NEONATAL SEIZURES

Trauma & Emergency System Perinatologi Division.Department of Child Health Medical 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
Failure of Na + -K + pump secondary to adenosine triphosphate Excess of excitatory neurotransmitter (eg.glutamic acidexcessive excitation)

DISORDER
Hypoxemia, ischemia, and hypoglycemia

Deficit of inhibitory neurotransmitter (i.e., relative excess of excitatory neurotransmitter) Membrane alteration Na + Hypocalcemia and Permeability hypomagnesemia _________________________________________________________________
Volpe JJ.Neonatal Seizures:Neurology of the Newborn.4th ed.

Hypoxemia, ischemia and hypoglycemia Pyridoxine dependency

Classification of Neonatal Seizures

Clinical Electroencephalographic

Classification
I. Clinical Seizure Subtle Tonic Clonic Myoclonic II. Electroencephalographic seizure Epileptic Non-epileptic

..Clinical Classification
1. Subttle Usually 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

..Clinical Classification
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
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
4. Myoclonic

Focal, multifocal, or generalized Focal 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 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

Electroencephalographic seizures
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)

Relation between Clinical seizure and EEG seizure

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.

Does absence of EEG seizure activity indicate that a clinical seizure 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 surfacerecorded EEG or inconsistently propagated to the surface

Surface 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

Benign Movements that are Not Seizures

Jitteriness Sleep apnea Isolated sucking movements Benign neonatal sleep myoclonus

Jitteriness Versus Seizure

CLINICAL FEATURE JITTERINESS SEIZURE

Abnormality of gaze or eye movement Movements exquisitely stimulus sensitive Predominant movement Movements cease with passive flexion Autonomic changes The flexion and extension phases are equal in amplitude EEG abnormalities

+ -

Tremor
+

Clonic jerking
-

+
-

+ +/-

------------------------------------------------------------------------------------------------------------------

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

Sleep Apnea
Not 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 Movements

Random, infrequent and not well sustained sucking movements are not seizures.

Benign 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.

Most Common Causes of Seizures

HIE Infections (TORCH, meningitis, septicemia) Hypoglycemia, hypocalcemia, hypomagnesemia CNS bleed (intraventricular, subdural, trauma, etc.)

Less 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

Diagnosis 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 infections Delivery 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

..Diagnosis of Seizures
Postnatal history Neonatal seizures in infants without uneventful antenatal history and delivery may result from postnatal cause Tremulousness may be secondary to drug withdrawal or hypocalcemia Temperature and blood pressure instability may suggest infection.

Laboratory 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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.Laboratory Investigations, cont

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

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Management 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

Stopping Seizures with Anticonvulsants

Drug Dose Comments Side Effects

Phenobarbital Loading dose:

It is the drug of Hypotension 10-20 mg/kg. choice. Apnea Add 5 mg/kg to Administer IV a maximum of over 5 minutes. 40 mg/kg Therapeutic level: 20-40 g/ml. Maintenance: Administer IM, Monitor 3-5 mg/kg/day respiratory IV, or PO every in divided status during 12 hours. doses every 12 Begin therapy administration hours. and assess IV 12 hours after site. loading dose. 27

Stopping Seizures with Anticonvulsants

Drug Dose Comments Side Effects

When seizures are not controlled with phenobarbital alone. Phenytoin Loading dose: Administer IV at 15-20 mg/kg IV a maximum rate over 30 min. of 0.5 mg/kg/min Maintenance: 4 Maintenance: 8 mg/kg/day by 3-5 mg/kg/day. 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

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Stopping Seizures with Anticonvulsants

Drug Dose Comments Side Effects

For treatment of status epilepticus.

Benzodiazepines Lorazepam: Administer IV. Respiratory 0.05 0.1 mg/kg Repeat every 15 depression, Diazepam: 0.1 minutes for 2-3 Interferes with 0.3 mg/kg/dose. doses if needed. bilirubin binding to Maximum dose is albumin 2-5 mg. It can be given once as a PO dose of 0.1-0.3 mg/kg. 29

When to Stop Anticonvulsant Drugs / AEDS

No specific practice guidelines for the timing for stopping these medications, however: AEDs two weeks after last seizure episode is acceptable as prolonged medication can adversely affect the developing brain.

Stopping

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When to Stop Anticonvulsant Drugs / AEDS (cont)

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.

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Determinants of Duration of anticonvulsant therapy for neonatal seizures

Neonatal neurological examination

Cause of neonatal seizure

Electroencephalogram

Prognosis
Two most useful approaches in utilizing outcome

EEG Recognition of the underlying neurological disease

Complications

Cerebral palsy Hydrocephalus Epilepsy Spasticity Feeding difficulties

Consultations

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

Further 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

References
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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