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NEONATAL Sz

OBJECTIVES
Describe the incidence; aetiology; risk
factors; clinical signs and symptoms; role
of EEG, US, CTS, MRI; Pharmacological
treatment(s) of choice
DEFINITION
Neonatal seizures or neonatal convulsions
are epileptic fits occurring from birth to the
end of the neonatal period.
EPIDEMIOLOGY
Incidence:
0.2% to 1.4% of all newborns
20% in newborns with BW <2500g
Associated mortality:
15 to 40%*
Risk of epilepsy:
10 to 30 %*
* Depends largely on underlying aetiology
AETIOLOGY
Frequency of neonatal epileptic syndromes is very
low.
Major aetiologies:
Hypoxia-ischemia
Intracranial hemorrhage
CNS Infection
Infarction
Metabolic
- Hypoglycemia
- Hypocalcemia
- Hypomagnesemia
Chromosomal anomalies
AETIOLOGY
Major aetiologies:
Congenital abnormalities of the brain
Neurodegenerative disorders
Inborn errors of metabolism
Benign neonatal convulsions
Benign familial neonatal convulsions
Drug withdrawal or intoxication:
Maternal opiates
Convulsions from maternal cocaine use due to:
IU brain damage rather than withdrawal:
Infarctions
Anomalies
Cause unknown in 3-25% of cases
HIE
Most common cause of neonatal seizures:
HIE brain injury.
Asphyxial injury:
IU:
Decreased uteroplacental perfusion:
Placental Abruption
Cord compression
Pre-eclampsia
Chorioamnionitis
Postnatal:
PPHN
CCHD
Sepsis
Meningitis
Onset of HIE seizures is generally within the first 24 hours
ICH
Hypoxic-ischemic injury
Traumatic injury
These two frequently associated
Subarachnoid or subdural haemorrhage:
Onset of seizures on DOL 2/3
GMH-IVH:
Onset of seizures on DOL 3
INFECTION
Congenital infections can cause severe
encephalopathic disease:
Viruses:
Cytomegalovirus
Rubella
Herpes
Others
Toxoplasmosis
Bacteria:
Escherichia coli
GBS
METABOLIC
Metabolic disturbances:
Hypoglycemia:
Most at risk for hypoglycemia:
PT
IDM:
LGA
SGA
Hypocalcemia
Hypomagnesemia
Most at risk for these:
LBW
IDM
Hypoxic-ischemic injury
METABOLIC
Local anesthetic intoxication
Hyponatremia
Hpernatraemia
IEM:
Amino acid:
Convulsion after DOL 2
Galactosaemia:
Convulsion after DOL 2
MSUD:
Build-up of ketoacids in the blood and urine:
Leucine, isoleucine, and valine and their toxic by-
products
Pyridoxine dependency or deficiency:
Rare
Kernicterus
OTHER CAUSES
Congenital anomalies:
Cerebral cortical dysgenesis
Polycythaemia
Congenital thyrotoxicosis
Adrenal haemorrhage
Acidosis
Abnormal body temperature
Coagulopathy
Liver dysfunction
PATHOPHYSIOLOGY
Clinical seizure results from excessive depolarization of
neurons in the central nervous system.
Pathophysiology of excessive depolarization thought to be
related to:
Energy production failure
Membrane alteration
Excess excitatory neurotransmitters
Deficit of inhibitory neurotransmitters
Hypoxemia, ischemia and hypoglycemia:
Significantly decreased energy production
Increased release of glutamate:
Principal excitatory neurotransmitter in the cerebral
cortex.
Hypocalcemia and hypomagnesemia:
increased sodium influx across the neuronal cell membrane:
Increased depolarization.
INCREASED SUSCEPTIBILITY
Immature brain:
Imbalance between excitation and inhibition
GABA pathways not well developed early
in life:
Impaired inhibition
Delayed maturation of other forms of
postsynaptic inhibition
Overabundance of excitatory receptors
Seizures:
Through stimulating neuronal activity, likely
interferes, with the natural pruning of excess
dendrites and synapses
SEIZURE EFFECTS ON THE IMMATURE BRAIN
short intermittent seizures in neonatal rat:
No neuronal necrosis
Morphological changes involving cortical
neuronal activation and density
Functional effects on learning and memory
when mature
Status epilepticus in the adolescent animals
previously primed by short Sz in the neonatal
period leads to substantially increase
neuronal loss
Holmes GL, 1998; Schmid R, 1999
SEIZURE EFFECTS ON THE IMMATURE BRAIN
Seizures have been shown to activate hundreds of
genes that lead to:
Axonal growth
Neosynaptogenesis
Prolonged seizures:
Shown to cause synaptic reorganization with
aberrant growth of axons
Long-term studies in adolescents or adults rats:
impaired memory and visual-spatial auditory
discrimination
Limited uncontrolled human data:
Suggests subtle long-term alteration in cognitive
function
Generally felt, however, that neonates are less likely
to incur seizure related injury.
CLASSIFICATION
Seizures:
First identified and characterized clinically
Classified further based on pathophysiology.
CLASSIFICATION

