Brain & Development 23 (2001) 654–657

www.elsevier.com/locate/braindev
Review article

High-dose vitamin B6 treatment in West syndrome

Yasuhisa Toribe*
Division of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health,840, Murodo-cho, Izumi,
Osaka 594-1101, Japan
Received 4 June 2001; received in revised form 30 July 2001; accepted 2 August 2001

Abstract
Approximately 10–30% of patients with West syndrome respond to high-dose vitamin B6 treatment. The response to vitamin B6 is rapid;
seizures disappear within the first 2 weeks of treatment. Mild side effects, such as gastrointestinal symptoms and liver dysfunction, are
observed in 40–70%, but these resolve after discontinuation or a reduction of the dosage of vitamin B6. High-dose vitamin B6 treatment is
useful as a first line agent in treating West syndrome. q 2001 Elsevier Science B.V. All rights reserved.
Keywords: Infantile spasms; West syndrome; Vitamin B6; Pyridoxine; Pyridoxal phosphate

1. Background vitamin B6. The last form is vitamin B6 responsiveness,

Natural vitamin B6 consists of pyridoxine, pyridoxal, and
pyridoxamine. All these three types of vitamin B6 are
converted to pyridoxal-5-phosphate, which serves as a coen-
zyme and is involved in many metabolic pathways (espe-
cially in amino acid metabolism). There are three types of
seizures related to vitamin B6. The first is vitamin B6 defi-
ciency. Coursin reported that convulsive seizures occurred
in infants fed with a liquid, autoclaved commercial milk
formula that contained insufficient pyridoxine [1]. In addi-
tion, a number of antimetabolites that can produce vitamin
B6 deficiency are known to cause seizures. This type of
seizure responds to physiological doses of vitamin B6
(0.2–0.5 mg/day in infancy). The second is vitamin B6
dependency [2]. This type is inherited autosomal recessive
and is known to respond immediately to pharmacological
doses of vitamin B6 (0.2–30 mg/kg/day). Seizures usually
occur within hours after birth. Continuous treatment with
vitamin B6 is necessary to prevent relapse of seizures. Bank-
ier et al. suggested a wider spectrum of vitamin B6 depen-
dency [3]. Several authors have reported atypical clinical
manifestations of vitamin B6 dependency [4–7] and atypical
presentations include: (1) seizures that begin after the
neonatal period, (2) seizures that initially respond to antic-
onvulsants before vitamin B6 supplementation, (3)
prolonged seizure-free intervals that occur after the discon-
tinuation of vitamin B6, and (4) poor initial response to
* Tel.: 181-725-56-1220; fax: 181-725-56-5682.
E-mail address: toribe@mch.pref.osaka.jp (Y. Toribe).
0387-7604/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved.
PII: S03 87- 7604(01)0029 2-3
which was proposed by Hansson and Hagberg [8,9].
Seizures respond to the administration of high-dose vitamin
B6 exceeding the physiological daily requirement, although
no disturbances in vitamin B6 intake or metabolism are
found.
In 1940, the use of vitamin B6 in epilepsy was reported by
Spies [10]. Since then, several articles regarding vitamin B6
treatment in epilepsy have been reported [8,9,11–13]. Since
Ohtahara first attempted to treat West syndrome with high-
dose vitamin B6 [14], it had been recognized as a treatment
of choice in West syndrome, especially in Japan [15,16].
The detailed mechanism of vitamin B6 in West syndrome
is unknown, but one possibility includes influence of vita-
min B6 on gamma-aminobutyric acid (GABA), which is the
main inhibitory neurotransmitter in the human central
nervous system. Some investigators indicated that the cere-
brospinal fluid (CSF) GABA levels in patients with West
syndrome were lower than in controls [17,18]. Furthermore,
Kurlemann et al. reported a patient, in whom the GABA
concentration in CSF increased to within normal ranges
after high-dose vitamin B6 therapy [18]. In this article, treat-
ment using high-dose vitamin B6 is discussed.
2. Efficacy
Data concerning the efficacy of high-dose vitamin B6 in
West syndrome are very limited (Table 1). In all cases, high-
dose vitamin B6 was prescribed as the first line agent in
treating West syndrome. Ohtsuka et al. reported the first
 Y. Toribe / Brain & Development 23 (2001) 654–657
Table 1
Reported response to high-dose vitamin B6 in West syndrome a
Vitamin B6 Authors (year) N Response (%)
PALP Ohtuska et al. (1987) [21] 118
Yoshida et al. (1993) [22] 59
Suzuki et al. (1996) [23] 25
Toribe et al. (2000) [27] 50
PIN–HCL Pietz et al. (1993) [25] 17
Scholl et al. (2000) [26] 63
a
PALP: pyridoxal phosphate, PIN–HCL: pyridoxine–hydrochloride.
systematic treatment of West syndrome with vitamin B6
[19–21]: 15 of 118 patients (12.7%) responded to pyridoxal
phosphate (30–400 mg daily), and efficacy was higher in
cryptogenic patients (36.7%) than in symptomatic cases
(9.6%). From the electroencephalographic point of view,
hypsarrhythmia disappeared in all responders. In 1993,
Yoshida et al. reported in detail 59 patients treated with
pyridoxal phosphate [22]. Treatment was initiated with a
daily dose of 20–30 mg/kg. Three days after the initiation
of treatment, the dose was increased to 40–50 mg/kg. The
response rate reached 15.3%. At follow-up, three of nine
responders (33.3%) relapsed (epileptic spasms 1, complex
partial seizures 2). In 1996, Suzuki et al. described that two
of 25 patients (8%) with West syndrome had a complete
resolution of spasms with pyridoxal phosphate (a daily
dose of 20–30 mg/kg increased up to 40–50 mg/kg) [23].
