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NEONATAL SEIZURES NEONATAL SEIZURES Trauma & Emergency System Trauma & Emergency System Perinatologi Division.Department of Perinatologi Division.Department of Child Health Child Health Medical Faculty of Hasanuddin Medical Faculty of Hasanuddin University University

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NEONATAL SEIZURESNEONATAL SEIZURES

Trauma & Emergency SystemTrauma & Emergency SystemPerinatologi Division.Department of Child Perinatologi Division.Department of Child

HealthHealthMedical Faculty of Hasanuddin UniversityMedical Faculty of Hasanuddin University

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DefinitionDefinition

Seizures are transient disturbances in brain function manifesting as episodic impairments in consciousness in association with abnormal motor or automatic activity.

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Probable Mechanisms of Some Neonatal Seizures

PROBABLE MECHANISM DISORDER

Failure of Na + -K + pump secondary to Hypoxemia, ischemia, adenosine triphosphate and hypoglycemiaExcess of excitatory neurotransmitter (eg.glutamic acid—excessive excitation) Hypoxemia, ischemia and hypoglycemiaDeficit of inhibitory neurotransmitter Pyridoxine dependency (i.e., relative excess of excitatory neurotransmitter) Membrane alteration— Na + Hypocalcemia and Permeability hypomagnesemia

_________________________________________________________________Volpe JJ.Neonatal Seizures:Neurology of the Newborn.4th ed.

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Classification of Neonatal Classification of Neonatal SeizuresSeizures

Clinical

Electroencephalographic

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Classification Classification I. Clinical Seizure Subtle Tonic Clonic Myoclonic

II. Electroencephalographic seizure

Epileptic Non-epileptic

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……..Clinical Classification..Clinical Classification

1. SubttleUsually occurs in association with other

types of seizures and may manifest with: Stereotypic movements of the

extremities such as bicycling or swimming movements. Deviation or jerking of the eyes with

repetitive blinking Drooling, sucking or chewing

movements. Apnea or sudden changes in respiratory

patterns. Rhythmic fluctuations in vital signs More in preterm than in term

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2. Tonic Primarily in Preterm May be focal or generalized Sustained extension of the upper and lower

limbs (mimics decerebrate posturing) Sustained flexion of upper with extension of

lower limbs (mimics decorticate posturing) Signals severe ICH in preterm infants In 85% of cases are not associated with any

autonomic changes such as increases in heart rate or blood pressure, or skin flushing.

……..Clinical Classification..Clinical Classification

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3. Clonic

Consist of slow (1-3 /minute) rhythmic jerking movements of the extremities. They may be focal or multi-focal. Each movement is composed of a rapid phase followed by a slow one.

Changing the position or holding the moving limb does not suppress the movements.

Commonly seen in full-term neonates >2500 grams Consciousness may be preserved Signals focal cerebral injury, infarction or metabolic

disturbances.

……..Clinical Classification..Clinical Classification

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……..Clinical Classification..Clinical Classification

4. Myoclonic

Focal, multifocal, or generalizedFocal myoclonic seizures typically

involve the flexor muscles of the extremities.

Multi-focal myoclonic seizures present as asynchronous twitching of several parts of the body.

Generalized myoclonic seizures present as massive flexion of the head and trunk with extension or flexion of the extremities. They are associated with diffuse CNS pathology

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Electroencephalographic seizureElectroencephalographic seizure

I. Epileptic Consistently associated with electro-

cortical seizure activity on the EEG Cannot be provoked by tactile stimulation Cannot be suppressed by restraint of

involved limb or repositioning of the infant Related to hyper synchronous discharges of

a critical mass of neuron

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Electroencephalographic Electroencephalographic seizuresseizures

II. Non-epileptic No electro-cortical signature: seizures

are initiated in the subcortical area and are not usually associated with any EEG changes.

Provoked by stimulation Suppressed by restraint or repositioning Brainstem release phenomena (reflex)

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ELECTROENCEPHALOGRAPHIC SEIZURE

CLINICAL SEIZURE COMMON UNCOMMON

Subtle +*Clonic Focal + Multifocal +Tonic Focal + Generalized +Myoclonic Focal, multifocal + Generalized +---------------------------------------------------------------------------------------------------------------*Only specific varieties of subtle seizures are commonly associate with simultaneous Electroencephalographic seizure activity.

