What is the initial approach to treating West syndrome?

Initial Approach to West Syndrome

Vigabatrin is the first-line treatment for West syndrome, initiated at 50 mg/kg/day and titrated to 100-150 mg/kg/day over 7 days, with spasm cessation expected within 14 days in responders. 1

Immediate Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with:

• EEG demonstrating hypsarrhythmia (the characteristic chaotic, high-amplitude pattern) 2
• Clinical documentation of infantile spasms (clusters of brief flexor/extensor spasms, typically occurring upon awakening) 2
• Brain MRI to identify structural etiologies (cortical malformations, tuberous sclerosis, hypoxic-ischemic injury) 2, 3
• Genetic and metabolic testing to classify etiology as cryptogenic, symptomatic, or idiopathic 2

First-Line Treatment Algorithm

Vigabatrin Dosing Protocol

• Start at 50 mg/kg/day divided twice daily 1
• Titrate over 7 days to 100-150 mg/kg/day (maximum dose demonstrated effective in clinical trials) 1
• Assess response at 14 days: If spasm-free for 7 consecutive days with EEG confirmation showing resolution of hypsarrhythmia, continue treatment 1
• Continue vigabatrin for 6 months total duration in responders, based on post-hoc analysis showing no recurrence after this treatment period 1

Expected Response Rates

• High-dose vigabatrin (100-148 mg/kg/day) achieves spasm freedom in 15.9% of patients within 14 days 1
• Low-dose vigabatrin (18-36 mg/kg/day) achieves spasm freedom in only 7.0%, making high-dose the preferred approach 1
• Overall response rate to vigabatrin as first-line therapy is approximately 26% in mixed populations 4

Second-Line Treatment: ACTH

If spasms persist after 14-15 days of vigabatrin at 150 mg/kg/day, switch to ACTH or corticosteroids. 3

ACTH Dosing Strategy

• For cryptogenic West syndrome: Start with low-dose ACTH 3-6 IU/kg/day 4, 5
• For symptomatic West syndrome: Use 6-12 IU/kg/day 5
• Treat for 2 weeks, then taper if response is achieved 2
• High doses are not more effective than low doses but cause significantly more side effects 4

Alternative Corticosteroid Option

• Oral prednisolone 40-60 mg/day for 14 days is effective and better tolerated than high-dose ACTH 2

Critical Monitoring Requirements

For Vigabatrin

• Baseline ophthalmologic examination (including visual field testing if possible) within 4 weeks of starting treatment 1
• Repeat ophthalmologic examination every 3 months during therapy 1
• Final examination 3-6 months after discontinuation 1
• Visual field defects occur in 18-34% of infants, most frequently with treatment duration >6 months 2, 3

For ACTH/Corticosteroids

• Monitor blood pressure (arterial hypertension is dose-related) 5, 3
• Monitor for Cushing syndrome (occurs universally with ACTH) 3
• Monitor for cardiac hypertrophy (dose-related complication) 5
• Monitor for cerebral ventricle dilatation (dose-related) 5
• One death from acute gastric bleeding has been reported during ACTH treatment 3

Etiology-Based Prognostic Considerations

Cryptogenic West Syndrome

• All cryptogenic cases respond to low-dose ACTH (3-6 IU/kg/day) within 2-3 weeks 4
• Normal psychomotor development is expected in 50% of cryptogenic cases 3

Symptomatic West Syndrome

• Only 50% of symptomatic cases respond to ACTH 4
• 76.2% develop severe psychomotor retardation regardless of seizure control 3
• 42.8% develop chronic epilepsy after West syndrome resolves 3
• 14.2% progress to Lennox-Gastaut syndrome 3

Tuberous Sclerosis

• Initial response rate to ACTH is 73% in tuberous sclerosis patients 4
• Vigabatrin is equally effective in this subgroup 4

Common Pitfalls to Avoid

• Do not delay treatment beyond diagnosis: Shorter lag time to treatment is essential for better neurodevelopmental outcomes 2
• Do not use low-dose vigabatrin (<100 mg/kg/day): The efficacy difference between low and high doses is statistically significant 1
• Do not continue vigabatrin beyond 6 months in responders: This increases risk of irreversible visual field defects without additional benefit 1, 2
• Do not use high-dose ACTH routinely: Low doses are equally effective with fewer severe complications 4, 5
• Do not assume vigabatrin failure means ACTH failure: Some non-responders to vigabatrin will respond to ACTH 4, 3

Alternative Therapies for Refractory Cases

If both vigabatrin and ACTH fail:

• Topiramate shows promise in systematic reviews 6
• Ketogenic diet demonstrates efficacy in refractory cases 6
• Levetiracetam, zonisamide, or sodium valproate with benzodiazepines (clonazepam or nitrazepam) may be considered 6