On the other hand, some authors used pyridoxine hydro-
chloride, which is converted in the body to the active form,
pyridoxal phosphate. In 1986, Blennow et al. reported three
patients in whom spasm control was achieved using a total
dose of 200–400 mg/kg pyridoxine hydrochloride [24].
Subsequently, Pietz et al. treated 17 patients with 100 mg/
kg/day pyridoxine hydrochloride, given orally in three doses
and increased within 6 days to 300 mg/kg/day and the
response rate was as high as 29.4% [25]. At follow-up,
40% of responders had relapsed into other seizures. In
2000, Scholl et al. reported 63 patients treated with pyri-
doxal hydrochloride [26]. Treatment was started with
60 mg/kg and increased up to a maximum 250 mg/kg.
Eleven (17%) patients showed immediate and sustained
response. Three (5%) patients had a transient response.
Further studies are required to elucidate the difference in
efficacy between two different types of vitamin B6 (pyri-
doxal phosphate and pyridoxine hydrochloride).
Recently, we also reviewed 50 patients (cryptogenic 5
and symptomatic 45) treated with high-dose pyridoxal phos-
phate [27]. The treatment was started with a daily dose of
20–30 mg/kg. Three or 4 days after the initiation of treat-
ment, the dose was increased to 40–50 mg/kg, depending on
seizure control and tolerability. Six symptomatic patients
(12.0%) showed complete resolution of spasms. Similar to
other previous reports [19,22,25], the spasms ceased within
the first 2 weeks of treatment, but at follow-up, four patients
(66.7%) relapsed; two patients had recurrence of epileptic
655
Relapse (%) Side effects (%)
12.7 13.3 –
15.3 33.3 55.9
8 0 36
12 66.7 42
29.4 40 71
22.2 21.4 –
spasms and the remaining two developed complex partial
seizures.
There has been only one long-term follow-up study
reported for 25 patients (cryptogenic 8 and symptomatic
17) with West syndrome who were responsive to vitamin
B6 [28], in which 21 patients (84%) continued to be seizure
free at the last follow-up examination. All cryptogenic
patients and seven symptomatic patients had intelligent
quotient or developmental quotient scores of 75 or higher.
Vitamin B6 therapy was discontinued without seizure
relapse in four cryptogenic and four symptomatic patients.
In all responders, the electroencephalograms (EEGs)
showed no epileptic discharges.
High-dose vitamin B6 combined with standard agents has
also been used in the treatment of West syndrome. Seki
reported the successful treatment of age-related epilepsies
with a combination of pyridoxal phosphate (40–50 mg/kg/
day) and low dosages of adenocorticotrophic hormo-
ne(ACTH) (tetracosactide acetate Zn, 0.01 mg/kg/day)
[29]. Ito et al. reported the treatment of West syndrome
with a combination of vitamin B6 and valproate [30], and
they concluded that this combination may be more effective
than valproate monotherapy in controlling West syndrome.
3. Side effects
The reported incidence of side effects associated with
high-dose vitamin B6 is relatively high at approximately
40–70% (Table 1). Side effects included appetite loss,
vomiting, diarrhea, constipation, hemorraghic gastritis,
liver dysfunction, apathy, marked abdominal flatulence,
peripheral polyneuropathy and rhabdomyolysis
[18,21,22,25,31]. Of these, the most common side effects
were gastrointestinal symptoms. Most of these side effects
were mild and resolved after discontinuation or reduction of
the dosage of vitamin B6.
4. Report of a case
The patient was a female neonate, the second child of
healthy non-consanguineous parents, born at 25 gestational
weeks. The birth weight was 762 g and Apgar scores were 1
at 1 min and 8 at 5 min. She required assisted ventilation
656 Y. Toribe / Brain & Development 23 (2001) 654–657
during the first 2 months because of insufficient respiration.
She developed intraventricular hemorrhage on day 2, and
septic meningitis at 3 weeks of age. At the age of 3 months,
Fig. 1. Resolution of hypsarrythmia after vitamin B6 treatment. Before
vitamin B6 treatment, interictal EEG of a 11-month-old girl with sympto-
matic West syndrome showed a picture of hypsarrhythmia with generalized
slowing of the background activity of high voltage and multi focal sharp
waves (A). Her spasms ceased after 3 days of Vitamin B6 treatment. The
EEG taken 2 weeks after the start of vitamin B6 treatment , showed no
hypsarrhythmia or paroxysmal discharge (B). The horizontal and vertical
calibration marks denote 1 s and 50 mV, respectively.
she underwent a ventriculo-peritoneal shunt operation
because of post-hemorrhagic hydrocephalus. At the age of
11 months, she started to have epileptic spasms in series.
The EEG showed hypsarrhythmia (Fig. 1A). She was started
on vitamin B6 at a daily dose of 25 mg/kg. Three days after
the initiation of treatment, spasms completely ceased and
the EEG showed no hypsarrhythmia (Fig. 1B).
5. Conclusion
Based on the rapid response (within first 2 weeks) and
few serious side effects, we consider that high-dose vitamin
B6 therapy is useful and worthwhile as a first line agent in
the treatment of West syndrome. However, it should be
noted that the response rate is lower than for ACTH or
valproate. Further studies are necessary to determine the
optimal dosing schedule and to identify the patients most
likely to respond.
Acknowledgements
The author would like to thank Dr. Y. Suzuki, Division of
Pediatric Neurology, Osaka Medical Center and Research
Institute for Maternal and Child Health, for his helpful
suggestion.
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