of oral administration of DN-1417, a TRH analog, in patients with intractable epilepsy. Epilepsia. 1989;30:438–445
  6. Kubek MJ, Liang D, Byrd KE, Domb AJ. Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation. Brain Res. 1998;809:189–197
  7. Matsumoto A, Kumagai T, Takeuchi T, Miyazaki S, Watanabe K. Clinical effects of TRH for severe epilepsy in childhood (A comparative study with ACTH therapy). Epilepsia. 1987;28:49–55
  8. Matsumoto A, Kumagai T, Takeuchi T, Miyazaki S, Watanabe K. Factors influencing effectiveness of TRH therapy for severe epilepsy in childhood (Significance of serum prolactin levels). Epilepsia. 1989;30:45–49
  9. Takeuchi Y, Tominaga M, Mitsufuji N, et al.  Thyrotropin-releasing hormone in treatment of intractable epilepsy (Neurochemical analysis of CSF monoamine metabolites). Pediatr Neurol. 1995;12:139–145
  10. Matsuishi T, Yano E, Inanaga K, et al.  A pilot study on the anticonvulsive effects of a TRH analog in intractable epilepsy. Brain Dev. 1983;5:421–428
  11. Takeuchi Y, Matsushita H, Kawano H, Sakai H, Yoshimoto K, Sawada T. TRH increases cerebrospinal fluid concentration of kynurenine. Neuroreport. 1999;10:3601–3603
  12. Tanaka C, Maegaki Y, Koeda T, Ohta S, Takeshita K. Successful treatment of progressive myoclonus epilepsy with TRH. Pediatr Neurol. 1998;18:442–444
  13. Guiloff RJ. Use of TRH analogues in motorneurone disease. Ann NY Acad Sci. 1989;553:399–421
  14. Ferrari E, Cucinotta D, Albizatti MG, et al.  Effectiveness and safety of Posatirelin in the treatment of senile dementia (A multicenter, double blind, placebo-controlled study). Arch Gerontol Geriatr. 1998;6(Suppl):163–174
  15. Ballard RA, Ballard PL, Cnaan A, et al.  Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group. N Engl J Med. 1998;338:493–498
  16. Takeuchi Y. TRH (Protirelin) (Role in the treatment of epilepsy). CNS Drugs. 1996;6:341–350
  17. Zegher FD, Vanhole C, Van Den Berghe G, Christiaens B, Devlieger H, Spitz B. Thyroid function 6 years after prenatal treatment with TRH. Pediatrics. 1997;100:1042–1043
  18. Maeda K, Tanimoto K. Epileptic seizures induced by thyrotropin releasing hormone. Lancet. 1981;1:1058–1059
  19. Munsat TL, Lechan R, Taft JM, Jackson IMD, Reichlin S. The use of TRH in amyotrophic lateral sclerosis (ALS). TRH and diseases of the motor system. Ann NY Acad Sci. 1989;553:388–398
  20. Elmore MA, Griffiths EC, O’Connor B, O’Cuinn G. Further characterization of the substrate specificity of a TRH hydrolysing pyroglutamate aminopeptidase from guinea-pig brain. Neuropeptides. 1990;15:31–36
  21. Friedman TC, Yanovski JA, Jayasvasti V, Yanovski SZ, Koenig RJ, Wilk S. Pyroglutamyl peptidase-II (“thyroliberinase”) activity in human serum (Influence of weight and thyroid status). J Clin Endocrin Metab. 1995;80:1086–1089
  22. O’Leary R, O’Connor B. TRH. J Neurochem. 1995;65:953–963
  23. Cummins PM, O’Connor B. Pyroglutamyl peptidase (An overview of the three known enzymatic forms). Biochim Biophys Acta. 1998;1429:1–17
  24. deGortari P, Fernandez-Guardiola A, Martinez A, Cisneros M, Joseph-Bravo P. Changes in TRH and its degrading enzyme pyroglutamyl peptidase II, during the development of amygdaloid kindling. Brain Res. 1995;679:144–150
  25. Kubek MJ. TRH (Localization of specific hypothalamic and extrahypothalamic sites of CNS modulation). In:  Frederickson RCA,  Hendrie H,  Hingtgen JN,  Aprison MH editor. Neuroregulation of autonomic, endocrine and immune systems. Boston: Martinus-Nijhoff; 1986;p. 265–301
