Abstract
Aim: To study the difference between pyridoxine (PN) and its active form, pyridoxal phosphate, (PLP) in control of idiopathic intractable epilepsy in children.
Methods: Among 574 children with active epilepsy, 94 (aged 8 months to 15 years) were diagnosed with idiopathic intractable epilepsy for more than six months. All received intravenous PLP 10 mg/kg, then 10 mg/kg/day in four divided doses. If seizures recurred within 24 hours, another dose of 40 mg/kg was given, followed by 50 mg/kg/day in four divided doses. For those patients whose seizures were totally controlled, PLP was replaced by the same dose of oral PN. If the seizure recurred, intravenous PLP was infused followed by oral PLP 50 mg/kg/day.
Results: Fifty seven patients had generalised seizures (of whom 13 had infantile spasms) and 37 had focal seizure. Eleven had dramatic and sustained responses to PLP; of these, five also responded to PN. Within six months of treatment with PLP or PN, five of the 11 patients were seizure free and had their previous antiepileptic medicine tapered off gradually. Two were controlled with pyridoxine and the other three needed PLP to maintain seizure freedom. The remaining six responders needed PLP exclusively for seizure control. Six of the 11 responders to PLP had infantile spasms (46%); four of them needed PLP exclusively. The other five responders were in the remaining 81 patients with other seizure type.
Conclusions: PLP could replace PN in the treatment of intractable childhood epilepsy, particularly in the treatment of infantile spasms.
Full Text
The Full Text of this article is available as a PDF (65.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bajaj A. K., Rastogi S., Misra A., Misra K., Bajaj S. Occupational and systemic contact dermatitis with photosensitivity due to vitamin B6. Contact Dermatitis. 2001 Mar;44(3):184–184. doi: 10.1034/j.1600-0536.2001.440308-5.x. [DOI] [PubMed] [Google Scholar]
- Bass N. E., Wyllie E., Cohen B., Joseph S. A. Pyridoxine-dependent epilepsy: the need for repeated pyridoxine trials and the risk of severe electrocerebral suppression with intravenous pyridoxine infusion. J Child Neurol. 1996 Sep;11(5):422–424. doi: 10.1177/088307389601100519. [DOI] [PubMed] [Google Scholar]
- Battaglioli G., Rosen D. R., Gospe S. M., Jr, Martin D. L. Glutamate decarboxylase is not genetically linked to pyridoxine-dependent seizures. Neurology. 2000 Jul 25;55(2):309–311. doi: 10.1212/wnl.55.2.309. [DOI] [PubMed] [Google Scholar]
- Baumeister F. A., Gsell W., Shin Y. S., Egger J. Glutamate in pyridoxine-dependent epilepsy: neurotoxic glutamate concentration in the cerebrospinal fluid and its normalization by pyridoxine. Pediatrics. 1994 Sep;94(3):318–321. [PubMed] [Google Scholar]
- Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child. 1999 Nov;81(5):431–433. doi: 10.1136/adc.81.5.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baxter P., Griffiths P., Kelly T., Gardner-Medwin D. Pyridoxine-dependent seizures: demographic, clinical, MRI and psychometric features, and effect of dose on intelligence quotient. Dev Med Child Neurol. 1996 Nov;38(11):998–1006. doi: 10.1111/j.1469-8749.1996.tb15060.x. [DOI] [PubMed] [Google Scholar]
- Chou M. L., Wang H. S., Hung P. C., Sun P. C., Huang S. C. Late-onset pyridoxine-dependent seizures: report of two cases. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1995 Nov-Dec;36(6):434–437. [PubMed] [Google Scholar]
