OU Neurology

Update in Pediatric

Epilepsy

Cherie Herren, MD

Assistant Professor

OUHSC, Department of Neurology

September 20, 2018

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Disclosures

◼None

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Objectives

◼1. Identify common pediatric epilepsy

syndromes

◼2. Describe diagnostic evaluations for

new onset seizures

◼3. Describe treatment options in pediatric

epilepsy

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Definitions

◼Seizure: the clinical manifestation of an abnormal and excessive synchronization of a population of cortical neurons

◼Epilepsy: two or more recurrent seizures unprovoked by any systemic or acute neurological insult

◼Therefore, not all seizures are epilepsy

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Causes of acute provoked seizures

◼ Fever (age 6 months to 6 years)

◼ Infection

◼ Acute head trauma

◼ Hypoglycemia

◼ Hyponatremia/hypocalcemia/hypomagnesium

◼ Renal failure

◼ Hyperthyroidism

◼ Cerebral anoxia

◼ Alcohol/benzodiazepine withdrawal

◼ Drug toxicity/intoxication

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Normal CNS function

ExcitationInhibition

glutamate,

aspartateGABA

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Hyperexcitability reflects both increased

excitation and decreased inhibition

Excitation

Inhibition

GABA

glutamate,

aspartate

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Epidemiology

◼Seizures • Incidence: 80/100,000 per year

• Lifetime incidence: 9%

◼Epilepsy • Incidence: 45/100,000 per year

• Cumulative lifetime incidence: 3%

• 1% of entire US population

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Etiology of epilepsy

Idiopathic (genetic)

Congenital

Trauma

Vascular

Tumor

Infection

Degenerative

Ages <15 Ages 15-34

Ages 35-64 Ages >64

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ILAE classification of seizures

Seizures

Partial Generalized

Simple Partial

Complex Partial

Secondarily

Generalized

Absence

Myoclonic

Atonic

Tonic

Tonic-Clonic

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Generalized seizure

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Partial seizure

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Evaluation of a first seizure

◼ History (witnesses)

◼ Physical/neurological examination

◼ Blood tests: CBC, electrolytes, glucose, calcium,

magnesium, phosphate, hepatic and renal function

◼ Lumbar puncture

➢ Only if meningitis or encephalitis suspected

◼ Blood or urine screen for drugs

◼ Electroencephalogram (EEG)

◼ CT or MRI brain scan

◼ Screen for inborn errors of metabolism (<12 months)

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Electroencephalogram (EEG)

◼ EEG is the most important neurophysiological

study for the diagnosis, prognosis, and treatment

of epilepsy

◼Graphical depiction of cortical electrical activity,

usually recorded from the scalp

◼ Abnormal findings consistent with epilepsy are

called “epileptiform activity” and include spikes

and sharp waves

◼ Activation procedures (sleep deprivation, photic

stimulation, hyperventilation)

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EEG

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Normal Background

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MRI Brain

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Seizures and Epilepsy

◼ Seizure

➢Simple Febrile

Seizures

➢Complex Febrile

Seizures

◼ Epilepsy Syndromes

➢Childhood Absence

Epilepsy

➢Juvenile Myoclonic

Epilepsy

➢Benign Rolandic

Epilepsy

➢Infantile Spasms

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Simple febrile seizures

◼Occur in children 6 months to 5 years

➢Neurologically normal children

➢1 in 24 hours

➢Last <15 minutes

➢GTC

➢No work-up or treatment typically

➢3% chance of developing epilepsy

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Complex febrile seizure

◼Complex febrile seizures – occur in

neurologically normal children 6 months to

5 years

➢Multiple in 24 hours

➢Prolonged

➢Focal

➢May get EEG or MRI

➢Could consider treating based on results

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Childhood Absence Epilepsy

◼Previously called “petit mal”

◼Onset between 4-10 years

◼Normal developmental and neurologic exam

◼Multiple staring spells per day lasting ~15 seconds

◼Thought to be genetic (inheritance is unknown)

