In the name of

GOD

Seizure & epilepsy Seizure & epilepsy in childrenin children

S. InalooS. Inaloo Department of PediatricDepartment of Pediatric

Shiraz University of Medical SciencesShiraz University of Medical Sciences

DefinitionsDefinitions Seizure: the clinical manifestation of Seizure: the clinical manifestation of

an abnormal and excessive excitation an abnormal and excessive excitation and synchronization of a population and synchronization of a population of cortical or brain stem neuronsof cortical or brain stem neurons

Epilepsy: two or more recurrent Epilepsy: two or more recurrent seizures with interval more than 24 seizures with interval more than 24 hours unprovoked by systemic or hours unprovoked by systemic or acute neurologic insultsacute neurologic insults

Convulsion : motor seizure Convulsion : motor seizure

Epidemiology of Epidemiology of Seizures and Seizures and

EpilepsyEpilepsy Seizures Seizures

Incidence: approximately Incidence: approximately 80/100,000 per year80/100,000 per year

Lifetime prevalence: 9% Lifetime prevalence: 9% (1/3 benign febrile convulsions)(1/3 benign febrile convulsions)

Epilepsy Epilepsy Incidence: approximately Incidence: approximately

45/100,000 per year45/100,000 per yearPoint prevalence: 0.5-1%Point prevalence: 0.5-1%

International International League Against League Against Epilepsy (ILAE)Epilepsy (ILAE)

Classification Classification of epilepsyof epilepsy

19891989( ( ILAEILAE ) )classificationclassification

1.1. Localization related epilepsy (focal or Localization related epilepsy (focal or partial) partial)

a.a. Simple Simple b.b. ComplexComplexc.c. Partial with secondary generalization Partial with secondary generalization

2.2. Generalize (convulsive Generalize (convulsive –– non convulsive) non convulsive)a.a. Absence (typical, atypical)Absence (typical, atypical)b.b. Myoclonic Myoclonic c.c. Clonic Clonic d.d. Tonic Tonic e.e. Tonic clonic (grandmal) Tonic clonic (grandmal) f.f. Atonic Atonic

3.3. Unclassified Unclassified

ClassificationClassification

Primary (idiopathic)Primary (idiopathic)

Secondary (symptomatic)Secondary (symptomatic)

Cryptogenic Cryptogenic

Reactive seizure (F.C, toxic, Reactive seizure (F.C, toxic, metabolic, infection, early post- metabolic, infection, early post- trauma) trauma)

Special syndromes Special syndromes

Diagnosis of seizureDiagnosis of seizure

Clinical Hx: (aura, postictal, video Clinical Hx: (aura, postictal, video monitoring) monitoring)

Repeated EEGRepeated EEG

EEG after sleep deprivation, EEG after sleep deprivation, hyperventilation, or 24 hr hyperventilation, or 24 hr

ambulatory EEGambulatory EEG

Prolactin Prolactin

Questions Raised by a Questions Raised by a First SeizureFirst Seizure

Seizure or not?Seizure or not?

Focal onset?Focal onset?

Evidence of interictal CNS dysfunction?Evidence of interictal CNS dysfunction?

Metabolic precipitant?Metabolic precipitant?

Seizure type? Syndrome type?Seizure type? Syndrome type?

Studies?Studies?

Start AED?Start AED?

Seizure PrecipitantsSeizure Precipitants Metabolic and Electrolyte ImbalanceMetabolic and Electrolyte Imbalance Stimulant/other proconvulsant intoxication and Stimulant/other proconvulsant intoxication and

medication medication Sedative or ethanol withdrawalSedative or ethanol withdrawal Sleep deprivationSleep deprivation Antiepileptic medication reduction or inadequate Antiepileptic medication reduction or inadequate

AED treatmentAED treatment Hormonal variationsHormonal variations Stress, excitation, fatigueStress, excitation, fatigue HV, Alkalosis HV, Alkalosis Fever or systemic infectionFever or systemic infection Concussion and/or closed head injuryConcussion and/or closed head injury

Evaluation of a First Evaluation of a First SeizureSeizure

History, physical (HC, BP, ophtal, skin, CV, NE)History, physical (HC, BP, ophtal, skin, CV, NE) Blood tests: CBC, electrolytes, Blood tests: CBC, electrolytes, glucoseglucose, ,

