Lennox Gastaut Syndrome

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Lennox Gastaut Syndrome

• Enrique Feoli MD
• North East Regional Epilepsy Group

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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

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Syndrome types in different age groups

• Early Childhood (1-5y)
• -LGS
• -Febrile Seizures
• Adolescence
• -JME
• -Juvenile Absence epilepsy

• Infancy
• -West Syndrome
• -Ohtahara Synd.
• -Dravet Syndrome
• Late Childhood (5-10y)
• -Absence Epilepsy
• -Landau-K syndrome
• -Benign Rolandic E.

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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

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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 Leighs
  encephalomyelopathy or Channelopathies.

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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

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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

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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

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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.

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LGS treatment

• Antiepileptic drugs
• Surgery
• -Vagus Nerve stimulator VNS shows a 2442
  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

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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

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LGS treatment with AEDs

• Often used
• Valproic acid, Clonazepam
• Limited utility (may exacerbate seizures)
• CBZ, Phenobarbital, Primidone

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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

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What Medication to use first

• Based on Syndrome
• Based on gender
• Based on side effects
• Choices Depakote, Topiramate, Lamotrigine,
  Felbamate.

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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

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Diet for LGS

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

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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 bodys fuel source from
  glucose to fat.

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History

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

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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.

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Efficacy

• 20-30 seizures were completely controlled
• 50-70 - seizure frequency decreased by 50
• 20-30 - not effective

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Modified Atkins

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

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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

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Modified Atkins

• Is it Effective?
• 60 to 70 gt50 improvement,
• 20 to 30 gt90 improvement
• 5 to 10 seizure free

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Surgical Options

• Vagus Nerve stimulator VNS shows a 2442 global
  seizure reduction. Comparable outcome to corpus
  callosotomy without invasive surgery.
• Corpus callosotomy
• most beneficial for atonic seizures

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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