  26. Meldrum BS. Neuropathological consequences of chemically and electrically induced seizures. Ann NY Acad Sci. 1986;462:186–193
  27. Fisher RS. Animal models of the epilepsies. Brain Res Rev. 1989;14:245–278
  28. Racine RJ, Ivy GO, Milgram NW. Kindling (Clinical relevance and anatomical substrate). In:  Bolwig TG,  Trimble MR editor. The clinical relevance of kindling. New York: John Wiley & Sons; 1989;p. 15–34
  29. Meyerhoff JL, Bates VE, Kubek MJ. Elevated TRH levels in pyriform cortex after partial and fully-generalized kindled seizures. Brain Res. 1990;525:144–148
  30. Shapiro S, Kubek MJ, Sanders S, Durbin S, Goodwin S, Javed T. Regional changes in central nervous system TRH after pentylenetetrazol-induced seizures in dogs. Neurosurgery. 1992;31:935–939
  31. Kubek MJ, Knoblach SM, Sharif NA, Burt DR, Buterbaugh GG, Fuson KS. TRH gene expression and receptors are differentially modified in limbic foci by seizures. Ann Neurol. 1993;33:70–76
  32. Jaworska-Feil L, Turchan J, Przewlocka B, Budziszewska B, Leskiewicz M, Lason W. Effects of pentylenetetrazole-induced kindling on TRH biosynthesis and receptors in rat brain. Neuroscience. 1999;90:695–704
  33. Jaworska-Feil L, Turchan J, Przewlocka B, Budziszewska B, Leskiewicz M, Lason W. Effects of pilocarpine- and kainate-induced seizures on thyrotropin- releasing hormone biosynthesis and receptors in the rat brain. J Neural Transm. 1999;106:395–407
  34. Pekary AE, Sattin A. Lloyd RL. Electroconvulsive seizures increase levels of PS4, the TRH-enhancing peptide [prepro-TRH(160–169)], in rat brain. Neuroendocrinology. 1997;65:377–384
  35. Pekary AE, Lloyd RL, Sattin A. Predominance of pGlu-His-Pro-Gly among all TRH precursor peptides in rat limbic forebrain after electroconvulsive seizures. Ann NY Acad Sci. 1994;739:330–333
  36. Kubek MJ, Knoblach SM, Fuson KS, Durbin S. Thyrotropin-releasing hormone (TRH) and TRH mRNA is increased in specific hippocampal subregions following electroconvulsive seizures (ECS) as determined by in situ hybridization (ISHH) and RIA. [Abstract] Endocr Soc. 1991;73:266
  37. Yamashita K, Mori A, Otsuki S. Changes in brain thyrotropin-releasing hormone (TRH) of seizure-prone EI mice. Exp Neurol. 1990;108:71–75
  38. Ujihara H, Renming X, Sasa M, et al.  Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats. Eur J Pharmacol. 1991;196:15–19
  39. Renming X, Ishihara K, Sasa M, et al.  Antiepileptic effect of CNK-602A, a novel TRH analog, on absence-like and tonic seizures of spontaneously epileptic rats. Eur J Pharmacol. 1992;223:185–192
  40. Jaworska-Feil L, Kajta M, Budziszewska B, Leskiewicz M, Lason W. Protective effects of TRH and its stable analogue, RGH-2202, on kainate-induced seizures and neurotoxicity in rodents. Epilepsy Res. 2001;43:67–73
  41. Loscher W. Animal models of intractable epilepsy. Prog Neurobiol. 1997;53:239–258
  42. Racine RJ. Modification of seizure activity by electrical stimulation (II. Motor seizure). Electroencephalogr Clin Neurophysiol. 1972;32:281–294
  43. McNamara JO. Drugs effective in the therapy of the epilepsies. In:  Hardman JG,  Goodman Gilman A,  Limbird LE editor. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: McGraw Hill; 1996;p. 461–486
  44. McNamara JO. Cellular and molecular basis of epilepsy. J Neurosci. 1994;14:3417–3425
  45. McNamara JO, Bonhaus DW, Shin C. The kindling model of epilepsy. In:  Schwartzkroin PA editors. Epilepsy (Models, mechanisms, and concepts). Cambridge: Cambridge University Press; 1993;p. 27–47
