NEONATAL SEIZURESTrauma & Emergency SystemNeonatologi Division.Department of Child HealthMedical Faculty of Hasanuddin University

Definition

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

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 acidexcessive 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.

Classification of Neonatal Seizures

Clinical

Electroencephalographic

Classification I. Clinical SeizureSubtleTonicClonicMyoclonic

II. Electroencephalographic seizureEpileptic Non-epileptic

..Clinical Classification1. 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

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 infantsIn 85% of cases are not associated with any autonomic changes such as increases in heart rate or blood pressure, or skin flushing.

..Clinical Classification

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 gramsConsciousness may be preservedSignals focal cerebral injury, infarction or metabolic disturbances.

..Clinical Classification

..Clinical Classification4. 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

Electroencephalographic seizureI. EpilepticConsistently associated with electro-cortical seizure activity on the EEGCannot be provoked by tactile stimulationCannot be suppressed by restraint of involved limb or repositioning of the infantRelated to hyper synchronous discharges of a critical mass of neuron

Electroencephalographic seizuresII. Non-epilepticNo electro-cortical signature: seizures are initiated in the subcortical area and are not usually associated with any EEG changes.Provoked by stimulationSuppressed by restraint or repositioningBrainstem release phenomena (reflex)

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.4th ed.Relation between Clinical seizure and EEG seizure

Jitteriness Versus Seizure

CLINICAL FEATUREJITTERINESSSEIZURE

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 - +/-------------------------------------------------------------------------------------------------------------------

often seen in neonates with hypoglycemia, drug withdrawal, hypocalcemia, hypothermia and in (SGA) neonates.spontaneously resolve within few weeks.

......Jitteriness (cont)

Most Common Causes of SeizuresPerinatal asphyxia Hypoxic Ischemic EnchephalopathyIntracranial hemorrhage : subarachnoid, perivntricular/intraventricular, subduralMetabolic disturbances (Hypoglycemia, hypocalcemia, hypomagnesemia)Infections (TORCH, meningitis, septicemia)

Less Common Causes of SeizuresCongenital brain anomaliesInborn errors of metabolismMaternal drug withdrawal (heroin, barbiturates, methadone, cocaine, etc.)Kernicterus Pyridoxine (B6) dependency, and hyponatremia

Diagnosis of Seizures

A. HistoryObtain a good maternal and obstetric history;Pregnancy history is importantSearch for history that supports TORCH infectionsHistory of fetal distress, preeclampsia or maternal infectionsMaternal drug historyDelivery history: type of delivery and antecedent eventsApgar 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

..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.

Diagnosis of Seizures

A. Physical examinationDetermine :Gestational ageBlood pressurePresence of skin lesionPrecense of hepatosplenomegaly

B. Neurologic evaluationC. Notation of the seizure pattern ( onset, spread, nature, duration, and level of conciousness)

*Laboratory InvestigationsPrimary testsBlood glucoseBlood calcium and magnesiumComplete blood count, differential leukocytic count and platelet countElectrolytesArterial blood gasCerebral spinal fluid analysis and culturesBlood cultures

*TORCH titers, ammonia level, head sonogram and amino acids in urine.EEG Normal in about 1/3 of casesCranial ultrasound For hemorrhage and scarringCT To diagnose cerebral malformations and hemorrhage

.Laboratory Investigations, cont

*Management of SeizuresManagement goalsTo minimize brain damageAchieve systemic homeostasis (airway, breathing and circulation).Correct the underlying cause if possible.

*Stopping 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.

*Stopping Seizures with Anticonvulsants

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 Anticonvulsants

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

Medical Management :10% dextrose solution (2cc/kg IV) empirically to any seizing neonate.Anticonvulsant drugsCalcium 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

*When to Stop Anticonvulsant Drugs / AEDS 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.

*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 / AEDS (cont)

Determinants of Duration of anticonvulsant therapy for neonatal seizures

Neonatal neurological examination

Cause of neonatal seizure

Electroencephalogram

PrognosisTwo most useful approaches in utilizing outcome EEG

Recognition of the underlying neurological disease

ComplicationsCerebral palsyHydrocephalusEpilepsySpasticityFeeding difficulties

Further Outpatient CareNeurology outpatient evaluationDevelopmental evaluation for early identification of physical or cognitive deficitsOrthopedic evaluations if with joint deformitiesConsider physical medicine/physical therapy referral if indicated

References1.Volpe JJ.Neonatal seizures. In:Neurology of the newborn.4th ed.Philadelphia,Pa:WB Saunders's Co;2001:178-2142.Hahn J,Olson D.Etiology of neonatal seizures.NeoReviews.2004;5:327-3353.Riviello,J.Drug therapy for neonatal seizures:Part I.NeoReviews.2004;5:215-2204.Riviello,J.Drug therapy for neonatal seizures:Part II.NeoReviews.2004;5:262-2685.Fanaroff A,Martin R,Neonatal seizures.In:Neonatal-Perinatal Medicine-Diseases of the fetus and infant.6th ed.St.Louis,MO:Mosby-Yearbook Inc.1997:899-9116.Sheth R, Neonatal seizures;Emedicine.com

Thank You

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