- Clayton P. T., Surtees R. A. H., DeVile C., Hyland K., Heales S. J. R. Neonatal epileptic encephalopathy. Lancet. 2003 May 10;361(9369):1614–1614. doi: 10.1016/s0140-6736(03)13312-0. [DOI] [PubMed] [Google Scholar]
- Cormier-Daire V., Dagoneau N., Nabbout R., Burglen L., Penet C., Soufflet C., Desguerre I., Munnich A., Dulac O. A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31. Am J Hum Genet. 2000 Sep 7;67(4):991–993. doi: 10.1086/303087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ekelund H., Gamstorp I., Von Studnitz W. Apparent response of impaired mental development, minor motor epilepsy and ataxia to pyridoxine. Acta Paediatr Scand. 1969 Nov;58(6):572–576. doi: 10.1111/j.1651-2227.1969.tb04764.x. [DOI] [PubMed] [Google Scholar]
- FRENCH J. H., GRUETER B. B., DRUCKMAN R., O'BRIEN D. PYRIDOXINE AND INFANTILE MYOCLONIC SEIZURES. Neurology. 1965 Feb;15:101–113. doi: 10.1212/wnl.15.2.101. [DOI] [PubMed] [Google Scholar]
- Gospe S. M., Jr Current perspectives on pyridoxine-dependent seizures. J Pediatr. 1998 Jun;132(6):919–923. doi: 10.1016/s0022-3476(98)70384-1. [DOI] [PubMed] [Google Scholar]
- Gospe S. M., Jr, Olin K. L., Keen C. L. Reduced GABA synthesis in pyridoxine-dependent seizures. Lancet. 1994 May 7;343(8906):1133–1134. doi: 10.1016/s0140-6736(94)90236-4. [DOI] [PubMed] [Google Scholar]
- Gospe Sidney M. Pyridoxine-dependent seizures: findings from recent studies pose new questions. Pediatr Neurol. 2002 Mar;26(3):181–185. doi: 10.1016/s0887-8994(01)00407-6. [DOI] [PubMed] [Google Scholar]
- Goutières F., Aicardi J. Atypical presentations of pyridoxine-dependent seizures: a treatable cause of intractable epilepsy in infants. Ann Neurol. 1985 Feb;17(2):117–120. doi: 10.1002/ana.410170203. [DOI] [PubMed] [Google Scholar]
- Haenggeli C. A., Girardin E., Paunier L. Pyridoxine-dependent seizures, clinical and therapeutic aspects. Eur J Pediatr. 1991 May;150(7):452–455. doi: 10.1007/BF01958419. [DOI] [PubMed] [Google Scholar]
- Hagberg B., Hamfelt A., Hansson O. Tryptophan load tests and pyridoxal-5-phosphate levels in epileptic children. I. Non-progressive brain damage and degenerative brain disorders. Acta Paediatr Scand. 1966 Jul;55(4):363–370. doi: 10.1111/j.1651-2227.1966.tb08807.x. [DOI] [PubMed] [Google Scholar]
- Hagberg B., Hamfelt, Hansson O. Tryptophan load tests and pyridoxal-5-phosphate levels in epileptic children. II. Cryptogenic epilepsy. Acta Paediatr Scand. 1966 Jul;55(4):371–384. doi: 10.1111/j.1651-2227.1966.tb08808.x. [DOI] [PubMed] [Google Scholar]
- Hammen A., Wagner B., Berkhoff M., Donati F. A paradoxical rise of neonatal seizures after treatment with vitamin B6. Eur J Paediatr Neurol. 1998;2(6):319–322. doi: 10.1016/s1090-3798(98)80007-x. [DOI] [PubMed] [Google Scholar]
- Hansson O., Hagberg B. Effect of pyridoxine treatment in children with epilepsy. Acta Soc Med Ups. 1968;73(1):35–43. [PubMed] [Google Scholar]
- Hirai K., Seki T., Takuma Y. Cerebrospinal fluid somatostatin in West syndrome: changes in response to combined treatment with high-dose pyridoxal phosphate and low-dose corticotropin. Neuropeptides. 1998 Dec;32(6):581–586. doi: 10.1016/s0143-4179(98)90089-0. [DOI] [PubMed] [Google Scholar]
- Ito M., Seki T., Takuma Y. Current therapy for West syndrome in Japan. J Child Neurol. 2000 Jun;15(6):424–428. doi: 10.1177/088307380001500615. [DOI] [PubMed] [Google Scholar]
- Jiao F. Y., Gao D. Y., Takuma Y., Wu S., Liu Z. Y., Zhang X. K., Lieu N. S., Ge Z. L., Chui W., Li H. R. Randomized, controlled trial of high-dose intravenous pyridoxine in the treatment of recurrent seizures in children. Pediatr Neurol. 1997 Jul;17(1):54–57. doi: 10.1016/s0887-8994(97)00035-0. [DOI] [PubMed] [Google Scholar]
