NEONATAL

SEIZURE
 LEARNING
OBJECTIVES
 To identify the early signs of neonatal seizures
 Better understanding of the condition for proper
evaluation and treatment
 Understanding of the prognosis to enable to support
the parents
INTRODUCTION
Neonatal seizures are a
neurologic dysfunction in the first
28 days of life in an infant.
Seizures in neonates are
relatively common, with variable
clinical manifestations. The first
sign of neurologic dysfunction
are powerful predictors of long-
term cognitive and
developmental impairment.
PATHOPHYSIOLOGY
A clinical seizure results from excessive synchronized
depolarization of the neurons within the central nervous system
resulting in excessive synchronous electrical discharge. This
excessive depolarization of the neurons might occur remains
unknown. Theories were suggested include the following:
 Imbalance between excitatory and inhibitory neurotransmitter
like excessive excitatory amino acid or deficient inhibitory
neurotransmitter.
 Failure of energy production due to disruption of ATP
dependent resting membrane potentials resulting in failure of
sodium potassium pump which in turn leading to movement of
sodium into the neuron and potassium out of the neuron.
 Neuronal hyper excitability state in the neonatal period, as
evidenced by the extremely low threshold to seizures in
general and that this is the period of highest incidence of
seizures across the life span.
 Among the factors that cause increase excitability are
incomplete myelination and neuropeptides particularly
corticotrophin releasing hormone (CRH).
PATHOPHYSIOLOGY

 Experimental and clinical evidence exists for early microglial activation

and inflammatory cytokine production in the developing brain in both
hypoxia/ischemia and inflammation Importantly, microglia have been
shown to be highly expressed in immature white matter in rodents and
humans during cortical development.

 Genetic predisposition as most of the cases of Benign Familial Neonatal

Seizures (BFNS) are due to mutations in two genes, KCNQ2 and
KCNQ3, which do not encode amino acids but may affect channel
expression.
CAUSES:
• Hypoxic ischemic encephalopathy (HIE)
The most common cause of neonatal seizures accounting for over
50% of cases. It happens during perinatal asphyxia or focal (i.e.
arterial infarction).
• History of difficulty during labor and delivery with alterations of the
fetal heart rate
• Decreased umbilical artery pH
• Apgar score <5 at 5minutes.
• Intracranial hemorrhages (ICH)
It happens during normal delivery with instrumentation or trauma
associated with more subarachnoid hemorrhages. Subdural
hemorrhages are related to large infant size, breech delivery and
instrumentation due to tears in the falx, the tentorium or superficial
cerebral veins.
• CNS infections such as :
• cytomegalovirus(CMV), toxoplasma, rubella and herpes viruses.
• Microcephaly, poor intrauterine growth, prematurity
• Meningoencephalitis, cerebral calcification and dysgenesis
• Post natal sepsis : group B streptococcus or Escherichia coli
CAUSES
• Acute Metabolic Disorders

These are remediable conditions such as:

 Hypoglycemia
 Dextrose 10% 2-3ml/kg IV

 Hypocalcaemia
 Calcium Gluconate, 5% (50 mg/ml), 100-200 mg/kg IV 10%
(100mg/ml) 50-100 mg/kg IV if inadequate time for dilation

 Hypomagnesaemia
 Magnesium Sulphate , 12.5% (125 mg/ml) 50-100 mg/kg IV

 Hypernatremia
 Furosemide 1 mg/kg IV
 3% NaCl 1-3 ml/kg over 15 to 30 minutes
 CAUSES
• Malformations / structural lesions
Cerebral dysgenesis – severe disorders such as hemimegalencephaly,
lissencephaly and polymicrogyrias.

• Inborn errors of metabolism

An enzyme defect in metabolic pathways of carbohydrates, protein or
may that cause disease due to accumulation of toxic products that are
unable to proceed along the appropriate metabolic pathways.

• Epilepsy Syndromes
Benign familial neonatal convulsions occur in well infants on day 2 or 3
of life. Seizures may be focal clonic or tonic. This disorder is associated
with abnormality of voltage-gated potassium channels usually KCNQ2
and less frequently KCNQ3.
CLINICAL CLASSIFICATIONS
 Focal/Multifocal Clonic
 Not generalized
 Migratory
 Not necessarily focal etiology
 Focal Tonic
 Not usually generalized
 Generalized Myoclonic
 Subtle (“Hypomotor”)
 Motor activity arrest
 Apnea
 Eye deviation
 Autonomic changes
 Motor automatisms
 Oral-buccal-lingual movements
 Swimming
 Bicycling
 EVALUATION
• Serum electrolytes (Glucose, Calcium, Magnesium,
Sodium)
• CSF
• Head ultrasound
• EEG
• Tox screen
• CT or MRI of brain
• Metabolic screening, congenital infection work up.
MANAGEMENT:
 Rule out hypoxia – check ABG, start oxygen, KIV intubate and
ventilate / optimise ventilator settings if already intubated
 Check hypocount – if low glucose, give IV D10% (2ml/kg)
 Correct electrolyte abnormalities – sodium, calcium, magnesium
 Anti-convulsants – (to be discussed on next slides)
 Treat Infection – IV CP/Genta, KIV IV acyclovir (HSV encephalitis)
 Polycythemia – partial plasma exchange
 Hydrocephalus – may need repeat LPs / VP shunt
 Close follow up for possible neurologic sequelae and
developmental delay
 Refer to pediatric neurologist for recurrent seizures.
TREATMENT OF
SEIZURE
Phenobarbital – limits the spread of seizure activity, possibly by increasing
inhibitory neurotransmission.
Loading dose: 20mg/kg IV, given slowly over 10 to 15 minutes.
Refractory seizures: Additional 5 mg/kg doses, up to a total of 40 mg/kg
Maintenance: 3 to 4 mg/kg per day beginning 12 to 24 hours after the load.
Route: IV slow push,IM, PO, PR
Compatibility: NS, D5%, D10%
Strength: 30mg/ml

Reconstitution and Dilution Guide:

Take 1 ml of Phenobarbitone and dilute with 2ml of diluents to obtain a
concentration of 10 mg/ml.
*IV infusion over 10-15 minutes. Do not administer intra-arterially.
TREATMENT OF
SEIZURE
Phenytoin (Dilantin) – is an anti-epileptic drug also called anti-convulsant. It
works by slowing down impulses in the brain that causes seizures.
Loading dose: 15 to 20 mg/kg IV infusion over at least 30 minutes.
Maintenance Dose: 4 to 8 mg/kg every 24 hours IV slow push
Route: IV and PO. Avoid using in central lines because of the risk of
precipitation. IM route not acceptable, drug crystallizes in muscle.
Compatibility: NS
Strength: 250 mg/ 5ml

Reconstitution and Dilution Guide:

Take 1 ml of Phenytoin and dilute with 9 ml of diluents to obtain a
concentration of 5 mg/ml
*Infuse over at least 30 minutes. IV injections should be followed by NS to
avoid local irritation of the vein.
TREATMENT OF
SEIZURE
Midazolam – is used to produce sleepiness or drowsiness and to relieve
anxiety before surgery or certain procedures. It works by slowing activity in
the brain to allow relaxation and sleep.
Loading Dose: 0.15 mg/kg (150mcg/kg) IV over at least 5 minutes
Maintenance Dose: 0.06 to 0.4 mg/kg per hour (1 to 7 mcg/ kg per minute)
Route: IV infusion
Compatibility: NS, D5%, D10%, SWFI
Strength: 5mg/ml
Reconstitution and Dilution Guide:
Dilute dose = Wt in KG (=mg of midazolam) in 50 ml of D5% and at a rate of
0.5 ml/hr = 10 mcg/kg/hr
1.0 ml/hr = 20 mcg/kg/hr
1.5 ml/hr = 30 mcg/kg/hr
2.0 ml/hr = 40 mcg/kg/hr
*Slow IV bolus over 5 minutes. IV infusion at 10-60 mcg/kg/hr. Max rate
= 120 mcg/kg/hr
TREATMENT OF
SEIZURE
Midazolam
Formula 1: ml/hr = Mcg/kg/hr x weightx 50 ml
Mcg
Example:
Doctor ordered for 40mcg/kg/hr of midazolam, to dilute with 50ml of Normal saline. Baby’s birth
weight is 3800 grams.

