What is the treatment and management approach for a child with Lennox-Gastaut syndrome?

Treatment and Management of Lennox-Gastaut Syndrome

Valproate is the recommended first-line treatment for newly diagnosed Lennox-Gastaut syndrome, followed by sequential addition of lamotrigine and then rufinamide if seizure control remains inadequate. 1, 2, 3

Initial Pharmacological Management

First-Line Therapy

• Valproate (sodium valproate) should be initiated as monotherapy for all patients with newly diagnosed LGS 1, 2, 3
• This recommendation is consistent across multiple expert consensus statements and represents the strongest evidence-based starting point 1, 3

Second-Line Adjunctive Therapy

If valproate monotherapy fails to control seizures:

1. Add lamotrigine as the first adjunctive agent 1, 2

   • Lamotrigine has FDA approval for LGS and demonstrated efficacy in controlled trials 2
   • Titrate slowly to minimize risk of serious rash

2. If seizures persist, add rufinamide as the second adjunctive agent 1, 2

   • Rufinamide is FDA-approved specifically for LGS and has shown efficacy in reducing drop attacks 4, 2, 3

Third-Line Adjunctive Options

When valproate plus two adjunctive agents fail, consider adding (in alphabetical order, as evidence does not clearly favor one over another):

• Cannabidiol (highly purified pharmaceutical grade) - FDA-approved for LGS with demonstrated efficacy 5, 1, 2
• Clobazam - FDA-approved with strong efficacy data, though benzodiazepine tolerance is a concern 6, 2
• Felbamate - FDA-approved but reserved due to risk of aplastic anemia and hepatotoxicity 2, 7
• Fenfluramine - FDA-approved with novel mechanism of action 1, 2
• Topiramate - FDA-approved with demonstrated efficacy in controlled trials 4, 2, 3

Critical caveat: Use no more than two antiseizure medications simultaneously whenever possible to minimize polypharmacy complications 1

Non-Pharmacological Interventions

These should be implemented in conjunction with (not instead of) pharmacological therapy:

Dietary Therapy

• Ketogenic diet should be considered early in the treatment course, particularly in younger children 6, 3, 7
• Evidence supports efficacy for seizure reduction in LGS 6, 7

Neuromodulation

• Vagus nerve stimulation (VNS) is an established option for drug-resistant LGS 6, 3, 7
• Can be considered when 2-3 appropriate medication trials have failed 6

Surgical Options

• Corpus callosotomy should be considered for patients with frequent drop attacks causing injury 1, 6, 3
• This is particularly effective for reducing atonic and tonic seizures that cause falls 6, 7

Special Management Considerations

Patients Evolving from Other Epilepsy Types

• Transition to valproate if not already prescribed, then follow the same algorithm as newly diagnosed LGS 1
• Many cases of LGS evolve from infantile spasms or other early-onset epilepsies 7

Established LGS in Older Patients

• Annual review by an experienced epileptologist is mandatory 1
• The transition from pediatric to adult care is a critical vulnerability period requiring structured handoff 6
• Adult neurologists may underdiagnose LGS due to evolution of clinical features and EEG patterns 6

Diagnostic Confirmation

• Brain MRI must be obtained to identify structural abnormalities, as perinatal events are the predominant etiological factors 8
• Early identification is critical because LGS is profoundly impairing with poor medication responsiveness 8

Comprehensive Management Beyond Seizures

Comorbidity Management

Address the following systematically:

• Cognitive impairment - Most patients develop moderate intellectual disability within years of onset 7
• Behavioral problems - Inattention, hyperactivity, and aggression are common 6, 7
• Sleep disturbances - Require specific evaluation and management 6
• Physical disability - Related to frequent falls and injuries from drop attacks 6

Quality of Life Optimization

• Educational and employment support must be integrated into the care plan 6
• Social disability requires multidisciplinary intervention 6
• Early intervention may improve mental and behavioral development, emphasizing the importance of prompt diagnosis and treatment initiation 8

Common Pitfalls to Avoid

• Do not delay non-pharmacological interventions - ketogenic diet and VNS should be considered relatively early, not as last resorts 6, 3
• Avoid excessive polypharmacy - more than two ASMs simultaneously rarely improves outcomes and increases adverse effects 1
• Do not use cannabis products other than FDA-approved pharmaceutical-grade cannabidiol (Epidiolex) - unregulated products lack quality control and efficacy data 5
• Recognize that complete seizure freedom is rarely achievable - treatment goals should focus on reducing drop attacks and improving quality of life rather than complete seizure elimination 6, 3