Definition A seizure is defined clinically as a paroxysmal alteration in neurologic function (i.e., behavioral, motor, or autonomic function). Includes phenomena that are associated temporally with seizure activity identifiable on an EEG and, therefore, are clearly epileptic Also includes paroxysmal clinical phenomena that are not consistently associated temporally with EEG seizure activity Pathophysiology Immature brain has many differences from the mature brain that render it more excitable and more likely to develop seizures. Delay in Na+ , K+ -adenosine triphosphatase maturation and increased NMDA and AMPA receptor density. Delay in the development of inhibitory GABAergic transmission GABA in the immature brain has an excitatory function Causes of Neonatal seizures The majority of neonatal seizures occur in the context of acute neurologic disorders. Thus most neonatal seizures may be considered acute symptomatic seizures, which have been defined as seizures occurring at the time of a systemic insult or in close temporal association (often 1 week) with a documented brain insult. The current IL AE classifies seizure causes as genetic, structural/metabolic, and unknown. Within that classification scheme, the majority of neonatal seizures are structural/ metabolic in etiology. The most common underlying etiologies are HIE, stroke, intracranial hemorrhage, intracranial infections, and cerebral dysgenesis. Less common but important etiologies include Inborn errors of metabolism and Neonatal epileptic syndromes, such as benign familial neonatal epilepsy, benign nonfamilial neonatal seizures, early myoclonic epilepsy, early infantile epileptic encephalopathy, and malignant migrating partial seizures of infancy  Types of Neonatal Seizures Four essential clinically evident seizure types can be recognized: subtle, clonic, tonic, and myoclonic Subtle seizures do not have a clear position in the most recent ILAES classification report, but they are very common in newborns A critical fifth seizure type to consider in newborns is a seizure with no observable clinical correlate, which have been referred to as EEG-only seizures An important initial distinction in classifying a seizure is whether it has a generalized or focal mechanism of onset Subtle Seizures Transient eye deviations, nystagmus, blinking, mouthing, Abnormal extremity movements (rowing, swimming, bicycling, pedalling, and Stepping), Fluctuations in heart rate, hypertension episodes, and apnea. More commonly in premature Clonic Seizures Focal: Involve face upper + /- lower extremities on one site “axial structures (neck / trunk) Usually associated with neuropathology (i.e. Cerebral infarction and intra cerebral haemorrhage) Multi focal: Involve several body parts and often migrate in a non-jacksonian (random) manner may also involve the face. Consider the neonatal equivalent of generalized tonic – clonic seizures.

1. Neonatal Seizures
Presenter ; Dr. Amsalu ( PCHR- Year II)
Moderator; Dr. Fitsum ( Neonatologist)

2. Outline Of Presentation
• Definition
• Epidemiology
• Pathophysiology
• Etiology
• Types of Neonatal Seizure
• Differentiation of Seizures from Nonconvulsive Movements
• Diagnosis
• Management and Follow Up.

3. Definition
• A seizure is defined clinically as a paroxysmal alteration in neurologic
function (i.e., behavioral, motor, or autonomic function).
• Includes phenomena that are associated temporally with seizure
activity identifiable on an EEG and, therefore, are clearly epileptic
• Also includes paroxysmal clinical phenomena that are not consistently
associated temporally with EEG seizure activity

4. Pathophysiology
• Immature brain has many differences from the mature brain that
render it more excitable and more likely to develop seizures.
• Delay in Na+ , K+ -adenosine triphosphatase maturation and
increased NMDA and AMPA receptor density.
• Delay in the development of inhibitory GABAergic transmission
• GABA in the immature brain has an excitatory function

5. Causes of Neonatal seizures
• The majority of neonatal seizures occur in the context of acute neurologic
disorders.
• Thus most neonatal seizures may be considered acute symptomatic
seizures, which have been defined as seizures occurring at the time of a
systemic insult or in close temporal association (often 1 week) with a
documented brain insult.
• The current IL AE classifies seizure causes as genetic,
structural/metabolic, and unknown.
• Within that classification scheme, the majority of neonatal seizures are
structural/ metabolic in etiology.

