Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.
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.
Maeda
H
H
Department of Radiological Technology, College of Medical Technology, Nagoya University.
Furune
S
S
Nomura
K
K
Kitou
O
O
Ando
Y
Y
Negoro
T
T
Watanabe
K
K
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
D000927:Anticonvulsants; D014867:Water; D001224:Aspartic Acid; D000324:Adrenocorticotropic Hormone; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline