Neonatal seizures (NSz)

Definition

Paroxysmal alteration in neurological function i.e., motor, behavior and / or autonomic function

Types

• Electrographic seizure
• Electroclinical seizure

Classification

Subtle seizures

• mild motor, behavioral or autonomic paroxysms
• most common type of seizures
• Examples
  • ocular - tonic horizontal fixation of eyes (term), sustained eye opening (preterm) or cycled fluttering
  • oral-facial-lingual movements - chewing, tongue thrusting, lip smacking
  • Limb movements - cycling, paddling, boxing jabs, hooking etc..
  • Autonomic phenomenon - Tachycardia or bradycardia
  • Apnea

Clonic seizures

• rhythmic movement of muscle groups with rapid phase followed by a slow return
• 1-3 jerks/sec
• commonly associated with EEG changes
• can be focal or generalised
• Focal clonic seizure has the best prognosis

Tonic Seizures

• sustained flexion or extension of axial or appendicular muscle groups
• resemble decerebrate or decorticate positioning
• not associated with EEG changes in 85% of cases
• represent brainstem release phenomenon secondary to severe brain injury

Myoclonic seizures

• single or multiple lightening fast jerks of the upper or lower limbs
• predilection for flexor muscle groups
• worst prognosis

Pathophysiology

• reduced connectivity in the developing brain
• therefore neonatal seizures are mostly focal and rarely generalized
• excitatory circuits develop earlier and inhibitory circuits develop later
• sometimes even GABA act as a excitatory neurotransmitter due to alteration in the chloride channel

Clinical seizure can occur without electrographic change (paroxysms), Electrographic change can occur without seizure (uncoupling)

Etiology of neonatal seizures

Hypoxic ischemic encephalopathy

• most common cause in LMIC
• 50-65% has onset within 12-24 hours of life, rest manifests in 24-48 hours
• additional problems can co-exist
• subtle seizures are the most common type of seizure in HIE

Metabolic Causes

• Most common causes include
  • hypoglycemia
  • hypocalcemia
  • hypomagnesemia
  • hypo and hypernatremia
  • inborn errors of metabolism
  • pyridoxine dependent seizures
  • folic acid responsive seizures

Infection

• Bacterial meningitis - in latter part of first week of life
• Meningoencephalitis - secondary to intrauterine infection

Intracranial hemorrhage and vascular causes

• IVH in preterms
• SAH, intraparenchymal hemorrhage and SDH in terms
• seizure in a well baby in day 2-3 of life

Developmental defects

• cerebral dysgenesis and neuronal migration disorders

Miscellaneous

• polycythemia, maternal narcotic withdrawal, drug toxicity, phacomatosis (tuberous sclerosis, incontinentia pigmentii)

Approach to infant with neonatal seizures

History

seizure history

• history of eye movements, restrain of episode by passive flexion, change in skin color, autonomic phenomenon
• seizure in day 1-3 are associated with perinatal asphyxia, intracranial hemorrhage
• seizure in day 4-7 are associated with sepsis, meningitis, developmental defects

Antenatal history

• intrauterine infection, maternal diabetes, narcotic addiction

Perinatal history

• perinatal asphyxia is the most common cause of neonatal seizure
• detailed history should be elicited regarding
  • fetal distress
  • decreased fetal movements
  • instrument delivery
  • need for resuscitation in labor room
  • APGAR score
  • abnormal cord blood pH<7
  • base deficit >12 mEq/L

Feeding history

• late onset hypocalcemia - seen in children fed on cow’s milk
• inborn errors of metabolism - immediately following feeding
  • lethargy
  • poor activity
  • drowsiness
  • vomiting

Family history

• consanguinity in parents
• family history of seizures

Examination

• vital signs
• general examination - gestation, birth weight, malformations
  • seizure in a well baby might be due to SAH
• CNS examination - bulging fontanelle
• systemic examination - HSM or abnormal urine odor - IEM; presence of neurocutaneous markers’

Diagnosis

EEG showing

• stereotyped repeated waveforms (rhythmic activity with distinct beginning and end)

• focal in origin

• evolving in morphology and frequency

• minimum of 2μV peak to peak voltage and >/= 10 second duration no evidence of clinical seizure required

• Continued video EEG is the gold standard

Investigations

Essential Investigations	Additional Investigations
blood sugar	Hematocrit (if plethoric or at risk of polycythemia)
serum sodium and calcium	bilirubin (if icteric)
CSF (withheld if hemodynamically unstable)	Magnesium
EEG	Blood gas (if lethargic, vomiting, family history)
Cranial ultrasound - for intracranial hemorrhage	CT/MRI (if no etiology is found)
	TORCH screening - if HSM, thrombocytopenia, IUGR, SGA, chorioretinitis
	Inborn errors of metabolism

Management

Initial management (within 2-5 mins)

• temperature
• airway
• breathing
• circulation
• oxygen
• IV access
• blood glucose
• quick relevant history

Hypoglycemia and Hypocalcemia correction

• 2ml/kg of 10D followed by continuous glucose infusion of 6-8 mg/kg/min
• 2ml/kg of 10% calcium gluconate IV over 10 mins if hypoglycemia ruled out
• if hypocalcemia is proven then 8ml/kg/day of calcium gluconate to be continued for 3 days
• if seizure continues despite calcium, add 0.25ml/kg of 50% magnesium sulphate given IM

Antiseizure medication

Phenobarbitone

• drug_of_choice in neonatal seizures
• close respiratory monitoring is required
• 20 (loading) + 10 (additional) + 10 (additional) can be given every 20-30 mins (max 40 mg/kg/day)
• maintenance at 3-5 mg/kg/day (not necessary)

Phenytoin

• after phenobarbitone fails
• adverse effects - respiratory depression, hypotension, bradycardia
• 20 mg/kg/dose slowly at least over 20 mins
• oral suspension to be avoided in neonates as absorption is erratic

Fosphyenytoin

• less adverse effects than phenytoin
• 1.5 mg/kg of fosphenytoin is equivalent to 1 mg/kg of phenytoin

Benzodiazapines

• required in 15-20% of NSz
• lorazepam and midazolam
• lorazepam - 0.05 mg/kg IV bolus over 2-5 minutes
• Midazolam - 0.15 mg/kg IV bolus followed by 0.1 to 0.4 mg/kg/hour

Levetiracetam

• 20-50 mg/kg/day
• can be used as first line due to low adverse effect profile

Refractory seizures

Lidocaine

• 4 mg/kg IV loading followed by infusion of 2 mg/kg/hr
• adverse effects - arrhythmia, hypotension and seizures

Paraldehyde

• 0.1 to 0.2 ml/kg/dose IM or 0.3 ml/kg/dose mixed with coconut oil in 3:1 may be used in rectal route
• additional doses can be used after 30 mins and q4h-q6h
• adverse effects include pulmonary edema, pulmonary hemorrhage, hypotension, liver injury

Sodium Valproate

• 20 to 25 mg/kg followed by 5-10 mg/kg every 12 hours
• high risk of hepatotoxicity in children less than 2 years of age
• to be used cautiously

Vigabatrin

• used in infantile spasms
• 50 mg/kg/day

Topiramate

• neuroprotective in seizures
• higher volume of distribution compared to other drugs - high initial and maintenance doses of approximately 3 mg/kg

Other therapy

Pyridoxine

• last resort
• IV is preferred, but not readily available
• can cause hypotension and apnea
• 1ml of Neurobion (contain 50mg) in each gluteal region

Exchange transfusion

• indicated in life threatening metabolic disorders, bilirubin encephalopathy, transplacental transfer of maternal drugs

Principles to be followed

• monotherapy is the goal, preferably 3-5 mg/kg/day of phenobarbitone
• if uncontrolled additional second line drug to be added

when to stop AED

• as early as possible, preferably at discharge
• if discharged on AED, review in 1 month
• at 1 month, if neurological examination is abnormal, plan EEG
• stop when EEG is not overly paroxysmal
• reassess at 3 months and 3 monthly till 1 year of age