latest updates included in neonatal seizure classification, emergency management, choosing anti-epileptics..

1. Dr. Shalika Widyaratna
Neonatology Unit
Teaching Hospital
Kurunegala

2. Why important???
• Most Common may be the First and only
manifestation of a Neurological disorder in
neonatal period
• Very difficult to recognize easily missed because
brief and not organized
• Range from benign, self limiting very severe to
life threatening
• Risk of death survivors are at risk of
Neuro/Cognitive impairment, development
delay and later epilepsy

3. • Incidence higher among neonates than any
other age group due to hyperxcitability of
imature brain and multiple risk factors
• Imature CNS mostly incapable to organise a
generalized seisure so unusual pesentation
• Most frequent during 1st 10 days of life
• Confuse with nonepileptic phenomena like
gitteriness,benign sleep myoclonus and
gneralised tonic posture

4. Definition…
• A stereotypic Paroxysmal alteration in
neurological function motor, behavior and/or
autonomic
• First 28 days of a term
• Upto 44 weeks of GA of a preterm

5.  ICH- SAH/SDH(term),
IVH(preterm)
 HIE (term)
Hypoglyecemia
 Ca+2(most common) Mg+2, Na+
Na+
IEM AA metabolism
Meningitis
Encephalitis -CMV,
rubella, herpes,
toxoplasma
septicaemia
Cerebral dysgenesis
Hydrocephalus
Microcephaly
Neuronal migration
defects-lissencephayBenign familial seizures
Drug induced-opiate withdrawal
Benign idiopathic seizures(5ths day

6. Age of onset Likely etiology
<24h HIE,severe birth trauma,Congenital CNS
abnormality,B6(pyridoxine), deficiency, hypoglycaemia,drug
withdrawal,intra uterine infections
24-48h All above,mild birth trauma,low Ca+2,low Mg+2,some IEM
48-72h All above + low/high Na+,sepsis,enceplalitis,meningitis,abscess
72h to 1 week All above + benign/familial neonatal seizures,kernicterus
1-4 weeks Sepsis,meningitis,encephalitis,hydrocephalus,cerebral
deysgenesis,Late hypocalaemia(hypoparathyroidism),epileptic
syndromes,some IEMs

7. Incidence
Cause incidence
HIE(mostly in term babies within 1st 24h) 30-50%
ICH (in preterms, Hb drops) 10-17%
hypocalaemia 6-15%
CNS infections(commenly by grp B streptococci and Ecoli) 5-14%
Hypoglycaemia( commanly in IUGR/preterm)p 6-10%
unknown 10%
Infarctions(on day2-3 otherwise well babies) 7%
CNS malformations 5%
IEM 3%
Full term babies 0.25-0.35%
In preterm 10-22%

8. Clinical recognition
Spontaneous, paroxysmal, repititive,motor or autonomic
phenomina
 Substallip smacking,Sucking,chewing,extending
tongue,drooling,respiratory irregularities,,apnoea,
cycling/paddling ,rapid eye movements,blinking/fluttering of
eye will cover >50%
 Myoclonic jerks-brief fast movements of limbs
 Clonic - unifocal/multifocal/generalised 2-4Hz cycling or boxing
movements
 Tonic postre +/- abnormal gaze
Usually not stimlus sensitive, can not be stopped by restraining
Usually have an underline etiology not idiopathic

9. Nonepileptic phenomena vs epilepsy
phenomina features
jitteriness Provoked by stimulation
Stoppable by restrain(passive flection)
Never involve the face and eye
Benign neonatal sleep myoclonus Occurs during sleep only, abolished by arousal
resolve spont in weeks
Bilatereal or unilateral
Syncronised or asyncronised
Stimulus provoked myoclonus With severe CNS dysfunction
focal or generalised
EEG changes seen
Stiff man syndrome Very rare familial disorder
Generalised myoclonus
Provokedby stimuli(noice,touch)
Severe hypertonia may have apnoea and bradycardia
Responds to BDZ
Apnoea lasts>10-20 sec, ass with bradycardia not
Tachycardia

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11. Clinical Approch
• History:- family hx, antinatalmaternal
infections, perinatalpreeclampsia,fetal
distress,obstructed labour,apgar
• Examintion :- pattern,?stoppable, ?stimulus
sensitive,tone,vitals,dysmorphism
• Investigations:- CBS,FBC,Mg,Ca,SE,uss
brain,CRP,Blood culture,LP,Torch screenig,EEG,IEM
screening serum AA, urine organic acids,CSF lactate

