Voltage‐gated Na+ current is reduced by acid solution. Protons reduce peak Na+ conductance by lowering single channel conductance and shift the voltage range of gating by neutralizing surface charges. Structure‐function studies identify six carboxyls and a lysine in the channel's outer vestibule. We examined the roles of the superficial ring of carboxyls in acid block of Nav1.4 (the rat skeletal muscle Na+ channel isoform) by measuring the effects of their neutralization or their substitution by lysine on sensitivity to acid solutions, using the two‐micropipette voltage clamp in Xenopus oocytes. Alteration of the outer ring of carboxylates had little effect on the voltage for half‐activation of Na+ current, as if they are distant from the channels' voltage sensors. The mutations did not abolish proton block; rather, they all shifted the pKa (‐log of the dissociation constant) in the acid direction. Effects of neutralization on pKa were not identical for different mutations, with E758Q > D1241A > D1532N > E403Q. E758K showed double the effect of E758Q, and the other lysine mutations all produced larger effects than the neutralizing mutations. Calculation of the electrostatic potential produced by these carboxylates using a pore model showed that the pKa values of carboxylates of Glu‐403, Glu‐758, and Asp‐1532 are shifted to values similar to the experimentally measured pKa. Calculations also predict the experimentally observed changes in pKa that result from mutational neutralization or introduction of a positive charge. We propose that proton block results from partial protonation of these outer ring carboxylates and that all of the carboxylates contribute to a composite Na+ site.

Vagus nerve stimulation (VNS) is approved by FDA for treatment of intractable epilepsy in children over 12 years of age. We assessed the efficacy of VNS therapy in younger children. The study was a retrospective review of the medical records of medically refractory epilepsy patients under 12 years old at VNS implantation. Out of 42 patients studied, 28 had at least 50% decrease in seizure frequency, one-half of patients had 75% decrease in seizures, and 7% became seizure-free. A total 69% of patients reported improved mood and alertness. Complication rate was 7%. Age at VNS implantation, prior duration of epilepsy, electroencelphographic focality, and etiology of epilepsy did not influence the outcome (p?>?0.05). Our cohort demonstrated a lasting benefit of VNS therapy over 5 years, including seizure reduction and improved mood and alertness. VNS is a safe and effective adjunctive therapy for young children with medically intractable epilepsy.

Seizures are common in the pediatric population; however, most children do not go on to develop epilepsy later in life. Selecting appropriate diagnostic modalities to determine an accurate diagnosis and appropriate treatment as well as with counseling families regarding the etiology and prognosis of seizures, is essential. This article will review updated definitions of seizures, including provoked versus unprovoked, as well as the International League Against Epilepsy operational definition of epilepsy. A variety of specific acute symptomatic seizures requiring special consideration are discussed, along with neonatal seizures and seizure mimics, which are common in pediatric populations.

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We report a 10-year-old boy with mild developmental delay and epilepsy with new events of right back tickling and emotional upset. These initially appeared behavioral, causing postulation of habit behaviors or psychogenic nonepileptic seizures. Several ictal and interictal EEGs were unrevealing. Continuous EEG revealed only poorly localized frontal ictal activity. Given that his clinical symptoms suggested a parietal localization, double-density EEG electrodes were placed to better localize the epileptogenic and symptomatogenic zones. These revealed evolution of left greater than right frontoparietal discharges consistent with seizures at the time of the attacks. Medical management has significantly reduced the patient's seizures.