Calcium, Magnesium, phosphate, hepatic and Calcium, Magnesium, phosphate, hepatic and renal functionrenal function

Lumbar puncture only if meningitis or Lumbar puncture only if meningitis or encephalitis or subarachnoid hemorrhage encephalitis or subarachnoid hemorrhage suspected and potential for brain herniation is suspected and potential for brain herniation is ruled outruled out

Blood or urine screen for drugsBlood or urine screen for drugs EEGEEG CT or MRI brain scanCT or MRI brain scan

Indication of CT or MRIIndication of CT or MRI

1.1. Abnl neurologic exam Abnl neurologic exam 2.2. Dysmorphic featureDysmorphic feature3.3. Skin lesion Skin lesion 4.4. Focal EEG abnormalities (63%) *Focal EEG abnormalities (63%) *5.5. Hx of neonatal seizure (100%) *Hx of neonatal seizure (100%) *6.6. Hx of compatible with simple partial or Hx of compatible with simple partial or

complex partial seizure * complex partial seizure * 7.7. Before epileptic surgery Before epileptic surgery 8.8. Sign of Sign of ICP ICP9.9. Unresponsive to anticonvulsant Unresponsive to anticonvulsant 10.10. Change of seizure type Change of seizure type 11.11. Seizure after trauma Seizure after trauma

EEG AbnormalitiesEEG Abnormalities Background abnormalities: significant Background abnormalities: significant

asymmetries and/or degree of slowing asymmetries and/or degree of slowing inappropriate for clinical state or ageinappropriate for clinical state or age

Interictal abnormalities associated Interictal abnormalities associated with seizures and epilepsywith seizures and epilepsy SpikesSpikes Sharp wavesSharp waves Spike-wave complexesSpike-wave complexes

May be focal, lateralized, generalizedMay be focal, lateralized, generalized

Medical Treatment of Medical Treatment of First SeizureFirst Seizure

Whether to treat first seizure is Whether to treat first seizure is

controversialcontroversial

16-62% will recur within 5 years16-62% will recur within 5 years

Relapse rate might be reduced by antiepileptic drug Relapse rate might be reduced by antiepileptic drug treatmenttreatment

Abnormal imaging, abnormal neurological exam, Abnormal imaging, abnormal neurological exam, abnormal EEG or family history increase relapse riskabnormal EEG or family history increase relapse risk

Quality of life issues are importantQuality of life issues are important

Reference: First Seizure Trial Group. Randomized Clinical Trial on the efficacy of antiepileptic drugs in reducing Reference: First Seizure Trial Group. Randomized Clinical Trial on the efficacy of antiepileptic drugs in reducing the the risk of relapse after a first unprovoked tonic-clonic seizure. Neurology 1993; 43 (3, part1): 478-483.risk of relapse after a first unprovoked tonic-clonic seizure. Neurology 1993; 43 (3, part1): 478-483.Reference: Camfield P, Camfield C, Dooley J, Smith E, Garner B. A randomized study of carbamazepine versus Reference: Camfield P, Camfield C, Dooley J, Smith E, Garner B. A randomized study of carbamazepine versus no medication after a first unprovoked seizure in childhood. Neurology 1989; 39: 851-852.no medication after a first unprovoked seizure in childhood. Neurology 1989; 39: 851-852.

Choosing Antiepileptic Choosing Antiepileptic DrugsDrugs

Seizure typeSeizure type Age and sex Age and sex Epilepsy syndromeEpilepsy syndrome Pharmacokinetic profilePharmacokinetic profile Interactions/other medical conditionsInteractions/other medical conditions EfficacyEfficacy Expected adverse effectsExpected adverse effects CostCost Availability Availability

Febrile seizure is the most Febrile seizure is the most

common ped. neurologic common ped. neurologic

problems incidenceproblems incidence

33 – – 5%5% 10%-15% 10%-15%

DefinitionDefinition Age (2 month-6 yr) Age (2 month-6 yr)

Fever (Temp >38)Fever (Temp >38)

