Untreated epileptic encephalopathies in children may potentially have disastrous outcomes. Treatment with antiepileptic drugs (AEDs) often may not control the seizures, and even if they do, this measure is only symptomatic and not specific. It is especially valuable to identify potential underlying conditions that have specific treatments. Only a few conditions have definitive treatments that can potentially modify the natural course of disease. In this paper, we discuss the few such conditions that are responsive to vitamin or vitamin derivatives. 1. Introduction Epileptic encephalopathies (EEs) are conditions in which progressive cognitive and neuropsychological regression occurs, attributable to excessive ictal and interictal epileptogenic activity during brain maturation [1]. The progression in such disorders is mostly relentless and leads to irreversible damage to the developing brain. Original classification of International League Against Epilepsy (ILAE) included only a few conditions under strict criteria of EE; however, in 2010, they extended the definition to any form of epilepsy that can cause encephalopathic effect [2]. Most of these conditions are managed symptomatically with AEDs; very rarely do these conditions have treatable underlying causes, including genetic, metabolic, autoimmune, and nutritional causes. Treatment with a specific vitamin or vitamin derivative in these specific cases may halt such inexorable progression. 2. Pyridoxine Dependent Epilepsy (PDE) Hunt and colleagues reported the first case of intractable epilepsy in an infant controlled by pyridoxine in 1954 [3]. Subsequently, many anecdotal case reports surfaced [4, 5]. For a while, it was speculated that a mutation affecting Glutamate decarboxylase (GAD) was the cause for PDE. However, Battaglioli and colleagues showed that GAD mutation is not linked to PDE [6]. In 2006, Mills et al. for the first time reported that alpha aminoadipic semialdehyde dehydrogenase (antiquitin) deficiency due to ALDH1A7 mutation is a cause for PDE [7]. It usually manifest in neonatal period. The affected neonates usually manifest within the first few hours after birth with seizures. The seizure evolves into status epilepticus despite adequate treatment with AEDs. An antenatal history of unusual fetal movements indicating intrauterine seizures may be present although this is not very common. The seizure semiology is quite variable with focal, generalized, myoclonic, epileptic spasms, and/or mixed seizure patterns. PDE can be easily confused with hypoxic ischemic encephalopathy or sepsis due
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