Objectives: Stuff to know about pediatric seizures…

Definitions Epidemiology Seizure classification Approach to acute seizures Status epilepticus Antiepileptic therapy Conclusion Quiz

What is a seizure?

The clinical manifestations (signs and symptoms) of excessive, synchronous, usually self-limited, abnormal electrical activity of neurons in the cerebral cortex.

Other definitions

Semiology – the clinical manifestation of a seizure (what it looks like)

Epilepsy – a condition in which a patient has 2 or more unprovoked seizures.

Seizure statistics

Ten percent of people will experience a seizure in their lifetime.

Up to 0.1% of people have epilepsy. Seizures and epilepsy are more common in children than

adults. Epilepsy: 700/100,000 <16 years old, 330/100,000 adults

WHO data

Classification of Seizures

What part of the brain is affected?1. Partial (or focal) one or multiple areas affected

2. Generalized both cerebral hemispheres affected synchronously

Partial seizures can become generalized seizures (secondarily generalized)

Classification of Seizures

How does the seizure affect consciousness?1. Simple consciousness is preserved throughout the seizure

2. Complex consciousness is impaired at the onset of the seizure

Classification of Seizures

Symptomatic underlying etiology present Includes structural and metabolic causes

Idiopathic/cryptogenic no identifiable etiology Presumed genetic cause

Seizure axis description

Axis 1 Axis 2 Axis 3 Axis 4 Axis 5

Ictal phenomenology

Seizure type Syndrome Etiology Disability

What did it look like?

include localization and precipitating stimuli when possible

Not always applicable

when known Describes impact on quality of life

Johnny has focal onset clonic seizures with secondary generalization that start with left hand jerking and proceed to generalized clonic jerking with impairment of consciousness. His seizures can be provoked with hyperventilation and are due to right frontal cortical dysplasia. Johnny’s epilepsy causes him social stigmatization and prevents him from scuba diving, which was his favorite activity.

Engel, Epilepsia 2001

Seizure types

Tonic – sudden stiffening of part of the body, usually < 20 sec

Clonic – rhythmic jerking Tonic clonic – tonic phase followed by jerking. Myoclonic – brief jerk. Atonic – loss of tone often causing fall. Absence – staring spells with behavioral

arrest, can occur with automatisms or changes in tone.

Epilepsy.com

Stages of tonic-clonic seizure

Causes of acute seizures

• Fever• CNS Infection• Metabolic

derangements– Hypoglycemia– Hypocalcemia– Hypo/hypernatremia– Uremia– Hyperammonemia– Hypoxia

• Toxins– Alcohol– Illegal drugs– Prescription medications

• Structural lesions– Trauma– Stroke– Tumor– Malformation

Left frontal cortical dysplasia. Duncan et al. Lancet 2006

Evaluation of acute seizures - History

Before the seizure: illness, ingestion, lethargy, other medical or neurologic/developmental conditions? If they have epilepsy, are they taking their medicine? FHx.

During the seizure: what was the very first indication of the seizure? Aura, behavioral change, eye or head deviation, mouth, face or

limb movements, loss of tone, incontinence, falling, cyanosis. How long did it last? How often do they occur?

After the seizure: postictal confusion, Todd’s paralysis, when did patient return to normal?

Evaluation of acute seizures - exam

ABC’s first Mental status and motor exam are important for ensuring

that the seizure is over. Complete multisystem exam (look for signs of infection,

trauma, systemic disease). Complete neurologic exam.

http://library.med.utah.edu/neurologicexam/html/home_exam.html

Evaluation of acute seizures - testing

Consider glucose, electrolytes, CBC, toxin screen, AED levels.

CT in ER for focal neurologic deficits after a few hours, or concern for trauma/mass.

LP if concern for infection or CT-negative subarachnoid hemorrhage. **image before LP.

Evaluation - of acute seizures testing

EEG Routine if patient returns to baseline LTM if concern for ongoing seizures/status

epilepticus or in some cases of suspected psychogenic nonepileptic seizures (PNES).

