The document provides a protocol for the management of neonatal seizures. Some key points: - Neonatal seizures are the most common manifestation of neurological disease in newborns and can be caused by hypoxic-ischemic encephalopathy, hypoglycemia, hypocalcemia, infections, and inborn errors of metabolism. - Immediate management of ongoing seizures involves stabilizing the neonate, treating any underlying causes like hypoglycemia, and administering anti-seizure medications like phenobarbital or phenytoin intravenously. - Long-term management requires identifying and treating the underlying etiology as well as considering long-term prognosis. Prompt treatment of seizures is important to

1. Protocol for ManagementProtocol for Management
of Neonatal Seizuresof Neonatal Seizures
Soumya Ranjan ParidaSoumya Ranjan Parida
Basic B.Sc. Nursing 4Basic B.Sc. Nursing 4thth
yearyear
Sum Nursing CollegeSum Nursing College

2. IntroductionIntroduction
 Most common manifestation of neonatalMost common manifestation of neonatal
neurological diseaseneurological disease
 Paroxysmal alteration of neurologicalParoxysmal alteration of neurological
function having behavioural,motor andfunction having behavioural,motor and
autonomic changes.autonomic changes.
 Seen in 0.5-3% of term and 11-60% ofSeen in 0.5-3% of term and 11-60% of
preterm babiespreterm babies
 Hyperexcitability of neonatal brain, inHyperexcitability of neonatal brain, in
addition to multiple risk factors, isaddition to multiple risk factors, is
responsibleresponsible

3. Non-seizure eventsNon-seizure events
 JitterinessJitteriness
 Benign sleep myoclonusBenign sleep myoclonus
 Tonic posturings /opisthotonusTonic posturings /opisthotonus

4. why seizures are more common in newborn period :why seizures are more common in newborn period :
 Decreased seizure threshold in newbornDecreased seizure threshold in newborn
– the newborn brain has a transient over-the newborn brain has a transient over-
development of excitatory systems compared todevelopment of excitatory systems compared to
inhibitory systems.inhibitory systems.
– the immature brain has a transientthe immature brain has a transient
overexpression in the density of excitatoryoverexpression in the density of excitatory
amino acid (primarily glutamate) receptorsamino acid (primarily glutamate) receptors
– a relative paucity of glutamate reuptakea relative paucity of glutamate reuptake
transporters.transporters.
 immature glutamate receptorsimmature glutamate receptors
 immature GABA may be depolarizing (i.e.,immature GABA may be depolarizing (i.e.,
excitatory) rather than hyperpolarizing (i.e.,excitatory) rather than hyperpolarizing (i.e.,
inhibitory)inhibitory)
 cellular factors, differential development of neuralcellular factors, differential development of neural
systemssystems

5.  True seizures are usually not stimulus
sensitive, cannot be stopped with
restraint and are associated with
altered sensorium, autonomic or ocular
phenomena
 EEG is helpful in differentiation but is
not mandatory for acute management,
which is based on clinical assessment

6. Types of SeizuresTypes of Seizures
 Subtle seizures (50%): PSubtle seizures (50%): Paroxysmal, repetitive,aroxysmal, repetitive,
motor,autonomic or behavioral phenomena likemotor,autonomic or behavioral phenomena like
lip smacking, sucking, chewing, eye movementslip smacking, sucking, chewing, eye movements
(deviation, nystagmus), cycling or paddling(deviation, nystagmus), cycling or paddling
movements, changes in skin color, respiratorymovements, changes in skin color, respiratory
irregularities (tachypnoea or apnoea),irregularities (tachypnoea or apnoea),
tachycardia, etctachycardia, etc
 Tonic seizures : Focal or generalized, with orTonic seizures : Focal or generalized, with or
without eye movementswithout eye movements
 Clonic: Unifocal, multifocal or generalizedClonic: Unifocal, multifocal or generalized
 MyoclonicMyoclonic

