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# Lennox-Gastaut Syndrome (LGS)
## Overview
Lennox-Gastaut syndrome is a severe-early onset developmental and epileptic encephalopathy characterized by multiple seizure types (tonic, atonic, absence), slow spike-and-wave EEG patterns, and cognitive impairment. Treatment is often polytherapeutic and rarely achieves complete seizure freedom.
## Primary Indications
Adjunctive therapy for seizures associated with LGS. Commonly FDA-approved agents include: Clobazam, Rufinamide, Topiramate, Lamotrigine, Felbamate, and Cannabidiol (CBD).
## Adult Dosing
* **Clobazam:** Start 5–10 mg/day; titrate to 20 mg/day. Max: 40 mg/day.
* **Rufinamide:** Start 400–800 mg/day in two divided doses; titrate by 400–800 mg every 2 days. Max: 3200 mg/day.
* **Topiramate:** Start 25 mg/day; titrate slowly by 25–50 mg/week. Target: 200–400 mg/day.
* **Cannabidiol (CBD):** Start 2.5 mg/kg BID (5 mg/kg/day); after 1 week, increase to 5 mg/kg BID (10 mg/kg/day). Max: 20 mg/kg/day.
* **Felbamate:** Start 1200 mg/day in 3–4 divided doses; titrate by 1200 mg/week. Max: 3600 mg/day (Rarely used due to hematologic/hepatic risks).
## Pediatric Dosing
* **Clobazam (≥2 years):** Weight <30 kg: Start 5 mg/day; target 10–20 mg/day. Weight ≥30 kg: Start 5–10 mg/day; target 20–40 mg/day.
* **Rufinamide (≥1 year):** Start 10 mg/kg/day in two divided doses; titrate by 10 mg/kg/day every 2 days. Max: 45 mg/kg/day or 3200 mg/day.
* **Cannabidiol (≥1 year):** Same as adult weight-based dosing (target 10–20 mg/kg/day).
* **Lamotrigine:** Highly variable due to titration schedules; requires slow escalation to avoid rash (e.g., Stevens-Johnson Syndrome).
## Dose Adjustments
* **Renal/Hepatic:** Most LGS medications require significant dose reduction in hepatic impairment (e.g., Clobazam, Felbamate, CBD). Adjust Rufinamide for severe renal impairment.
* **Drug-Drug Interactions:** Genetic polymorphisms (e.g., CYP2C19 for Clobazam) and enzyme inducers (e.g., Carbamazepine/Phenytoin) significantly alter plasma concentrations of most LGS drugs.
## Contraindications
* **Felbamate:** History of aplastic anemia or hepatic impairment.
* **Rufinamide:** Familial Short QT syndrome.
* **General:** Known hypersensitivity to the specific molecule or class.
## Adverse Effects
* **Common:** Somnolence, fatigue, dizziness, gastrointestinal distress (CBD), decreased appetite, and ataxia.
* **Severe:** Suicidality (all AEDs), SJS/TEN (Lamotrigine, Rufinamide), Aplastic anemia/Hepatotoxicity (Felbamate), and status epilepticus (abrupt withdrawal of benzodiazepines).
## Key Drug Interactions
* **Clobazam:** Potentiates CNS depression with other sedatives/opioids. Inhibited by CYP2C19 inhibitors (e.g., omeprazole, fluoxetine).
* **CBD:** Significantly increases serum levels of *N-desmethylclobazam* (active metabolite), often necessitating a 50% dose reduction of clobazam.
* **Topiramate/Felbamate:** May decrease efficacy of oral contraceptives.
## Monitoring
* **Baseline/Routine:** CBC with differential (Felbamate), LFTs (CBD, Felbamate, Valproate), and EKG (Rufinamide if cardiac risk).
* **Clinical:** Monitor for "worsening seizures," behavioral changes, mood disturbances, and adherence.
## Clinical Pearls
* **Avoid Abrupt Withdrawal:** Always taper AEDs slowly to prevent rebound seizures or status epilepticus.
* **Titration:** "Start low and go slow" is the golden rule, especially with Lamotrigine and Topiramate, to improve tolerability.
* **Standard of Care:** Protocols vary by institution regarding the "first-line" choice; always consult your facility’s specific pediatric neurology formulary.
* **CBD:** Epidiolex is the only FDA-approved CBD; purity and concentration of over-the-counter hemp products are unreliable and not recommended for LGS.
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**Educational Disclaimer:** This information is for educational purposes only and does not supersede local institutional protocols. Always consult the most recent FDA-approved prescribing information (package inserts) and formal pharmacy drug databases (e.g., Lexicomp, Micromedex) before prescribing or administering medication.