Non-urgent MRI in patients with… significant cognitive or motor impairment of

unknown etiology unexplained abnormalities on neurologic exam focal seizure EEG that does not represent a benign partial

epilepsy of childhood or primary generalized epilepsy

children under one year of age

Hirtz et al 2000, 2003

Differential Diagnosis – not everything that shakes is a seizure.

Cardiac arrhythmia Breath holding spells Tremor/jitteriness Dystonia Stereotypies Hypoglycemia

Benign sleep myoclonus

Confusional arousal GERD, intussusception Psychiatric (ADHD,

anxiety) PNES

Counseling after first seizure

Recurrence risk After 1 unprovoked seizure, 30-50% After 2 unprovoked seizures, >70% Recurrence risk is highest in first 6-24 months.

Avoid dangerous activities No driving for 6 months No swimming in open water No unsupervised bathing

Counseling after first seizure

Avoid triggers: sleep deprivation, EtOH How to use an abortive (see meds) Seizure first aid (place patient on their side, don’t put

anything in the mouth) When to call 9-1-1

If seizure doesn’t stop with first abortive Any concern for persistent altered mental status, ongoing

seizure or other concerns.

http://ewct.org.nz

Seizure first aid

Abortive therapy at home

Give after 5 minutes of continuous seizure activity or for seizure cluster (typically 3 seizures in one hour)

Repeat if needed after 2-4 minutes and call 911 No need to go to ER if patient is waking up and

there’s no concern for serious infection. Midazolam IN – 0.2mg/kg up to 10mg. Divide dose

between two nostrils. Diazepam PR (Diastat) – 0.5mg/kg, up to 20mg.

Adjust dose for age and weight.

Status epilepticus

Continuous seizure for >30* minutes, or multiple seizures without a return to baseline between seizures. * the length of a seizure qualifying as status epilepticus is a

matter of debate. There is irreversible neuronal damage after 30 minutes, but seizures lasting > 5-10 minutes generally do not stop on their own.

Nonconvulsive status epilepticus can also occur. Less is known about the long term consequences and how long a seizure must last in order to cause irreversible damage.

A medical emergency due to possibility of respiratory failure, arrhythmia and brain injury.

Causes of status epilepticus

Hirsch et al. Continuum 2013

Abortive therapy in the hospital(for status epilepticus)

ABCs, IV access, look for treatable causes. Proceed to next step after 5 minutes Lorazepam 0.1mg/kg up to 4mg Midazolam IN/IM 0.2mg/kg up to 10mg May repeat phenobarbital. Keppra and Vimpat may also be

considered. Some institutions go from fospheny to midazolam (skipping phenobarbital).

Pentobarbital infusion

Midazolam infusion

Phenobarbital 20mg/kg*

Fosphenytoin 10mgPE/kg

Fosphenytoin 20mgPE/kg

Benzodiazepine

Selecting chronic AED therapy

Select antiepileptic drug based on seizure type, side effect profile and interactions.

60-80% of people respond to first or 2nd AED. Prepare the family for breakthrough seizures despite

AED – may need dose adjustment or a different med.

AED by seizure type

Focal seizures Generalized seizures

Tonic clonic Absence Myoclonic Atonic/clonic

1st choices

OxcarbazepineLevetiracetamCarbamazepine

LevetiracetamTopiramateZonisamideLamotrigine

Ethosuxidmide LevetiracetamValproateClobazam

ValproateClobazam

Also used

TopiramateZonisamidePhenobarbitalValproateLamotrigineVigabatrinPregabalinLacosamide

PhenytoinPhenobarbitalLacosamide

ValproateLamotrigineTopiramate

TopiramateZonisamideLamotriginePhenobarbitalClonazepam

TopiramateLamotrigineClonazepam

Antiepilpetic drugs mechanisms of action (for interest only – you are not responsible for this information)

Bailer and White, 2010

Bailer and White, 2010

Antiepilpetic drugs mechanisms of action (for interest only – you are not responsible for this information)

AED selection

There is little data guiding AED selection. In common practice levetiracetam is often the first

choice. In the neonatal period phenobarbital is usually the first

choice. The only seizure type with a clear best AED is absence

seizures which are treated with ethosuximide (Zarontin).

