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Indian Pediatr 2012;49:
13-14 |
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Iron Deficiency, Febrile Seizures and Brain
Development |
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Michael V Johnston
Professor of Neurology and Pediatrics, Johns Hopkins
University School of Medicine, and Attending Physician, John Hopkins
Hospital and Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD
21205, USA.
Email:
[email protected]
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I
ron deficiency anemia is one of the most prevalent
micronutrient deficiencies in young children in India and other parts of
the world, and it is strongly associated with persistent cognitive and
motor delays even after the anemia and iron deficit have been repaired.
Madan, et al. [1] reported recently that children aged 6-23 months
with moderate to severe iron deficiency anemia had lower mental and
psychomotor scores that persisted to as long as 19 years of age. These
children also had lower scholastic achievement and needed more special
education assistance than iron sufficient children. These impairments may
be related to several effects of iron deficiency in the developing brain
including altered development of neurons in the hippocampus that encodes
memories, impaired energy metabolism, delayed maturation of myelin, and
slowed visual and auditory evoked potentials [2]. Iron deficiency has also
been associated with alterations in synaptic neurotransmitter systems
including norepinephrine, dopamine, serotonin, glutamate and gamma-aminobutyric
acid (GABA). In addition, a paper by Kumari, et al. [3] in this
issue of Indian Pediatrics provides evidence that iron deficiency
is also a risk factor for febrile seizures in children 6 months to three
years of age. This carefully done case-control study with a large sample
size showed a highly significant association between iron deficiency and
febrile seizures. As expected, a family history of febrile seizures or
epilepsy in first degree relatives was also linked to the occurrence of
febrile seizures in these children. The findings are consistent with
another recent case-control study from Kenya of children 3-156 months of
age, which reported that iron deficiency is a risk factor for simple
febrile seizures but not for other types of acute seizures [4]. An
important practical lesson from this study is that preventing iron
deficiency may be an effective way to reduce the incidence of febrile
seizures.
These new data are also important because they suggest
that there may be a mechanistic link between febrile seizures associated
with iron deficiency and two other disorders that cause enhanced brain
excitability: restless leg syndrome (RLS) and attention deficit
hyperactivity disorder (ADHD). RLS occurs in children and adults and is
characterized by an urge to move the legs, usually associated with an
unpleasant sensation while lying down for sleep at night [5]. Family
studies and genome wide association studies suggest a genetic contribution
to RLS, but it is also strongly associated with reduced serum ferritin
levels, and magnetic resonance imaging (MRI) has shown reduced iron stores
in brain in many patients. Altered metabolism of dopamine also appears to
play a role in enhanced neuronal excitability in spinal motor and sensory
nerves in RLS, and it usually responds well to dopaminergic agonists along
with replenishment of iron. Iron deficiency has also been implicated in
the pathogenesis of ADHD. Juneja, et al. [6] reported that there
was a significant negative correlation between serum ferritin levels and
the Connors Rating Scale for ADHD. Low iron levels have also been measured
in the thalamus of children with ADHD using MRI, and the serum ferritin
level has been shown to predict the optimal dose of amphetamine needed to
treat ADHD. Gilbert, et al. [7] recently reported that children
with ADHD have impaired cortical inhibition in response to transcranial
magnetic stimulation that correlates with the severity of ADHD. These
three disorders, febrile seizures, RLS and ADHD, may reflect different
facets of altered brain excitability that is enhanced by iron deficiency
and also influenced by genetic factors. Iron is clearly important for
brain development as well as for prevention of anemia, and more study is
warranted to understand its role in these common neurodevelopmental
disorders.
Funding: None; Competing interests: None
stated.
References
1. Madan N, Rusia U, Sikka M, Sharma S, Shankar N.
Developmental and neurophysiologic deficits in iron deficiency in
children. Indian J Pediatr. 2011;78:58-64.
2. Carlson ES, Tkac I, Magid R, O’Connor MB, Andrews
NC, Schallert T, et al. Iron is essential for neuron development
and memory function in mouse hippocampus. J Nutr. 2009;139:672-9.
3. Kumari PL, Nair MK, Nair SM, Kailas L, Geetha S.
Iron deficiency as a risk factor for simple febrile seizures - a case
control study. Indian Pediatr. 2011;49:17-9 .
4. Idro R, Gwer S, Williams TN, Otieno T, Uyoga S,
Fegan G, et al. Iron deficiency and acute seizures: results from
children living in rural Kenya and a meta-analysis. PLoS One.
2010;5:e14001.
5. Trenkwalder C, Paulus W. Restless legs syndrome:
pathophysiology, clinical presentation and management. Nat Rev Neurol.
2010;6:337-46.
6. Juneja M, Jain R, Singh V, Mallika V. Iron
deficiency in Indian children with attention deficit hyperactivity
disorder. Indian Pediatr. 2010;47:955-8.
7. Gilbert DL, Isaacs KM, Augusta M, Macneil LK,
Mostofsky SH. Motor cortex inhibition: a marker of ADHD behavior and motor
development in children. Neurology. 2011;76:615-21.
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