◼Rare generalized tonic clonic seizures

◼Frequently outgrow seizures

◼https://www.youtube.com/watch?v=9HiKwTm755o

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Absence Epilepsy

3 Hz

generalized

spike and

wave

discharges

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◼Treatment

➢Ethosuximide

➢Valproic Acid

➢Lamotrigine

➢Topiramate

➢Zonisamide

◼AVOID carbamazepine, oxcarbazepine,

Phenytoin

Absence Epilepsy

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Juvenile Myoclonic Epilepsy

◼ Onset 12-18 years

◼ May evolve from childhood absence

◼ Myoclonic seizures, quick jerks often of the arms

◼ More common in the morning and after sleep deprivation

◼ Photosensitive

◼ Precipitated by alcohol

◼ Often have generalized tonic clonic seizures also

◼ https://www.youtube.com/watch?v=dU8R0LCCn6k

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Juvenile Myoclonic Epilepsy

4-6 Hz

generalized

spike/

polyspike

and wave

discharges

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◼Treatment

➢Levetiracetam

➢Valproic Acid

➢Lamotrigine

➢Topiramate

➢Zonisamide

◼AVOID carbamazepine, oxcarbazepine,

Phenytoin

Juvenile Myoclonic Epilepsy

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Benign rolandic epilepsy (BECTS)

◼ Most common epilepsy syndrome in children

◼ Onset 3-13 years

◼ Normal development and neurologic exam

◼ Most outgrow by age 14-18 years

◼ Semiology➢ Unilateral facial sensorimotor symptoms (30% of patients)

➢Oropharyngolaryngeal manifestations (53% of patients)

➢ Speech arrest (40% of patients),

➢ Hypersalivation (30% of patients)

➢ Hemiconvulsion/GTC (50%)

◼ Likely genetic

◼ Confirmed by centrotemporal spikes on EEG

◼ Oxcarbazepine considered first line treatment

◼ https://www.youtube.com/watch?v=196lMKRhrYM

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West syndrome

◼ Infantile spasms: onset in 1st year of life

◼ Cognitive impairment

◼ Hypsarrythmia

◼ Etiology: 61-80%1-2 known cause➢ Hypoxic ischemic encephalopathy (HIE)

➢ Chromosomal (Trisomy 21)

➢ Congenital brain malformations

➢ Ischemic stroke

➢ Tuberous sclerosis

➢ Peri-ventricular leukomalacia (PVL)

➢ Hemorrhage

◼ https://www.youtube.com/watch?v=TcSegvM0qOk

1. Osborne, J.P., et al (2010). The underlying etiology of infantile spasms (West syndrome): Information from the United

Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia: 51(10):2168–2174.

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Case 1- EEG- Hypsarrythmia

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West syndrome- Treatment and

Outcome

◼ Treatment options➢ ACTH vs oral steroids, Vigabatrin

➢ Ketogenic diet, Epilepsy surgery

◼ 60% epilepsy - ~1/3 evolve to Lennox Gastaut Syndrome

◼ 75% developmental delay

Lagae, L. et al (2010). Treatment and long term outcome in West syndrome: The clinical reality. A multicentre follow up study.

Seizure: Apr;19(3):159-64.

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Epilepsy Treatment

◼Medications

◼Medications

◼Medications…

◼Alternative treatments

➢Epilepsy surgery

➢Ketogenic diet

➢Vagal nerve stimulator

➢CBD oil

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Epilepsy Treatment

◼ Medication: Antiepileptic drugs (AEDs) are first line for majority of patients

◼ Refractory epilepsy: patients who have failed >2 medications

◼ AEDs:➢ Levetiracetam (Keppra): broad spectrum

➢ Valproic Acid (Depakote): broad spectrum

➢ Topiramate (Topamax): broad spectrum

➢ Lamotrigine (Lamictal): broad spectrum

➢ Zonisamide (Zonegran): broad spectrum

➢ Oxcarbazepine/Carbamazepine (Trileptal/Tegretol): avoid in primary generalized epilepsy