7. Common causes ofCommon causes of
seizuresseizures
 Perinatal complications-Perinatal complications-
-Birth asphyxia and intracranial injuries-50%-Birth asphyxia and intracranial injuries-50%
 HypocalcemiaHypocalcemia
-serum calcium <7mg/dl-serum calcium <7mg/dl
 HypoglycemiaHypoglycemia
-to maintain blood sugar b/w 70-120 mg/dl-to maintain blood sugar b/w 70-120 mg/dl
-more common in severe IUGR,large for date-more common in severe IUGR,large for date
babies, babies of diabetic mother.babies, babies of diabetic mother.
 HypomagnesemiaHypomagnesemia

8. Causes of seizuresCauses of seizures
 Other causes of neonatal encephalopathy likeOther causes of neonatal encephalopathy like
bilirubin encephalopathy, hypertensivebilirubin encephalopathy, hypertensive
encephalopathy, dyselectrolytaemias, etcencephalopathy, dyselectrolytaemias, etc
 InfectionsInfections
-intrauterine infections and neonatal septicemia.-intrauterine infections and neonatal septicemia.
-1/3rd of meningitis presents with seizures.-1/3rd of meningitis presents with seizures.
-CSF examination is mandatory.-CSF examination is mandatory.
-Tetanus neonatorum should be excluded.-Tetanus neonatorum should be excluded.
 Inborn errors of metabolismInborn errors of metabolism
-intractable to therapy-intractable to therapy
-h/o of similar disorder in previous siblings-h/o of similar disorder in previous siblings
-appear after introduction of milk feeding.-appear after introduction of milk feeding.
-other associated symptoms and signs--other associated symptoms and signs-
vomiting,severevomiting,severe
jaundice,hepato-splenomegaly,malodours urine.jaundice,hepato-splenomegaly,malodours urine.

9. Causes of seizuresCauses of seizures
 Developmental defectsDevelopmental defects
 Acute systemic illnessAcute systemic illness
-severe respiratory distress and septicemia.-severe respiratory distress and septicemia.
-due to hemorrhagic infarction due to DIC and-due to hemorrhagic infarction due to DIC and
hypoxia.hypoxia.
 Miscellanous conditionsMiscellanous conditions
-neonatal narcotic withdrawal or abstinence-neonatal narcotic withdrawal or abstinence
syndrome.syndrome.
-drug toxicity-drug toxicity
-local anesthetics-local anesthetics
-Epileptic-Epileptic
syndromessyndromes
Benign idiopathic or familial neonatal seizures areBenign idiopathic or familial neonatal seizures are
rare diagnoses of exclusion in a well neonaterare diagnoses of exclusion in a well neonate
with normal neurological outcomewith normal neurological outcome

10. 
S.noS.no
EtiologyEtiology IncidenceIncidence
(%)(%)
1.1.
Cerebral hypoxia-ischemiaCerebral hypoxia-ischemia
a. Global (e.g., perinatal asphyxia)a. Global (e.g., perinatal asphyxia)
b. Focal infarction (arterial or venousb. Focal infarction (arterial or venous ))
4040
1515
2.2. Intracranial hemorrageIntracranial hemorrage 1515
3.3. CNS infectionCNS infection 55
4.4. Metabolic diseaseMetabolic disease
a.Transienta.Transient
b.Inborn errors of metabolismb.Inborn errors of metabolism
55
11
5.5. Cerebral dysgenesisCerebral dysgenesis 55
6.6. Neonatal epileptic syndromesNeonatal epileptic syndromes 11
7.7. Neonatal abstinence syndromeNeonatal abstinence syndrome 11
8.8. UnknownUnknown 1010

11. DiagnosisDiagnosis
 Time of onset of seizures .Time of onset of seizures .
 positive family history.positive family history.
 associated conditions.associated conditions.
 Investigations .Investigations .

