Cerebrospinal fluid purine metabolite and neuron-specific enolase concentrations after febrile seizures.

If febrile seizures cause significant compromise of neuronal metabolism (whether permanent or reversible), this should be reflected in an increase in the cerebrospinal fluid concentrations of neuron-specific enolase (NSE) and/or adenosine triphosphate (ATP) breakdown products. In the present study, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and NSE concentrations were determined in the cerebrospinal fluid of 90 children 1 h after febrile seizure (73 simple febrile seizures (SFS); 17 complex febrile seizures (CFS)), and in a control group of 160 children. There was no statistically significant difference between the SFS group and the control group for any of the substances determined, suggesting that SFS neither significantly depletes neuronal ATP concentration, nor significantly increases NSE concentration; thus, SFS do not appear to constitute a threat to neuronal integrity. However, patients with CFS showed significantly lower IMP concentrations and significantly higher adenine concentrations than controls, and significantly higher AMP concentrations than SFS patients; these results suggest that CFS may affect energy metabolism in the brain. However, NSE concentrations were normal in the cerebrospinal fluid of both SFS and CFS patients, suggesting that neither type of seizure causes significant neuronal damage, at least early after the seizure.

Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency.

Adenylosuccinate lyase (ADSL) deficiency (MIM 103050) is an autosomal recessive inborn error of purine synthesis characterized by the accumulation in body fluids of succinylaminoimidazolecarboxamide (SAICA) riboside and succinyladenosine (S-Ado), the dephosphorylated derivatives of the two substrates of the enzyme. Because ADSL-deficient patients display widely variable degrees of psychomotor retardation, we have expressed eight mutated ADSL enzymes as thioredoxin fusions and compared their properties with the clinical and biochemical characteristics of 10 patients. Three expressed mutated ADSL enzymes (M26L, R426H and T450S) were thermolabile, four (A2V, R141W, R303C and S395R) were thermostable and one (del206-218), was inactive. Thermolabile mutations decreased activities with SAICA ribotide (SAICAR) and adenylosuccinate (S-AMP) in parallel, or more with SAICAR than with S-AMP. Patients homozygous for one of these mutations, R426H, displayed similarly decreased ADSL activities in their fibroblasts, S-Ado:SAICA riboside ratios of approximately 1 in their cerebrospinal fluid and were profoundly retarded. With the exception of A2V, thermostable mutations decreased activity with S-AMP to a much more marked extent than with SAICAR. Two unrelated patients homozygous for one of the thermostable mutations, R303C, also displayed a much more marked decrease in the activity of fibroblast ADSL with S-AMP than with SAICAR, had S-Ado:SAICA riboside ratios between 3 and 4 in their cerebrospinal fluid and were mildly retarded. These results suggest that, in some cases, the genetic lesion of ADSL determines the ratio of its activities with S-AMP versus SAICAR, which in turn defines the S-Ado:SAICA riboside ratio and the patients' mental status.

Concentrations of nucleotides, nucleosides, purine bases and urate in cerebrospinal fluid of children with meningitis.

The release of agents mediating inflammation in meningitis may bring about neuronal hypoxia, under which circumstances ATP concentrations decrease and its degradation products increase and are released into the cerebrospinal fluid. In this study of alterations in neuronal energy metabolism in meningitis, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high performance liquid chromatography in the cerebrospinal fluid of 54 children aged between 1 month and 13 years suffering from meningitis (25 viral, 24 bacterial and 5 tuberculous cases) and 63 controls. Compared to the controls, patients with viral meningitis exhibited high concentrations of IMP, adenosine, guanosine, adenine, guanine and xanthine; patients with bacterial meningitis exhibited high concentrations of IMP, inosine, guanosine, adenosine, hypoxanthine, xanthine and urate; and patients with tuberculous meningitis exhibited high concentrations of AMP, guanosine, xanthine and urate. Viral and bacterial cases did not differ significantly for any of the metabolites studied. AMP and urate concentrations were significantly higher in patients with tuberculous cases compared with viral or bacterial meningitis cases.

Purine metabolites and pyrimidine bases in cerebrospinal fluid of children with simple febrile seizures.

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and pyrimidine bases were determined in the CSF of 18 children after simple febrile seizures and in a control group. There was no statistically significant difference between the two groups for any of these metabolites. This suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuron adenosine triphosphate ATP levels.

[Cyclic adenosine monophosphate in the cerebrospinal fluid of patients with liver disease (author's transl)]. / Adenosín monofosfórico cíclico en líquido cefalorraquídeo de enfermos hepáticos.

The concentration of adenosine 3':5'-cyclic monophosphate in the spinal fluid of ten patients with liver dysfunction was analyzed. Ages of the patients ranged from 31 to 75 years. The state of consciousness varied between normality and stupor. After a liver biopsy the diagnoses were as follows: cirrhosis in six cases, porphyria cutanea tarda in one case, hepatic metastases in two cases and Wilson's disease in one case. Mean values in these patients (22.91 +/- 4.18 pM/ml) have been significantly greater (p less than 0.0005) than those in ten control individuals (15.55n control individuals (15.44 +/- 3.66 pM/ml). Values corresponding to two patients in coma were still higher (52.62 and 36.50 pM/ml respectively). A previous lumbar puncture carried out in one of these patients when he was conscious showed a figure of 23 pM/ml. These results suggest a progressive rise of cyclic adenosine monophosphate in the spinal fluid in relation to clinical impairment, and may indicate a similar behaviour for this nucleotide to that of tryptophan, as reported by other authors. These findings point toward the role of the alteration of neurotransmitters in the pathogenesis of hepatic coma.

Phosphodiesterase and adenyl-cyclase activities in the cerebral cotex of the aging rat.

In an effort to determine the factors responsible for the four-fold decrease in cyclic-AMP content of the rat cerebral cortex, observed to occur between the ages of 3 and 6 months, studies were performed on adenyl-cyclase and phosphodiesterase, the cyclic-AMP synthesizing and hydrolyzing enzymes. The activities and kinetic characteristics were determined for both enzymes as obtained from the cerebral cortex of rats ranging in age from one to 24 months. No age dependence was observed either in adenyl-cyclase activity, assayed with or without fluoride ion, or in phosphodiesterase activity. It was concluded that age related changes in factors other than the direc levels of these enzymes underlie the age related decline in cortical cyclic-AMP levels.