Protocol for Management Protocol for Management of Neonatal Seizuresof Neonatal Seizures

Soumya Ranjan ParidaSoumya Ranjan ParidaBasic B.Sc. Nursing 4Basic B.Sc. Nursing 4thth year yearSum Nursing CollegeSum Nursing College

IntroductionIntroduction

Most common manifestation of neonatal Most common manifestation of neonatal neurological diseaseneurological disease

Paroxysmal alteration of neurological Paroxysmal alteration of neurological function having behavioural,motor and function having behavioural,motor and autonomic changes.autonomic changes.

Seen in 0.5-3% of term and 11-60% of Seen in 0.5-3% of term and 11-60% of preterm babiespreterm babies

Hyperexcitability of neonatal brain, in Hyperexcitability of neonatal brain, in addition to multiple risk factors, is addition to multiple risk factors, is responsibleresponsible

Non-seizure eventsNon-seizure events

JitterinessJitteriness Benign sleep myoclonusBenign sleep myoclonus Tonic posturings /opisthotonusTonic posturings /opisthotonus

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 to development of excitatory systems compared to inhibitory systems.inhibitory systems.

– the immature brain has a transient the immature brain has a transient overexpression in the density of excitatory overexpression in the density of excitatory amino acid (primarily glutamate) receptorsamino acid (primarily glutamate) receptors

– a relative paucity of glutamate reuptake a 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 neural cellular factors, differential development of neural systemssystems

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

Types of SeizuresTypes of Seizures Subtle seizures (50%): PSubtle seizures (50%): Paroxysmal, repetitive, aroxysmal, repetitive,

motor,autonomic or behavioral phenomena like motor,autonomic or behavioral phenomena like lip smacking, sucking, chewing, eye movements lip smacking, sucking, chewing, eye movements (deviation, nystagmus), cycling or paddling (deviation, nystagmus), cycling or paddling movements, changes in skin color, respiratory movements, changes in skin color, respiratory irregularities (tachypnoea or apnoea), irregularities (tachypnoea or apnoea), tachycardia, etctachycardia, etc

Tonic seizures : Focal or generalized, with or Tonic seizures : Focal or generalized, with or without eye movementswithout eye movements

Clonic: Unifocal, multifocal or generalizedClonic: Unifocal, multifocal or generalized Myoclonic Myoclonic

Common causes of Common 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

Causes of seizuresCauses of seizures Other causes of neonatal encephalopathy like Other causes of neonatal encephalopathy like

bilirubin encephalopathy, hypertensive bilirubin 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,severe vomiting,severe jaundice,hepato-splenomegaly,malodours urine. jaundice,hepato-splenomegaly,malodours urine.

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 are Benign idiopathic or familial neonatal seizures are rare diagnoses of exclusion in a well neonate rare diagnoses of exclusion in a well neonate with normal neurological outcome with normal neurological outcome

S.noS.no EtiologyEtiology Incidence Incidence (%)(%)

1.1. Cerebral hypoxia-ischemiaCerebral hypoxia-ischemia a. Global (e.g., perinatal asphyxia)a. Global (e.g., perinatal asphyxia)

b. Focal infarct ion (arterial or venousb. Focal infarct ion (arterial or venous )) 4040 1515

2.2. Intracranial hemorrage Intracranial hemorrage 1515

3.3. CNS infection CNS infection 55

4.4. Metabolic diseaseMetabolic disease a.Transienta.Transient b.Inborn errors of metabolism b.Inborn errors of metabolism

55 1 1

5.5. Cerebral dysgenesis Cerebral dysgenesis 55

6.6. Neonatal epileptic syndromesNeonatal epileptic syndromes 11

7.7. Neonatal abstinence syndromeNeonatal abstinence syndrome 11

8.8. UnknownUnknown 1010

DiagnosisDiagnosis

Time of onset of seizures .Time of onset of seizures . positive family history.positive family history. associated conditions.associated conditions. Investigations .Investigations .

Age of Onset and EtiologyAge 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

Deleterious effect of seizures which Deleterious effect of seizures which necessiates the necessary and prompt necessiates the necessary and prompt interventionintervention

significant hemodynamic and respiratory significant hemodynamic and respiratory disturbances –which can extend brain disturbances –which can extend brain injury.injury.

disrupt cerebral pressure autoregulation.disrupt cerebral pressure autoregulation. massive amount of energy are consumed massive amount of energy are consumed

energy depletion compromises recovery. energy depletion compromises recovery. release large amounts of glutamate ,inhibit release large amounts of glutamate ,inhibit

reuptake causes accumulation of glutamate reuptake causes accumulation of glutamate to toxic levels.to toxic levels.

ManagementManagement

Stabilization of the neonate and Stabilization of the neonate and treatment of the seizuretreatment of the seizure

Detection and treatment of underlying Detection and treatment of underlying causecause

Long term planning and Long term planning and prognosticationprognostication

Stabil izationStabil ization

Any neonate with seizures is an Any 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 be Facilities for intubation should be

availableavailable Establish IV accessEstablish IV access

Immediate management Immediate management of the ongoing seizureof the ongoing seizure

Do a bedside blood sugar test for a first seizure of Do a bedside blood sugar test for a first seizure of unknown originunknown origin

If < 40 mg% give a bolus of 2ml/Kg of 10%D If < 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

11 stst and 2 and 2 ndnd l ine drugs for l ine 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 a repeat @ 5mg/Kg every 5 min till control or to a total dose of 40mg/kg (avoid more than 20 total 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 in If 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/hr Any seizure lasting > 1 min or > 2 seizures/hr should be treatedshould be treated

