This document provides an overview of neonatal seizures. Key points include: - Neonatal seizures have an incidence of 10.3 per 1000 live births and are more common in preterm infants. - They are defined as abnormal excessive neuronal activity causing alterations in motor, behavioral or autonomic functions. - Common causes include hypoxic-ischemic encephalopathy, structural brain lesions, infections, and metabolic disturbances. - Seizures are classified based on their clinical presentation and EEG findings as subtle, clonic, tonic, myoclonic or EEG-only. - Differentiating seizures from non-seizure events like apnea or jitteriness is important.

1. NEONATAL
SEIZURES
DR PRAMAN
DRNB NEONATOLOGY RESIDENT

2. OVERVIEW
▪ Epidemiology
▪ Definition
▪ Pathogphysiology
▪ Classification
▪ Non seizure events
▪ Etiology
▪ Approach to management
▪ Management
▪ Prognosis

3. 1. INTRODUCTION
▪ RED ALERT
▪ SECONDARY BRAIN INJURY
▪ FOCAL OR MULTIFOCAL : SINGLE HEMISPHERE
▪ MAJORITY SUBCLINICAL OR SUBTLE
▪ LESS SEIZURE THRESHOLD BUT BETTER PROGNOSIS.

4. 2. Epidemiology
▪ Incidence
▪ 10.3 per 1000 live- births (NNPD)
▪ 58 per 1000 live births in VLBWs
▪ 1 – 3.5 per 1000 live births in Terms

5. 3. DEFINITION
Abnormally excessive or synchronous neuronal
activity in the brain causing paroxysmal
disturbances in neurological function manifesting
clinically as alteration in motor, behavioral and/or
autonomic functions
CAN ANYONE DEFINE EPILEPSY ?

6. 4. Pathophysiology
 Imbalance between neurotransmitters

7. Incresed Seizure Susceptibility
• ↑excitatory neurotransmitters (glutamate)
• ↓inhibitory neurotransmitters (GABA)
• GABA acting as excitatory neurotransmitter
ATP-dependent Na-K pump Failure
NMDA
AMPA

9. ▪ Onset is focal /multifocal, spread within one hemisphere only
▪ Immature mylenation of cortical efferent systems & commissure.
▪ Advanced Cortical development in Limbic system - Subtle

10. Energy dependent ion
pumping
Decreased ATP &
Phosphocreatine
Stimulation of
glycolysis and ↑ Lactate
Vasodilation & ↑ blood
supply
SEIZURE EPISODE
Incresed
blood
pressure
Increased
Cerebral
blood flow
This fall in brain glucose
concentration and rise in
brain lactate are directly
reminiscent of a hypoxic-
ischemic brain insult

12. Time Course of Epileptogenesis
▪ Seconds to minutes – gene induction and translation of receptor and ion-channel proteins
▪ hours to days - neuronal death, inflammation, and altered transcriptional regulation
▪ weeks to months - mossy fiber sprouting, gliosis, neurogenesis

13. 5. Classification
▪ Types of Neonatal seizure
▪ Clinical Seizure
▪ Electro - clinical Seizure
▪ EEG - Only

14. Types of Clinical Seizures

15. Subtle
▪ Most common type
▪ Preterms > Terms
▪ Paroxysmal & Repetitive
▪ Oral-buccal-lingual movements
▪ Progression movements
▪ EEG+/- (Tonic eye deviation – a/w EEG)

17. Clonic
▪ Repetitive, rhythmic contractions of specific muscle groups
▪ Slow rate of repetition
▪ Close relationship to the EEG seizure pattern
▪ Mimics - jitteriness, tremulousness, and myoclonus
FOCAL MULTIFOCAL
Face , trunk, extremity on one side of
body
Several body parts, often migrating ()
usually focal neuropathology e.g.
infarction
Non jacksonian march

19. Tonic
▪ Hallmark of several neonatal epilepsy syndromes
▪ sustained flexion or extension of muscle groups
▪ Sustained, but transient, asymmetrical posturing
▪ Tonic deviation of the eyes (upward)
▪ Poor prognosis, a/w IVH & Kernicterus
FOCAL GENERALIZED
Sustained, asymmetrical Posturing Decerebrate/decorticate like posturing
Mostly EEG discharges + 15% EEG +

20. Myoclonic
▪ Contractions of muscle groups of well-defined regions
▪ rapid, isolated jerk or may be repetitive
▪ Rate of recurrence may be slow, irregular, or erratic
▪ EEG discharges absent.
▪ Types :
▪ Focal – Typically upper extremity, flexor groups.
▪ Multifocal – involving several body parts , asynchronous twitching.
▪ Generalized - bilateral, symmetric jerking of all extremities and/or
muscles of the trunk and neck. EEG +,

22. EEG Only Seizures
▪ High incidence
▪ Similar duration and encephalopathy degree to electroclinical
▪ electromechanical dissociation
▪ electroclinical EEG only
▪ caudal-to-rostral maturation of cl- transporters
▪ brainstem & spinal cord motor system chloride levels decreases before
cortical neuronal levels.

