What is the best treatment for Idiopathic Epileptic Seizure Syndrome (IESS) in children?

Treatment of Infantile Epileptic Spasms Syndrome (IESS) in Children

ACTH (adrenocorticotropic hormone) is the first-line treatment for IESS, with a clinical remission rate of approximately 65% at two weeks and superior electrographic outcomes compared to oral corticosteroids or vigabatrin. 1

First-Line Treatment Options

The standard first-line therapies for IESS include ACTH, oral corticosteroids (prednisolone), or vigabatrin 2, 1. However, the evidence strongly favors ACTH as the optimal initial choice:

ACTH Protocol

• ACTH achieves 65% clinical remission at two weeks and 40% continued response at three months 1
• EEG improvement at three months occurs in 74% of ACTH-treated patients versus 20% with vigabatrin 1
• For children with trisomy 21 and IESS specifically, ACTH demonstrates superior efficacy for both clinical and electrographic outcomes 1

Oral Corticosteroid Alternative

If ACTH is unavailable or insurance barriers exist (which affect 72% of treatment centers 2), oral corticosteroids are an acceptable alternative:

• Intravenous dexamethasone or methylprednisolone for 3-5 consecutive days, followed by oral prednisone 2 mg/kg/day for 60-90 days with tapering over 1-2 months 3
• High-dose prednisone (4 mg/kg/day for 9-11 days) shows no significant advantage over usual-dose (2 mg/kg/day) regimens, with similar seizure freedom rates of 55.6% versus 51.9% at days 13-14 3
• Oral corticosteroids achieve 33% clinical remission at two weeks and 83% EEG improvement at three months 1

Vigabatrin Considerations

• Vigabatrin should be reserved for cases where hormonal therapy is contraindicated or for children with tuberous sclerosis complex 2, 1
• Vigabatrin shows lower efficacy with only 40% clinical remission at two weeks and 20% EEG improvement at three months 1

Sequential vs. Combination Therapy

Most centers (63%) recommend sequential therapy, trying one agent before adding another, rather than immediate combination therapy 2. This approach allows assessment of individual drug efficacy and minimizes polypharmacy-related adverse effects. Only 17% of major epilepsy centers recommend upfront combination therapy with both hormonal treatment and vigabatrin 2.

Monitoring and Response Assessment

Early Response Indicators

• Assess clinical spasms remission at two weeks post-treatment initiation 1
• Obtain EEG within one month of starting ACTH therapy 4
• Patients showing epileptic discharge in the parieto-occipital region within one month post-ACTH have high risk of relapse 4

Three-Month Evaluation

• Reassess clinical spasms remission and EEG for hypsarrhythmia resolution 1
• Only 32% of children maintain continued clinical response at three months across all first-line treatments 1

Treatment-Refractory Cases

For persistent epileptic spasms after first-line therapy, 54% of centers provide specific recommendations 2:

Third-Line Options

• Ketogenic diet is mentioned in 58% of treatment pathways 2
• Epilepsy surgery evaluation is recommended in 46% of protocols 2
• Consider levetiracetam as adjunctive therapy, starting at 20 mg/kg/day in two divided doses (10 mg/kg BID), increasing by 20 mg/kg increments every 2 weeks to a maximum of 60 mg/kg/day 5

Adverse Event Management

Gastrointestinal prophylaxis and blood pressure monitoring are the most common side-effect mitigation strategies, implemented in 79% of treatment centers 2. The usual-dose and high-dose corticosteroid regimens show similar adverse event profiles with comparable tolerance 3.

Prognostic Factors

Etiology-Based Outcomes

• Treatment response at days 13-14 and days 14-42 is similar across different etiological subgroups 3
• Unknown etiology shows significantly higher resolution of hypsarrhythmia compared to structural or genetic causes 3
• IESS with periventricular leukomalacia has particularly poor long-term prognosis, with only 2 of 7 initial ACTH responders remaining seizure-free at final follow-up 4

Long-Term Outcomes

• Patients achieving normal EEG within one month post-ACTH therapy have better long-term seizure freedom 4
• Median age at IESS onset is 7 months, with treatment typically initiated around 9 months 4

Common Pitfalls to Avoid

• Do not delay treatment while awaiting insurance authorization for ACTH—initiate oral corticosteroids immediately if ACTH access is delayed, as 72% of centers report insurance barriers 2
• Do not use high-dose prednisone (4 mg/kg/day) routinely—it offers no advantage over usual-dose (2 mg/kg/day) and may increase adverse effects 3
• Do not choose vigabatrin as first-line therapy except for tuberous sclerosis complex—it has significantly lower efficacy than hormonal treatments 1
• Do not assume initial response predicts long-term outcome—58% of IESS patients with periventricular leukomalacia initially respond to ACTH, but most relapse 4