6. Causes.. Continued
• The most common underlying etiologies are HIE, stroke, intracranial
hemorrhage, intracranial infections, and cerebral dysgenesis.
• Less common but important etiologies include
• Inborn errors of metabolism and
• Neonatal epileptic syndromes, such as benign familial neonatal epilepsy, benign
nonfamilial neonatal seizures, early myoclonic epilepsy, early infantile epileptic
encephalopathy, and malignant migrating partial seizures of infancy

8. Etiology
Hypoxic-Ischemic
Encephalopathy
Brain
Malformations
Infarction &
Hemorrhage
Genetic Metabolic
Infections
HIE (35 - 45%)
Infarction & Hemorrhage (20-30%)
Brain Malformations (5-10%)
Infections (5-20%)
Metabolic (7-20%)
Genetic (6-10%)
Unknown/ Other (10%)

9. Types of Neonatal Seizures
• Four essential clinically evident seizure types can be
recognized: subtle, clonic, tonic, and myoclonic
• Subtle seizures do not have a clear position in the most recent
ILAES classification report, but they are very common in
newborns
• A critical fifth seizure type to consider in newborns is a seizure
with no observable clinical correlate, which have been referred
to as EEG-only seizures
• An important initial distinction in classifying a seizure is whether
it has a generalized or focal mechanism of onset

10. Subtle Seizures
• Transient eye deviations, nystagmus, blinking, mouthing,
• Abnormal extremity movements (rowing, swimming, bicycling,
pedalling, and Stepping),
• Fluctuations in heart rate, hypertension episodes, and apnea.
• More commonly in premature

11. Clonic Seizures
• Focal:
• Involve face upper + /- lower extremities on
• one site “axial structures (neck / trunk)
• Usually associated with neuropathology (i.e. Cerebral infarction and intra
cerebral haemorrhage)
• Multi focal:
• Involve several body parts and often
• migrate in a non-jacksonian (random) manner may also involve the face.
• Consider the neonatal equivalent of generalized tonic – clonic seizures.

12. Tonic Seizures
• Focal :
• Sustained posturing of a limb or
• Asymmetric posturing of the trunk and / or neck
• Generalized :
• Decerebrate posturing
• Decorticate posturing
• Usually associated with apnea and upward gaze of eyes
• Usually indicates structural brain damage and IVH

13. Myoclonic Seizures
• Myoclonus is defined as a rapid, isolated jerk that can
affect one or multiple muscle groups
• They are usually not associated with EEG discharges
• Distinguished from clonic movements by the faster speed
of the myoclonic jerk and the predilection for flexor
muscle groups.
• There are three categories of myoclonic seizures: focal,
multifocal, and generalized myoclonic seizures.
• Presence suggests severe diffuse brain damage

14. Differentiation of Seizures from Nonconvulsive
Movements
Jitteriness
• Is not accompanied by ocular phenomena (i.e., eye fixation or
deviation
• Exquisitely stimulus sensitive
• The dominant movement in jitteriness is tremor
• Movements of limbs usually can be stopped by gentle passive flexion of
the affected limb
• Is not accompanied by autonomic changes

15. Nonepileptic Myoclonus
• May be benign or pathologic.
• Healthy premature infants often demonstrate occasional spontaneous myoclonus.
• Benign neonatal myoclonus typically is most prominent in sleep
• Benign neonatal myoclonus may be differentiated from pathologic benign myoclonus
can be stopped by rousing the infant and typically does not involve the face myoclonus
in that The episodes usually last for several minutes or more and occur only during
sleep
• The episodes can be exacerbated or provoked by treatment with benzodiazepines and
resolve within ~ 2 months.

16. • Neurologic outcome is normal
• Pathologic Myoclonus is attributed to a brainstem release
phenomenon from loss of cortical inhibition of lower circuits.
• It is frequently seen in infants with severe global brain injury
from hypoxia-ischemia, severe IVH, and toxic-metabolic
disturbances including drug withdrawal and glycine
encephalopathy.
• These newborns have abnormal neurologic exams and
abnormal background patterns on EEG.