  46. Racine R. Kindling (The first decade). Neurosurgery. 1978;3:234–252
  47. Sato M, Morimoto K, Wada JA. Antiepileptic effects of TRH and its new derivative, DN-1417, examined in feline amygdaloid kindling preparation. Epilepsia. 1984;25:537–544
  48. Okamoto M, Sato M, Moriwake T, et al.  The prophylactic and anticonvulsant effects of a TRH analog (DN-1417) on amygdaloid kindling model of epilepsy. Folia Psychiatr Neurol Jpn. 1985;39:313–316
  49. Sato M, Morimoto K. Anti-epileptic effects of TRH-T and DN-1417. Kurume Med J. 1983;30:57–64
  50. Yatsugi S, Yamamoto M. Anticonvulsive properties of YM-14673, a new TRH analogue, in amygdaloid-kindled rats. Pharmacol Biochem Behav. 1991;38:669–672
  51. Sakai S, Baba H, Sato M, Wada JA. Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio. Epilepsia. 1991;32:16–21
  52. Mori N, Fukatsu T. Anticonvulsant effect of DN-1417, a derivative of TRH, and liposome-entrapped DN-1417, on amygdaloid-kindled rats. Epilepsia. 1992;33:994–1000
  53. Nakamura J, Mine K, Yamada S. Effects of anticonvulsants on the electroconvulsive threshold lowered by DA, 5-HT or GABA depletion. Kurume Med J. 1990;37:253–259
  54. Knoblach SM, Durbin S, Kubek MJ. Subregional changes in hippocampal TRH (TRH) after amygdaloid kindling in rats. [Abstract] Soc Neurosci. 1989;15:778
  55. Knoblach SM, Kubek MJ. Changes in TRH levels in hippocampal subregions induced by a model of human temporal lobe epilepsy (effect of partial and complete kindling). Neuroscience. 1997;76:97–104
  56. Knoblach SM, Kubek MJ. Increases in TRH mRNA expression induced by a model of human temporal lobe epilepsy (Effect of partial and complete kindling). Neuroscience. 1997;76:85–95
  57. Rosen JB, Cain CJ, Weiss SRB, Post RM. Alterations in mRNA of enkephalin, dynorphin and TRH during amygdala kindling (An in situ hybridization study). Mol Brain Res. 1992;15:247–255
  58. Mantyh PW, Hunt SP. Localization by light microscopic autoradiography in rat brain using (3H)(3-Me-His2)TRH as the radioligand. J Neurosci. 1985;5:551–561
  59. Sharif NA, Burt DR. Biochemical similarity of rat pituitary and CNS TRH receptors. Neurosci Lett. 1983;39:57–63
  60. Burt DR. Pituitary and CNS TRH Receptors. In:  Marangas PJ,  Campbell IC,  Cohen RM editor. Brain receptor methodologies, Part B (Amino acid, peptides, psychoactive drugs). Miami, FL: Academic Press; 1984;p. 129–149
  61. Calza L, Giardino L, Ceccatelli S, Zanni M, Elde R, Hokfelt T. Distribution of TRH receptor messenger RNA in the rat brain (An in situ hybridization study). Neuroscience. 1992;51:891–909
  62. Cao J, O’Donnell D, Vu H, et al.  Cloning and characterization of a cDNA encoding a novel subtype of rat TRH receptor. J Biol Chem. 1998;273:32281–32287
  63. Sharif NA. Quantitative autoradiography of TRH receptors in discrete brain regions of different mammalian species. Ann NY Acad Sci. 1989;553:147–175
  64. Eymin C, Champier J, Duvernoy HM, Martin D, Kopp N, Jordan D. Distribution of TRH binding sites (Autoradiographic study in infant and adult human hippocampal formation). Brain Res. 1993;605:139–146
  65. O’Dowd BF, Lee DK, Huang W, et al.  TRH-R2 exhibits similar binding and acute signaling but distinct regulation and anatomic distribution compared with TRH-R1. Mol Endocrinol. 2000;14:183–193
  66. Shin C, McNamara JO, Morgan JI, Curran T, Cohen DR. Induction of c-fos mRNA expression by afterdischarge in the hippocampus of naive and kindled rats. J Neurochem. 1990;55:1050–1055
