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Role of pyridoxine in the management
of infantile spasms
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Sangeeta Ravat, Mansi Shah
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 03/20/2024
Website: West syndrome (WS) was first described by
www.neurologyindia.com the English physician William James West,
in Lancet in 1841, based on his own son’s
DOI:
disability. It classically presents with a triad
10.4103/0028-3886.227278
consisting of infantile spasms, a characteristic
PMID: electroencephalography (EEG) pattern
xxxx known as hypsarrythmia or its variants, and
neuro‑regression. According to the international
definition, two out of these three components are
sufficient to establish an unequivocal diagnosis.
West syndrome could be idiopathic or secondary
to structural or metabolic pathology. It warrants
an aggressive treatment as soon as it is diagnosed,
to prevent a devastating and irreversible damage
to the child’s development.
Even though 180 years have passed since its
description, we do not have a standardized
and curative treatment for the disease till date.
Treatment options which are widely used are
adreocorticotropic hormone (ACTH)/steroids,
vigabatrin and valproate. ACTH and steroids
are highly efficacious in treating WS but have
a significant side effect profile and also a high
relapse rate. Vigabatrin has the possibility of
causing a visual field loss, but still, it is the
drug of choice for patients of WS secondary to
tuberous sclerosis. ACTH and vigabatrin are
costly and most of our patients cannot afford the
treatment; in addition, these medications are also
not very freely available in our country. In the
wake of these circumstances, the introduction of
novel medication combinations are welcome for
providing an effective treatment of WS.
Department of The role of pyridoxine in treating epilepsy
Neurology, Seth G.S. has been studied since the earlier half of the
Medical College twentieth century. In 1954, pyridoxine dependent
and K.E.M Hospital, epilepsy (PDE) was first described by Hunt
Mumbai, Maharashtra, et al., [1] who reported the case of an infant
India with refractory epilepsy, where a significant
response to pyridoxine was obtained. Over the
Address for years, it became clear that PDE is an autosomal
correspondence: recessive disorder with varied presentations.
Dr. Sangeeta Ravat,
Department of Neurology,
Seth G.S. Medical College This is an open access article distributed under the terms of the Creative
and K.E.M Hospital, Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which
Mumbai, Maharashtra, allows others to remix, tweak, and build upon the work non‑commercially,
as long as the author is credited and the new creations are licensed under
India.
the identical terms.
E-mail: ravatsh@yahoo.
com For reprints contact: reprints@medknow.com
330 © 2018 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
The diagnosis was always based on the response
to pyridoxine and the recurrence of seizures
on withdrawal of pyridoxine in the past;
after genetic studies have become available, a
defect in the lysine degradation pathway has
been identified in 2006. The gene responsible
was discovered to be ALDH7A1 (aldehyde
dehydrogenase 7 family member A1) encoding
for the proteins, α‑aminoadipic semialdehyde
dehydrogenase (α‑AASA) or antiquitin (ATQ).
Since then, more than 80 mutations have been
identified in the exons of this gene. Antiquitin
deficiency interferes with lysine metabolism
and leads to accumulation of pipecolic acid
in the cerebrospinal fluid and serum, and the
elevation of α‑AASA in the urine and plasma,
which leads to the chemical inactivation of
pyridoxal phosphate. Recently, the PROSC gene,
which encodes a pyridoxal‑5‑phosphate binding
protein, has been implicated in this disease.
It is very important to diagnose this rare
condition in refractory epilepsy because of its
excellent response to pyridoxine therapy and
the resistance of this variety of epilepsy to all
other antiepileptic drugs. The clinical diagnosis
can be very confusing owing to the wide range
of presentations, multisystem involvement in
infants, structural abnormalities on magnetic
resonance imaging [MRI] (hypoplasia of the
posterior part of corpus callosum, cerebellar
hypoplasia, intraventricular/subarachnoid
hemorrhage and white matter changes),
partial response to antiepileptic drugs and
delayed/incomplete response to pyridoxine.[2]
There may also be a delayed age of presentation
of the epilepsy. Hence, it is important to not
only consider a trial of pyridoxine in refractory
epilepsy of infancy and childhood, but also to do
a biochemical test for pipecolic acid and α‑AASA,
and subsequently a genetic study for ALDH7A1
in suspected patients.
In this background, it was a good initiative
by Kunnanayaka et al.,[3] to explore the role
of pyridoxine in the management of infantile
spasms. The diagnostic criteria were well
How to cite this article: Ravat S, Shah M. Role of
pyridoxine in the management of infantile spasms.
Neurol India 2018;66:330-1.
