Lennox Gastaut Syndrome Felicia Gliksman DO MPH Pediatric

Lennox Gastaut Syndrome Felicia Gliksman, DO, MPH Pediatric Neurology Joseph M Sanzari Children’s Hospital Hackensack University Medical Center

Lennox Gastaut Syndrome �OUTLINE �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 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 brain injury ❖Meningitis &Encephalitis/Congenital infections ❖Neurocutaneous syndromes-Tuberous sclerosis

Etiology cont. ❖History of infantile spasms ❖Trauma ❖Brain tumors ❖Metabolic syndromes (Leigh’s) ❖ 30 -35% cause is unknown

LGS Diagnosis in Pediatrics ❖ Onset 3 to 8 years of age ❖ Seizures type ❖ -Tonic-atonic drop attacks ❖ -Tonic clonic ❖ - Atypical absences ❖ Gradual onset and termination ❖ Arrest of activity/staring ❖ Clonic activity

LGS Diagnosis in Pediatrics ❖ May present as non-convulsive status epilepticus in 50 to 75 % of patients ❖ Cognitive impairment ❖ most impaired: reaction time and processing prolonged ❖ Mood instability, personality disturbances, or slowing and/or arrest of psychomotor development and educational progress. ❖ The main characteristics of mental deterioration are reported as apathy, memory disorders, impaired visuomotor speed, and perseverance. ❖ 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) • • valproate, lamotrigine, felbamate, topiramate, clobazam, rufinamide 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 • Clobazam, Felbamate (~50 -70% reduction in drop attacks) • Lamotrigine, Rufinamide(~40% reduction) • Topiramate (~10% reduction) Effective in open label trials • 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 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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