Advertisement

Thyrotropin-releasing hormone: role in the treatment of West syndrome and related epileptic encephalopathies

      Abstract

      Thyrotropin-releasing hormone (TRH) has been successfully used for treating children with neurologic disorders including epilepsy. The effectiveness of TRH and a TRH analog has been reported in West syndrome, Lennox–Gastaut syndrome, and early infantile epileptic encephalopathy that were intractable to anticonvulsants and adrenocorticotrophic hormone (ACTH). However, the peptide has not been widely studied as a treatment of intractable epilepsy outside Japan. TRH is safe in children and effective in some cases of West syndrome and Lennox–Gastaut syndrome. TRH is considered as a possible new strategy for treating West syndrome and Lennox–Gastaut syndrome prior to ACTH therapy, especially for the patient with an infection, immunosuppression, or severe organic lesions in the brain. The mechanisms of its antiepileptic action may differ from those of other antiepileptic drugs. One possibility is that TRH may act as an antiepileptic through a kynurenine mechanism, considering that kynurenic acid acts as an antagonist on the N-methyl-d-aspartate receptor complex.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Winokur A
        • Utiger R.D
        Thyrotropin-releasing hormone. Regional distribution in rat brain.
        Science. 1974; 185: 265-266
        • Metcalf G
        Regulatory peptides as a source of new drugs – the clinical prospects for analogues of TRH which are resistant to metabolic degeneration.
        Brain Res Rev. 1982; 4: 389-408
        • Schimmer B.P
        • George S.R
        Thyroid hormones and antihyperthyroid drugs.
        in: Kalant H Roschlau W.H.E Principles of medical pharmacology. BC Decker, New York, NY1989: 444-450
        • Simasko S.M
        Pituitary hormones.
        in: Smith C.M Reynard A.M Textbook of pharmacology. Saunder, Philadelphia, PA1992: 664-682
        • Takeuchi Y
        • Fujiwara K
        • Ishimura K
        • Shimada Y
        • Ochi M
        • Sawada T
        • et al.
        Efficacy of thyrotropin-releasing hormone in the treatment of cerebellar ataxia.
        Pediatr Neurol. 1989; 5: 107-110
        • Takeuchi Y
        • Miyanomae Y
        • Komatsu H
        • Oomizono Y
        • Nishimura A
        • Sawada T
        • et al.
        Efficacy of thyrotropin-releasing hormone in the treatment of spinal muscular atrophy.
        J Child Neurol. 1994; 9: 287-289
        • Sobue I
        • Yamamoto H
        • Konagawa M
        • Iida M
        • Takayanagi T
        Effects of thyrotropin-releasing hormone on ataxia of spinocerebellar degeneration.
        Lancet. 1980; 1: 418-419
        • Tzeng A.C
        • Chengn J
        • Fryczynski H
        • Niranjan V
        • Stitik T
        • Takeuchi Y
        • et al.
        A study of thyrotropin-releasing hormone for the treatment of spinal muscular atrophy: a preliminary report.
        Am J Phys Med Rehabil. 2000; 79: 435-440
        • Takeuchi Y
        Thyroptropin-releasing hormone: role in the treatment of epilepsy.
        CNS Drugs. 1996; 6: 341-350
        • Kubek M.J
        • Garg B.P
        Thyrotropin-releasing hormone (TRH) in the treatment of intractable epilepsy.
        Pediatr Neurol. 2002; 26 (in press)
        • Lagenstein I
        • Willig R.P
        • Kuhne D
        Reversible cerebral atrophy caused by corticotropin.
        Lancet. 1979; 1: 1246-1247
        • Lyen L.R
        • Holland I.M
        • Lyen Y.C
        Reversible cerebral atrophy in infantile spasms caused by corticotropin.
        Lancet. 1979; 2: 37-38
        • Riikonen R
        • Donner M
        ACTH therapy in infantile spasms: side effects.
