What are the diagnostic criteria and first-line treatments for Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) in children?

Epileptic Encephalopathy with Electrical Status Epilepticus in Sleep (ESES)

Diagnostic Criteria

ESES is diagnosed when a child presents with epilepsy, acquired cognitive or behavioral regression, and a characteristic EEG pattern showing continuous spike-and-wave discharges occupying ≥85% of non-rapid eye movement sleep. 1

Core Diagnostic Features:

• EEG Pattern: Continuous spike-and-wave activity during ≥85% of non-REM sleep, documented by overnight EEG, 24-hour ambulatory EEG, or minimum 3-hour video EEG 1, 2

• Clinical Manifestations: Acquired impairment in cognition, behavior, language, or motor function that develops after a period of normal or near-normal development 1

• Epileptic Seizures: Various seizure types may be present, though seizure control does not correlate with cognitive outcome 3

Clinical Subtypes:

• Atypical Rolandic Epilepsy: 67% achieve favorable cognitive outcomes with treatment 3
• Landau-Kleffner Syndrome: 33% regain pre-ESES cognitive function 3
• Symptomatic Etiology: Only 19% return to baseline cognitive level 3

Prognostic Indicators:

Unfavorable cognitive outcomes are predicted by younger age at ESES diagnosis, lower IQ at diagnosis, and lack of treatment response on EEG. 3 The presence of structural brain abnormalities and abnormal development before ESES onset also predict worse outcomes 1

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First-Line Drug Treatment

Corticosteroids represent the most effective first-line treatment for ESES, with 81% improvement rates in cognition or EEG, significantly superior to other medical therapies. 1

Treatment Hierarchy Based on Efficacy:

1. Corticosteroids (First-Line)

• Overall improvement rate: 81% (75% in consecutively reported cases) 1
• Most effective medical therapy for both EEG normalization and cognitive improvement 1
• Should be initiated promptly given the time-sensitive nature of cognitive recovery 3

2. Benzodiazepines (Second-Line)

• Overall improvement rate: 68% (59% in consecutively reported cases) 1
• Clonazepam combined with levetiracetam shows particular efficacy: 93% (14/15) achieved significant EEG improvement or normalization 2
• Short-term clonazepam (2 months) added to levetiracetam resulted in controlled seizures and normalized EEG in children who failed levetiracetam monotherapy 2

3. Levetiracetam (Alternative First-Line or Add-On)

• Seizure control: 63.5% became seizure-free or had remarkable reduction 4
• EEG improvement: 56.2% achieved disappearance of ESES pattern 4
• Dosing: 30-50 mg/kg/day divided twice daily 4, 5
• Better efficacy in idiopathic cases (64.3% EEG response) versus symptomatic cases (45.2%) 4
• Well-tolerated with minimal side effects (fatigue and anorexia most common) 4, 5
• Critical limitation: Only 45% EEG response rate overall, with 25% relapse rate among initial responders 5

4. Valproate + Ethosuximide (Traditional Combination)

• Treatment response: Only 18% (3/17) achieved abolition of ESES 3
• Significantly inferior to steroids and benzodiazepines 1
• May be considered when other options are contraindicated, but should not be first-line 3

5. Other Antiepileptic Drugs

• Overall improvement: 49% (34% in consecutively reported cases) 1
• Least effective medical option 1

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Recommended Treatment Algorithm

Step 1: Initiate Corticosteroids

• Begin with corticosteroid therapy as first-line treatment given 81% improvement rate 1
• Monitor with repeat overnight EEG at 1 month and 6 months 2

Step 2: Add Benzodiazepines if Inadequate Response

• Add clonazepam if steroids alone provide insufficient EEG or cognitive improvement 1
• Consider levetiracetam 30-50 mg/kg/day combined with short-term clonazepam (2 months) as this combination achieved 93% EEG improvement 2

Step 3: Consider Levetiracetam Monotherapy

• May be used as initial therapy in mild cases or when steroids are contraindicated 4, 5
• Expect EEG response within 3-4 months; if no improvement, escalate therapy 5
• Critical caveat: Response significantly associated with shorter ESES duration, later age at onset, and idiopathic etiology 5

Step 4: Surgical Evaluation for Non-Responders

• Surgery achieves 90-93% improvement rates in appropriately selected patients 1
• Consider early surgical evaluation in patients with focal structural lesions who fail medical therapy 1
• 50% (8/16) of medical non-responders in one series underwent epilepsy surgery 3

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Critical Treatment Principles

Treatment response must be documented with repeat overnight EEG recordings, not just clinical seizure control. 3 Seizure freedom does not guarantee cognitive recovery; EEG normalization is the therapeutic target 3, 1

Early treatment initiation is essential. Younger age at ESES diagnosis predicts worse cognitive outcomes, emphasizing the need for prompt aggressive therapy 3

Most children (69%) will experience permanent cognitive impairment despite treatment. 3 Realistic counseling about prognosis is necessary, particularly for symptomatic cases and those with delayed treatment response 3

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Common Pitfalls to Avoid

• Do not rely on seizure control alone as a treatment endpoint—EEG normalization and cognitive function are the critical outcomes 3

• Do not delay treatment while attempting multiple antiepileptic drug trials—steroids or benzodiazepines should be initiated early given their superior efficacy 1

• Do not assume levetiracetam monotherapy will be sufficient—only 45% achieve EEG improvement, and 25% of initial responders relapse 5

• Do not overlook surgical candidacy—surgery has the highest success rate (90-93%) and should be considered early in focal symptomatic cases 1

• Do not use valproate + ethosuximide as first-line therapy—this combination has only 18% efficacy and is significantly inferior to steroids 3, 1