 Ravat and Shah: Role of pyridoxine in infantile spasms
outlined and adhered to for inclusion in the study. Two groups
were compared for treatment – one who received only steroids
and one who received steroids as well as pyridoxine. No
difference was found between the two groups in the proportion
of children responding with spasm cessation and resolution of
hypsarrythmia on day 14. Initially, four patients responded
to pyridoxine therapy prior to the randomization and were
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excluded – these patients probably had the underlying genetic
defect in ALDH7A1, which could have been looked into. It
would have been interesting to note the clinical presentation
and MRI findings in these 4 pyridoxine responsive patients.
It could have been seen if those patients who did not respond
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 03/20/2024
to either steroids or a combination of steroid plus pyridoxine
therapy had a different presentation or MRI features.
Pietz et al., from Germany, established the use of high dose
pyridoxine (300mg/kg/day) as a first line therapy of infantile
spasms with a 29.4% responder rate.[4] They suggested the use
of high dose pyridoxine in all cases of infantile spasms as a
first line therapy owing to the variable response rate and the
side effect profile of ACTH/steroids and valproate. A study
by Imai et al., suggested that a retrial of pyridoxine at a later
date could be worthwhile in cases of symptomatic WS who
had not responded previously and had relapsed after ACTH.[5]
Miyajima et al., from Japan tried a combination of valproate,
pyridoxine and low dose ACTH but found no conclusive
benefit by administering pyridoxine.[6]
Despite this, pyridoxine has not been considered as a first line
or adjunctive therapy in the management of infantile spasms
on a routine basis. Since the past two decades, researchers from
China, Japan and Germany have studied the role of pyridoxine
in infantile spasms in isolation, as well as in combination with
other drugs with mixed results, although long term responses
are not known. Hence, it is surprising that this medication
has not been studied in other countries. Earlier, there was no
genetic testing available, but now since the past ten years, a lot
of mutations have been identified and the clinical spectrum of
ALDH7A1 mutations has been widening. Hence, it may become
more feasible to plan the biochemical and genetic work up in all
suspected cases along with a pyridoxine trial. Those who have a
Neurology India | Volume 66 | Issue 2 | March‑April 2018
negative biochemical and genetic work up may not respond to
this treatment. The reason for the non‑responsiveness to various
treatments in various studies done in the past was perhaps
because genetic testing was not performed for the presence
of ALDH7A1 mutation, which would have rendered these
patients immensely responsive to treatment with pyridoxine.
However, one Chinese study by Jiao et al., done in 2016, has
described ten infants with WS who had a normal ALDH7A1
gene but nevertheless did respond to pyridoxine.[7] Also, it has
been seen that pyridoxine helps in symptomatic WS due to
Sturge Weber syndrome or tuberous sclerosis, where it is likely
that some different mechanism may be responsible. Hence,
future research is warranted in collaboration with genetic
studies to ascertain the role of pyridoxine in patients with a
negative genetic work up. Additional genetic abnormalities
may be discovered in the future.
References
1. Hunt AD Jr, Stokes J Jr, McCRORY WW, Stroud HH. Pyridoxine
dependency: Report of a case of intractable convulsions in an infant
controlled by pyridoxine. Pediatrics 1954;13:140‑5.
2. Mills PB, Footitt EJ, Mills KA, Tuschl K, Aylett S, Varadkar S,
et al. Genotypic and phenotypic spectrum of pyridoxine‑dependent
epilepsy (ALDH7A1 deficiency). Brain 2010;133:2148‑59.
3. Kunnanayaka V, Jain P, Sharma S, Seth A, Aneja S. Addition of
pyridoxine to prednisolone in the treatment of infantile spasms: A
pilot, randomized controlled trial. Neurol India 2018;66:385-90.
4. Pietz J, Benninger C, Schäfer H, Sontheimer D, Mittermaier G,
Rating D. Treatment of infantile spasms with high‑dosage vitamin
B6. Epilepsia 1993;34:757‑63.
5. Ohtsuka Y. Reappraisal of vitamin B6 therapy for West syndrome.
Imai Y, Yoshinaga H, Ishizaki Y, Watanabe Y. No To Hattatsu
2009;41:457‑61.
6. Miyajima T, Ito M, Fujii T, Okuno T. Seizure and developmental
prognosis of West syndrome‑‑combination therapy with
high‑dose vitamin B6, valproate and low‑dose ACTH. No To
Hattatsu 2001;33:498‑504.
7. Xue J, Yang Z, Wu Y, Xiong H, Zhang Y, Liu X. Clinical
characteristics and prognosis analysis of vitamin B6 responsive
infantile spasms. Zhonghua Er Ke Za Zhi 2016;54:141‑4.
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