  67. Dragunow M, Robertson HA. Kindling stimulation induced c-fos protein(s) in granule cells of the rat dentate gyrus. Nature. 1987;329:441–442
  68. Saffen DW, Cole AJ, Worley PF, Christy BA, Ryder K, Baraban JM. Convulsant-induced increase in transcription factor messenger RNAs in rat brain. Proc Natl Acad Sci USA. 1988;85:7795–7799
  69. Lee S, Stewart K, Goodman RH. Structure of the gene encoding rat TRH. J Biol Chem. 1988;263:16604–16629
  70. Rosen JB, Abramowitz J, Post RM. Colocalization of TRH mRNA and Fos-like immunoreactivity in limbic structures following amygdala kindling. Mol Cell Neurosci. 1993;4:335–342
  71. Sloviter R, Dempster D. “Epileptic” brain damage is replicated qualitatively in the rat hippocampus by central injection of glutamate or aspartate but not by GABA or acetylcholine. Brain Res Bull. 1985;15:39–60
  72. Sloviter R. “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies. Brain Res Bull. 1983;10:675–697
  73. Sutula TP. Experimental models of temporal lobe epilepsy (New insights from the study of kindling and synaptic reorganization). Epilepsia. 1990;31(Suppl. 3):S45–S54
  74. Cavazos JE, Golarai G, Sutula TP. Mossy fiber reorganization induced by kindling (Time course of development, progression, and permanence). J Neurosci. 1991;11:2795–2803
  75. Represa A, Le Gall La Salle G, Ben-Ari Y. Hippocampal plasticity in the kindling model of epilepsy in rats. Neurosci Lett. 1989;99:345–350
  76. Sutula T, Cascino G, Cavazos J, Parada I, Ramirez L. Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol. 1989;26:321–330
  77. Sloviter RS. Reorganization hypothesis of epilepsy (Granule cell sprouting in rats is associated with decreased, not increased, excitability). Epilepsia. 1990;31:675
  78. Sloviter RS. The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. (review) Ann Neurol. 1994;35:640–654
  79. Rosen JB, Weiss SRB, Post RM. Contingent tolerance to carbamazepine (Alterations in TRH mRNA and TRH receptor binding in limbic structures). Brain Res. 1994;651:252–260
  80. Knoblach SM, Kubek MJ. TRH release is enhanced in hippocampal slices after electroconvulsive shock. J Neurochem. 1994;62:119–125
  81. Gershengorn MC, Osman R. Molecular and cellular biology of TRH receptors. Physiol Rev. 1996;76:175–191
  82. Wan RQ, Noguera EC, Weiss SR. Anticonvulsant effects of intra-hippocampal injection of TRH in amygdala kindled rats. Neuroreport. 1998;9:677–682
  83. Weiss SRB, Clark M, Rosen JB, Smith MA, Post RM. Contingent tolerance to the anticonvulsant effects of carbamazepine (Relationship to loss of endogenous adaptive mechanisms). Brain Res Brain Res Rev. 1995;20:305–325
  84. Itadani H, Nakamura T, Itoh J, et al.  Cloning and characterization of a new subtype of TRH receptors. Biochem Biophys Res Commun. 1998;250:68–71
  85. Bennett GW, Marsden CA, Fone KCF, Johnson JV, Heal DJ. TRH-catecholamine interactions in brain and spinal cord. Ann NY Acad Sci. 1989;553:106–120
  86. Marsden CA, Bennett GW, Fone KCF, Johnson JV. Functional interactions between TRH and 5-hydroxytryptamine (5-HT) and proctolin in rat brain and spinal cord. Ann NY Acad Sci. 1989;553:121–134
  87. Keller HH, Bartholini G, Pletscher A. Enhancement of cerebral noradrenaline turnover by TRH. Nature. 1974;248:528–529
  88. Rastogi RB, Singhal RL, Lapierre YD. Effects of MK-771, a novel TRH analogue, on dopaminergic and serotonergic systems. Eur J Pharmacol 198;73:307–12.
