Putative neurotransmitter abnormalities in infantile spasms: cerebrospinal fluid neurochemistry and drug effects.
The neuropharmacologic basis of infantile spasms and the mechanism by which adrenocorticotropic hormone (ACTH) exerts its therapeutic effects are unknown. This is a critical review of cerebrospinal fluid neurotransmitters or their metabolites in infantile spasms before and during treatment with ACTH, and of clinical drug trials with drugs acting on neurotransmission. Cerebrospinal fluid studies have shown lower gamma-aminobutyric acid (GABA), ACTH, and 5-hydroxyindoleacetic acid concentrations in patients with infantile spasms compared to controls, elevated lysine and glutamate, variable or no differences in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, norepinephrine, corticotropin-releasing hormone, and beta-endorphin. Chronic treatment with ACTH in infantile spasms reduces cerebrospinal fluid GABA, beta-endorphin, and somatostatin, increases norepinephrine and tyrosine, and has variable or no effect on homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, histamine, and tryptophan. Small therapeutic trials with drugs that act through different neurotransmitters such as methysergide, alpha-methylparatyrosine, various benzodiazepine agonists, and vigabatrin lend some support to a role for GABA and monoamines in infantile spasms. These data, though promising, provide only a hint of potential neurotransmitter disturbances, and more basic and clinical data are needed.
Pranzatelli
M R
MR
Department of Neurology, George Washington University, Washington, DC.
D000324:Adrenocorticotropic Hormone / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D013036:Spasms, Infantile / Q000134:cerebrospinal fluid* / Q000188:drug therapy
D000927:Anticonvulsants; D018377:Neurotransmitter Agents; D000324:Adrenocorticotropic Hormone