23. Autonomic Seizuers
▪ Clinical changes related to the autonomic nervous system
▪ Apneas often associated with tachycardia
▪ Alterations
▪ Heart rate – Tachy/Brady
▪ Respiration – Tachy / Brady
▪ Blood pressure
▪ Flushing
▪ Salivation
▪ Pupil dilatation

24. 6. Non-Seizure Events
▪ Absence of EEG change
▪ Provoked by stimulation
▪ Suppressed by restraining
▪ No autonomic disturbances
▪ No Head/ Eye deviation
▪ Temporal/Spatial summation - ↑ Intensity
▪ Few benign, but few needs evaluation
▪ Not All That Shakes Is A Seizure

25. ▪Apnea -
▪ Pause in breathing for greater
than 20 seconds
▪ Premature baby
▪ During active sleep
▪ Brainstem immaturity
▪ If (mostly term) accompanied with
eye closure /opening, eye
deviation, mouth movement,
hypertension, tachycardia –
Seizure

26. ▪ Jitteriness
▪ Very Common
▪ Excessive response to
stimulation
▪ Back-and-forth oscillation ,
Same amplitude &
frequency
▪ Hypocalcemia,
hypoglycemia, and hypoxic-
ischemic encephalopathy
▪ Head or eye deviation during
an episode → seizure

27. ▪ Benign neonatal sleep
myoclonus
▪ during sleep – NREM
▪ jerks are typically bilateral,
symmetric
▪ can be stopped by rousing the
infant
▪ does not involve the face
▪ Normal neurologically
▪ BZDs provokes / exacerbates
▪ Spontaneous resolution ~2 mo

28. ▪ Hyperekplexia (startle disease)
▪ Congenital stiff-man syndrome
▪ Startle & sustained tonic spasms response to stimuli
▪ Nocturnal myoclonus.
▪ “minor”  excessive startle
▪ “major”  stiffness while awake, nocturnal myoclonus, risk of SIDS
▪ Glycine receptor gene mutations
▪ Clonazepam - effective treatment
▪ Resolution by 2 yr age

29. Normal Motor Activities
▪ Roving, sometimes dysconjugate eye movements, with occasional
nonsustained nystagmoid jerks at the extremes of horizontal
movement
▪ Sucking, puckering – NO ocular fixation or deviation
▪ While - Asleep
▪ Fragmentary myoclonic jerks (may be multiple)
▪ Isolated, generalized myoclonic jerk as infant wakes from sleep

30. 7. Etiology
Hypoxic-ischemic encephalopathy
Structural brain lesions
Central nervous system (CNS) or systemic infections
Metabolic disturbances
Neonatal onset epilepsies and
▪ (According to a recent multicentre study - EEG seizures were confirmed 35%. Most common cause was hypoxic-
ischaemic encephalopathy 59%, followed by metabolic/genetic disorders 21% and stroke 13%)

33. a. Hypoxic Ischemic Encephalopathy
Most common cause
Presence of diagnostic cues
With short, frequent and refractory episodes
>50% - have subclinical seizures
Treatment is urgent & complicated
Can cause status in 15% term babies
Therapeutic hypothermia - ↓ Burden of seizures

34. b. Ischemic Stroke
▪ 2ND Most common cause
▪ Usually a well appearing neonate
▪ Diagnosis missed if seizure missed
▪ Risk factors - trauma, congenital heart disease,
coagulopathy and metabolic disturbances
▪ Cerebral sinus venous thrombosis
▪ diffuse and focal neurologic deficit
▪ Seizure in 1 in 8000 cases

36. c. Intracranial Hemorrhage
▪ 10 – 15%
▪ Instrumentation, Breech, Large for gestation
▪ Well appearing Neonates
▪ Subduaral – Falx tears

39. ▪ Preterms Neonates–
▪ IVH/GM
▪ Persistent tonic
▪ b/w 3-7 days of life
▪ Poor outcome
▪ First 3 days in GM and
Severe IVH
• Term Neonates
1. Subarachnoid hemorrhage
• infant delivered vaginally.
• second day focal seizure
• resolve rapidly
• good prognosis.
2. Subdural hematomas
• a/w trauma and cerebral
contusion.
• Focal seizures
• First 2 days

40. d. INFECTIONS
▪ 4 % of total
▪ Term = Preterms
▪ Acquired Prenatally –
▪ Intra Uterine Infections – TORCH
▪ Microcephaly; poor intrauterine growth; prematurity; and skin,
ophthalmic, and systemic findings
▪ Acquire postnatally –
▪ Meningitis – Bacterial / Viral / Fungal
▪ Associated clinical features