12. In terms mainly(focal cerebral injury)
Biphasic-fast contraction and slow
relaxation
Focal/multifocal
Focal clonic have best outcomes
z
EEG
epileptic
Non-
epileptic
Clinical
subtle
tonic
clonic
myoclonic Rare
Worst prognosis
Focal/multifocal/generalised
Lightning rapid contractions/jerks
of limbs UL>LL )
Commonest
term>Preterm
Mouth/tongue movements
Blinking/staring
Paddling
apnoeaIn preterms mainly(ICH)
Sustained extension of all four limbs
Sustained flexion of ULs with
extension of LLs
Sustained muscle contraction
Focal<generalised
Poor prognosis
CLASSIFICATION

13. Initial management
• Usual ABCD approch
• Check CBS common and treatable
• IV access Hypoglycaemia
<45mg/dl
200mg(2ml)/kg
10% dextrose
bolus followed by
10% dextrose drip
Repeat CBS in 10-
15mins
No
hypoglcaemia
IV
phenobarbitone
20mg/kg slowly
over 20mins
Repeat IV
phenobarbitone
10mg/kg every
30mins two doses

14. Seizure controled with
penobarbitone
Seizure not controled with
penobarbitone
Maintainance
phenob.5mg/kg/day once
daily after12h of last seizure
Continue for 72h
Iv phenytoin
20mg/kg over
20mins
IV clonazepam
100mcg/kg loadig
dose
IV clonazepam
10-40mcg/kg/h
infusion

15. • Consider LP and starting IV cefotaxime
• Correct Ca if hypocalaemia
• If no clinical signs of seizure in 72 hrs stop
phenobarbitone without tapering dose
• If more than one drug stop one by one .
Pnenobarbitone the last to stop
• USS brain

16. ABCDstart O2check CBSIV accsesscorrect CBS if abnl(2ml/kg of 10%dext)
Give 10% calgluconate 2ml/kg over 10mins if hypocalcaemia suspected
If not responding to calcium Give IM 0.25ml/kg of 50% mgso4
Iv phenobarbitone 20mg/kg over 20minsRpt 10mg/kg in 30mins
twisemaintanance 3-5mg/kg/day
Start BDZ as 3rd line IV lorazepam 0.05mg/kg over 5mins or Midazolam 0.15mg/kg IV
bolus 0.1-0.4mg/kg/hr infusion
Phenytoin 20mg/kg in N/S over 20mins Rpt 5-10mg/kg
IV Lidocaine 4mg/kg bolus(not with phenytoin*) 2mg/kg/hr infusion or Na valproate
25mg/kg 5-10mg/kg/day
Vigabatrin,Carbamezapine,lamotrigen.Topiramate,Paraldehyde,IM neurobion
1ml,pyridoxine therapeutic trial iv 50-100mg(With EEG monitoring)
Levatiracetam(7mg/kg daily*) like nowel AED with neurology openion
Draw blood for Ix Ca,Mg,SE,FBC,CRP,Bld Cult
Consider mechanical ventilation
EEGas soon as seisure occursidealy within 24hrs
EEG
CSF study
USS-B
IEM,TORCH screening

17. WHO recommandations in neonatal seizure
management
1. Seizures lasting>3mins,or are brief but serial should be treated
2. all electrical seizures should be treated even in absence of clinical seizures
3. In all neonatal seizures Hypoglyaecaemia has to be ruled out and treated if
present, before ACT
4. If CNS infection is suggestive should do LP and treated with Ab
appropriately
5. In all neonatal seizures Hypocalaemia should be checked for and treated
6. Phenobarbitone should be the 1st line
7. In absence of seizures neonates with HIE need not to give prophylactic
phenobarbitone therapy
8. All neonates with seizure should be confirmed with EEG where available
9. EEG should not be performed for the sole purpose of determining etiology
of a clinical seizure
10. USS-brain should not be done to evaluate the efficacy of treatments with
AED

18. Brigham and women’s hospital
(US)Neonatal seizure guideline
1. Phenobarbitonephenytoinmidazolammidazolam
infusionlevetiracetam
2. Appropriate duration of AET not defined. Shorter
treatment warrented
3. Phenobarbitone interefere maturation of synaps
and effect on apoptic neurodegeneration. also
incresed CP risk than Levetiracetam
4. 73%of paediatric neurologists recommend
levetiracetam and/or topiramate
5. Levetiracetam has better cognitive and
motor score at 12months compared to
phenobarbitone
6. Receptors for levetiracetam develops by 26 of POA
and reach close to adult level by 37weeks

