Neonatal seizures

NEONATAL

SEIZURESDr. VENKATESH

Postgraduate

Dept of Pediatrics

S V medical college

OBJECTIVES

To familiarize the varied presentations of neonatal

seizures.

To distinguish non seizure states from seizures.

To recognize the unique etiology of neonatal

seizures.

To familiarize the algorithm of management specific

to neonatal seizures.

To be able to decide the duration of antiepileptic

therapy and followup.

OVERVIEW

DEFINITION OF SEIZURE

TYPES OF NEONATAL SEIZURES

CAUSES OF NEONATAL SEIZURES

SEIZURE MIMICS

APPROACH TO NEONATAL SEIZURES

DURATION OF ANTICONVULSANT THERAPY

GUIDELINES

PROGNOSIS

SEIZURE is defined clinically as paroxysmal alteration in

neurologic function ie., motor, behaviour and/or

autonomic function.

It includes

1. Epileptic seizures - phenomenon associated with

corresponding EEG seizure activity.

Eg: clonic seizures.

2. Nonepileptic seizures - clinical seizures without

corresponding EEG correlate.

Eg: subtle and generalised tonic seizures.

3. EEG seizures - abnormal EEG activity with no clinical

correlation.

EPIDEMIOLOGY- INDIA(NNPD;2002-03)

Incidence : 10.3 per 1000 live births

The incidence is high in PRETERM

neonates (2 fold), VLBW( 4 fold) compared

to TERM neonates.

Term neonates- 8.4

Preterm neonates-20.8

VLBW-36.1

Why seizures are common in neonatal period ?

Seizures are common in neonatal period than any other

time in life due to decreased seizure threshold.

Transient overdevelopment of excitatory system than

inhibitory system.

Why generalised seizures are rare in neonates

?

Neonatal brain has reduced connectivity due to

incomplete myelination, so electrical discharges

spread incompletely.

TYPES OF NEONATAL SEIZURES

Four types of neonatal seizures

1. Subtle seizures

2. Clonic seizures

3. Tonic seizures

4. Myoclonic seizures

SUBTLE SEIZURES

Most common form(>50%)

It includes

a) Ocular - tonic horizontal deviation of eyes or sustained

eye opening with ocular fixation or cycled fluttering.

b) Oral facial lingual movements - chewing, tongue

thrusting, lip smacking etc.

c) Limb movements - cycling, paddling, boxing etc.

d) Autonomic phenomena-tachycardia or bradycardia.

e) Apnea may be a rare manifestation of seizure.

CLONIC SEIZURES

Rhythmic movements of muscle groups.

Have both fast and slow movements with frequency of 1-

3 jerks per second.

Commonly associated with EEG changes.

May be unifocal or multifocal.

Focal clonic has good prognosis.

TONIC SEIZURES Pattern is sustained posture of limbs or

asymmetrical truncal postures.

cause: diffuse neurological injury or IVH in preterm

or postasphyxial.

Usually no EEG changes.

Prognosis is poor except for postasphyxial cases.

MYOCLONIC SEIZURES

Non rhythmic lightning fast contraction.

Seen in diffuse brain damage as in perinatal

asphyxia, inborn errors of metabolism, cerebral

dysgenesis.

Worst prognosis in terms of neurodevelopmental

outcome and seizure recurrence.

ETIOLOGY

1.Perinatal events:

Hypoxic ischemic encephalopathy

Intracranial hemorrhage: Germinal

matrix intraventricular hemorrhage,

subdural hemorrhage, primary

subarachnoid hemorrhage (well baby

seizures)

ETIOLOGY

2. METABOLIC

Hypoglycemia

Hypocalcemia

Early: preterm, asphyxia, IDM

Late: Top feeding

Hypomagnesemia

Hyponatremia / hypernatremia

Pyridoxine deficiency

IEM: non-ketotic hyperglycinemia, urea cycle defects, maple syrup disease, glutaric aciduria, propionic aciduria,methyl malanoic aciduria, mitochondrial disease.

ETIOLOGY

3.INFECTIONS:

Bacterial meningitis

Non-bacterial infections: toxoplasmosis,

herpes simplex, rubella,cytomegalovirus

4.DEVELOPMENTAL PROBLEMS:

Cerebral cortical dysgenesis

Neuronal migration disorders

Pachygyria, polymicrogyria

ETIOLOGY

5.MISCELLANEOUS

Passive drug withdrawl

Accidental injection of local anesthetic into fetal scalp.

