Three Patients all LGS
• Etiology: All different, one had encephalitis at
3 months with prolonged status epilepticus.
One has a mutation in the SCN2A gene. One
has no known cause.
• They all have seizures that are called
generalized, that means both sides of the
brain seem to have simultaneous discharges.
• This is a key feature of LGS-generalize EEG
Decrease in Drop Seizures Following
• Graham D
Graham D et al. 2017
• Adults do not develop LGS.
• Infants and young children develop LGS.
– There often is a progression of seizure types with
– Young infants will have focal or infantile spasms
then go on to develop the key generalized seizures
of LGS, Tonic and Atonic seizures.
– Why does the developing brain develop this
• Lesion Genetic- 10-20%
• Lesion injury (early in life)-25%
• Somehow a change in the brain, often the
cortex that is present early in life and possibly
only on one side can cause the whole brain or
at least both sides to have a discharge
Conceptualizing Lennox–Gastaut syndrome as a secondary
Archer et al 2014
Take home points
• LGS is due to a usurping of the normal
networks that develop in childhood.
Abnormalities in the cortex in one or many
sites can drive the aberrant connections. The
network becomes “to linked” and that causes
seizures and cognitive problems.
So what to do?
• If there is a cortical driver take it out.
– Clear from TS and focal developmental disorders
and the first patient I showed with encephalitis
you can find cortical drivers in the network and
removing them can improve seizures and
• Earlier you take it out the better (probably)
• What about manipulating the network? A
work in progress?
• Electrical-Deep Brain Stimulation- Unclear still
what target though the thalamus is the most
often targeted site.
• Genetic- There are at least 40 companies
currently in phase 1-2 trials for gene
replacement. Though rare in brain disorders,
at least 2 are showing success.
• Genetic Counselor