Download Lennox Gastaut syndrome - Dr. Felicia Gliksman

Lennox Gastaut Syndrome
Felicia Gliksman, DO, MPH
Pediatric Neurology
Joseph M Sanzari Children’s Hospital
Hackensack University Medical Center
Lennox Gastaut Syndrome
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OUTLINE
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Definition
Clinical presentation
Workup
Prognosis
Treatment
Definition
Multiple seizure types
Distinctive brain-wave pattern
Some degree of impaired intellectual functioning or
information processing, along with developmental
delays, and behavioral disturbances
Seizure Types
Tonic (muscle stiffening)
Atonic (loss of muscle tone / drop attacks)
Tonic-clonic (grand mal)
Absence (staring) seizures
Myoclonic (sudden muscle jerks)
Irregular, generalized 2 to 2 ½ Hz spikes and
wave pattern
Clinical Presentation by Age
Group
Infancy
West Syndrome
Otahara Syndrome
Dravet Syndrome
Early Childhood
Febrile Seizures
LGS
Clinical Presentation by Age
Group
Late Childhood
Childhood Absence Epilepsy
Landau-Kleffner
Adolescence
Juvenile Myoclonic Epilepsy
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 %
The peak age of onset is between ages 3 and 5, with a slightly
greater prevalence in males than females.
Estimates of 10 percent to 40 percent of children with LGS
have a prior history of infantile spasms.
Diagnosis and treatment are difficult and seizure remission is
rare.
Etiology
❖ Brain
malformations
❖cortical
dysplasia (pachy/polymicrogyria)
❖ Hypoxic-ischemic
❖ Meningitis
brain injury
&Encephalitis/Congenital infections
❖ Neurocutaneous
syndromes-Tuberous sclerosis
Etiology cont.
❖ History
of infantile spasms
❖Trauma
❖ Brain
tumors
❖ Metabolic
❖ 30-35%
syndromes (Leigh’s)
cause is unknown
LGS
Diagnosis in Pediatrics
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Onset 3 to 8 years of age
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Seizures type
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-Tonic-atonic drop attacks
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-Tonic clonic
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- Atypical absences
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Gradual onset and termination
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Arrest of activity/staring
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Clonic activity
LGS
Diagnosis in Pediatrics
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May present as non-convulsive status epilepticus in 50 to 75 % of
patients
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Cognitive impairment
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most impaired:reaction time and processing prolonged
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Mood instability, personality disturbances, or slowing and/or arrest of
psychomotor development and educational progress.
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The main characteristics of mental deterioration are reported as
apathy, memory disorders, impaired visuomotor speed, and
perseverance.
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EEG: irregular, generalized 2 to 2 ½ Hz spikes and wave pattern
LGS Diagnosis
in Adolescents/Adults
Onset 4 to 8 years of age
Cognitive impairment and developmental delay
Older children with LGS experience character problems, acute
psychotic episodes, or chronic forms of psychosis with
aggressiveness, irritability, or social isolation.
The most impaired of the cognitive functions are reaction time and
information processing, which are prolonged.
The main characteristics of mental deterioration are reported as
apathy, memory disorders, impaired visuomotor speed, and
perseverance.
LGS Diagnosis
in Adolescents/Adults
Seizures Type
Childhood onset tonic-atonic drop attacks
Complex partial/frontal lobe seizures
Vocalizations
LGS Diagnosis
in Adolescents/Adults
❖Background; normal (rare) to diffuse slowing
❖EEG: (variable) diffuse attenuation,
generalized irregular 2 to 2 ½ Hz spikes/wave
generalized might lateralized without clear
focal findings.
Approach to treatment
❖goals
of treatment for patients with LGS are the same
as for all patients with epilepsy:
the best quality of life with the fewest seizures (ideally,
none)
the fewest adverse treatment effects
the least number of medications.
LGS treatment
Antiepileptic Drugs (AEDs)
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valproate, lamotrigine, felbamate, topiramate, clobazam,
rufinamide
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There is usually no single antiepileptic medication that will
control seizures. Children who improve initially may later show
tolerance to a drug or have uncontrollable seizures
Surgery
Vagus Nerve Stimulator
Ketogenic OR Modified Atkins diet.
LGS treatment with AEDs
Effective in randomized, double blind
placebo controlled trial, approved by FDA
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Clobazam, Felbamate (~50-70% reduction
in drop attacks)
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Lamotrigine, Rufinamide(~40% reduction)
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Topiramate (~10% reduction)
Effective in open label trials
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Vigabatrin, Zonisamide
AEDs Additive effects
Clobazam trial
Found that average reduction in drop
seizures was greater for either
combination (CLB+ LTG or CLB +VPA) vs
placebo from baseline to 12 weeks.
Efficacy was dose dependent
What Medication to use first
Based on syndrome
Based on gender
Based on side effects
Options: Valproate, 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,
Benzodiazepines, Levetiracetam (also
Valproate, Topiramate, Lamotrigine,
Felbamate)
AED treatment
requires a careful balance between the best
possible seizure control and potential toxic side
effects such as fatigue, nausea and unsteadiness
of movement.
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.
Diet
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
Potential side effects: hypoglycemia,
elevated lipids and cholesterol, slow growth,
kidney stones, fractures, constipation
Efficacy
20-30% – seizures may be completely
controlled
50-70% - seizure frequency decrease 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
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callosotomy
most beneficial for atonic seizures
Social Considerations
The severity of the seizures, frequent injuries,
developmental delays, and behavior problems take
a large toll on even the strongest parents and family
structures.
Pay attention to the psychosocial needs of the
family (especially siblings).
The proper educational setting is important to help
the patient with LGS reach his/her maximal
potential
Outcome
Tonic seizures may persist and be more difficult to
control over time
Myoclonic and atypical absences appear easier to
control.
Mortality rate is reported at 3% to 7%.
Death often is related to accidents. A high rate of
injuries is associated with atonic and/or tonic
seizures
Summary
Difficult treat epileptic encephalopathy
Onset in childhood
Persists into adult life
Optimal Treatment
Requires identification of the syndrome
Selection of effective therapy
Avoid treatments that exacerbate seizures
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