Neonatal epileptic syndromes

Benign familial neonatal convulsions

Benign idiopathic neonatal convulsions

(fifth day fits)

Early myoclonic encephalopathy

Early infantile epileptic encephalopathy (Ohtahara’ssyndrome)

Malignant migrating partial seizures in infancy( coppola syndrome)

NEONATAL SEIZURES – TIME OF ONSET

Time of

onset

Etiology

< 24 hrs HIE, severe birth trauma, hypoglycemia, hypocalcemia,

drug withdrawl, congenital CNS anomalies,

intracranial hemorrhage

1-3 days All above , subarachnoid hemorrhage, IEM, benign

familial neonatal seizures

> 3 days sepsis ,meningitis, progressive hydrocephalus,

epileptic syndromes, herpes encephalitis, IEM

SPECIFIC ETIOLOGIES

Hypoxic Ischemic Encephalopathy

Most common cause of neonatal seizures usually

in the first 24 hours.

In perinatal asphyxia, seizures occur in context of

history of difficulty during labour , delivery with fetal

HR alterations, low Apgar scores.

Intra cranial hemorrhages

Sub arachnoid hemorrhages cause seizures

usually on second day and have a very good

outcome.

In preterm infant, seizures occur with extension

of germinal matrix hemorrhage to parenchyma

typically after 3 days of life and it is not

assosciated with good outcome.

Acute metabolic disorders

Hypoglycemia

Hypocalcemia : Whole blood ionized calcium is the best

measure.

ionised calcium < 1.1 mmol/lit in > 1500gm.

ionised calcium < 1 mmol/lit in < 1500gm.

Hypomagnesemia: Levels < 1.4mg/dl (0.6 mmol/lit ) are

considered low.

Hypo/Hypernatremia

Neonatal seizure syndromes

Benign familial neonatal seizures

Benign idiopathic neonatal seizures ( fifth day fits )

Early infantile epileptic encephalopathy ( Ohtahara

syndrome )

Malignant migrating partial seizures ( Coppala syndrome

)

SEIZURE MIMICS

1. Jitteriness – suppress with passive flexion,

increases with stimulation, not associated with

autonomic accompaniments and eye movements.

2.Epileptic apnea – associated with tachycardia.

3.Benign neonatal sleep myoclonus - occur as

synchronus myoclonic jerks during non REM sleep

disappear when baby is awake, EEG is normal and

spontaneously resolve by 2 months of age.

Clinical

character

seizures jitteriness

Increases with

stimulation

rare common

Suppress with

passive flexion

absent present

Autonomic

phenomena

present absent

Eye or facial

movements

present absent

Rate of

movement

Clonic seizures show

rapid alteration of fast

and slow phase of

movements

Rate of movement

is identical in

either direction.

EEG

abnormalities

Yes No

APPROACH TO NEONATAL SEIZURES

HISTORY

Seizure history – regarding type of seizure , associated

movements , day of onset.

Antenatal history - intrauterine infection , maternal

diabetes , narcotic addiction.

Perinatal history - H/o fetal distress, instrumental

delivery, need for resuscitation in labour room, apgar

scores .

Feeding history – appearance of lethargy, poor activity

and vomiting after initiation of breast feeding may be

suggestive of IEM.

Family history – H/o consanguinity in parents , family

h/o seizures or MR , early fetal or neonatal deaths would

be suggestive of IEM.

H/o seizures in either parent or sibling in neonatal period

may be suggestive of benign familial neonatal

convulsion.

EXAMINATION

Vitals – HR, RR, CRT, Temp, BP.

General examination – gestation , birth wt and wt for

age

- Seizures in term well baby may be due to SAH.

- Seizures in large for date babies may be due to

hypoglycemia.

CNS examination – presence of bulging AF may be

suggestive of meningitis or ICH

- consciousness (alert /drowsy/comatose).

- tone (hypo/hyper).

- fundus examination for chorioretinitis.

Systemic examination – presence of

hepatosplenomegaly or abnormal urine odour may

be suggestive of IEM

- skin should be examined for neurocutaneous

markers .

INVESTIGATIONS Essential

- Blood sugar

- Serum electrolytes

- CSF examination

- Cranial ultrasound

- EEG

Additional

Hematocrit (if plethoric and/or at risk for

polycythemia)

Serum bilirubin (if icteric)

Serum magnesium

Arterial blood gas and anion gap (lethargy,

vomiting, family history, etc.)