19. Queensland Clinical Guideline:
Neonatal seizures
1. Treating the underlying cause of the seizures is critical to
prevent clinical deterioration, further brain damage and
poor long term neuro-developmental outcomes
2. Subclinical seizures may manifest as apnoea in the term
baby however when it is the sole sign of a seizure it is not
usually accompanied by bradycardia
3. Commence treatment when:
o Clinically apparent seizure lasts more than three minutes
o More than two briefer seizures occur
o Electroencephalographic seizures are present
4. Phenobarbital is the preferred first line medication
5. To maximum dosage before introducing another

20. 6.Second line drug Phenytoin 15-20 mg/kg IV,Midazolam
0.15 mg/kg IV, Levetiracetam 10 mg/kg IV twice per
day, Topiramate 5 mg/kg orally, Clonazepam 100
micrograms/kg IV, Lignocaine 2 mg/kg IV, and follow
with IV infusion
7.If seizures intractable within hours of birth & resistant
to AEDs consider pyridoxine 50–100 mg IV
8.Blood Lactate, Ammonia,LFT, FOR Metabolic screen,
Acylcarnitines, Biotinidase, Copper, caeruloplasmin and
hair analysis, Plasma amino acids, FOR Congenital
infection screen Toxoplasma, Rubella, CMV, HSV,
Syphilis, Enterovirus, Varicella zoster, Parovirus B19
• CSFCSF amino acids,Paired CSF and plasma glucose
and lactate, Neurotransmitters,HSV,enterovirus,
Lactate, pyruvate and amino acids

21. • Urine Urine Culture, Amino acids, Organic acids, Alpha
aminoadipic semialdehyde,CMV
• Consider genetic tests
9 . Treat both clinical and subclinical seizures as they have
similar pathophysiology
10. Optimal duration of treatment with anticonvulsants is
unknown
11. Experimental data shows commonly used AEDs may cause
neurotoxicity and neuronal apoptosis
12. Cease anticonvulsants when free of seizures for 72 hours
and neurological examination is normal

22. 13. Consider ceasing AEDs if Seizures controlled
and neurological examination normal OR
Neurological examination abnormal but EEG
normal
14. Anticonvulsant drugs may not stop
electroencephalographic seizures even if they
are effective in reducing or eliminating the
clinical manifestations

23. Prognosis
GOOD
POOR
Uncomplicated
hypoglycaemia
SAH
Abnormal EEG
Myoclonic attacks
Early onset <24h
Complications
•CP
•Hydrocephalus
•Epilepsy
•Growth faltering
Cause % of normal neurodevelopment
Hypocalaemia late onset 100%
Benign familial neonalat conv 100%
SAH 90%
HIE 50%
Bact meningitis 50%
hypoglycemia 50%
Hypocalcaemia early onset 50%
Developmental malformation 0%

24. Commanly used Antiepileptics
Drug Dose Side effects Special points
phenobarbitone Max dose 40mg/kg/day
3-5mg/kg/day bd
Resp depression
,hypotention
1st line drug
phenytoin 15-20mg/kg(1mg/kg/min)
4-8mg/kg/day
Hypotention
Arrythmias,cvs
collapse
Don’t mix with
dextrose
midazolam 0.15mg/kg then
0.1-0.4mg/kg/hr
apnoea Fast onset of action
lorazepam 0.05mg/kg over 5mins Respi arrest Longer duration of
action
Levetiracetam 10 mg/kg IV twice per day minimal
Levetiracetam as 1st line Rx prospective study with 16 neonates(journal of
pediatric neurosciences india) Resultsall patients responded to Rx,noone
needed a 2nd line drug,no major side effects were observed

25. Duration of anticonvulsions
Once seisure controled wean off all ACT except phenobarbitone
Do Neurological examination prior to discharge
If normal-omit
phenobarbitone
If abnormal-cont
phenobarbitone for 1 month
Repeat Neurological examination
If normal-taper phenobarbitone
over 2-4weeks
If abnormal
examination
Do EEG
If normal EEG-taper
phenobarbitone
over 2-4weeks
If abnormal EEG-
continue
phenobarbitone
reassess in 3/12

26. Follow up
• Psycological support to family
• Physiotherapy
• Early identification of physical/cognitive
deficits
• Follow up by multidisciplinary team to asses
developmental outcomes

27. • Swaiman’s Pediatric Neurology
• Neonatology at a glance
• Oxford Hand book of Neonatology
• Srilankan collage of pediatricians 2019 standered
treatment protocol
• Brigham and women’s hospital Neonatal seizure
guideline
• WHO guideline in neonatal seizure management
• Queensland Neonatal clinical guideline
References