12. Age of Onset and Etiology
Age of
onset
Likely etiology
< 24 hrs HIE, severe birth trauma, congenital anomalies of
CNS, pyridoxine dependency, hypoglycaemia, drugs
24-48 hrs All the above + milder birth trauma, hypocalcaemia,
hypomagnesaemia, infarcts, some IEMs
>48-72 hrs All the above + dyselectrolytaemias, sepsis, other
encephalopathies
>72hrs-
1week
All the above + benign neonatal seizures
>1-4
weeks
Late hypocalcaemia, sepsis, progressive
hydrocephalus, cerebral dysgenesis, epileptic
syndromes, herpes encephalitis, some IEMs

13. Deleterious effect of seizures whichDeleterious effect of seizures which
necessiates the necessary and promptnecessiates the necessary and prompt
interventionintervention
 significant hemodynamic and respiratorysignificant hemodynamic and respiratory
disturbances –which can extend braindisturbances –which can extend brain
injury.injury.
 disrupt cerebral pressure autoregulation.disrupt cerebral pressure autoregulation.
 massive amount of energy are consumedmassive amount of energy are consumed
energy depletion compromises recovery.energy depletion compromises recovery.
 release large amounts of glutamate ,inhibitrelease large amounts of glutamate ,inhibit
reuptake causes accumulation of glutamatereuptake causes accumulation of glutamate
to toxic levels.to toxic levels.

14. ManagementManagement
Stabilization of the neonate andStabilization of the neonate and
treatment of the seizuretreatment of the seizure
Detection and treatment of underlyingDetection and treatment of underlying
causecause
Long term planning andLong term planning and
prognosticationprognostication

15. StabilizationStabilization
 Any neonate with seizures is anAny neonate with seizures is an
emergency and must be admittedemergency and must be admitted
 Maintain airway by positioning, suctionMaintain airway by positioning, suction
 Give oxygen if requiredGive oxygen if required
 Facilities for intubation should beFacilities for intubation should be
availableavailable
 Establish IV accessEstablish IV access

16. Immediate managementImmediate management
of the ongoing seizureof the ongoing seizure
 Do a bedside blood sugar test for a first seizure ofDo a bedside blood sugar test for a first seizure of
unknown originunknown origin
 If < 40 mg% give a bolus of 2ml/Kg of 10%DIf < 40 mg% give a bolus of 2ml/Kg of 10%D
followed by drip @ 8 mg/kg/minfollowed by drip @ 8 mg/kg/min
 If hypoglycemic and seizure is not controlled,If hypoglycemic and seizure is not controlled,
repeat above bolusrepeat above bolus
This step may be omitted in recurrent seizures of
known etiology other than hypoglycemia

17. 11stst
and 2and 2ndnd
line drugs forline drugs for
ongoing seizureongoing seizure
 Inj Phenobarbitone 20 mg/Kg slowly over 10 min;Inj Phenobarbitone 20 mg/Kg slowly over 10 min;
repeat @ 5mg/Kg every 5 min till control or to arepeat @ 5mg/Kg every 5 min till control or to a
total dose of 40mg/kg (avoid more than 20total dose of 40mg/kg (avoid more than 20
mg/Kg if ventilator is NA)mg/Kg if ventilator is NA)
 If not controlled : Inj Phenytoin (20mg/Kg inIf not controlled : Inj Phenytoin (20mg/Kg in
NS@1mg/Kg/min); repeat @ 5mg/Kg if requiredNS@1mg/Kg/min); repeat @ 5mg/Kg if required
Any seizure lasting > 1 min or > 2 seizures/hrAny seizure lasting > 1 min or > 2 seizures/hr
should be treatedshould be treated

18. Benzodiazepines as thirdBenzodiazepines as third
line drugs for uncontrolledline drugs for uncontrolled
seizuresseizures
Use any of the following if seizures still persist:Use any of the following if seizures still persist:
 Inj Midazolam:Inj Midazolam:0.15mg/kg (bolus) IV0.15mg/kg (bolus) IV, then, then .06-.06-
0.4mg/Kg/hr infusion0.4mg/Kg/hr infusion
 Inj Lorazepam:Inj Lorazepam: 0.05mg/Kg(bolus) IV0.05mg/Kg(bolus) IV, repeat, repeat
 Inj Clonazepam:Inj Clonazepam: .01-.02 mg/Kg (bolus) IV.01-.02 mg/Kg (bolus) IV, then, then ..
01-.03 mg/Kg/hr01-.03 mg/Kg/hr
Avoid Inj Diazepam due to short anticonvulsantAvoid Inj Diazepam due to short anticonvulsant
action, long sedative action, respiratoryaction, long sedative action, respiratory
depression and benzyl alcohol as preservativedepression and benzyl alcohol as preservative