Seizures in newborns can be


classified as:
Subtle
Clonic
Tonic
Myoclonic
CLASSIFICATION
SUBTLE SEIZURES:
Often difficult to recognize
Occur more frequently in premature infants
Not always correlated with electroencephalographic
seizure activity.
Examples:
Bicycling movements
Autonomic dysfunction
Horizontal eye deviation
Repetitive facial movements
CLONIC SEIZURES:
Slow, rhythmic movements
Focal or multifocal
CLASSIFICATION

Tonic seizures:
Can be focal
More commonly its generalized.
Sustained extension and/or flexion posturing.
Myoclonic seizures:
Rapid flexion twitching or jerking movements.
Focal
Multifocal
Generalized
MANIFESTATION: AGE

The clinical manifestations of seizures in


newborns differ significantly from that seen in
older children and adults as the human
neonatal brain is still in the process of
organization and development.
Premature infants:
Have a higher frequency of seizures
Seizures are less organized
DISTINGUISHING FEATURES OF CONVULSIONS & SPASMS

PROBLEM TYPICAL FINDINGS


Generalized convulsion Repetitive jerking movements of limbs or face
Continuous extension or flexion of arms and legs, either synchronous or
asynchronous
Apnoea (spontaneous cessation of breathing for more than 20 seconds)
Baby may appear unconscious or awake but unresponsive)

Repetitive blinking
Subtle convulsion Eye deviation
Staring
Repetitive movements of mouth or tongue
Purposeless movement of the limbs, as if bicycling or swimming
Apnoea
Baby may be conscious

Spasm Involuntary contraction of muscles that lasts a few seconds to several minutes Fists
often persistently and tightly clenched
Trismus (tight jaw; the babys mouth cannot be opened and the lips may be pursed
together in a fish mouth expression
Opisthotonos (extreme hyperextension of the body, with the head and heels bent
backward and the body arched forward
Triggered by touch, light, or sound
Baby is conscious throughout, often crying with pain
JITTERINESS
Can occur with:
Hypocalcaemia
Hypoglycaemia
HIE
Drug withdrawal
No eye signs
No clonic jerking
External stimulation induced
Ceases with passive flexion of the limb
HISTORY & EXAM
History:
Family
Maternal
Perinatal
Exam:
Skull
Anterior fontanelle
COH
INVESTIGATION FOR AETIOLOGY
Important to determine the aetiology early:
Affect management decisions
Determine outcome
Comprehensive antenatal, family & perinatal history
Comprehensive PE
Laboratory tests to look for metabolic and infectious
aetiologies
Focal clonic and focal tonic associated with:
Focal injury
Some metabolic disturbances
CNS infections
Generalized tonic, subtle sz, some myoclonic sz
associated with:
More diffuse brain injury
ROLE OF NEUROIMAGING
Cranial US:
Limited by range of lesions it can identify
Allows for early diagnosis of:
Haemorrhage
Hydrocephalus
Brain CT:
Limited in diagnosing:
White matter injury
Migrational disorders
Not portable
Superior to US and MR in detecting:
Haemorrhage
Calcifications
ROLE OF NEUROIMAGING
MR:
Not portable
Time consuming
Exceptional for detecting:
Even subtle injury
Developmental abnormalities
Technetium brain scan also good
These images can identify Lesions of hypoxic-
ischemic injury within the first 2-3 days after the
asphyxial event
ROLE OF EEG
Major values of the electroencephalogram:
Determine if subtle signs have electrographic
correlation
Determine if paralyzed infant is experiencing
convulsions
Define interictal background electrical activity:
Valuable in estimating prognosis
STUDIES
Blood:
Glucose, Electrolytes, urea, Calcium, Magnesium,
Phosphorus, CBC, TORCH, blood and urine culture
Urine:
Culture
UA for metabolic screening
CSF:
Infection & haemorrhage
Subdural tap:
Subdural effusion
Haematoma
Transillumination of head
Plain SXR
Transfontanelle ultrasound
STUDIES
CTS
MRI
Technetium brain scan
EEG
TREATMENT