41. Acquired Prenatally
▪ TORCH Infections
▪ Toxoplasmosis, rubella and CMV –
▪ Seizures as sole manifestation
▪ Occur in first 3 days in the neonatal period
▪ Specific diagnostic clues
▪ HSV & Enterovirus causing encephalitis
▪ HSV – Seizure after 7 days

42. HSV
▪ CNS Involvement - 57%,Disseminated - 22%, SEM – Rare
▪ type 2 HSV – acquired during delivery
▪ Fetal scalp monitoring - a risk factor
▪ Neuroimaging - diffuse brain abnormalities
▪ In case of high suspicion - Empirical acyclovir therapy
ASAP

43. Acquired Postnatally
▪ Bacterial meningitis - seizures later in the first post natal week
▪ Group B streptococci, listeria, Escherichia coli and other GM-

44. e. Structural malformation
▪ 4 - 5 %
▪ Most are seizure free in neonatal period
▪ Outcome – based on type & severity of malformation
▪ Seizures often refractory to medications
▪ Cerebral dysgenesis can cause seizures from the first day of life
▪ Examples - tuberous sclerosis, focal cortical dysplasia,
hemimegalencephaly, lissencephaly, subcortical band heterotopia,
periventricular nodular heterotopia, schizencephaly, and
polymicrogyria

45. f. Transient Metabolic Disturbances
▪ 4 % - Transient disturbances
▪ Rapidly remediable conditions
▪ focus of the initial investigations
1. hypoglycemia
2. hypocalcemia
3. Hypomagnesemia (rare)
▪ 3% - Inborn error of metabolism

46. Hypoglycemia
▪ Most frequent in SGAs and IDMs
▪ Can be a part of other etiologies
▪ Symptoms of neuroglycopenia should prompt treatment
▪ Determinant for seizure probability – time elapsed
▪ Neurological symptoms commonly - jitteriness, stupor, hypotonia,
apnea, and seizures.
▪ Treatment at <40 mg/dL <24 hours and <50 after 24 hours

47. Hypocalcemia
▪ Has two major peaks
▪ 1st Peak -DOL 2-3 LBWs, IDMs, IUGRs, Perinatal Asphyxia
▪ 2nd Peak- Late neonatal age in large, full-term
▪ Consumption of cow milk or wrong formula
▪ Hypomagnesemia is a frequent accompaniment
▪ a/w endocrinopathy (hypoparathyroidism)
▪ Jitteriness, muscle jerks, seizures, and rarely laryngospasm.
▪ Therapeutic response to IV calcium correlating with etiology

48. g. Inborn Errors of Metabolism
▪ 1-3% seizures, seizures may occur in virtually all IEM
▪ enzyme defect in the metabolic pathways and accumulation of
toxic products
▪ initially appear well - placental clearance
▪ seizures > 2 to 3 days
▪ ↓Glucose, ↑pH,↑ ammonia are few of biochemical markers
▪ Diagnosis f/b counseling for later pregnancies
▪ Clues - family history of consanguinity, early sibling death along
with organomegaly on examination

49. Cont.
▪ Presentation –
▪ Vomiting and anorexia or failure to feed
▪ Lethargy that can progress to coma
▪ Seizures
▪ Rapid, deep breathing that can progress to apnea
▪ Hypothermia
▪ Rhabdomyolysis
▪ Unexpected infant death

50. Amino acid or organic acid metabolism Defect
▪ Most common
1. Non-ketotic hyperglycinemia (Burst suppression)
2. Sulfite oxidase deficiency,
3. Multiple carboxylase deficiency,
4. Multiple acyl-coenzyme A dehydrogenase deficiency
5. Urea cycle defect
▪ Hyperammonemia or/and acidosis present
▪ glycine cleavage enzyme defect
▪ CSF glycine levels diagnostic.
▪ resolves spontaneously after ~6 weeks of age

51. Pyridoxine dependency
▪ Rare but treatable cause
▪ defect in the ALDH7A1/antiquitin gene
▪ Deficiency alpha amino-adipic semialdehyde (α-AASA)
dehydrogenase
▪ Impact the metabolism of the neurotransmitters glutamate and
GABA.
▪ Seizures present early, sometimes “in utero”
▪ seizure cessation and resolution of EEG abnormalities after IV
Pyridoxine 100 mg is diagnostic.