➢ Phenytoin (Dilantin): avoid in primary generalized epilepsy

➢ Phenobarbital: Used primarily in infants

➢ Ethosuximide (Zarontin): Used for absence only

➢ Newer AEDs: Clobazam (Onfi), Rufinamide (Banzel), Lacosamide (Vimpat)

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Success with Anti-epileptic Drug

(AED) Regimens

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Treatment - Epilepsy Surgery

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Semiology EEG

MRIPET

SPECT

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EEG

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PET

ScanMRI

Brain

SPECT

Scan

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Neuropsych testing

◼Helps to identify cognitive areas of the

brain that aren’t functioning well

◼Can help to identify potential areas where

seizures are originating

◼Ex. Verbal memory problems may suggest

left temporal dysfunction

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Engel Classification

◼Class Ia: completely seizure-free

◼Class I: seizure-free or auras only or

convulsions with drug withdrawal only

◼Class II rare seizures (90% seizure

reduction)

◼Class III: reduction of seizure frequency

>75%

◼Class IV: reduction of seizure frequency

<75% Engel J, Rasmussen TB. Outcome with respect to seizures.

1993:609–621.

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Outcomes

◼ Etiology- % seizure free ➢ Tumor 80.2%

➢ Cortical dysplasia 62.9%

➢ Hippocampal sclerosis 81.8%

➢ Vascular 75.9%

➢ Neurocutaneous 83.3

➢ Other 54.5%

◼ Surgery type- % seizure free ➢ Lobar 74.7%

➢ Multilobar 38.5

➢ Hemispherectomy 81.0%

◼ Location

➢ Temporal 79.5%

➢ Frontal 58.8%

➢ Parietal 75.0%

➢ Occipital 75.0%

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Ketogenic diet

◼Special diet for patients with intractable

epilepsy

◼High fat low carb diet

◼Must be started in the hospital to monitor

glucose and other side effects

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Ketogenic diet

◼ Cream

◼ Fat

◼ Fruit or vegetable

◼ Protein

◼ NO bread, pasta, grains, cereal

◼ NO sugar or sweets

◼ NO starchy fruit or vegetables (corn, peas, potatoes)

◼ No juice or milk, no regular sodas

◼ Vigilant exclusion/monitoring

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Ketogenic diet- side effects

◼Acidosis

◼Constipation

◼Hyperlipidemia

◼Hypoproteinemia

◼Kidney stones

◼Osteoporosis

◼Decreased growth

◼Pancreatitis

◼Hepatitis

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Ketogenic diet- Efficacy

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Epilepsy Treatment- VNS

◼ Vagal Nerve Stimulator: ➢ Implanted device sends

electrical pulse to vagus nerve

➢ About 1/3 of patients have had the number of their seizures reduced by half or more; less than 5% of patients become seizure free

➢ About 1/3 have shown benefit but have had their seizure frequency reduced by less than half

➢ About 1/3 have had no worthwhile benefit

➢ Side effects: cough, hoarseness

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CBD Oil

◼ Cannabadiol (CBD)- non-psychoactive chemical in the cannabis

plant

◼ Legal in Oklahoma for families to acquire for intractable epilepsy

◼ Exact antiepileptic mechanism unknown but may act on receptors in

the hippocampus

◼ Studies show 50-60% reduction in seizures in difficult to treat

epilepsy (children and adults)

➢ No placebo control

➢ May interfere with metabolism of other medications

➢ No specific diagnoses respond better

➢ Side Effects- sedation, nausea, vomiting, elevated liver enzymes,

behavioral problems, insomnia

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Take home points…

◼Epilepsy has a variable presentation and

prognosis

◼Categorizing patients into epilepsy

syndromes can help determine etiology,

best treatment options and prognosis

◼ Identifying patients who may benefit from

non-medication options is important early

to minimize morbidity

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Questions??????