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 seizuresSeizures; 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