19. When to give Calcium?When to give Calcium?
 If hypocalaemia is suspected or documentedIf hypocalaemia is suspected or documented
 Suspect in a well neonate with multifocal, clonicSuspect in a well neonate with multifocal, clonic
seizures, specially if around 5seizures, specially if around 5thth
day of lifeday of life
 Give 2-4ml/Kg of 10% Ca gluconate (dil1:1 withGive 2-4ml/Kg of 10% Ca gluconate (dil1:1 with
5%D) under cardiac monitoring (stop if HR falls5%D) under cardiac monitoring (stop if HR falls
by > 20/min)by > 20/min)
Do not give Calcium in all cases before startingDo not give Calcium in all cases before starting
anticonvulsants. Do not wait for report inanticonvulsants. Do not wait for report in
suspected cases but collect sample beforesuspected cases but collect sample before
administration of calciumadministration of calcium

20. Maintenance doses onceMaintenance doses once
seizures are controlledseizures are controlled
 Inj Phenobarbitone 4-5 mg/Kg IV or orally inInj Phenobarbitone 4-5 mg/Kg IV or orally in
one or two divided dosesone or two divided doses
 Inj Phenytoin 3-5 mg/Kg/day IV or orally inInj Phenytoin 3-5 mg/Kg/day IV or orally in
two divided dosestwo divided doses
Switch to oral as soon as possible. Stop allSwitch to oral as soon as possible. Stop all
anticonvulsants except Phenobarbitone ifanticonvulsants except Phenobarbitone if
seizure-free for > 72 hrsseizure-free for > 72 hrs

21. Treatment of refractoryTreatment of refractory
seizuresseizures
 Try Inj Pyridoxine 50-100mgIV if cause isTry Inj Pyridoxine 50-100mgIV if cause is
not knownnot known
 Consider drugs like Valproate,Consider drugs like Valproate,
Carbamazepine or Lamotrigine afterCarbamazepine or Lamotrigine after
investigations and consultation withinvestigations and consultation with
neonatologist or neurologistneonatologist or neurologist
Refractory seizures are those which are not
controlled with more than 2
anticonvulsants in adequate doses

22. Clinical EvaluationClinical Evaluation
 History: Ask for h/o fetal compromise, birthHistory: Ask for h/o fetal compromise, birth
asphyxia, resuscitation, IUGR, drugs,asphyxia, resuscitation, IUGR, drugs,
consanguinity, infections,early deaths in familyconsanguinity, infections,early deaths in family
 Examination: Look for birth trauma, toneExamination: Look for birth trauma, tone
abnormalities, dysmorphic features, head size,abnormalities, dysmorphic features, head size,
stigmata of intrauterine infections,stigmata of intrauterine infections,
neurocutaneous markers, abnormal odors,neurocutaneous markers, abnormal odors,
features of sepsisfeatures of sepsis
In many cases of neonatal seizures examination
may be normal

23. InvestigationsInvestigations
 Hb/PCV, blood glucose, calcium,Hb/PCV, blood glucose, calcium,
magnesium and electrolytes in all casesmagnesium and electrolytes in all cases
 Septic workup: complete blood count,Septic workup: complete blood count,
peripheral smear, CRP, I:T ratio, lumbarperipheral smear, CRP, I:T ratio, lumbar
puncture, blood, CSF and urine cultures inpuncture, blood, CSF and urine cultures in
suspected sepsissuspected sepsis
 pH, lactate, ammonia, aminoacids, organicpH, lactate, ammonia, aminoacids, organic
acids, fatty acids and urinary ketones :acids, fatty acids and urinary ketones :
Restrict rare investigations to rare cases ofRestrict rare investigations to rare cases of
suspected Inborn Errors of Metabolismsuspected Inborn Errors of Metabolism
(IEMs)(IEMs)