17. Diagnosis
- History: Maternal drug abuse, Intrauterine infection, metabolic
disease, natal history, etc.
• Physical examination
• The first laboratory tests to be performed are directed against the two
disorders that are dangerous but readily treated when recognized promptly
: hypoglycemia and bacterial meningitis. (LP and RBS)
• Serum electrolytes(Na+, K+, Ca, phosphorus, and magnesium )
• Imaging and laboratory studies should be directed by specific clinical
features

18. • Focal seizures should lead to neuroimaging because of the
frequency of focal ischemic cerebral lesions, and MRI is
preferred modality.
- EEG
- Provides important diagnostic and prognostic information
- Assist in the determination of whether clinical events are
correlated with electrical seizures requiring anticonvulsant
medication or with nonepileptic events in which
anticonvulsant medication administration can be avoided.

19. • Continuous electroencephalogram (cEEG): >3 hours of
monitoring is gold standard for the diagnosis of neonatal
seizures
• Including video analysis can be very helpful
• Routine neonatal EEG recording, typically of 1 hour duration,
allows assessment of background activity, including cycling
state change, developmental maturity, and sometimes, epileptic
potential.
• Amplitude-integrated electroencephalogram (aiEEG): a
bedside technique increasingly being used by neonatologists
for neuromonitoring

20. Management of Neonatal seizures
• The WHO guideline on neonatal seizures recommended
treatment of all clinical and electrographic seizures
• The goal of therapy is the elimination of electrical seizure
activity, based on the fact that many seizures in the newborn
infant are clinically silent.

21. Initial management:
• Achieve a patent airway, adequate breathing and circulation.
• Correct the underlying cause
• Hypoglycaemia: D10W IV (2 ml/kg) over one min, followed by a
continuous infusion.
• Hypocalcaemia: calcium gluconate 2 ml/kg IV slow infusion, with
observation of HR repeat q6 hrs over the first 24 hrs.
• Sepsis: antibiotics after obtaining appropriate culture

22. Anticonvulsants:
• Phenobarbitone: preferred initial drug. An initial IV loading
dose of 20 mg/kg may be followed by increments of 10
mg/kg IV to a total of 40 mg/kg, with higher doses associated
with improved efficacy.
• Maintenance dose should be started at 5 mg/kg/day divided
twice daily.
• If there is no IV, use oral dose as above and reload after four to
six hours as the absorption of oral doses takes long hours.

23. • Phenytoin: it is the second agent selected when Phenobarbitone fails.
• Loading dose is 20 mg/kg; maintenances dose is 4 to 6
mg/kg daily
• Benzodiazepines (Diazepam): is used in status epilepticus, when
immediate cessation of seizure activity is required.
• It should be administered after dilution of 0.2 ml of diazepam with 0.8 ml of
NS.
• Initial dose is 0.1 to 0.3 mg/kg slowly IV until seizures stop.
• Disadvantage: It contains sodium benzoate which interferes with binding
of bilirubin to albumin --- jaundice.
• It has short anticonvulsant effect but prolonged respiratory suppressant
effect.
• Lorazepam: the current recommended dose is 0.05 mg/kg/dose over two
to five minutes

24. • Refractory seizures: give pyridoxine 50 to 100 mg IV with EEG
monitoring “therapeutic trial”; seizures will stop within minutes if
pyridoxine dependency is the cause.
• In such cases, maintain an oral pyridoxine (10 to 100 mg/day).
• Give a trial of folinic acid for 24 to 48 hrs in infants failing to
respond to anticonvulsants and pyridoxine (starting dose is 2.5
mg twice/day, but it can be increased to 8 mg/ kg/day

25. Follow up anticonvulsant medications:
• If the neonate takes more than one anticonvulsant medication,
phenobarbitone will be the last one to be tapered and
discontinued.
• Discontinuation of drugs before discharge from the NICU is generally
recommended, because then clinical assessments of arousal, tone,
and behaviour will not be hampered by a medication effect
• However, newborns with congenital or destructive brain lesions on
neuroimaging or those with persistently abnormal findings on
neurologic examination at the time of discharge may require a slower
taper off medication over several weeks or months.

26. Indications for discontinuations of antiepileptic
drugs
■ Normal findings on examinations
■ Absence of recurrent seizure
■ Non-epileptic EEG

27. Complications
■ Cerebral palsy
■ Hydrocephalus
■ Epilepsy
■ Learning disability, mental retardation

28. References
• Fanaroff and Martin’s Neonatal- Perinatal Medicine 11th edition
• Clinical Reference Manual for Advanced Neonatal Care in Ethiopia ,
Ministry of Health 2021