No Hx of previous afebrile seizure No Hx of previous afebrile seizure

No acute systemic metabolic abnormality that No acute systemic metabolic abnormality that may produce convulsion may produce convulsion

No CNS infection or inflammation No CNS infection or inflammation

Simple Simple

Febrile seizure Duration > 15 -Febrile seizure Duration > 15 -30 min 30 min

Complex > 1 episode / 24 Complex > 1 episode / 24 hrhr

Focal seizure or Focal seizure or todd’stodd’s

paralysis paralysis

Indication for AdmissionIndication for Admission

1.1. Suspicion of a more serious Suspicion of a more serious underlying condition underlying condition

2.2. Complex F.SComplex F.S

3.3. Age less than 18 months Age less than 18 months

4.4. Early review by a doctor is not Early review by a doctor is not possiblepossible

5.5. Home circumstance are inadequate Home circumstance are inadequate or parents unable to cooperate or parents unable to cooperate

InvestigationsInvestigations

B.S B.S ± ± calcium calcium ± ± electrolyte electrolyte

Age < 12m specially < 6 monthsAge < 12m specially < 6 months Lp Long lasting or otherwise atypical convulsion Lp Long lasting or otherwise atypical convulsion Faille promptly to recover full consciousness Faille promptly to recover full consciousness Suspicious to meningitis or encephalitis or Suspicious to meningitis or encephalitis or

subarachnoidsubarachnoid hemorrhagehemorrhage EEG EEG

Neuroimaging Neuroimaging

Prognosis Prognosis single of FC 60- single of FC 60-70%70%

> 3 episodes > 3 episodes 9% 9%

2-3 episodes 2-3 episodes Others Others

Risk of afebrile seizure Risk of afebrile seizure 2-5% 2-5%

TreatmentTreatment

- Long term Anti convulsant therapy Long term Anti convulsant therapy (PB VPA) (PB VPA) 2/3 in recurrence 2/3 in recurrence

- PHT, CBZ not effectivePHT, CBZ not effective- Diazepam prophylaxy 1 mg/kg/day Diazepam prophylaxy 1 mg/kg/day

Divided Q 8 hr during febrile illness Divided Q 8 hr during febrile illness - Rectal diazepamRectal diazepam 0.3-0.5 mg/kg/dose 0.3-0.5 mg/kg/dose

if seizure happen if seizure happen

Diazepam rectally during seizureDiazepam rectally during seizure

Children 1-3 y/o or < 10 kg Children 1-3 y/o or < 10 kg 5mg 5mg

Children over 3 y/o and adult or > 10 kg Children over 3 y/o and adult or > 10 kg

10mg 10mg

if necessary repeated after 5 min.if necessary repeated after 5 min.

Management of seizure Management of seizure (acute)(acute)

1. ABC1. ABC

2. IV line2. IV line D/W 10% 5cc/kgD/W 10% 5cc/kg

3. Diazepam IV 0.1-0.3 mg/kg 2mg/min or3. Diazepam IV 0.1-0.3 mg/kg 2mg/min or rectal 0.3 rectal 0.3 –– 0.5 mg/kg 0.5 mg/kg

Dilanthin 15-30 mg/kg IV (1mg/kg/min) [N/S]Dilanthin 15-30 mg/kg IV (1mg/kg/min) [N/S]12 hr later 3-9 mg/kg Q 12yr 12 hr later 3-9 mg/kg Q 12yr Or phenobarbital 15-20 mg/kg over 10-30 min Or phenobarbital 15-20 mg/kg over 10-30 min then 3- then 3- mg/kg Q12 hr mg/kg Q12 hr

Seizure type Seizure type Generalize Tonic Clonic Generalize Tonic Clonic

Aura Aura partial seizure partial seizure

Postictal ± Postictal ±

Drug Drug CarbamazepinCarbamazepin lamotriginelamotrigine

Valporate, Valporate, TopiramateTopiramate

Phenytoin Phenytoin OxcarbazepinOxcarbazepin

PrimidonePrimidone Zonisamide Zonisamide

Phenobarbital Phenobarbital LevetiracetaLevetiraceta

Absence (petitmal)Absence (petitmal)