Treatment of neonatal seizures should focus


on:
General measures
The primary aetiology:
Specific management
Direct seizure control
TREATMENT
General:
Manage ABCs
Minimal & gentle handling
Monitor VS
O2
IV support
IP/OP
TREATMENT
Specific:
Hypoglycaemia:
2-4 ml/kg D10W
Then 6-8 mg/kg/min D10W
Hypocalcaemia:
2 mL (2.5mL)/kg IV over 10 min of Ca-Gluconate:
Max 10ml.
Hypomagnesaemia:
Treatment:
0.1-0.2 ml/kg 50% MgSo4 im, then 0.25ml/kg/d po.
Prevention:
3mEq/L to IVF if IV therapy is prolonged
If above fails, pyridoxine hydrochloride:
50-100mg im/iv
TREATMENT
Hyponatraemia:
Correct over 24h.
Restrict fluid if dilutional.
3% NaCl if < 120:
Deficit = 134-current value x kg x 0.7
(0.3 & 0.6 in older persons)
Monitor q6-8h
Hypernatraemia:
20ml/ kg RL or 10ml/kg WB over 1-2h
Then 60ml/kg 5%/10% dextrose over 2-10h
Depending on hydration
Other approaches.
AED
No consensus on first DOC
Many prefer phenobarbital as first DOC:
Most extensively studied agent in neonates
Widespread use questioned:
Moderate efficacy
Potential for long-term neurocognitive adverse effects
Intravenous route is preferred:
More rapid onset of action
More reproducible effects on blood levels
LD:
20 mg/kg IV x 10-20min:
Therapeutic level of approximately 20 g/ml.
Repeatable w/ 5-10/kg over 5-10m. to max. of 30-40/kg
MD:
Lower in the first week of life:
3.5 mg/kg/day
Increased to 5-8 mg/kg/day with increasing postnatal age
Divided in 2 doses.
AED
Phenytoin:
Often the second DOC
Added when seizures are not controlled by
phenobarbital alone
LD:
20 mg/kg IV x 20 min:
Therapeutic level of approximately 15 g/ml.
MD:
5-8 mg/kg/day
Oral phenytoin is poorly absorbed from the
infant GIT
AED
Lorazepam:
Useful for infants with seizures unresponsive
to phenobarbital and phenytoin
0.05 - 0.1 mg/kg per dose x 2-5 min IV
Possibility of respiratory depression:
Especially with phenobarbital already in
use
Safest use:
After ventilatory support has been
initiated
AED
Others:
Paraldehyde:
2ml/kg im/iv/pr.
OR 200mg/kg/hr:
In D5W/D10W
Primidone
Clonazepam:
As adjunct to phenobarbitone
Acetazolamide:
As an adjunct
Sodium valporate not recommended
Diazepam not recommended in neonates with jaundice:
Sodium benzoate carrier interferes with bilirubin binding
Can severely depress respiration if combined with phenobarbitone
Continuous midazolam infusion can be used for intractable Sz.
PHENOBARBITAL ADVERSE EFFECTS
Short-term adverse effects:
Hypotension
Excessive sedation
Respiratory depression
Poor feeding
Deleterious effects on the developing brain have been noted in
rats
Phenobarbital for infants with febrile seizures was noted to
effect cognitive development (Farwell JR, 1990)
Effect truly due to phenobarbital per se or confounding
factors ????
Effect persists post therapy ????:
In one study of older children adverse cognitive effects
were reversible upon discontinuation of Rx (Riva D,
1996)
Good practice to discontinue therapy with phenobarbital early
or as soon as possible
PROGNOSIS
Varies as a function of:
Primary aetiology
GA
Background EEG activity also correlates with
outcome:
In both term and preterm infants:
Normal background activity less likely to have
neurological sequelae:
As opposed to those with moderate to severe
abnormalities such as:
Burst-suppression pattern
Voltage suppression
Electrocerebral silence
REFERENCES
Volpe JJ, editor. Neurology of the newborn. 5th ed.
Philadelphia: Saunders Elsevier, 2008. p.203-44.
2. Tekgul H, Gauvreau K, Soul J, Murphy L, Robertson R,
Stewart J, et al. The current etiologic profile and
neurodevelopmental outcome of seizures in term newborn
infants. Pediatrics 2006;117:1270-80.
3. Mizrahi EM, Kellaway P, editors. Diagnosis and
management of neonatal seizures. Lippincott-Raven, 1998. p.
15-35 4.
Painter MJ, Scher MS, Stein MD, Armatti S, Wang Z, Gardner
JC et al. Phenobarbitone compared with phenytoin for
treatment of neonatal seizures. N Engl J Med 1999;341:485-9
Clinical Management of Seizures, 2nd edition. Solomon GE,
Kutt H, Plum F (eds.). WB Saunders.:Philadelphia 1983.