Possible association between moderate intellectual disability and weight gain in valproic acid–treated patients with epilepsy

Yukiko Tanamachi,1 Junji Saruwatari,1 Madoka Noai,1 Ryoko Kamihashi,1 Hiromi Soraoka,1 Yuki Yoshimori,1 Naoki Ogusu,1 Kentaro Oniki,1 Norio Yasui-Furukori,2 Takateru Ishitsu,3,4 Kazuko Nakagawa1,5 1Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan; 3Kumamoto Saishunso National Hospital, Koshi, Japan; 4Kumamoto Ezuko Ryoiku Iryo Center, Kumamoto, Japan; 5Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan Background: Although patients with moderate intellectual disability (ID) are known to have higher rates of being overweight and obese than those without ID, there are no current data regarding the relationship between ID and weight gain in epilepsy patients treated with valproic acid (VPA). Patients and methods: The possible association between moderate ID and an overweight status at the time of initiation of VPA therapy (baseline) was investigated using a logistic regression analysis in 143 patients with epilepsy. Among the 119 nonoverweight patients at baseline, the longitudinal association between moderate ID and the weight status during VPA therapy was retrospectively examined using a Cox hazards regression analysis and the generalized estimating equations approach, while also paying careful attention to associations with other patient characteristics. Results: The proportion of patients with moderate ID was 52.4% among the 143 study subjects. The presence of moderate ID was not associated with an overweight status at baseline (P=0.762). Among the nonoverweight patients at baseline, 16 subjects were newly diagnosed as being overweight during treatment with VPA (3.6±2.1 years). The presence of moderate ID was significantly associated with the incidence of an overweight status after starting VPA therapy (adjusted hazard ratio =6.72, P=0.007). The patient age at baseline and treatment with co-administered carbamazepine, clobazam, and zonisamide significantly influenced the degree of weight fluctuation during VPA therapy among the patients with moderate ID (P<0.001, P<0.001, P=0.002, and P=0.028, respectively), whereas only patient age at baseline affected this parameter among the patients without moderate ID (P=0.022). Conclusion: The present findings suggest that the weight status should be carefully monitored in VPA-treated patients with moderate ID, especially those receiving other co-administered antiepileptic drugs that facilitate weight gain, such as carbamazepine. Keywords: overweight, weight status, obesity, antiepileptic drug, longitudinal analysis&nbsp

Aicardi-Goutières syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21

We have studied 23 children from 13 families with a clinical diagnosis of Aicardi-Goutières syndrome. Affected individuals had developed an early-onset progressive encephalopathy that was characterized by a normal head circumference at birth, basal ganglia calcification, negative viral studies, and abnormalities of cerebrospinal fluid comprising either raised white cell counts and/or raised levels of interferon-α. By means of genomewide linkage analysis, a maximum-heterogeneity LOD score of 5.28 was reached at marker D3S3563, with α=.48, where α is the proportion of families showing linkage. Our data suggest the existence of locus heterogeneity in Aicardi-Goutières syndrome and highlight potential difficulties in the differentiation of this condition from pseudo-TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus types 1 and 2) syndrome