Reduced ACTH, while normal beta-endorphin CSF levels in early epileptic encephalopathies
Related Experiment Videos
Insights
Infantile spasms in babies may stem from a deficiency in adrenocorticotropic hormone (ACTH) and altered neuropeptide pathways. This study found lower ACTH levels in infants with these seizures, suggesting a potential central cause.
Area of Science:
- Neuroendocrinology
- Pediatric Neurology
- Epileptology
Background:
- Adrenocorticotropic hormone (ACTH) and opioids have opposing effects on seizures.
- Infantile spasms with hypsarhythmia represent an early-onset epileptic encephalopathy.
- Neuropeptide pathways are implicated in seizure activity.
Purpose of the Study:
- To investigate cerebrospinal fluid (CSF) levels of ACTH and beta-endorphin (beta-EP) in infants with infantile spasms.
- To explore the potential role of ACTH deficiency and neuropeptide imbalance in the etiology of these seizures.
Main Methods:
- Measurement of CSF ACTH and beta-EP levels in 6 infants (4-8 months) with infantile spasms and 8 age-matched controls.
- Comparison of beta-EP/ACTH ratios between patients and controls.
- Analysis of a patient in remission after ACTH treatment.
Main Results:
- CSF beta-EP levels were comparable between patients and controls.
- Infants with infantile spasms exhibited significantly reduced CSF ACTH levels compared to controls (p < 0.01).
- The beta-EP/ACTH ratio was elevated in patients, normalizing after ACTH treatment in a patient in remission.
Conclusions:
- Findings support the hypothesis that some infantile seizures may result from central ACTH deficiency.
- An imbalance in neuropeptidergic pathways could contribute to the pathogenesis of infantile spasms.
- These results suggest a potential neuroendocrine basis for certain early-onset epileptic encephalopathies.
Abstract:
Since ACTH and the opioids display opposite effects on experimentally-induced seizures, cerebrospinal fluid (CSF) levels of ACTH and beta-endorphin (beta-EP) were measured in 6 children (4-8 months) affected by infantile spasms with hypsarhythmia, an idiopathic early onset encephalopathy, and in 8 age-matched controls. beta-EP levels in the patients (76.3 +/- 14.7 fmol/ml, M +/- SD) did not differ from those in controls (109.8 +/- 42.7) while babies with epileptic encephalopathy showed reduced ACTH levels in the CSF (3.8 +/- 1.5) as compared to controls (9.0 +/- 3.7, p less than 0.01). This resulted in an increased beta-EP/ACTH ratio. Another patient previously treated with ACTH showed a normal CSF level of ACTH (9.0) with a normal beta-EP/ACTH ratio while in clinical and EEG remission. These results are consistent with the hypothesis that some infantile seizures unrelated to brain injuries could originate from an ACTH deficiency at central level and/or an imbalance of neuropeptidergic pathways.