Lecture Notes

Role of Vigabatrin

• Indication:
  • Approved treatment for infantile spasms, especially in TS-associated IS.

  Challenges in Studying Medications for IS

  • Inhibits GABA-transaminase, increasing GABA levels in the brain.

  Proven Treatments for IS

  1. Adrenocorticotropic Hormone (ACTH):

     • One of the most commonly used therapies for IS.
     • Exact mechanism unclear but hypothesized to involve the brain-adrenal axis:
       • Downregulates excessive corticotropin-releasing hormone (CRH) expression in the brain.
       • CRH overexpression may cause spasms in IS.
     • Delivered via injection, which adds complexity to its use.

  2. Vigabatrin:

     • Approved in the US for IS treatment (available in the UK and Ireland since 1989).
     • Mechanism of Action:
       • Suicide substrate inhibiting gamma-aminobutyric acid-transaminase (GABA-T).
       • Inhibits the breakdown of GABA → Increases GABA concentrations in the brain → Suppresses seizures.
     • Pharmacological Advantages:
       • Does not strongly induce or inhibit hepatic enzymes.
       • Virtually unbound to serum protein → Minimal drug interactions.
       • Can be taken without regard to meals.
       • High solubility → Achieves bioavailability up to 70%.
     • Reported Drug Interaction:
       • May decrease phenytoin levels without leading to breakthrough seizures.

  Insufficient Evidence for Other Medications

  • Effective in controlling spasms and normalizing EEG in many cases.
  • Particularly beneficial in symptomatic IS with tuberous sclerosis.

  Comparison of ACTH and Vigabatrin

  • Risk of visual field defects with long-term use.
  • Requires regular ophthalmologic monitoring.

  Clinical Trials Overview

  1. Vigevano et al. (Original Comparative Study with ACTH)

  • Should be considered in cases of treatment-resistant IS.
  • Often used alongside ACTH or corticosteroids for synergistic effects.

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