Randomized, controlled trial of high-dose intravenous pyridoxine in the treatment of recurrent seizures in children

doi:10.1016/S0887-8994(97)00035-0

Pediatric Neurology

Volume 17, Issue 1, July 1997, Pages 54-57

https://doi.org/10.1016/S0887-8994(97)00035-0 Get rights and content

Abstract

To determine the efficacy of pyridoxine in treating seizures, 90 infants and children with recurrent convulsions primarily due to acute infectious diseases were enrolled in the present study. Forty patients were treated with high-dose pyridoxine (30 or 50 mg/kg/day) by intravenous infusion, and 50 subjects served as controls. Antiepileptic drugs and other therapies were similar in the two groups except for pyridoxine. Clinical efficacy criteria were based on the frequency of convulsions per day and on the duration of individual seizures after therapy was initiated. The results indicated that total response rates in the pyridoxine group and control group were 92.5% and 64%, respectively (chi-square = 14.68, P < .001). After initiation of therapy, seizures resolved after 2.4 ± 1.4 days in the pyridoxine group and after 3.7 ± 2.0 days in the control group (t = 3.67, P < .001). No adverse effects of pyridoxine were apparent during the observation period. We conclude that pyridoxine is an effective, safe, well-tolerated, and relatively inexpensive adjunct to routine antiepileptic drugs for treatment of recurrent seizures in children.

Reference (18)

ItoM. et al.
Vitamin B6 and valproic acid in treatment of infantile spasms
Pediatr Neurol
(1991)
TakumaY. et al.
Combination therapy of infantile spasms with high-dose pyridoxal phosphate and low-dose corticotropin
J Child Neurol
(1996)
PietzJ. et al.
Treatment of infantile spasms with high-dosage vitamin B6
Epilepsia
(1993)
HajailayR. et al.
Pyridoxine therapy in tetanus neonatorum
Indian Pediatr
(1983)
LeklemJ.E.
Vitamin B6
BernsteinA.L.
Vitamin B6 in clinical neurology
Ann NY Acad Sci
(1990)
BarnessL.A.
Pyridoxine (vitamin B6) deficiency
MolonyC.J.
Convulsions in young infants as a result of pyridoxine (vitamin 136) deficiency
JAMA
(1954)
CoursinD.B.
Convulsive seizures in infants with pyridoxinedeficient diet
JAMA
(1954)

There are more references available in the full text version of this article.

Cited by (18)

The association of nutrient intake with epilepsy: A cross-sectional study from NHANES, 2013-2014
2024, Epilepsy Research
Dietary nutrient supplements are helpful in the treatment of many diseases, but their effect on epilepsy is still controversial. This study aimed to evaluate the association between dietary intake of multiple nutrients and epilepsy.
A total of 3963 participants from the NHANES database were involved in this study. We compared the dietary intake of 14 nutrients between the normal population and those with epilepsy. Univariable and multivariable logistic regression were conducted to evaluate the association of these nutrients with epilepsy.
Compared with the normal population, the epilepsy patients showed lower intakes of protein, vitamin B1, vitamin B6, Fe, and Zn. Multivariable logistic regression showed the negative association of vitamin B1 (OR = 0.513, 95% CI: 0.293, 0.897) with epilepsy. When vitamin B1 was divided into 4 groups according to quartiles, the highest quartile showed a lower odds ratio (OR = 0.338, 95% CI: 0.115, 0.997) than that of the lowest quartile. In different population stratifications, the association of vitamin B1 with epilepsy was different. Vitamin B1 was negatively associated with the odds ratio of epilepsy among the elderly (OR = 0.243), low-income population (OR = 0.337), and current smokers (OR = 0.283).
Epilepsy patients had significantly lower intakes of vitamin B1, which was inversely associated with epilepsy risk. More detailed clinical trials are needed to accurately evaluate nutritional supplements for epilepsy.
Long-term outcome in pyridoxine-responsive infantile epilepsy
2015, European Journal of Paediatric Neurology
Citation Excerpt :
Apart from the clearly defined monogenic defects, pyridoxine may also have nonspecific therapeutic effects within various types of epilepsies, in particularly with unknown and etiologies for infantile spasms.3–6 Epileptic conditions may show a favourable response to treatment with pyridoxine in addition to conventional antiepileptic drugs.19 Vitamin B6 is a coenzyme of glutamate decarboxylase and may enhance GABA-ergic neuronal function20 which might be the mechanism of therapeutic action in our patients.
Dose regimens of pyridoxine (vitamin B6) for treatment of infantile spasms have varied from 200 mg/d to 300 mg/kg/d. Only two long-term outcome studies of the treated patients are available.
We asked all pediatric neurologists treating pediatric epilepsy in Finland if they had seen patients with pyridoxine-responsive infantile epilepsy. Five children with infantile spasms and hypsarrhythmia and one with focal epilepsy were reported as pyridoxine responders. Data on clinical presentation and outcome were collected from patient charts.
All B6 responders had un-known aetiology. Two patients were studied for pyridoxal 5′-phosphate oxidase (PNPO) deficiency and showed negative results. Ages at seizure onset ranged from 4 to 7 months. The maintenance dose of oral pyridoxine was 150 mg/day. Response occurred within 1-to 14 days (mean 5 days). Two patients were treated with concomitant antiepileptic drugs. Duration of pyridoxine therapy varied from 6 weeks to 4 years (mean 26 months). Four patients had later seizure recurrence: one at 15 months with motor seizures (stopped by valproate), another two in adolescence with focal epilepsy and one at 20 years with unclassified epilepsy. Intelligence was normal in five patients and one had a mild mental deficiency. Follow-up ranged from 8.5 to 24 years.
Rare patients with infantile epilepsy but not pyridoxine dependency may respond to smaller doses of pyridoxine than reported before. Long-term cognitive outcome appears to be good but late seizure recurrence (in adolescence or in adulthood) occur. So far it is unknown if the response was determined by genetic traits or disease-related factors.
Pyridoxine dependent epilepsy and antiquitin deficiency. Clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up
2011, Molecular Genetics and Metabolism
Citation Excerpt :
Apart from these clearly defined monogenic defects, pyridoxine may also have a non-specific therapeutic effect in patients with various types of cryptogenic and symptomatic epilepsies. In particular patients with infantile spasms or other catastrophic epileptic conditions may show a favorable response to treatment with pyridoxine in addition to conventional pharmacologic therapy [123–127]. Nutritional vitamin B6 deficiency is rare, but can be seen in severely malnourished children or with severe underlying disease.
Antiquitin (ATQ) deficiency is the main cause of pyridoxine dependent epilepsy characterized by early onset epileptic encephalopathy responsive to large dosages of pyridoxine. Despite seizure control most patients have intellectual disability. Folinic acid responsive seizures (FARS) are genetically identical to ATQ deficiency. ATQ functions as an aldehyde dehydrogenase (ALDH7A1) in the lysine degradation pathway. Its deficiency results in accumulation of α-aminoadipic semialdehyde (AASA), piperideine-6-carboxylate (P6C) and pipecolic acid, which serve as diagnostic markers in urine, plasma, and CSF.
To interrupt seizures a dose of 100 mg of pyridoxine-HCl is given intravenously, or orally/enterally with 30 mg/kg/day. First administration may result in respiratory arrest in responders, and thus treatment should be performed with support of respiratory management.
To make sure that late and masked response is not missed, treatment with oral/enteral pyridoxine should be continued until ATQ deficiency is excluded by negative biochemical or genetic testing. Long-term treatment dosages vary between 15 and 30 mg/kg/day in infants or up to 200 mg/day in neonates, and 500 mg/day in adults. Oral or enteral pyridoxal phosphate (PLP), up to 30 mg/kg/day can be given alternatively. Prenatal treatment with maternal pyridoxine supplementation possibly improves outcome.
PDE is an organic aciduria caused by a deficiency in the catabolic breakdown of lysine. A lysine restricted diet might address the potential toxicity of accumulating αAASA, P6C and pipecolic acid. A multicenter study on long term outcomes is needed to document potential benefits of this additional treatment.
The differential diagnosis of pyridoxine or PLP responsive seizure disorders includes PLP-responsive epileptic encephalopathy due to PNPO deficiency, neonatal/infantile hypophosphatasia (TNSALP deficiency), familial hyperphosphatasia (PIGV deficiency), as well as yet unidentified conditions and nutritional vitamin B6 deficiency.
Commencing treatment with PLP will not delay treatment in patients with pyridox(am)ine phosphate oxidase (PNPO) deficiency who are responsive to PLP only.
Down syndrome and epilepsy: A nutritional connection?
2004, Medical Hypotheses
Non-Asian individuals with Down syndrome are much more likely to develop epileptic seizure disorders than individuals without Down syndrome. Examination of nutrient and metabolite levels in patients with these two seemingly disparate disorders reveals numerous similarities. Compared to individuals without these disorders, individuals with Down syndrome and individuals with seizures may have lower levels of vitamin A, vitamin B1, folate, vitamin B12, vitamin C, magnesium, manganese, selenium, zinc, carnitine, carnosine, choline, and possibly serine. Excesses of copper, cysteine, phenylalanine, and superoxide dismutase are also sometimes encountered in both disorders. In addition to common nutritional lower levels and excesses, disorders of metabolism involving vitamin B6, vitamin D, calcium, and tryptophan may play a common role. This paper hypothesizes that nutritional factors may account for the high joint occurrence of these conditions. Further examination of these data may provide insights into nutritional, metabolic and pharmacological treatments for both conditions.
Pyridoxine-dependent seizures: Findings from recent studies pose new questions
2002, Pediatric Neurology
Pyridoxine-dependent seizures, although a rare clinical entity, have been recognized as an etiology of intractable seizures in neonates and infants for more than 45 years. Recent research has focused on the molecular and neurochemical aspects of this disorder, as well as the optimal treatment of the condition. This review discusses the clinical features and management of patients with pyridoxine-dependent seizures together with a new hypothesis suggesting that an abnormality of pyridoxine transport may underlie the pathophysiology of this autosomal-recessive disorder.
Current perspectives on pyridoxine-dependent seizures
1998, Journal of Pediatrics

View all citing articles on Scopus

View full text

Randomized, controlled trial of high-dose intravenous pyridoxine in the treatment of recurrent seizures in children

Abstract

Pediatr Neurol

Combination therapy of infantile spasms with high-dose pyridoxal phosphate and low-dose corticotropin

J Child Neurol

Treatment of infantile spasms with high-dosage vitamin B6

Epilepsia

Pyridoxine therapy in tetanus neonatorum

Indian Pediatr

Vitamin B6

Vitamin B6 in clinical neurology

Ann NY Acad Sci

Pyridoxine (vitamin B6) deficiency

Convulsions in young infants as a result of pyridoxine (vitamin 136) deficiency

JAMA

Convulsive seizures in infants with pyridoxinedeficient diet

JAMA