Side effects of commonly used AEDs

Hoffman 2009

Oxcarbazepine 10-20mg/kd/d up to 60mg/kg/d sedation, ataxia, rash hyponatremia

Phenytoin 20mg/kg load 5mg/kg/d arrhythmia, ataxia Purple glove

Phenobarbital 20mg/kg load 4mg/kg/d sedation, rash, ataxia pancytopenia

Fatigue, dizziness, behavior changes

Important side effects of phenytoin and valproate Phenytoin and fosphenytoin differ in the pH at which they

are soluble and therefore differ by the vehicle in which they are dissolved. Phenytoin requires a very high pH so should not be infused

through a small peripheral IV. Extravasation leads to skin necrosis and purple glove syndrome.

Fosphenytoin is preferred for kids who dislodge their IVs.

Valproate causes platelet dysfunction, hepatotoxicity, weight gain, metabolic syndrome and is teratogenic. Do not use valproate in girls who could become pregnant.

When to stop AEDs.

For most patients, after two years of seizure freedom we order EEG.

If EEG is normal, seizure medication can be weaned after counseling on the possibility of recurrent seizure and the use of abortive medication.

What if AEDs don’t work?

If two drugs don’t control seizures, the chance that a 3rd drug will be successful is 4%.

Alternative therapies include: Ketogenic diet Vagal nerve stimulator Corpus callosotomy for atonic seizures causing injurious falls. Epilepsy surgery for resection of seizure focus.

http://www.vabrainandspine.com

http://www.nairaland.comA delicious ketogenic diet meal.

Vagal nerve stimulatorEpilepsy surgery with subdural/cortical electrodes.

Summary

Seizures are most common in childhood. Seizures are classified by location, effect on

consciousness and motor movements. Evaluation of first time seizure includes EEG and some

form of neuroimaging. Start seizure medication after 2nd unprovoked seizure

due to risk of recurrence. Consider weaning off medication after 2 years of seizure

freedom.

Summary

Status epilepticus is a medical emergency with first line therapy usually being benzodiazepine.

Antiepileptic drugs are chosen based on seizure type, side effects and drug interactions.

Up to 20% of epilepsy patients will develop medication resistant epilepsy (i.e. 2 medications failed to control seizures), possibly requiring alternative surgical or dietary treatments.

References Fenichel G. Clinical Pediatric Neurology: A Signs and Symptoms Approach. Michael A. Rogawski & Wolfgang Löscher Nature Reviews Neuroscience 5, 553-564 (July 2004) Hirtz D, Berg A, Bettis D et al. Practice parameter: Treatment of the child with a first unprovoked

seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society Neurology 2003;60;166-175

Hirtz D, Ashwal S, Berg A et al. Practice parameter: Evaluating a first nonfebrile seizure in children : Report of the Quality Standards Subcommittee of the American Academy of Neurology, the Child Neurology Society and the American Epilepsy Society Neurology 2000;55;616-623

LaRoche and Helmers JAMA. 2004;291(5):605-614 Bailer and White. Nature Reviews Drug Discovery 9, 68-82 (January 2010) Epilepsy Foundation National Institute of Neurologic Disorders and Stroke eMedicine Medscape Hoffman M. How should a patient with a new-onset seizure be managed? The Hospitalist,

October 2009

Quiz

Thank you!

For questions please contact Dr. Ream at Margie.Ream@nationwidechildrens.org

Survey

We would appreciate your feedback on this module. Click on the button below to complete a brief survey. Your responses and comments will be shared with the module’s author, the LSI EdTech team, and LSI curriculum leaders. We will use your feedback to improve future versions of the module.

The survey is both optional and anonymous and should take less than 5 minutes to complete.

Survey