        Arch Dis Child. 1990; 55: 664-672
        • Matsumoto A
        • Kumagai T
        • Takeuchi T
        • Miyazaki S
        • Watanabe K
        Clinical effects of thyrotropin-releasing hormone for severe epilepsy in childhood: a comparative study with ACTH therapy.
        Epilepsia. 1987; 28: 49-55
        • Matsumoto A
        • Kumagai T
        • Takeuchi T
        • Miyazaki S
        • Watanabe K
        Factors influencing the effectiveness of thyrotropin-releasing hormone therapy for severe epilepsy in childhood: significance of serum prolactin levels.
        Epilepsia. 1989; 30: 45-49
        • Takeuchi Y
        • Tominaga M
        • Mitsufuji N
        • Yamazoe Y
        • Kawase S
        • Nishimura A
        • et al.
        Thyrotropin-releasing hormone in treatment of intractable epilepsy: neurochemical analysis of CSF monoamine metabolites.
        Pediatr Neurol. 1995; 12: 139-145
        • Takeuchi Y
        • Matsushita H
        • Kawano H
        • Sakai H
        • Yoshimoto K
        • Sawada T
        TRH increases cerebrospinal fluid concentration of kynurenine.
        NeuroReport. 1999; 10: 3601-3603
        • Takeuchi Y
        • Komatsu H
        • Matsuo S
        • Hirai K
        • Kawase S
        • Nishimura A
        • et al.
        Monoamine metabolites in the cerebrospinal fluid in infantile spinal muscular atrophy.
        NeuroReport. 1994; 5: 898-900
        • Takeuchi Y
        • Matsushita H
        • Sakai H
        • Kawano H
        • Yoshimoto K
        • Sawada T
        • et al.
        Developmental changes in CSF concentrations of monoamine-related substances revealed with a coulochem electrode array system.
        J Child Neurol. 2000; 15: 267-270
        • Takeuchi Y
        • Matsushita H
        • Sakai H
        • Kawano H
        • Yoshimoto K
        • Ochi M
        Developmental changes in CSF concentrations of monoamine-related substances in patients with DRPLA.
        J Child Neurol. 2001; 16: 79-82
        • Swartz K.J
        • During M.J
        • Freese A
        • Beal W.F
        Cerebral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors.
        J Neurosci. 1990; 10: 2965-2973
        • Stone T.W
        • Connick J.H
        Quinolinic acid and other kynurenines in the central nervous system.
        Neuroscience. 1985; 15: 597-617
        • Gramsbergen J.P
        • Hodgkins P.S
        • Rassoulpour A
        • Turski W.A
        • Guidetti P
        • Schwarcz R
        Brain-specific modulation of kynurenic acid synthesis in the rat.
        J Neurochem. 1997; 69: 290-298
        • Ogawa T
        • Matson W.R
        • Beal M.F
        • Myers R.H
        • Bird E.D
        • Milbury P
        • et al.
        Kynurenine pathway abnormalities in Parkinson's disease.
        Neurology. 1992; 42: 1702-1706
        • Hodgkins P.S
        • Schwarcz R
        Interference with cellular energy metabolism reduces kynurenic acid formation in rat brain slices: reversal by lactate and pyruvate.
        Eur J Neurosci. 1998; 10: 1986-1994
        • Yamamoto H
        Studies on CSF tryptophan metabolism in infantile spasms.
        Pediatr Neurol. 1991; 7: 411-414
        • Widner B
        • Weiss G
        • Fuchs D
        Tryptophan degradation to control T-cell responsiveness.
        Immunol Today. 2000; 21: 250
        • Hwu P
        • Du M.X
        • Lapointe R.L
        Indoleamine 2,3-dioxygenase reduction by human dendritic cells results in the inhibition of T cell proliferation.
        J Immunol. 2000; 164: 3596-3599
        • Widner B
        • Leblhuber F
        • Walli J
        Tryptophan degradation and immune activation in Alzheimer's disease.
        J Neural Transm. 2000; 107: 343-353