- Kuo Meng-Fai, Wang Huei-Shyong. Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine. Pediatr Neurol. 2002 Feb;26(2):146–147. doi: 10.1016/s0887-8994(01)00357-5. [DOI] [PubMed] [Google Scholar]
- Kure S., Sakata Y., Miyabayashi S., Takahashi K., Shinka T., Matsubara Y., Hoshino H., Narisawa K. Mutation and polymorphic marker analyses of 65K- and 67K-glutamate decarboxylase genes in two families with pyridoxine-dependent epilepsy. J Hum Genet. 1998;43(2):128–131. doi: 10.1007/s100380050053. [DOI] [PubMed] [Google Scholar]
- LIVINGSTON S., JENG M. H., PETERSEN D. C. Ineffectiveness of pyridoxine (vitamin B6) in the treatment of epilepsy. Pediatrics. 1955 Aug;16(2):250–251. [PubMed] [Google Scholar]
- McLachlan R. S., Brown W. F. Pyridoxine dependent epilepsy with iatrogenic sensory neuronopathy. Can J Neurol Sci. 1995 Feb;22(1):50–51. doi: 10.1017/s0317167100040506. [DOI] [PubMed] [Google Scholar]
- Merrill A. H., Jr, Henderson J. M. Vitamin B6 metabolism by human liver. Ann N Y Acad Sci. 1990;585:110–117. doi: 10.1111/j.1749-6632.1990.tb28047.x. [DOI] [PubMed] [Google Scholar]
- Morra M., Philipszoon H. D., D'Andrea G., Cananzi A. R., L'Erario R., Milone F. F. Sensory and motor neuropathy caused by excessive ingestion of vitamin B6: a case report. Funct Neurol. 1993 Nov-Dec;8(6):429–432. [PubMed] [Google Scholar]
- Nakagawa E., Tanaka T., Ohno M., Yamano T., Shimada M. Efficacy of pyridoxal phosphate in treating an adult with intractable status epilepticus. Neurology. 1997 May;48(5):1468–1469. doi: 10.1212/wnl.48.5.1468. [DOI] [PubMed] [Google Scholar]
- Ohtsuka Y., Ogino T., Asano T., Hattori J., Ohta H., Oka E. Long-term follow-up of vitamin B(6)-responsive West syndrome. Pediatr Neurol. 2000 Sep;23(3):202–206. doi: 10.1016/s0887-8994(00)00185-5. [DOI] [PubMed] [Google Scholar]
- Ohtsuka Y., Ogino T., Asano T., Hattori J., Ohta H., Oka E. Long-term follow-up of vitamin B(6)-responsive West syndrome. Pediatr Neurol. 2000 Sep;23(3):202–206. doi: 10.1016/s0887-8994(00)00185-5. [DOI] [PubMed] [Google Scholar]
- Pietz J., Benninger C., Schäfer H., Sontheimer D., Mittermaier G., Rating D. Treatment of infantile spasms with high-dosage vitamin B6. Epilepsia. 1993 Jul-Aug;34(4):757–763. doi: 10.1111/j.1528-1157.1993.tb00458.x. [DOI] [PubMed] [Google Scholar]
- Schaumburg H., Kaplan J., Windebank A., Vick N., Rasmus S., Pleasure D., Brown M. J. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. 1983 Aug 25;309(8):445–448. doi: 10.1056/NEJM198308253090801. [DOI] [PubMed] [Google Scholar]
- Scriver C. R., Whelan D. T. Glutamic acid decarboxylase (GAD) in mammalian tissue outside the central nervous system, and its possible relevance to hereditary vitamin B6 dependency with seizures. Ann N Y Acad Sci. 1969 Sep 30;166(1):83–96. doi: 10.1111/j.1749-6632.1969.tb54259.x. [DOI] [PubMed] [Google Scholar]
- Takuma Y. ACTH therapy for infantile spasms: a combination therapy with high-dose pyridoxal phosphate and low-dose ACTH. Epilepsia. 1998;39 (Suppl 5):42–45. doi: 10.1111/j.1528-1157.1998.tb05149.x. [DOI] [PubMed] [Google Scholar]
- Takuma Y., Seki T. Combination therapy of infantile spasms with high-dose pyridoxal phosphate and low-dose corticotropin. J Child Neurol. 1996 Jan;11(1):35–40. doi: 10.1177/088307389601100109. [DOI] [PubMed] [Google Scholar]
- Watanabe K. Medical treatment of West syndrome in Japan. J Child Neurol. 1995 Mar;10(2):143–147. doi: 10.1177/088307389501000217. [DOI] [PubMed] [Google Scholar]