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Therapeutic efficacy of ACTH in symptomatic infantile spasms with hypsarrhythmia
1Division of Pediatric Neurology, University of Minnesota Medical School, Minneapolis, USA.
Insights
Early ACTH treatment for infantile spasms is crucial. Prompt therapy, especially for infants over 8 months, significantly improves outcomes and reduces developmental regression.
Area of Science:
- Pediatric Neurology
- Neonatal Medicine
- Pharmacology
Background:
- Infantile spasms (IS) with hypsarrhythmia are a severe epilepsy syndrome.
- Early diagnosis and treatment are critical for optimal neurodevelopmental outcomes.
- Adrenocorticotropic hormone (ACTH) is a primary treatment, but optimal dosing and timing remain debated.
Purpose of the Study:
- To evaluate the efficacy of varying ACTH dosages and treatment initiation times.
- To identify factors influencing treatment response in infants with symptomatic IS and hypsarrhythmia.
- To correlate treatment outcomes with age of onset and duration of untreated spasms.
Main Methods:
- Retrospective review of 26 infants diagnosed with symptomatic infantile spasms and hypsarrhythmia.
- Analysis of ACTH dosages, treatment initiation timing, and spasm cessation rates.
- Comparison of outcomes between responders and non-responders based on clinical and demographic data.
Main Results:
- 65% of infants achieved complete cessation of spasms with ACTH therapy.
- No significant difference in response rates was observed between different ACTH dosages or pre-treatment spasm duration.
- Favorable outcomes were strongly associated with later age of onset (>8 months) or treatment initiation within 1 month of spasm onset with adequate ACTH dosage (>80 U/m2).
- Delayed treatment (>2 months) was associated with a 57% non-response rate.
- Infants with early onset (<4 months) who did not respond had the worst prognoses, including developmental regression.
Conclusions:
- ACTH is effective for treating symptomatic infantile spasms, but outcomes depend more on age of onset and treatment timeliness than dosage.
- Prompt initiation of ACTH therapy, particularly for infants with later onset, is key to improving seizure control and neurodevelopmental trajectories.
- Non-response in infants with early onset (<4 months) indicates a poorer prognosis, highlighting the need for aggressive early intervention.
Abstract:
The records of twenty-six infants with both symptomatic infantile spasms and classic hypsarrhythmia were reviewed to determine the efficacy of various ACTH dosages and time of initiation of therapy. Mean age of infantile spasm onset was 6.4 months. Most patients (13) had sustained perinatal hypoxic-ischemic insults. Seventeen patients (65%) had complete cessation of spasms. Between these responders and the 9 nonresponders there was no difference in duration of spasms prior to treatment (2.6 and 2.0 months) or mean ACTH dose (87.4 and 84.5 U/m2, respectively). Infants treated with high-dose ACTH (> 100 U/m2) did not have an improved response rate. The most favorable outcomes were associated with spasm onset at > 8 months of age (all of whom were responders, regardless of dose) or when treatment was started within 1 month of onset of infantile spasms with > 80 U/m2 ACTH (88% responders). Infants treated more than 2 months after onset often did not respond (57%) regardless of dose. Nonresponders with spasm onset at < 4 months of age had the worst prognoses; all had poorly controlled seizures and regressed developmentally. Although all infants in the study were neurologically abnormal, development either improved or did not deteriorate in most responder infants following spasm resolution and one-half remained seizure free. Nonresponder infants continued to have infantile spasms or other seizure types. These data suggest that ACTH is valuable in the treatment of significantly impaired infants with symptomatic infantile spasms, but the most important determinants of outcome may be age of onset and rapidity of treatment rather than dosage.