Benzodiazepines as third Benzodiazepines as third l ine drugs for uncontrol led l ine drugs for uncontrol led 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 anticonvulsant Avoid Inj Diazepam due to short anticonvulsant

action, long sedative action, respiratory action, long sedative action, respiratory depression and benzyl alcohol as preservativedepression and benzyl alcohol as preservative

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, clonic Suspect in a well neonate with multifocal, clonic

seizures, specially if around 5seizures, specially if around 5 thth day of life day of life Give 2-4ml/Kg of 10% Ca gluconate (dil1:1 with Give 2-4ml/Kg of 10% Ca gluconate (dil1:1 with

5%D) under cardiac monitoring (stop if HR falls 5%D) under cardiac monitoring (stop if HR falls by > 20/min)by > 20/min)

Do not give Calcium in all cases before starting Do not give Calcium in all cases before starting anticonvulsants. Do not wait for report in anticonvulsants. Do not wait for report in

suspected cases but collect sample before suspected cases but collect sample before administration of calciumadministration of calcium

Maintenance doses once Maintenance doses once seizures are controlledseizures are controlled Inj Phenobarbitone 4-5 mg/Kg IV or orally in Inj 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 in Inj Phenytoin 3-5 mg/Kg/day IV or orally in

two divided dosestwo divided doses

Switch to oral as soon as possible. Stop all Switch to oral as soon as possible. Stop all anticonvulsants except Phenobarbitone if anticonvulsants except Phenobarbitone if

seizure-free for > 72 hrsseizure-free for > 72 hrs

Treatment of refractory Treatment of refractory seizuresseizures

Try Inj Pyridoxine 50-100mgIV if cause is Try Inj Pyridoxine 50-100mgIV if cause is not knownnot known

Consider drugs like Valproate, Consider drugs like Valproate, Carbamazepine or Lamotrigine after Carbamazepine or Lamotrigine after investigations and consultation with investigations and consultation with neonatologist or neurologistneonatologist or neurologist

Refractory seizures are those which are not controlled with more than 2 anticonvulsants in adequate doses

Clinical EvaluationClinical Evaluation History: Ask for h/o fetal compromise, birth History: Ask for h/o fetal compromise, birth

asphyxia, resuscitation, IUGR, drugs, asphyxia, resuscitation, IUGR, drugs, consanguinity, infections,early deaths in family consanguinity, infections,early deaths in family

Examination: Look for birth trauma, tone Examination: 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 sepsisIn many cases of neonatal seizures examination

may be normal

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, lumbar peripheral smear, CRP, I:T ratio, lumbar puncture, blood, CSF and urine cultures in puncture, blood, CSF and urine cultures in suspected sepsissuspected sepsis

pH, lactate, ammonia, aminoacids, organic pH, lactate, ammonia, aminoacids, organic acids, fatty acids and urinary ketones :acids, fatty acids and urinary ketones : Restrict rare investigations to rare cases of Restrict rare investigations to rare cases of

suspected Inborn Errors of Metabolism suspected Inborn Errors of Metabolism (IEMs)(IEMs)

InvestigationsInvestigations EEG should definitely be done in all cases of EEG should definitely be done in all cases of

unknown etiology or in refractory seizures for unknown etiology or in refractory seizures for prognosisprognosis

Subtle and tonic seizures may not be Subtle and tonic seizures may not be associated with EEG changesassociated with EEG changes

Interictal background activity is important for Interictal background activity is important for prognosisprognosis

Burst suppression, voltage suppression or Burst suppression, voltage suppression or isoelectric background are poor prognostic isoelectric background are poor prognostic signssigns

In many cases it is not possible or advisable to treat seizures to electrical quiescence and clinical control suffices

InvestigationsInvestigations

USG - for IVH and cerebral edema USG - for IVH and cerebral edema CT Scan- for hemorrhage, infarcts or CT Scan- for hemorrhage, infarcts or

structural abnormalitiesstructural abnormalities MRI- for greater detail of structure and MRI- for greater detail of structure and

myelination. Diffusion weighted MRI and MR myelination. Diffusion weighted MRI and MR spectroscopy for functionspectroscopy for function

MRI is only recommended for refractory MRI is only recommended for refractory cases or those with significant neurological cases or those with significant neurological

deficits or delaydeficits or delay

Long term Long term AnticonvulsantsAnticonvulsants

If seizure-free and neurologically normal after 2 If seizure-free and neurologically normal after 2 weeks or at discharge (whichever is earlier)-stop weeks or at discharge (whichever is earlier)-stop all anticonvulsantsall anticonvulsants

If seizure free but neurologically abnormal-give If 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 before Repeat EEG every 3 months till normal before

stoppingstopping If seizures persist or recur at any time change/

restart / add anticonvulsants

PrognosisPrognosis Seizures due to hypocalcaemia and Seizures due to hypocalcaemia and

subarachnoid hemorrhage have good subarachnoid hemorrhage have good prognosisprognosis

Seizures due to cerebral dysgenesis,HIE Seizures 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 have Myoclonic, tonic, seizures or refractory have poor prognosispoor prognosis

Isoelectric or burst suppression interictal EEG Isoelectric or burst suppression interictal EEG have bad prognosishave bad prognosis

Preterms have a worse prognosis as Preterms have a worse prognosis as compared to termscompared to terms

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

Key messagesKey messages

Seizures are the most common Seizures are the most common manifestation of serious neurological manifestation of serious neurological dysfunction in the neonatal perioddysfunction in the neonatal period

Seizures in the newborn are often difficult to Seizures in the newborn are often difficult to recognize clinically because of their subtle recognize clinically because of their subtle and fragmentary natureand fragmentary nature

Ongoing or recurrent seizures should be Ongoing or recurrent seizures should be treated energetically in a step-wise mannertreated energetically in a step-wise manner

Prognosis depends on etiology and type of Prognosis depends on etiology and type of seizureseizure