  89. Sattin A, Kubek MJ, Low WC, Staley CJ, Simon JR. Some regional anatomical relationships of TRH to 5-HT in rat limbic forebrain. Neurochem Res. 1992;17:469–474
  90. Narumi S, Nagai Y, Miyamoto M, Nagawa Y. Thyrotropin-releasing hormone (TRH) and its analog (DN-1417) (Interaction with pentobarbital in choline uptake and acetylcholine synthesis of rat brain slices). Life Sci. 1983;32:1637–1645
  91. Toide K, Shinoda M, Takase M, Iwata K, Yoshida H. Effects of a novel TRH analogue, JTP-2942, on extracellular acetylcholine and choline levels in the rat frontal cortex and hippocampus. Eur J Clin Pharmacol. 1993;233:21–28
  92. Mouginot D, Feltz P, Schlichter R. Modulation of GABA-gated chloride currents by intracellular Ca2+ in cultured porcine melanotrophs. J Physiol. 1991;437:109–132
  93. Renaud LP, Blume HW, Pittman QJ, Lamour Y, Tan AT. TRH selectively depresses glutamate excitation of cerebral cortical neurons. Science. 1979;205:1275–1277
  94. Renaud LP, Martin JB. Thyrotropin releasing hormone (TRH) (Depressant action on central neuronal activity). Brain Res. 1975;86:150–154
  95. Nie Y, Schoepp DD, Kubek MJ. TRH inhibits [K+]-stimulated glutamate release from hippocampal slices in vitro. [Abstract] Soc Neurosci. 1997;23:2314
  96. Nemeroff CB, Prange AJ, Bissette G, Breese GR, Lipton MA. TRH (TRH) and its beta-alanine analogue (Potentiation of the anticonvulsant potency of phenobarbital in mice). Psychopharmacology. 1975;1:305–317
  97. Marangell LB, George MS, Bissette G, Pazzaglia P, Huggins T, Post RM. Carbamazepine increases cerebrospinal fluid thyrotropin-releasing hormone levels in affectively ill patients. Arch Gen Psychiatry. 1994;51:625–628
  98. Renaud L, Martin J. Thyrotropin releasing hormone (TRH) (Depressant action on central neuronal activity). Brain Res. 1975;86:150–154
  99. Renaud LP. Peptides as neurotransmitters of neuromodulators. In:  Lipton MA,  DiMascio A,  Killam KF editor. Psychopharmacology (A generation of progress). New York: Raven Press; 1978;p. 423–430
  100. Koenig ML, Yourick DL, Meyerhoff JL. TRH (TRH) attenuates glutamate-stimulated increases in calcium in primary neuronal cultures. Brain Res. 1996;730:143–149
  101. Stone TW, MacGregor DG, Smith RA, Jones P, Behan WM, Graham DI. Basic mechanisms of kynurenine actions in the central nervous system. Adv Exp Med Biol. 1996;398:195–201
  102. Yamamoto H, Shindo I, Egawa B, Horiguchi K. Kynurenic acid is decreased in cerebrospinal fluid of patients with infantile spasms. Pediatr Neurol. 1994;10:9–12
  103. Yamamoto H, Murakami H, Horiguchi K, Egawa B. Studies on cerebrospinal fluid kynurenic acid concentrations in epileptic children. Brain Dev. 1995;17:327–329
  104. Beyer HS, Matta SG, Sharp BM. Regulation of the messenger ribonucleic acid for corticotropin-releasing factor in the paraventricular nucleus and other brain sites of the rat. Endocrinology. 1988;123:2117–2123
  105. Kovacs KJ, Mezey E. Dexamethasone inhibits corticotropin-releasing factor gene expression in rat paraventricular nucleus. Neuroendocrinology. 1987;46:365–368
  106. Kakucska I, Qi Y, Lechan RM. Changes in adrenal status affect hypothalamic TRH gene expression in parallel with corticotropin-releasing hormone. Endocrinology. 1995;136:2795–2802
