Recently, genetic causes have been identified in severe myoclonic epilepsy in infancy and certain epilepsy syndromes in which the phenotypes are similar to common idiopathic epilepsies. Interestingly, almost all such genetic abnormalities were detected in genes encoding ion channels expressed in the brain. Such channels include GABA_A receptor and K⁺ channels each of which plays an important role in the neuronal inhibitory system. Mutations of the genes encoding several subunits of GABA_A receptor, a ligand-gated ion channel, were identified as underlying causes of various epilepsy syndromes: A missense mutation of the gene encoding α 1 subunit of the receptor, GABRA1 was found to be associated with autosomal dominant juvenile myoclonic epilepsy and several missense mutations of γ 2 were found in febrile seizure related epilepsy syndromes such as autosomal dominant epilepsy with febrile seizures plus or generalized epilepsy with febrile seizures plus. Mutations within the same gene can result in different epilepsy phenotypes. Abnormality of γ 2 subunit of GABA_A receptor may be also associated with severe myoclonic epilepsy in infancy. Mutations of two KCNQ K⁺ -channel genes, KCNQ2 and KCNQ3, were identified in benign familial neonatal convulsions. Mutation of another K⁺ -channel gene, KCNA1, can cause episodic ataxia type 1 and epilepsy.

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Pharmacokinetics and metabolism of valproate (VPA) has been discussed in relation to the risk and prevention of VPA teratogenicity. Prospective epidemiological studies have shown that high VPA dosages (≥1,000 mg/day) and high VPA concentrations (≥70 μg/ml) together with VPA polypharmacy (especially coadministration with enzyme-inducing antiepileptic drugs) are regarded as clinical risk factors for increased VPA teratogenicity. An animal experiment has also shown that high peak concentration after single dosing of VPA during the early stage of pregnancy correlates well with the incidence of neural tube defects. All of these risk factors enhance metabolic conversion from VPA to its toxic metabolite, 2-propyl-4-pentenoic acid (4-en). On the other hand, the use of slow-release formulation of valproate (VPA-SR) results in reduced formation of 4-en as well as decreased diurnal fluctuations in VPA concentrations. These pharmacokinetic and metabolic alterations by using VPA-SR may be helpful in reducing VPA teratogenicity. We therefore recommend that high VPA dosages, high VPA concentrations and VPA polypharmacy should be avoided in epileptic women of childbearing age. Conventional VPA, when used in these subjects, should be replaced with VPA-SR before pregnancy to diminish the risk of VPA teratogenicity.

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Midazolam was administered intravenously in the treatment of status epilepticus in 71 children (episodes of 89 convulsions) from 1997 to 2002. Among those episodes, intravenous midazolam was employed for 42 episodes as the first-line agent, 34 episodes as the second-line agent, and 12 episodes as the third-line agent. The itemized etiologies of 89 episodes were as followed: epilepsy in 43, febrile convulsions in 11, theophylline-induced seizures in 12, and acute encephalopathy/encephalitis in 17. Complete cessation of status epilepticus was obtained in 75 episodes (84.2%) totally, among which 35 episodes (83.3%) in the first-line administration, 28 episodes (82.3%) in the second-line, and 11 episodes (91.7%) in the third-line. Midazolam was administered as an intravenous bolus dose of 0.05-0.4 mg/kg, followed by continuous intravenous infusion with the dose of 0.06-0.6 mg/kg/hr. The duration of continuous infusion ranged from 1 to 240 hours with mean duration of 51.2 hours. In all episodes except four, the status epilepticus stopped within 1 minute without any serious adverse effects. No endotracheal intubation was needed during all midazolam infusions. In the meanwhile, intravenous diazepam was employed in the treatment of 159 episodes of status epilepticus during the same period as midazolam series. Of which, cessation of convulsion was obtained in 106 episodes (66.7%). However, transient endotracheal intubation or mechanical ventilation were needed for 14 patients due to respiratory suppression. These results suggest that midazolam is more useful in the meaning of both effectiveness and safety comparing with diazepam as a therapy of status epilepticus in children.

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Depression is a common occurrence among epileptic patients. Most interictal depressive disorder is called interictal dysphoric disorder (IDD) or dysthymic-like disorder of epilepsy (DLDE). It is characterized by a chronic dysthymic state in which symptoms tend to occur intermittently and intermixed with brief euphoric moods, explosive irritability, anxiety, and somatoform symptoms, and is often improved by antidepressants medications. There are few reports that epileptic patients with major depression need to receive hospital treatment because of severe depressive state or suicide idea. We report 3 epileptic cases diagnosed major depression, who have severe depressive state and suicide idea. Depressive state is drug resistance and many kinds of antidepressants need to be used at full dose to evaluate the effect. Seizures were induced with maprotiline and clomipramine. Other drug had no seizures induction.

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We report a case of frontal lobe epilepsy that developed postictal psychosis after bouts of complex partial seizures. A 17-year old right-handed man had been treated with antiepileptic drugs after a single seizure at age 18 months. Complex partial seizures consisting of motion arrest developed at age 14 years. At age 17 years, the patient experienced several complex partial seizures which were longer in duration than usual. One day after such a cluster of seizures, he became restless and aggressive. He experienced continuing irritability, dysphoria, and aggression, involving recurrent brief episodes of psychomotor excitement and impulsive violence. These psychotic symptoms completely resolved within 3 weeks without use of antipsychotics. His neuroimaging findings showed broad hypofunction in the left hemisphere which included both the frontal and temporal lobes. We found some differences between the symptoms of postictal psychosis in our case and those found in temporal lobe epilepsy as reported in previous studies. These differences may be due to the association here with frontal lobe dysfunction.

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Human autosomal recessive primary microcephaly (MCPH) is a rare disorder in which the head circumference is reduced because of a congenital deficiency of fetal brain growth, particularly affecting the cerebral cortex. The MCPH brain, although small, is structurally normal, and the phenotypic result is mental retardation without any other neurological defect or epilepsy. We reported three cases of MCPH aged 11 months to 4 years associated with epilepsy. All three cases exhibited symptomatic localization-related epilepsy (frontal lobe) and their seizure types were complex partial seizures or secondary generalized tonic seizures. Seizures in two of three cases were well controlled by valproic acid, but one case had intractable epileptic seizures. Genetic malformations of the cerebral cortex have been recognized in recent years as a major underlying cause for epilepsy in pediatric patients. Different types of cortical malformation may show different epileptogenicity.

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