Lennox Gastaut Syndrome Enrique Feoli MD North East Regional Epilepsy Group

Goals Understand the definition of LGS Outline the clinical presentation of LGS Compare the different medications available to treat LGS Develop a rational treatment approach for LGS

Syndrome types in different age groups Infancy; -West Syndrome -Ohtahara Synd. -Dravet Syndrome Late Childhood (5-10y) -Absence Epilepsy -Landau-K syndrome -Benign Rolandic E. Early Childhood (1-5y) -LGS -Febrile Seizures Adolescence -JME -Juvenile Absence epilepsy

LGS Prevalence and Incidence Prevalence is 1 to 10 % of all childhood epilepsy Incidence rate for LGS of all new onset epilepsies is 0.6 %

Etiology  Brain malformations  Hypoxic-ischemic brain injury  Meningitis &Encephalitis/Congenital infections  Neurocutaneous syndromes-Tuberous sclerosis  Trauma  Brain tumors  Cortical dysplasia/Bilateral perisylvian syndrome  17-30% with LGS will have history of infantile spasms.  Few have metabolic issues such as Leigh’s encephalomyelopathy or Channelopathies.

LGS Diagnosis; Pediatrics  -Onset 3 to 8 years of age  -Seizures type; -Tonic-atonic drop attacks -Tonic clonic - Atypical absences; Gradual onset and termination Behavioral pause/stare (30 + seconds) Clonic activity

LGS Diagnosis; Pediatrics Cont  May present as non-convulsive status epilepticus in 50 to 75 % of patients  -Cognitive impairment and developmental delay.  -EEG; irregular, gneneralized 2 to 2 ½ Hz spikes and wave pattern

LGS Diagnosis; adult Onset 4 to 8 years of age Cognitive impairment and developmental delay Seizures Type; Childhood onset tonic-atonic drop attacks Complex partial/frontal lobe seizures Seizures; arms asymetrically elevated Vocalization 5 to 20 seconds duration

LGS Diagnosis; adult EEG (variable) - Background; normal (rare) to diffuse slowing - Ictal; diffuse attenuation generalized irregular 2 to 2 ½ Hz spikes/wave generalized might lateralized without clear focal findings.

LGS treatment Antiepileptic drugs Surgery; -Vagus Nerve stimulator VNS shows a 24%– 42% global seizure reduction. Comparable outcome to corpus callosotomy without invasive surgery (a) -Corpus callosotomy most beneficial for atonic seizures  Diet; Ketogenic, Modified Atkins diet. a-Lancman et al. AES 2011 Abstract 3.313

LGS treatment with AEDs Effective in randomized, double blind placebo controlled trial, approved by FDA; Clobazam, Felbamate,Lamotrigine, Rufinamide, Topiramate. Effective in open level trials Vigabatrin, Zonisamide

LGS treatment with AEDs Often used Valproic acid, Clonazepam Limited utility (may exacerbate seizures) CBZ, Phenobarbital, Primidone

Aeds Additive effects Post-hoc sub analysis of the CLB trial; Evaluated drop seizures rate from baseline to 12 week in patient receiving CLB with LTG or VPA. Average reduction in drop seizures was grater for either combination vs placebo. Efficacy was dose dependent

What Medication to use first Based on Syndrome Based on gender Based on side effects Choices; Depakote, Topiramate, Lamotrigine, Felbamate.

What medication to use Next Based on the first medicine Based on Additive effect Based on side effects Options; Rufinamide, Zonisamide, Vigabatrin, same as the previous list, Benzodiazepines, Levetiracetam

Diet for LGS Ketogenic Diet Modified Atkins diet for Epilepsy Low glycemic index diet

Ketogenic diet A treatment option for epilepsy (LGS) A very strict diet that involves fluid restriction, high fat and low carbohydrate + protein intake. The goal: alter the body’s fuel source from glucose to fat.

History The basis of the diet – fasting Devised in the 1920’s at Johns Hopkins University School of Medicine. Popularity faded in the 40’s and 50’s when new anticonvulsant drugs were discovered Resurgence recently because, among others, of the TV movie based on Charlie Abrahams

Who is a candidate Children – usually 2-10 years of age Most effective in kids with “drop” type seizures The children considered have at least 3 seizures/week The antiepileptic medication is not working.

Efficacy 20-30% – seizures were completely controlled 50-70% - seizure frequency decreased by 50% 20-30% - not effective

Modified Atkins Absence of protein, fluid, or calorie restriction 64% fat 30% protein 6% carbohydrate (10 to 20% on regular Atkins diet)

Modified Atkins The modified Atkins diet is a modification of the traditional ketogenic Foods are not weighed and measured, but carbohydrate counts are monitored by patients and parents. It is started outside of the hospital

Modified Atkins Is it Effective? 60 to 70 % >50% improvement, 20 to 30 % >90% improvement 5 to 10 % seizure free

Surgical Options  Vagus Nerve stimulator VNS shows a 24%–42% global seizure reduction. Comparable outcome to corpus callosotomy without invasive surgery.  Corpus callosotomy most beneficial for atonic seizures

Summary Lennox Gastaut Syndrome  Difficult epileptic encephalopathy  Onset in childhood  Persist into adult life  Optimal Treatment  Requires identification of the syndrome  Selection of effective therapy  Ovoid treatments that exacerbate seizures