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ACTH activates rapid eye movement-related phasic inhibition during REM sleep in patients with infantile spasms
J Kohyama1, M Shimohira, N Tanuma
1Department of Pediatrics, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Insights
Adrenocorticotropic hormone (ACTH) reduces infantile spasms (IS) by decreasing phasic chin muscle activity (PCMA) and the phasic inhibition index (PII). This dual action, mediated partly by corticosteroids, offers a potential therapeutic mechanism for IS.
Area of Science:
- Neuroscience
- Endocrinology
- Pediatric Neurology
Background:
- Phasic inhibition index (PII) quantifies simultaneous phasic chin muscle activity (PCMA) and rapid eye movement (REM) bursts during REM sleep (REMS).
- PII serves as a prognostic indicator in infantile spasms (IS).
Purpose of the Study:
- To investigate the impact of adrenocorticotropic hormone (ACTH) on REMS components, specifically PII, in patients with IS.
- To elucidate the mechanisms by which ACTH influences PII and PCMA.
Main Methods:
- Analysis of REMS parameters, including PII and PCMA, in 18 IS patients before and after ACTH treatment.
- Examination of corticosteroid (CS) effects on PII and PCMA in patients with congenital adrenal hyperplasia (CAH) and nephrotic syndrome (NS).
Main Results:
- ACTH treatment led to a decrease in both PII and PCMA in IS patients.
- In CAH patients, physiological CS doses normalized elevated ACTH and increased PII.
- Therapeutic CS doses in NS patients suppressed PCMA but did not alter PII.
Conclusions:
- ACTH exerts a dual effect: suppressing PCMA via corticosteroids and directly reducing PII.
- These combined actions suggest a potential mechanism for ACTH in resolving IS.
Objectives:
Phasic inhibition index (PII) is the rate of the simultaneous occurrence of phasic chin muscle activity (PCMA) and rapid eye movement bursts during rapid-eye-movement sleep (REMS). In naive patients with infantile spasms (IS), the PII value was found to reflect their prognosis. We studied the effects of adrenocorticotropic hormone (ACTH) on REMS components including PII in IS.
Methods:
REMS parameters were examined in 18 IS patients before and after ACTH treatment. The effects of corticosteroids (CSs) were examined in 3 patients with congenital adrenal hyperplasia (CAH) and 3 with nephrotic syndrome (NS).
Results:
ACTH decreased PII and PCMA in IS patients. In CAH patients, physiological doses of CSs corrected the increased intrinsic ACTH level and increased PII. In NS patients, therapeutic doses of CSs suppressed PCMA without affecting PII.
Conclusion:
ACTH suppressed PCMA through CSs, and reduced PII directly. ACTH was hypothesized to eliminate IS through these dual modes of action.