Volpe JJ.Neonatal Seizures:Neurology of the Newborn.4 th ed.

Relation between Clinical seizure and EEG seizure

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Does absence of EEG seizure Does absence of EEG seizure activity indicate that a clinical seizure activity indicate that a clinical seizure

is non- epileptic?is non- epileptic?

Certain clinical seizures in the human newborn originate from electrical seizures in deep cerebral structures (limbic regions), or in diencephalic, or brain stem structures and thereby are either not detected by surface-recorded EEG or inconsistently propagated to the surface

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Surface EEG-Silent SeizureSurface EEG-Silent Seizure

Can “ surface EEG-silent ” seizure in the newborn result to brain injury?

Can this be eliminated by conventional anticonvulsant therapy?

Further investigation needed

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Benign Movements that are Not Benign Movements that are Not SeizuresSeizures

JitterinessSleep apneaIsolated sucking movementsBenign neonatal sleep myoclonus

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Jitteriness Versus Seizure

CLINICAL FEATURE JITTERINESS SEIZURE

Abnormality of gaze or eye - + movementMovements exquisitely stimulus + - sensitivePredominant movement Tremor Clonic jerking

Movements cease with passive + - flexionAutonomic changes - +The flexion and extension phases + -are equal in amplitudeEEG abnormalities - +/-------------------------------------------------------------------------------------------------------------------

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often seen in neonates with hypoglycemia, drug withdrawal, hypocalcemia, hypothermia and in (SGA) neonates.

spontaneously resolve within few weeks.

......Jitteriness (cont)......Jitteriness (cont)

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Sleep ApneaSleep ApneaNot associated with abnormal movements and is usually associated with bradycardia.

When seizures are present with apnea, abnormal movements, tachycardia and increased blood pressure are present as well.

Isolated Sucking MovementsRandom, infrequent and not well sustained sucking movements are not seizures.

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Benign Neonatal Sleep MyoclonusBenign Neonatal Sleep Myoclonus

They differ from myoclonic seizures in the following:

– can be triggered by noise or motion.– suppressed by the waking state.– not associated with any autonomic changes.

Predominantly seen in preterm neonates during sleep. They can be focal, multi-focal, or generalized. They do not stop with restraint. Resolve spontaneously within a few minutes and require no medication.

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Most Common Causes of SeizuresMost Common Causes of Seizures HIE Infections (TORCH, meningitis, septicemia) Hypoglycemia, hypocalcemia,

hypomagnesemia CNS bleed (intraventricular, subdural, trauma,

etc.)Less Common Causes of SeizuresLess Common Causes of Seizures

Congenital brain anomalies Inborn errors of metabolism Maternal drug withdrawal (heroin,

barbiturates, methadone, cocaine, etc.) Kernicterus Pyridoxine (B6) dependency, and

hyponatremia

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Diagnosis of SeizuresDiagnosis of Seizures

Obtain a good maternal and obstetric history;Pregnancy history is important

Search for history that supports TORCH infections History of fetal distress, preeclampsia or maternal

infectionsDelivery history:

type of delivery and antecedent events Apgar scores offer some guidance : Low Apgar

score without the need for resuscitation and subsequent neonatal intensive care is unlikely to be associated with neonatal seizures

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……..Diagnosis of Seizures..Diagnosis of Seizures

Postnatal historyNeonatal seizures in infants without uneventful antenatal history and delivery may result from postnatal causeTremulousness may be secondary to drug withdrawal or hypocalcemiaTemperature and blood pressure instability may suggest infection.

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Laboratory InvestigationsLaboratory Investigations

Primary tests Blood glucose Blood calcium and magnesium Complete blood count, differential

leukocytic count and platelet count Electrolytes Arterial blood gas Cerebral spinal fluid analysis and cultures Blood cultures

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TORCH titers, ammonia level, head sonogram and amino acids in urine.

EEG Normal in about 1/3 of cases

Cranial ultrasound For hemorrhage and scarring

CT To diagnose cerebral malformations and hemorrhage

…….Laboratory Investigations, cont.Laboratory Investigations, cont

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Management of SeizuresManagement of Seizures

Management goals To minimize brain damage Achieve systemic homeostasis

(airway, breathing and circulation). Correct the underlying cause if

possible.