Brief arrest of consciousnessBrief arrest of consciousness

5 5 –– 10 sec 10 sec 20/day20/day

Aura Aura ΘΘ Postictal Postictal ΘΘ automatism ±automatism ±

64%64% 5-9 y/o5-9 y/o F>M F>M

EEG 3CPS EEG 3CPS 90% HV 90% HV

40% GTC40% GTC 70% Minor movement 70% Minor movement

Drug Drug Ethosuximide, Valporate, Lamotrigine, Ethosuximide, Valporate, Lamotrigine, Benzodiazepine, Levetiracetam, Topiramate, Benzodiazepine, Levetiracetam, Topiramate, ZonisamideZonisamide

Carbamazepine & Phenytoin, aggravate, absence Carbamazepine & Phenytoin, aggravate, absence

Juvenile myoclonic (Janz)Juvenile myoclonic (Janz)

30% absence 30% absence

Brief myoclonic jerk early morning awake Brief myoclonic jerk early morning awake

Age Age 15 y/o 15 y/o IQ IQ Nl Nl 1/day1/day

EEG EEG 3CPS 3CPS 4-6 HZ/sec 4-6 HZ/sec

1/3 photosensitive 1/3 photosensitive

Drug Drug Valporate, Lamotrigine, Valporate, Lamotrigine, Clonazepam, Levetiracetam, Topiramat, Clonazepam, Levetiracetam, Topiramat, ZonisamideZonisamide

Carbamazepine & Phenytoin, lamotrigine, Carbamazepine & Phenytoin, lamotrigine, aggravate, myoclonic aggravate, myoclonic

Complex partial seizureComplex partial seizure

Psychomotor seizure, temporal lobe epilepsy Psychomotor seizure, temporal lobe epilepsy

Focus Focus frontal, occipital, temporal frontal, occipital, temporal

Aura Aura automatism automatism Postictal ±Postictal ±

Flushing or pallor, rubbing, staring, Flushing or pallor, rubbing, staring, LOC, LOC, nausea, vomiting, oral movement, dreaming, nausea, vomiting, oral movement, dreaming, speech disorder, incontinence, aggressive speech disorder, incontinence, aggressive activity activity

Pathology Pathology MTS, Tumor MTS, Tumor

R/: CBZ, VPA, PHY, PMD, PB?, LMC, GBP, Tpx, R/: CBZ, VPA, PHY, PMD, PB?, LMC, GBP, Tpx, VGB, Oxcarbazepine, Levetiracetam, VGB, Oxcarbazepine, Levetiracetam, zonisamidezonisamide

Simple partialSimple partial

Most common form in child Most common form in child versive versive

EEG 1/3 EEG 1/3 nl nl

Focal motor seizureFocal motor seizure hemiplegic hemiplegic todd paralysis todd paralysis

R/: CBZ, VPA, PHY, PMD, PB?, LMC, R/: CBZ, VPA, PHY, PMD, PB?, LMC, GBP, Tpx, VGB, Oxcarbazepine, GBP, Tpx, VGB, Oxcarbazepine, Levetiracetam, zonisamideLevetiracetam, zonisamide

RolandicRolandicMost common idiopathic focal epilepsy Most common idiopathic focal epilepsy Benign childhood epilepsy with centrotemporal spike Benign childhood epilepsy with centrotemporal spike

sylvian epilepsysylvian epilepsyA.D. 10% of epilepsy A.D. 10% of epilepsy Age 5-10 y/o (75%)Age 5-10 y/o (75%) less frequent less frequent 3-4 episode 3-4 episodeAura Aura somatosensory somatosensory mouth & tongue speech arrest, mouth & tongue speech arrest,

or facial movement or facial movement ¾¾ in sleep in sleep EEG EEG mid temporal spike mid temporal spike R/: CBZR/: CBZ 2y or age 13-14 y.o 2y or age 13-14 y.o

Benign occipitalBenign occipital

15 m to 17 y.o15 m to 17 y.o visual symptomvisual symptom

EEG EEG near continous HV spike wave near continous HV spike wave occipital (HVSW) or post temporal occipital (HVSW) or post temporal (close eye) (close eye)

Good prognosis Good prognosis recovered = recovered = 13 y/o13 y/o

Eye open Eye open ΘΘ EEG EEG

Treatment: CBZTreatment: CBZ

Lennox Gastaut Syndrome Lennox Gastaut Syndrome (LGS)(LGS)

