Three boys, ages 4.5, 6, and 6.7 years, with attention deficit/hyperactivity disorder (ADHD) associated with giant somatosensory evoked potentials (SEP), who responded well to extended-release valproate (ER-VPA), are reported from the University of Tokushima Graduate, and Miyoshi Medical Clinic, Higashikagawa, Japan. Of 20 children with ADHD, 17 boys and 3 girls, ages 3 to 13 years, 6 showed giant SEPs, defined as peak-peak amplitude of N20-P25 that exceeded l0mcV, on median nerve stimulation. Three also had Tourette’s syndrome and were excluded. Of the 3 responders, 2 had the hyperactive-impulsive subtype of ADHD, and 1 had the ADD + HI combined type. All 3 had abnormal EEGs showing focal discharges in frontal areas. Two had received methylphenidate previously without benefit. ER-VPA was administered in one daily dose (9.5 to 18.8 mg/kg) each morning. Serum VPA concentrations ranged from 26 to 58 mcg/ml. Total ADHD-rating scale (RS-IV) scores were decreased following treatment with VPA, and the hyperactive-impulsive (H-I) symptoms were controlled more effectively than the inattentive type. Pretreatment and treatment scores for H-I decreased from 26-11, 22-10, and 26-25, for patients 1, 2, and 3, whereas those for inattention were 9-6, 9-9, and 24-21, respectively. SEP amplitudes following median nerve stimulation were decreased to normal voltage in two patients after VPA treatment. 
COMMENT. The authors recommend a trial of ER-valproate in children with ADHD, especially those with the hyperactive-impulsive subtype, when associated with giant somatosensory evoked potentials. It should be noted that the responders also had epileptiform EEGs, with frontal localization, areas known to be involved in ADHD. Giant SEPs may reflect hyperactivity and decreased GABA in the sensorimotor cortex, and g-aminobutyric acid (GABA) enhancers such as clonazepam and valproate would be expected to reduce amplitude of giant SEPs and benefit hyperactive-impulsive behavior. In methylphenidate nonresponders, somatosensory evoked potentials should be tested, and treatment with VPA given consideration. GABAergic dysfunction as well as dopaminergic mechanisms are postulated in the etiology of ADHD. The risks of valproate therapy and the necessity for monitoring with blood level and other laboratory tests could deter its frequent use in ADHD practice.
Predictors for persistent hyperactive behavior in 2 to 7 year-olds included maternal prenatal smoking, child male gender, maternal depression, and hostile parenting. In a population-based sample, 7 children in 100 were classified as hyperactive at both the 2-year and 7-year evaluations. Preventive intervention is recommended for high-risk families.