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ANATOMICAL
Neurite outgrowthdendritic and axonal ramificationsin
process
Synaptogenesis not complete
Deficient myelination in cortical efferent systems
PHYSIOLOGICAL
In limbic and neocortical regionsexcitatory synapses develop
before inhibitory synapses ( N-methyl-D-aspartate receptor
activity, gamma-aminobutyric acid excitatory)
Immature hippocampal and cortical neurons more susceptible to
seizure activity than mature neurons
Deficient development of substantia nigra system for inhibition of
seizures
Impaired propagation of electrical seizures, and synchronous
discharges recorded from surface electroencephalogram may
not correlate with behavioral seizure phenomena
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Volpe JJ.Neonatal Seizures.In:Neurology of the Newborn.4th ed.
Probable Mechanisms of Some Neonatal
Seizures
Clinical
Electroencephalographic
Classification
I. Clinical Seizure
Subtle
Tonic
Clonic
Myoclonic
Classification
II. Electroencephalographic seizure
Epileptic
Non-epileptic
Clinical Classification
1. Subtle
More in preterm than in term
Eye deviation (term)
Blinking, fixed stare (preterm)
Repetitive mouth and tongue movements
Apnea
Pedaling and tonic posturing of limbs
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
Clinical Classification
3. Clonic
Primarily in term
Focal or multifocal
Clonic limb movements(synchronous or
asynchronous, localized or often with no anatomic
order of progression)
Consciousness may be preserved
Signals focal cerebral injury
Clinical Classification
4. Myoclonic
Rare
Focal, multifocal or generalized
Lightning-like jerks of extremities
(upper > lower)
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
Provoked by stimulation
Suppressed by restraint or repositioning
Brainstem release phenomena (reflex)
Classification of Neonatal Seizures
ELECTROENCEPHALOGRAPHIC SEIZURE
Subtle +*
Clonic
Focal +
Multifocal +
Tonic
Focal +
Generalized +
Myoclonic
Focal, multifocal +
Generalized +
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*Only specific varieties of subtle seizures are commonly associate with simultaneous
Electroencephalographic seizure activity.
SLEEP
Fragmentary myoclonic jerksmay be multiple
Isolated, generalized myoclonic jerk as infant wakes from sleep
Hemorrhage
Hypoxia-ischemia
0 10 20 30 40 50
Incidence (%)
Fanaroff A, Martin R.Neonatal seizures. In:Neonatal and Perinatal Medicine, Diseases of the Fetus and Infant,6 th ed
Major Etiologies of Neonatal Seizures in
Relation to Time of
Seizure Onset and Relative Frequency
Indicated
Intravenous AEDs
High-dose phenobarbital: >30 mg/kg
Pentobarbital: 10 mg/kg, then 1 mg/kg per hour
Thiopental: 10 mg/kg, then 2 to 4 mg/kg per hour
Midazolam: 0.2 mg/kg, then 0.1 to 0.4 mg/kg per hour
Clonazepam: 0.1 mg/kg
Lidocaine: 2 mg/kg, then 6 mg/kg per hour
Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses
Paraldehyde: 200 mg/kg, then 16 mg/kg per hour
Chlormethiazole: Initial infusion rate of 0.08 mg/kg per minute
Dexamethasone: 0.6 to 2.8 mg/kg
Pyridoxine (B6): 50 to 100 mg, then 100 mg every 10 minutes
(up to 500mg)
Alternative AEDs for Neonatal
Seizures
Oral AEDs
Primidone: 15 to 25 mg/kg per day in 3 doses
Clonazepam: 0.1 mg/kg in 2 to 3 doses
Carbamazepine: 10 mg/kg, then 15 to 20 mg/kg per day in 2 doses
Oxcarbamazepine: no data on neonates, young infants
Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses
Vigabatrin: 50 mg/kg per day in 2 doses, up to 200 mg/kg per day
Lamotrigine: 12.5 mg in 2 doses
Topiramate: 3 mg/kg per day
Zonisamide: 2.5 mg/kg per day
Levetiracetam: 10 mg/kg per day in 2 doses
Folinic acid: 2.5 mg BID, up to 4 mg/kg per day
NeoReviews vol.5 no.6 June 2004
Determinants of Duration of
anticonvulsant therapy for neonatal
seizures
Electroencephalogram
Duration of anticonvulsant therapy-
Guidelines
Neonatal period
If neonatal neurological examination
becomes normal discontinue therapy
If neonatal neurological examination is
persistently abnormal,consider etiology and
obtain EEG
In most such cases- Continue phenobarbital
- Discontinue phenytoin
- Reevaluate in 1 month
Duration of anticonvulsant therapy-
Guidelines
One month after discharge
If neurological examination has become
normal, discontinue phenobarbital
If neurological examination is persistently
abnormal,obtain EEG
If no seizure activity on EEG, discontinue
phenobarbital
Prognosis
Two most useful approaches in utilizing outcome
EEG