Mixed type seizure Mixed type seizure MR, NDDMR, NDDSpike wave 1.5-2.5 Hz, multiple spike, Spike wave 1.5-2.5 Hz, multiple spike, slow background slow background

VPA, LMC, TPX, FBM, KDG, IVIG, ACTH, VPA, LMC, TPX, FBM, KDG, IVIG, ACTH, Prednisolone, BNZPrednisolone, BNZ

Infantile spasmInfantile spasm

Flexion extension mixed Flexion extension mixed

66% EEG hypsarrlythmia 66% EEG hypsarrlythmia R/: ACTH, prednisolon, Vit B6, BZN, R/: ACTH, prednisolon, Vit B6, BZN,

VGB VPA, LMC, TPxVGB VPA, LMC, TPx

Cryptogenic

Symptomatic (PKU, MSUD, T.S,

Pyridoxin, urea cycle, HIE,

CNS infection,

CNS dysgenesis)

Abdominal epilepsyAbdominal epilepsy

Periumblical pain Periumblical pain

5-10 min 5-10 min 24-36 hr 24-36 hr

awarness awarness

1.1. Abnl EEGAbnl EEG

2.2. Associated with other symptoms of Associated with other symptoms of epilepsy (cps)epilepsy (cps)

3.3. Good response to AEDGood response to AED

Follow-upFollow-up

Monitoring response of patients to Monitoring response of patients to medication medication

Drug adverse effect Drug adverse effect

Other work-up in follow-up? Other work-up in follow-up?

What time of DC drug? What time of DC drug?

Duration of therapyDuration of therapy

Dependent to Type of seizure Dependent to Type of seizure

Etiology of seizure Etiology of seizure

Response to treatment Response to treatment

At least two years At least two years

Taper over 2-6 monthsTaper over 2-6 months

Discontinuing AEDsDiscontinuing AEDs Seizure freedom for Seizure freedom for 2 years2 years

implies overall >60% chance of successful implies overall >60% chance of successful withdrawal in some epilepsy syndromeswithdrawal in some epilepsy syndromes

Favorable factorsFavorable factors Control achieved easily on one drug at low doseControl achieved easily on one drug at low dose No previous unsuccessful attempts at withdrawalNo previous unsuccessful attempts at withdrawal Normal neurologic exam and EEGNormal neurologic exam and EEG Primary generalized seizures except JMEPrimary generalized seizures except JME ““BenignBenign”” syndrome syndrome

Consider relative risks/benefits (e.g., Consider relative risks/benefits (e.g., driving, pregnancy)driving, pregnancy)

Non-Drug Treatment/Non-Drug Treatment/Lifestyle ModificationsLifestyle Modifications

Adequate sleepAdequate sleep

Avoidance of alcohol, stimulants, Avoidance of alcohol, stimulants, etc.etc.

Avoidance of known precipitantsAvoidance of known precipitants

Stress reduction Stress reduction —— specific specific techniquestechniques

Other therapyOther therapy

Ketogenic DietKetogenic Diet

Vagus nerve stimulation Vagus nerve stimulation

Surgery Surgery

IVIGIVIG

Steroid Steroid

Differential Diagnosis of Differential Diagnosis of seizureseizure

Breath-holding spellsBreath-holding spells SyncopeSyncope MigraineMigraine Cerebral ischemiaCerebral ischemia Movement disorder (Tic, Chorea, Movement disorder (Tic, Chorea,

…)…) Sleep disorderSleep disorder Psychiatric disturbancePsychiatric disturbance

First AidFirst AidTonic-Clonic SeizureTonic-Clonic Seizure

Turn person on side with face turned Turn person on side with face turned toward ground to keep airway clear, toward ground to keep airway clear, protect from nearby hazardsprotect from nearby hazards

Transfer to hospital needed for:Transfer to hospital needed for: Multiple seizures or status epilepticusMultiple seizures or status epilepticus Person is pregnant, injured, diabeticPerson is pregnant, injured, diabetic New onset seizuresNew onset seizures

DO NOT put any object in mouth or DO NOT put any object in mouth or restrainrestrain