Imaging: CT and/or MRI (if no etiology found

after essential investigations)

TORCH screen for congenital infections

Work-up for inborn errors of metabolism

NSG - excellent tool for detection of IVH and

parenchymal hemorrhage.

CT - diagnostic in SAH and developmental

malformations.

MRI - diagnostic in cerebral dysgenesis, lissencephaly

and other neuronal migration disorders.

EEG - diagnostic and prognostic role in seizures and

should be done in all neonates who need anticonvulsant

treatment.

Acute management of seizures

Neonate with seizures

•Identify and characterize the seizure

• Secure airway and optimize breathing, circulation, and temperature

• Secure IV access and take samples for baseline investigations

•If hypoglycemic : administer 2 ml/kg of 10% dextrose as

bolus followed by a continuous infusion of 6-8 mg/kg/min

• If serum calcium is abnormal, 2 ml/kg of calcium gluconate

(10%) should be given IV under cardiac monitoring

Seizures persist

Administer phenobarbitone 20mg/kg IV stat

over 20 minutes

Repeat phenobarbitone in 10 mg/kg/dose

aliquots until 40 mg/kg dose is reached

Seizures

continue

Seizures continue

Administer phenytoin 20 mg/kg IV slowly

over 20 minutes under cardiac monitoring

Lorazepam: 0.05 mg/kg IV bolus over 2-5 minutes; may be repeated

Midazolam: 0.15 mg/kg IV bolus followed by infusion of 1-7 mcg/kg/min

Clonazepam 0.1mg/kg;Consider ventilation.

Seizures continue

Seizures continue

Second line drugs like

Lidocaine[4mg/kg f/b 2mg/kg/hr]

Paraldehyde[0.1-0.2ml/kg/dose IM]

sodium valproate[20-25mg/kg f/b 5-10mg/kg/12h]

Topiramate(20mg/kg/day)

Levetiracetam(10-30mg/kg/day)

Vigabatrin(50mg/kg/day) Pyridoxine(100mgIVtestdose)

exchange transfusion[IEMs,drug toxicity,bilirubin encephalopathy]

Wean AEDs slowly to maintenance

phenobarbitone

Seizures controlled

MAINTENANCE DOSE

Phenobarbitone or phenytoin after

loading dose maintenance dose 3-5

mg/kg/day in two divided doses.

Wean slowly in a way, taper the last

given anti convulsant first and first

given phenobarbitone in last.

DURATION OF ANTICONVULSANT

THERAPY GUIDELINES

Newborn on anticonvulsant therapy

Stop

phenobarbitone

prior to discharge

Evaluate EEG

Normal

Normal examination

Taper drugs over

2 weeks

Abnormal EEG

Continue drug;

reassess at 3

months

Normal EEG

Taper drugs over 2

weeks

Wean all antiepileptic drugs except phenobarbitone once seizure

controlled

Perform neurological examination prior to discharge

Abnormal

Continue phenobarbitone for 1 month

Repeat neurological examination at 1 month

Abnormal examination

PROGNOSIS

Focal clonic seizures carry the best prognosis.

Myoclonic seizures carry the worst prognosis in

terms of neurodevelopmental outcome and seizure

recurrence.

Seizures due to SAH and late onset hypocalcemia

carry best prognosis in terms of long term

neurodevelopmental outcome.

Seizures related to hypoglycemia,cerebral

malformations and meningitis have adverse

outcome.

Neurological Disease Normal Development

Hypoxic-ischemic encephalopathy 50%

Primary subarachnoid hemorrhage 90%

Hypocalcemia

Early-onset 50%

Later-onset 100%

Hypoglycemia 50%

Bacterial meningitis 50%

SUMMARY

Seizures are common in neonatal period than any

other period of life.

Subtle seizures are the most common type of

neonatal seizures.

Hypoxic ischemic encephalopathy is the most

common cause of neonatal seizures.

Phenobarbitone is the drug of choice for neonatal

seizures.

Focal clonic seizures and seizures due to

subarachnoid hemorrhage and late onset

hypocalcemia carries best prognosis.

REFERENCES

AIIMS NICU PROTOCOL -2014

MANUAL OF NEONATAL CARE - CLOHERTY

NELSON TEXTBOOK OF PEDIATRICS

CARE OF THE NEWBORN – MEHARBAN SINGH

IAP TEXT BOOK OF PEDIATRICS

THANK YOU