24. InvestigationsInvestigations
 EEG should definitely be done in all cases ofEEG should definitely be done in all cases of
unknown etiology or in refractory seizures forunknown etiology or in refractory seizures for
prognosisprognosis
 Subtle and tonic seizures may not beSubtle and tonic seizures may not be
associated with EEG changesassociated with EEG changes
 Interictal background activity is important forInterictal background activity is important for
prognosisprognosis
 Burst suppression, voltage suppression orBurst suppression, voltage suppression or
isoelectric background are poor prognosticisoelectric background are poor prognostic
signssigns
In many cases it is not possible or advisable to
treat seizures to electrical quiescence and
clinical control suffices

25. InvestigationsInvestigations
 USG - for IVH and cerebral edemaUSG - for IVH and cerebral edema
 CT Scan- for hemorrhage, infarcts orCT Scan- for hemorrhage, infarcts or
structural abnormalitiesstructural abnormalities
 MRI- for greater detail of structure andMRI- for greater detail of structure and
myelination. Diffusion weighted MRI and MRmyelination. Diffusion weighted MRI and MR
spectroscopy for functionspectroscopy for function
MRI is only recommended for refractoryMRI is only recommended for refractory
cases or those with significant neurologicalcases or those with significant neurological
deficits or delaydeficits or delay

26. Long termLong term
AnticonvulsantsAnticonvulsants
 If seizure-free and neurologically normal after 2If seizure-free and neurologically normal after 2
weeks or at discharge (whichever is earlier)-stopweeks or at discharge (whichever is earlier)-stop
all anticonvulsantsall anticonvulsants
 If seizure free but neurologically abnormal-giveIf seizure free but neurologically abnormal-give
Syp Phenobarbitone x 1 monthSyp Phenobarbitone x 1 month
 At 1 month do EEGAt 1 month do EEG
 If EEG is normal stop PhenobarbitoneIf EEG is normal stop Phenobarbitone
 If EEG is abnormal- continue x 3 monthsIf EEG is abnormal- continue x 3 months
 Repeat EEG every 3 months till normal beforeRepeat EEG every 3 months till normal before
stoppingstopping
If seizures persist or recur at any time change/
restart / add anticonvulsants

27. PrognosisPrognosis
 Seizures due to hypocalcaemia andSeizures due to hypocalcaemia and
subarachnoid hemorrhage have goodsubarachnoid hemorrhage have good
prognosisprognosis
 Seizures due to cerebral dysgenesis,HIESeizures due to cerebral dysgenesis,HIE
Stage III,Grade III & IV IVH, extensive infarcts,Stage III,Grade III & IV IVH, extensive infarcts,
severe hypoglycemia have poor prognosissevere hypoglycemia have poor prognosis
 Myoclonic, tonic, seizures or refractory haveMyoclonic, tonic, seizures or refractory have
poor prognosispoor prognosis
 Isoelectric or burst suppression interictal EEGIsoelectric or burst suppression interictal EEG
have bad prognosishave bad prognosis
 Preterms have a worse prognosis asPreterms have a worse prognosis as
compared to termscompared to terms

28. 
S.no Etiology outcome %
1. Hypoxia-ischemia 50
2. Meningitis 50
3. Hypoglcemia 50
4. Subarachanoid hemorrage 90
5. Early hypocalcemia 50
6. Late hypocalcemia 100
7. Intraventricular hemorrage 10
8. Dysgenesis 0
9. Unknown 75

29. Key messagesKey messages
 Seizures are the most commonSeizures are the most common
manifestation of serious neurologicalmanifestation of serious neurological
dysfunction in the neonatal perioddysfunction in the neonatal period
 Seizures in the newborn are often difficult toSeizures in the newborn are often difficult to
recognize clinically because of their subtlerecognize clinically because of their subtle
and fragmentary natureand fragmentary nature
 Ongoing or recurrent seizures should beOngoing or recurrent seizures should be
treated energetically in a step-wise mannertreated energetically in a step-wise manner
 Prognosis depends on etiology and type ofPrognosis depends on etiology and type of
seizureseizure