  107. Kim SY, Post RM, Rosen JB. Differential regulation of basal and kindling-induced TRH mRNA expression by thyroid hormone in the hypothalamic and limbic structures. Neuroendocrinology. 1996;63:297–304
  108. Luo LG, Jackson IM. Glucocorticoids stimulate TRH and c-fos/c-jun gene co-expression in cultured hypothalamic neurons. Brain Res. 1998;791:56–62
  109. Luo LG, Bruhn T, Jackson IM. Glucocorticoids stimulate TRH gene expression in cultured hypothalamic neurons. Endocrinology. 1995;136:4945–4950
  110. Perez-Martinez L, Carreon-Rodriguez A, Gonzalez-Alzati ME, Morales C, Charli JL, Joseph-Bravo P. Dexamethasone rapidly regulates TRH mRNA levels in hypothalamic cell cultures (Interaction with the cAMP pathway). Neuroendocrinology. 1998;68:345–354
  111. Bruhn TO, Huang SS, Vaslet C, Nillni EA. Glucocorticoids modulate the biosynthesis and processing of proTRH (proTRH). Endocrine. 1998;9:143–152
  112. Schulkin J, Gold PW, McEwen BS. Induction of corticotropin-releasing hormone gene expression by glucocorticoids (Implication for understanding the states of fear and anxiety and allostatic load). Psychoneuroendocrinology. 1998;23:219–243
  113. Brunson KL, Schultz L, Baram TZ. The in vivo proconvulsant effects of corticotropin releasing hormone in the developing rat are independent of ionotropic glutamate receptor activation. Brain Res Dev Brain Res. 1998;111:119–128
  114. Hollrigel GS, Chen K, Baram TZ, Soltesz I. The pro-convulsant actions of corticotropin-releasing hormone in the hippocampus of infant rats. Neuroscience. 1998;84:71–79
  115. Baram TZ, Chalmers DT, Chen C, Koutsoukos Y, De Souza EB. The CRF1 receptor mediates the excitatory actions of corticotropin releasing factor (CRF) in the developing rat brain (In vivo evidence using a novel, selective, non-peptide CRF receptor antagonist). Brain Res. 1997;770:89–95
  116. Baram TZ, Schultz L. ACTH does not control neonatal seizures induced by administration of exogenous corticotropin-releasing hormone. Epilepsia. 1995;36:174–178
  117. Baram TZ. Pathophysiology of massive infantile spasms (Perspective on the putative role of the brain adrenal axis). Ann Neurol. 1993;33:231–236
  118. Baram TZ, Hirsch E, Snead OC, Schultz L. Corticotropin-releasing hormone-induced seizures in infant rats originate in the amygdala. Ann Neurol. 1992;31:488–494
  119. Baram TZ, Schultz L. Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat. Brain Res Dev Brain Res. 1991;61:97–101
  120. Smith MA, Weiss SR, Berry RL, et al.  Amygdala-kindled seizures increase the expression of corticotropin-releasing factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate hilus. Brain Res. 1997;745:248–256
  121. Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms (A prospective, randomized, blinded study). Pediatrics. 1996;97:375–379
  122. Heiskala H, Riikonen R, Santavuori P, et al.  West syndrome (Individualized ACTH therapy). Brain Dev. 1996;18:456–460
  123. Riikonen R, Amnell G. Psychiatric disorders in children with earlier infantile spasms. Dev Med Child Neurol. 1981;23:747–760
  124. Riikonen R, Donner M. ACTH therapy in infantile spasms (Side effects). Arch Dis Child. 1980;55:664–672

PII: S0887-8994(01)00321-6

Pediatric Neurology
Volume 26, Issue 1 , Pages 9-17 , January 2002