Abstract *Miki Inutsuka, †Yoko Ohtsuka, †Kousuke Nakano, †Junri Hattori, *Katsuhiro Kobayashi, and †Eiji Oka Department of Child Neurology, *Okayama University Medical School ; and †Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan . Purpose: To elucidate the effect of treatment of epilepsy with electrical status epilepticus during slow sleep (ESES) and factors related to the response to treatment. Methods: We studied 26 patients with ESES who were admitted to Okayama University Hospital (age range, 2y0m to 9y7m). Patients were treated with one or more of the following therapies: (a) high-dose valproate (VPA) therapy (plasma level, >100 μg/ml), (b) a combination therapy of VPA and ethosuximide (ESM), (c) a short cycle of high-dose diazepam (DZP; 0.54–1 mg/kg/day, orally or intrarectally for 6–14 days), and (d) synthetic adrenocorticotropic hormone (ACTH) therapy (Cortrosyn-Z; 0.01–0.036 mg/kg/day, intramuscularly, for 11–43 days). Basically, we started treatment with high-dose VPA therapy. When this failed or yielded adverse side effects, we tried the combination therapy of VPA and ESM. When both were unsuccessful, we tried a short cycle of high-dose DZP or synthetic ACTH therapy. All patients were followed up for ≥2 years. We also investigated response patterns to treatments and mental outcome in each patient. Results: Treatment effects: Regarding the initial effects, treatment was defined as effective when continuous spike–waves during slow-wave sleep (CSWSs) were suppressed (≥1 month with markedly decreased or no diffuse spike-waves during slow-wave sleep). In terms of initial effect, high-dose VPA was effective in 12 (50%) of 24 trials; combination therapy with VPA and ESM in six (43%) of 14 trials; a short cycle of high-dose DZP, in six (75%) of eight trials; and synthetic ACTH, in three (43%) of seven trials. However, CSWSs recurred within 1 year of treatment in two patients treated with high-dose VPA, in four treated with a short cycle of high-dose DZP, and in all three treated with synthetic ACTH. Response patterns and mental outcomes: Subjects were divided into two groups: 15 patients with favorable EEG response to the initial treatment maintained throughout the clinical course (group A), and 11 patients with no favorable EEG response to the initial treatment, or deterioration after an initial favorable response (group B). All patients except one in group A were treated with high-dose VPA or the combination therapy of VPA and ESM or both. All patients except two in group B were treated with a short cycle of high-dose DZP or synthetic ACTH after the failure of high-dose VPA or both or the combination therapy of VPA and ESM or both. Comparing these two groups, ages at onset of ESES were significantly lower in group B (p = 0.0009). Organic brain lesions such as brain malformations were seen more often in group B. Mental deterioration after the onset of ESES was observed significantly more often in group B (p = 0.037). Regarding mental outcome, patients with normal mentality or slight mental retardation predominated in group A, whereas those with severe mental retardation were found only in group B. Conclusions: Remission of ESES was achieved in approximately half of the patients treated with high-dose VPA therapy or combination therapy with VPA and ESM or both. Even when these treatments were ineffective, a short cycle of high-dose DZP or synthetic ACTH therapy was effective in most cases. However, the effects of the latter two treatments were only temporary. Group B was characterized by early-onset patients associated with organic brain lesions. These patients responded poorly to treatment and consequently had mental deterioration and poor mental outcomes. Thus response to ESES treatment may be related to the underlying organic brain lesion(s). To prevent poor mental outcome, we believe that it is critical to achieve remission as early as possible by using intensive treatment.
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