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Medical Management : 10% dextrose solution (2cc/kg IV) empirically to

any seizing neonate. Anticonvulsant drugs Calcium gluconate (200mg/kg IV), if

hypocalcemia is suspected . Magnesium sulfate 50%, 0.2ml/kg or 2 mEq/kg. In pyridoxine dependency give pyridoxine

50mg IV as a therapeutic trial. Seizures will stop within minutes.

Antibiotics in suspected sepsis. Be prepared to manage any complication

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Stopping Seizures with AnticonvulsantsStopping Seizures with Anticonvulsants

Drug Dose Comments Side Effects

Phenobarbital Loading dose: 10-20 mg/kg. Add 5 mg/kg to a maximum of 40 mg/kg

Maintenance:

3-5 mg/kg/day in divided doses every 12 hours.

It is the drug of choice.

Administer IV over 5 minutes.

Therapeutic level: 20-40 g/ml.

Administer IM, IV, or PO every 12 hours.

Begin therapy 12 hours after loading dose.

Hypotension Apnea Monitor

respiratory status during administration and assess IV site.

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Drug Dose Comments Side Effects When seizures are not controlled with phenobarbital alone.

Phenytoin

Loading dose: 15-20 mg/kg IV over 30 min.

Maintenance:

3-5 mg/kg/day.

Administer IV at a maximum rate of 0.5 mg/kg/min

Maintenance: 4-8 mg/kg/day by IV push or PO.

Divide total dose and administer IV every 12 hours.

Do not give IM. Toxicity is a

problem with this drug.

Cardiac arrhythmias

Cerebellar damage

Stopping Seizures with AnticonvulsantsStopping Seizures with Anticonvulsants

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Drug Dose Comments Side Effects For treatment of status epilepticus.

Benzodiazepines Lorazepam: 0.05 – 0.1 mg/kg

Diazepam: 0.1 – 0.3 mg/kg/dose.

Administer IV. Repeat every 15

minutes for 2-3 doses if needed.

Maximum dose is 2-5 mg.

It can be given once as a PO dose of 0.1-0.3 mg/kg.

Respiratory depression,

Interferes with bilirubin binding to albumin

Stopping Seizures with AnticonvulsantsStopping Seizures with Anticonvulsants

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When to Stop Anticonvulsant Drugs / When to Stop Anticonvulsant Drugs / AEDSAEDS

No specific practice guidelines for the timing for stopping these medications, however:

Stopping AEDs two weeks after last seizure episode is acceptable as prolonged medication can adversely affect the developing brain.

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Discontinuation before discharging from the neonatal unit is generally recommended unless the neonate demonstrates a significant brain lesion on head sonogram or CT, or abnormal neurological signs at the time of discharge.

When to Stop Anticonvulsant Drugs / When to Stop Anticonvulsant Drugs / AEDS (cont)AEDS (cont)

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Determinants of Duration of Determinants of Duration of anticonvulsant therapy for neonatal anticonvulsant therapy for neonatal

seizuresseizures

Neonatal neurological examination

Cause of neonatal seizure

Electroencephalogram

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PrognosisPrognosis

Two most useful approaches in utilizing outcome EEG

Recognition of the underlying neurological disease

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ComplicationsComplications

Cerebral palsy Hydrocephalus Epilepsy Spasticity Feeding difficulties

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ConsultationsConsultations

Neurology consult needed for - evaluation of seizures - evaluation of EEG and video EEG monitoring - management of anticonvulsant medications

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Further Outpatient CareFurther Outpatient Care

Neurology outpatient evaluation Developmental evaluation for early

identification of physical or cognitive deficits Orthopedic evaluations if with joint

deformities Consider physical medicine/physical therapy

referral if indicated

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ReferencesReferences

1.Volpe JJ.Neonatal seizures. In:Neurology of the newborn.4th ed.Philadelphia,Pa:WB Saunders's Co;2001:178-214

2.Hahn J,Olson D.Etiology of neonatal seizures.NeoReviews.2004;5:327-335

3.Riviello,J.Drug therapy for neonatal seizures:Part I.NeoReviews.2004;5:215-220

4.Riviello,J.Drug therapy for neonatal seizures:Part II.NeoReviews.2004;5:262-268

5.Fanaroff A,Martin R,Neonatal seizures.In:Neonatal-Perinatal Medicine-Diseases of the fetus and infant.6th ed.St.Louis,MO:Mosby-Yearbook Inc.1997:899-911

6.Sheth R, Neonatal seizures;Emedicine.com

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Thank You