title: Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.
abstract: Apparent brain atrophy has been frequently observed at CT and MRI after ACTH therapy in patients with infantile spasms. There are several hypotheses to explain ACTH-induced brain shrinkage: 1) a catabolic effect of ACTH on brain tissue, 2) a mineralocorticoid effect resulting in a loss of water and 3) an increase in cerebrospinal fluid (CSF) pressure compressing the brain. An average of 0.21 +/- 0.03 mg/kg of ACTH was administered to nine patients over a period of 14 to 17 days. Water content and concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline (Cho) were measured before, immediately after, and several months after the ACTH therapy by using in-vivo 1H magnetic resonance spectroscopy (MRS). Only NAA concentration exhibited a significant change during the study (6.6 +/- 1.5 mmol/kg, 5.4 +/- 1.1, and 7.0 +/- 1.5, p = 0.017). There was no significant change in Cr + PCr, in Cho, or in water content. These data suggest catabolic effects of ACTH on brain tissue, such as cell loss, decrease in NAA synthesis in mitochondria, and leakage of NAA from cell membrane.
authors.affiliation: Department of Radiological Technology, College of Medical Technology, Nagoya University.
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Furune
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: O
authors.initials: O
authors.lastname: Kitou
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Negoro
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000009:adverse effects*; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000009:adverse effects*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000187:drug effects; D001284:Atrophy; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002675:Child, Preschool; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011358:Product Surveillance, Postmarketing; D013036:Spasms, Infantile / Q000188:drug therapy* / Q000201:enzymology*; D013997:Time Factors; D014867:Water / Q000032:analysis
chemical_list: D000927:Anticonvulsants; D014867:Water; D001224:Aspartic Acid; D000324:Adrenocorticotropic Hormone; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline