Approach to First Unprovoked Seizure in Children

• Case scenario…

Introduction • One of the commonest neurological disorder in children

• Data from U.S:• 120,000 children seen annually for new onset seizure• 1% experience afebrile seizure by 14 years old• 5% experience febrile seizure by 6 years old• From those diagnosed epilepsy- >50% had their first seizure during

childhood or adolescent

• 1st seizure can cause significant anxiety to parents and medical practitioners

A.B. Chelse, et. al, Initial Evaluation and Management of a First Seizure in Children; Pediatric Annals (Impact Factor: 0.29). 12/2013; 42(12):244-8. DOI: 10.3928/00904481-20131122-08

Provoked vs. Unprovoked Seizure

• Provoked- characterized by specific trigger e.g. CNS infection, head trauma, fever, intoxication, hypoxia

• Unprovoked- not associated with obvious precipitating cause & may be related to epilepsy

Clinical History is the ‘KEY’ when

determining the likelihood recurrence after a

child experience FIRST afebrile seizure

5 questions that we should try to answer

1. Was the episode an epileptic seizure?

2. What is the cause of the seizure?

3. What investigations should I do?

4. Does the child require treatment?

5. What else should I think about?Aspasia Michoulas, Kevin Farrell, Mary Connolly: approach to a child with a first afebrile seizure; BC medical journal vol. 53 no. 6, July/August 2011

Q1: WAS THE EPISODE AN EPILEPTIC SEIZURE??

• Making correct diagnosis in 1st transient neurological event is

important

• Up to 30% of cases referred are misdiagnosed as epilepsy

• Need to identify more common non-epileptic paroxysmal

episodes

Common Imitators: Can be group according to the characteristic of seizures they imitate

• Movement Imitators

• Loss of Consciousness Imitators

• Confusion Imitators

• Psychological Imitators

• Day dreaming

• Stereotypes & tics

• Panic/anxiety attack

• Psychogenic non-epileptic seizure ( PNES a.k.a

pseudoseizure)

• Sleep disorder

• Migraine

• Transient ischemic attack/ stroke

• Paroxysmal movement disorder

• Syncope or reflex anoxic seizure that may

include:

Vasovagal syncope

Breath holding spells

Orthostatic hypotension

Cardiac abnormality (arrhythmias or

prolonged QT syndrome)

GERD (Sandifer syndrome)

Hyperventilation syncope

History:

• Description of whole events by eyewitness

• Followed by focused questions

• Pre-ictal

• Ictal

• Post-ictal

• Other important questions to ask:

• Previous seizure episode/ febrile seizure

• Developmental history

• Past medical history, current medications, possible intoxication, social history

• Family history of epilepsy

Pre-ictal:

• Was there any warning before the spell? If so, what was

it

• Did the child complain of abdominal discomfort, fear or

any other unpleasant sensation before the spell

• What was the child doing prior to spell

• Was the child asleep or awake prior to event

• Was the child sleep deprived

• Were there any triggers for the spell

• Was the child well before the spell or was there

any fever or illness

Ictal

• Was the child conscious during event

• Did the child remember anything that occur during the spell

• Were there any repetitive behaviors during the episode e.g. lip

smacking, pulling shirts

• Did any body movement occur

• Was there any perioral cyanosis

• What was the child skin color during the event

• Did the child have incontinence during the spell

• How long does the spell last

• How many episode has the child experienced

• How often does the spell occur

Post-ictal

• How did the patient feel after the spell

• Did the child seem confuse and tired after the

spell

• How long did it take for the child to get back to

baseline condition

Situational clues to paroxysmal events at different ageINFANT TODDLER CHILD ADOLESCENT

In sleep Benign neonatal sleep myoclonus

Night terrors • Parasomnias• Confusion

arousal

• Parasomnias REM sleep disorder (e.g. sleep paralysis)

• Sleep walkingOn feeding • GERD, Sandifer

Syndrome• Shuddering spells

GERD (Sandifer syndrome) - -

Fever, intercurrent illness

- Febrile seizure Syncope Syncope

Movement - (kineosogenic) Paroxysmal dystonia, dyskinesia

(kineosogenic) Paroxysmal dystonia, dyskinesia

(kineosogenic) Paroxysmal dystonia, dyskinesia

Pain, shock • Structural cardiac or dysrhythmia

• Reflex anoxic seizure

• Structural cardiac or dysrhythmia

• Reflex anoxic seizure• Cyanotic breath holding

• Structural cardiac or dysrhythmia

• Syncope

• Structural cardiac or dysrhythmia

• Syncope

INFANT TODDLER CHILD ADOLESCENTHot weather, prolonged standing

- - - Syncope

Tired, bored, meal times, bed times

Self-gratification events

Self-gratification events

- -

Tired, bored, stress

- - Tics Tics

Excitement, emotion

Shuddering spell - - Cataplexy

Boredom - Self gratification Ritualistic behavior*

Ritualistic behavior*

Absorbed in TV or computer games

- - Distracted Distracted

* Especially in children with learning difficulties

Types of seizureTYPES DESCRIPTIONS

Jerk, shake Clonic (rhythmic contractions followed by slightly slower relaxation) Typically occurring immediately after a tonic phase as part of tonic-clonic seizure

or confined to a body part as focal seizure

Myoclonic seizures Isolated lightning-fast, brief contractions occurring singly or in short runs They occur as infantile spasms but also in older children

Spasms Sometimes referred to as tonic spasms Have a slightly longer phase of sustained contraction than myoclonic jerk Typically occur in runs They occur as infantile spasms but may happen in older children** differentiating these seizure types may be challenging clinically, and is a particularly important purpose of EEG

Types of seizureTYPES DESCRIPTIONS

Stiff Usually tonic seizure (sustained contraction for several seconds) They may be low-amplitude ‘vibratory’ element to the contraction that is different

from a clonic movement

Fall Beware the phrase “drop attack”: it can be ambiguous Atonic seizure results in slump to the ground ‘as if a puppet had its string cut’ Tonic seizure resulting in rigidity and can cause the child to fall “ like a felled

tree” In large myoclonic jerk child can be thrown to the ground In some seizures these are combined, as in Doose syndrome

** many centres use EMG alongside EEG in order to determine whether, and for how long, there is muscle contraction associated with a seizure. This helps to distinguish tonic, atonic and myoclonic event

Types of seizureTYPES DESCRIPTIONS

Vacancy The word ‘absence’ creates a lot of confusion and diagnostic imprecision

An absence is a type of seizure (defined by its EEG features) that can cause LOC, but LOC can also occurs in focal seizure

Most absence are brief, few seconds, but they may occur many times per day Often associated with subtle automatism e.g. lip smacking, chewing,

fiddling with the hands, or eyelid flickeringFocal seizure (e.g. originating from temporal lobe) may be associated with LOC and unresponsiveness to surrounding. They would typically be longer (30s or more) and less frequent than

absences with more marked confusion or agitation EEG can make a valuable contribution to differentiate these 2 types

Q2: WHAT IS THE CAUSE OF SEIZURE??

• ILAE has 3 broad causal categories:

• Symptomatic

• Idiopathic

• Presumed symptomatic (previously known as cryptogenic)

Rob Forsyth, Richard Newton (eds.). Paediatric neurology. 2nd ed. Oxford: Oxford university press, 2012

Aspasia Michoulas, Kevin Farrell, Mary Connolly: approach to a child with a first afebrile seizure; BC medical journal vol. 53 no. 6, July/August 2011.

Aspasia Michoulas, Kevin Farrell, Mary Connolly: approach to a child with a first afebrile seizure; BC medical journal vol. 53 no. 6, July/August 2011.

Examples of Epilepsy SyndromesOnset Examples Neonatal Benign Familial Neonatal Seizures (BFNSs)

Benign Neonatal Seizure (BNSs) Early Infantile Epileptic Encephalopathy (EIEE) (Ohtahara syndrome) Early Myoclonic Encephalopathy (EME)

Infant Infantile Spasms (West Syndrome) Benign Myoclonic Epilepsy of Infancy (BMEI) Severe Myoclonic Epilepsy of Infancy (Dravet Syndrome)

Pre-schooler • Severe Myoclonic Epilepsy of Infancy (Dravet Syndrome)• Some progressive myoclonic epilepsies• Lennox Gastaut Syndrome • Epilepsy with Myoclonic-Astatic Seizures (Doose syndrome)

Rob Forsyth, Richard Newton (eds.). Paediatric neurology. 2nd ed. Oxford: Oxford university press, 2012

Onset Examples

Child Benign Childhood Epilepsy with centrotemporal spikes (BECTS- Rolandic Seizure)

Childhood absence epilepsy (CAE) Epilepsy with myoclonic absence (EMA) Childhood Epilepsy with Occipital Paroxysms (CEOP- Panayiotopolous type) Landau-Kleffner Syndrome (LKS)

Adolescent CEOP (Gastaut type) Juvenile Absence Epilepsy (JAE) JME Epilepsy with GTCS seizures on awakening

Rob Forsyth, Richard Newton (eds.). Paediatric neurology. 2nd ed. Oxford: Oxford university press, 2012

Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS) a.k.a Rolandic Seizure

THE MOST COMMON FOCAL ONSET EPILEPSY IN CHILDHOOD, YET OFTEN UNDER-RECOGNIZED

• Syndrome of brief, simple, partial, hemifacial motor seizures, frequently having associated somatosensory symptoms which have a tendency to evolve into generalized tonic clonic seizures (Secondary GTCS are reported between 1/3 to 2/3 of children)

• Both seizure types are often related to sleep

• Onset occurs between the ages of 3 and 13 years (peak 9–10 years) and recovery occurs before the age of 15–16 years

• Genetic predisposition is common, and there is a male predominance

• EEG has blunt high-voltage centrotemporal spikes, often followed by slow waves that are activated by sleep and tend to shift or spread from side to side

• Duration usually brief 1-2min but may become longer if seizures progress to convulsion

• Prognosis excellent with a less than 2% risk of developing infrequent generalized seizures in adult life; absence seizures may be more common than GTCS

Hemifacial sensorimotor seizures

• 1/3 of patients

• May be the only ictal manifestation but are often associated with inability to talk and hypersalivation

• Mainly motor seizures- that may be entirely localized to lower lip manifesting with sudden, continuous or burst of clonic contractions

• Lasting from few seconds to 1 minute

• Ipsilateral tonic deviation of the mouth is also common

• Rarely, hemifacial convulsions may appear nearly simultaneously or spread to ipsilateral upper extremity, involvement of leg is rare

• Hemifacial sensory seizures are less common and consist of numbness in the corner of the mouth

• Conscious level preserved

Oropharyngo-laryngeal ictal manifestation

• Occurred 53% of seizures• The most characteristic of all other ictal symptoms • Consist of unilateral sensory and motor manifestation inside

the mouth, tongue, inner cheek, gums, teeth and pharyngo-laryngeal region• Sensory- unilateral numbness/ paresthesia• Motor- strange sound e.g. death rattle, gargling, grunting,

guttural sounds and their combinations

Arrest of speech

• More of ananarthria (loss of power and coordination for the articulation of words)• Occurs in >40%• Child is inarticulate and attempts to communicate with

gestures• A few mainly laryngeal sounds, not words, may be uttered

particularly at the beginning • Hypersalivation • Often associated with other ictal symptoms

Management:

• May not need AED especially if seizures are • Infrequent• Mild or nocturnal• Onset is close to the age of natural remission of this age-limited disorder

• May need AEDs if:• Frequent seizures ± secondary GTCS• Comorbid- tics, ADHD, learning disability

• AEDs may reduce GTCS but not focal seizure

• Empirically – carbamazepine is preferred

• Other AEDs- gabapentin, levetiracetam, sulthiame, sodium valproate

Q3: WHAT INVESTIGATIONS SHOULD I DO??

BLOOD INVESTIGATIONS

• FBC/ electrolytes/glucose level

• Additional tests:• Hemorrhagic basis - Coagulation profile• Toxicology – blood or urine• Genetic disease - possible karyotypes and other test specific to

illness • Metabolic disease – ammonia, lactate, IEM screening

LUMBAR PUNCTURE• Indicated when suspicious of brain infection

EEG• Most useful• Recommended in all children who experienced unprovoked

seizure• Still, abnormal EEG may not necessarily means epilepsy and

children with epilepsy may have normal EEG

NEUROIMAGING• Best is MRI brain • Indicated when:• Onset before the age of 2 years old • Focal onset seizure• Focal neurological abnormality • Abnormal EEG• Abnormal neurological examination • CT scan brain may be indicated to look for acute

symptomatic seizure e.g. post trauma

Q4: DOES THE CHILD REQUIRE TREATMENT??

• Usually not started on treatment until 2nd unprovoked seizure

• Indications for consideration of medication after 1st unprovoked seizure:

• Patient who presents with status epilepticus

• Patient with multiple risk factors to develop 2nd seizure

• Patient with abnormal EEG

• Starting treatment – case by case basis and after thorough discussion

made between physician and caregivers/ patients

Q5: WHAT ELSE SHOULD I THINK ABOUT??

Recurrence risk after 1st unprovoked seizure

• Two year risk 40-52%

• 24% with no risk factor and normal EEG

• 65% remote neurological insult and epileptiform EEG

• Dutch Study:10 children with epileptiform EEG patterns after their first seizure had a 2-year risk of 71%

• Two unprovoked non febrile seizures, the chance by 4 years is 73%, with a 95% confidence interval 60–90%

Berg AT, Shinnar S. The risk of recurrence following a first unprovoked seizure. Neurology 1991;41:965–72 Kim LG, Johnson TL, Marson AG, et al. Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial. Lancet Neurol 2006;5:317–322 Shinnar S, Berg AT, Moshe SL, et al. Risk of seizure recurrence following a first unprovoked seizure in childhood: a prospective study. Pediatrics 1990;85:1076–1085

• Assessing a child fully correct assessments have to be made at least 4 levels

• Disease: am I sure this is an epilepsy & not either a disease causing recurrent acute symptomatic seizure, or a disease causing events that are not seizure at all

• Seizure types: what semiology(s) am I seeing?

• Epilepsy syndrome

• Etiology

• If child’s epilepsy treatment is proving ineffective, review at each of these four levels: • Am I sure it is epilepsy? • Have I misinterpreted the seizure descriptions and selected the wrong drugs? • Have I missed a possibly progressive underlying cause?

• Referral to neurologist: (Malaysian paediatric protocol 3rd edition)

• Immediately if:• Behavioral or developmental regression• Infantile spasms

• Non-urgent if:• Poor seizure control despite monotherapy with 2 different anti-epileptic medication• Difficulty to control epilepsies beginning in the first 2 years of life• Structural lesion on neuroimaging

Epilepsy and Daily Life

• Psychosocial consequences of epilepsy can be more debilitating than seizure disorder itself

• Informed choices about activities need to be made on individual basis depending on type and frequency of seizures and level of control with medications

• Aim should be made to maximize participations in all age- appropriate aspects of life whilst taking realistic approach to risk management

SCHOOLING• Most attend mainstream school – may have evidence of

underachievement

• Neuropsychometry is recommended to define educational strengths and weaknesses and aid tailoring educational support

• Other mechanisms of adverse impact on schooling include• Nocturnal seizure and poor sleep• Brief undetected epileptic discharge • Drug toxicity• Inappropriate teacher and parental expectations• Absence from school• Low self esteem• Anxiety to poor adjustment and stressor at home

EMOTIONAL ADJUSTEMENT• Involves living with unpredictability – may erode self esteem

and confidence• Family prefer to live with predictable seizure pattern than risk

AED manipulation in attempt to control seizure• Unwanted effects of medications e.g. weight gain, hirsutism –

detrimental to self esteem• High and low of successive treatment failures• Anxiety, depression

RESPONSES• Establish good communication between

health, patient, family • Education• Encourage self-esteem, avoid

unnecessary restrictions• Minimize time off for clinic• Ensure full education• Sensitive monitoring• Avoid seizure trigger

IN AND AROUND WATER• Should be accompanied

• Shower vs. bath tub

CYCLING• Avoid traffic

• Protective gear

PHOTOSENSITIVITY• Current IT gadgets/ TV screen /computer screen – flicker free

• Avoid getting too close with monitors

DRIVING• Depends on requirement, e.g. must be seizure free for

at least 12 months

DEATH IN EPILEPSY• Epilepsy-related death in children may be due to• Complications of seizure• Convulsive status epilepticus• Related underlying disorder

• SUDEP (Sudden Unexpected, non-traumatic and non-drowning death in in children with epilepsy)• Risk factors for SUDEP• Young adult male• Early age of onset of seizure• GTC seizures• Increased frequency of seizure• Polytherapy and poor adherence to AED treatment

Take Home Messages:

1. Differential diagnosis of 1st seizure is broad

2. Most important diagnostic modality in evaluation of 1st

seizure is the history and physical examination

3. Epilepsy may be diagnosed after 1 unprovoked seizure

and treatment may be initiated

4. 70% - may achieve full seizure control with treatment

5. AED decision- based on seizure type/epilepsy syndrome

6. Wrong AED may worsen seizure

References: 1. Rob Forsyth, Richard Newton (eds.). Paediatric neurology. 2nd ed. Oxford: Oxford university press, 2012

2. Aspasia Michoulas, Kevin Farrell, Mary Connolly: approach to a child with a first afebrile seizure; BC medical journal vol. 53 no. 6, July/August 2011

3. A.B. Chelse, et. al, Initial Evaluation and Management of a First Seizure in Children; Pediatric Annals (Impact Factor: 0.29). 12/2013; 42(12):244-8. DOI: 10.3928/00904481-20131122-08

4. Ghofrani M. Approach To The First Unprovoked Seizure- PART I. Iran J Child Neurol. 2013 Summer; 7(3): 1- 5

5. Robert S. Fisher et. al, A practical clinical definition of epilepsy; Epilepsia,55(4):475–482,2014 doi:10.1111/epi.12550

6. Malaysian Paediatric Protocol, 3rd Edition

7. Laura Speltz, M.D. , Assessing First Seizures in Children and Adolescents, A pediatric perspective, Gillette Children’s Specialty Healthcare, volume 23, Number 1, 2014

8. The Epilepsies: Seizures, Syndromes and Management, Panayiotopoulos CP, Oxfordshire (UK): Bladon Medical Publishing; 2005.

Thank you…