Cognitive Function and Valproate Monotherapy

A test battery to assess neuropsychological and behavioral changes associated with anticonvulsant, particularly valproate, therapy in children is proposed from the Departments of Pediatrics (Neurology), and Clinical Health and Psychology, University of Florida, Gainesville, FL.

COMMENT. The authors comment that the cognitive effects of valproate reported in normal adult volunteers and adults with epilepsy cannot reliably be applied to children. There is a relative paucity of well-controlled studies assessing memory and attentional differences in pediatric epilepsy patients treated with valproate monotherapy. Reports that cognitively impaired children on valproate therapy improve with L-acetylcarnitine supplements requires further study.
In one study involving children with epilepsy previously untreated, significant positive correlations were found between serum levels of valproate and the sum of 5 memory tests at 1 month and at 6 months after starting valproate monotherapy. Phenytoin had no adverse effects, whereas carbamazepine serum levels showed a negative correlation with memory and reading scores. (Forsythe I et al. Dev Med Child Neurol 1991;33:524). For reviews of Cognitive Effects of Antiepileptic Drugs, see Progress in Pediatric Neurology II. Chicago, PNB Publ, 1994.

CORPUS CALLOSUM SIZE IN TOURETTE'S SYNDROME
The size of the corpus callosum (CC) in Tourette's syndrome (TS) and ADHD was determined by analysis of MRI data in 77 children and adolescents, aged 6 to 16 years, including 27 controls, at the Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD. TS patients had significant increases in 4 of 5 subregions (splenium, isthmus/posterior body, mid-body, and rostral body), the total area, and the perimeter of the CC. ADHD was associated with a significant decrease in the rostral body size. Inspection of subgroup means demonstrated a statistical independence of the effects of ADHD versus effects of TS on CC size. The larger CC in TS was independent of age, handedness, intracranial area, and the association of ADHD. COMMENT. The authors comment that TS and ADHD may result from distinct neurodevelopmental processes, and the three syndrome groups, comprising TS only, ADHD, and TS + ADHD, may represent different degrees of expression of the same gene. In addition to genetic transmission, environmental influences include prenatal factors, anabolic steroids, and antineural antibodies induced by streptococcal infection. (Singer HS, in Progress in Pediatric Neurology II. 1994, pp 227-231). COMMENT. Even when children with specific learning disabilities are excluded, TS is associated with academic problems in one third. Tics themselves were not the reason for the school problems, but rather the associated comorbid ADHD. These findings confirm those of the Johns Hopkins group of investigators, who found that children with TS + ADHD were at higher risk for a specific learning disability than those with TS alone (32% v 0%). (Schuerholz LJ et al. Neurology 1996;46:958-965).

LEARNING DISABILITIES AND TOURETTE'S SYNDROME
For those readers interested in history, Lajonchere C et al, from Washington University, St Louis, MO, have published an English-language translation of an 1884 article by Gilles de la Tourette that led to his description of the Tourette syndrome published in 1885. (Arch Neurol June 1996;53:567-574).

ATTENTION DEFICITS AND THYROID FUNCTION
The relation between attention and thyroid function was examined in 85, 7-year-old, children with congenital hypothyroidism (CH) at the Hospital for Sick Children, Toronto, Canada. Children were assigned to subgroups on the basis of concurrent T4 and TSH levels. Almost 10% of children with CH had abnormally high levels of T4 and TSH. Those with this abnormal thyroid profile did not differ from other CH children in intelligence but they did perform more poorly on a measure of cognitive attention, while rating more favorably on parent behavior scales of hyperactivity and distractibility. The level of T4 was the stongest predictor of poorer cognitive attention, while TSH