Solution:
3800 grams = 3.8 kg
3.8 mg = 3800 mcg

ml/hr = 40 mcg/kg/hr x 3.8kg x 50 ml

3800mcg
= 7600 ml/hr
3800

Answer = 2ml/hr
TREATMENT OF
SEIZURE
Midazolam
How to compute for mcg/kg/hr if the doctor asks for Midazolam to
run for 2 ml/hr. Baby’s weight of 3800 grams.

Formula 2: mcg/kg/hr = mcg ÷ kg ÷ volume x rate

=3.8 mg ( 1000 mcg) ÷ 3.8 kg ÷ 50ml x 2 ml/hr

= 3800 mcg ÷ 3.8 kg ÷ 50ml x 2 ml/hr
=40 mcg/kg/hr

*Slow IV bolus over 5 minutes. IV infusion at 10-60 mcg/kg/hr.

Max rate = 120 mcg/kg/hr
TREATMENT OF
SEIZURE
Lorazepam - anticonvulsant, acute management of patients with seizures
refractory to conventional therapy.
Dose: 0.05 to 0.1 mg/kg per dose IV slow push.
Route: IV
Compatibility: D5W, NS, and SWFI
Strength: 2mg/ml or 4mg/ml

Reconstitute and Dilution Guide:

Take 1ml of the Lorazepam and dilute with 9 ml of compatibility fluid will have
concentration of 0.2mg/ml.
TREATMENT OF
SEIZURE
Magnesium Sulphate

Route : IV infusion over 2 – 4hrs

Compatibility: WFI, D5%, NS
Strength: 2.47 g/ 5ml (493 mg/ml)

Reconstitute and Dilution Guide:

Take 1 ml of magnesium sulphate and dilute with 5 ml of diluent o obtain a
concentration of approx. 80mg/ml.

= 493 mg ÷ 6 ml
= 82 mg/ ml or 80 mg/ml
NICU CARE PLAN
 Ensure safety and initiate seizure precautions. This includes
having suction set up and working, having an ambu-bag in
the room, padding side rails, not restrain them or putting
anything in their mouth if a seizure occurs, having all side
rails up, and so forth.
 Maintain patent airway.
 Assess, monitor and document seizure activity. To report
immediately to the physician any early recognition of seizure.
 Administer antiepileptics (PRN and scheduled) medications
per orders.
 Reevaluate effectiveness of medication given.
 Perform daily measurement of head circumference for cases
of intracranial hemorrhage. A rapid increase in HC may
indicate hydrocephalus.
 Educate the parents on hospital procedures.
 Provide emotional support.
OUTCOME
 45 % controlled after either phenobarbital or phenytoin
 60 % controlled with both
 30% of survivors develop epilepsy
 WORSE: HIE, meningitis, dysplasia
 REFERENCES
Volpe JJ, ed. Neonatal Seizures in Neurology of the Newborn 5th
ed. Philadelphia: WB Saunders
Silverstein FS, Jensen FE. Neonatal seizures
Leinekugel X, Medina I, Khalilov R, et al. Ca ++ oscillations
mediated by the synergistic excitatory actions of GABA – A and
NMDA receptors in the neonatal hippocampus. Neuron 1997; 18:
243 – 55.
Jensen F E. Neonatal Seizures: An Update on Mechanisms and
Management. Clinics in Perinatology 200; 36 : 881-900.
Prof Isam Zwaini, Neonatal seizures
Fakhraee SH. Neonatal seizures; A review. Iranian Journal of
Child Neurology 2007; 1: 7 – 11.
THANK YOU FOR LISTENING!