52. Pyridoxamine phosphate oxidase deficiency (PNPO)
▪ Fetal seizures
▪ Encephalopathy as well as seizures in premature
▪ Treatment with pyridoxal-5 phosphate
Folinic acid-responsive seizures
▪ Onset as early as the first hours of life
▪ Responsiveness to oral Folinic Acid 2-20 mg twice daily

53. h. Neonatal Epilepsy Syndromes
▪ Rare, accounting for about 1% of cases of seizures
▪ ILAE defines as “a complex of clinical features, signs, and
symptoms that together define a distinctive, recognizable clinical
disorder.”
▪ Major Epilepsy Syndromes With Onset in the Neonatal Period
1. Benign Familial Neonatal Epilepsy
2. Benign nonfamilial neonatal convulsions (fifth-day fits)
3. Early Myoclonic Epilepsy
4. Early Infantile Epileptic Encephalopathy (Ohtahara syndrome)
5. Malignant migrating partial seizures

54. Benign Familial Neonatal Epilepsy
▪ Otherwise well infants on DOL 2 or 3.
▪ Focal clonic or tonic (usually asymmetrical).
▪ Family history of seizures present
▪ Resolves usually within 6 months
▪ Abnormality of voltage-gated K channels, KCNQ2 & KCNQ3.
▪ Developmental outcome is normal
▪ 5% to 15% may have later non-febrile convulsions

55. Benign infantile neonatal seizures
▪ a/k/a “fifth day fits”
▪ suddenly on DOL 4 to 6.
▪ frequent seizures  status epilepticus.
▪ Seizures are focal clonic often with apnea
▪ Seizures resolves within 2 weeks. The etiology is unknown.

56. Early myoclonic epilepsy (EME)
▪ first few days of life
▪ focal motor seizures and myoclonus
▪ seizures are very refractory to medications.
▪ EEG - burst-suppression pattern - often exacerbated by sleep.
▪ Syndrome associated with underlying metabolic disorders
▪ Severely affected development

57. Early infantile epileptic encephalopathy
▪ a/k/a Ohtahara syndrome
▪ Early onset & refractory Seizures
▪ tonic spasms along with focal motor seizures.
▪ Burst-suppression pattern on EEG
▪ Brain structural lesions usually associated .
▪ Developmental prognosis poor
▪ Chaotic epileptiform pattern known as hypsarrhythmia on EEG

58. Malignant migrating partial seizures in infancy
▪ a/k/a Coppola syndrome
▪ Present from 1st to 10th month of age.
▪ Aggressively escalating Focal motor seizures
▪ Highly refractory to anticonvulsant medications.
▪ Developmental status is acutely affected
▪ Poor prognosis for normal outcome
▪ Etiology is unknown

59. Time Of Onset and Likely Etiology
Age of Onset Likely Etiology
<24 hrs HIE, Severe Birth Trauma, Congenital CNS
Anomalies, Pyridoxine Dependency, Hypoglycaemia
24 – 48 hrs All the above + milder birth trauma, hypocalcaemia,
hypomagnesaemia, infarcts, some IEMs
<48 – 72 hrs All the above + dys-electrolytaemias, sepsis,
other Encephalopathies
>72 hsr – 1 week All the above + benign neonatal seizures
<1 – 4 weeks Late hypocalcaemia, sepsis, progressive hydrocephalus,
cerebral dysgenesis, epileptic syndromes, herpes encephalitis, some I
EMs

60. 8. Approach to management
▪ expedited evaluation for the etiology is warranted
▪ Most are symptomatic manifestations of acute brain injury
▪ many require urgent, specific treatment
Diagnosis
History Examination Investigations

61. History
History
Birth
History
Antenatal
history
Feeding
history
Seizure
history
Family
history

62. History
Attempted to identify risk factors for seizures and
clues to the underlying etiology
Gestational and birth history –
Anoxic injury nuchal cord or cord thrombosis, fetal
heart rate decelerations, meconium, low Apgar scores,
and placental abnormalities.
Nature of the delivery operative vaginal delivery 
ICH
birth injury  macrosomia, maternal obesity, abnormal
fetal lie

63. Maternal history
miscarriages  congenital anomalies
gestational diabetes  neonatal hypoglycemia
STD or other infections neonatal Sepsis
Illness during pregnancy e.g. maternal rash and
fever could suggest in utero viral infection
clotting or bleeding tendencies (neonatal stroke or
hemorrhage).

64. Family history
Early sibling death from unknown causes
Consanguinity  inborn errors of metabolism)
Family history of epilepsy particularly neonatal(BFNC)

65. Perinatal history
▪ PERINATAL ASPHYXIA as the commonest cause
▪ History of
▪ fetal distress,
▪ decreased fetal movements,
▪ instrumental delivery,
▪ need for resuscitation in the labor room,
▪ Apgar scores, and
▪ abnormal cord pH (<7) & base deficit (>10 mEq/L)

66. Seizure History
▪ Description Of The Seizure
▪ History
▪ Associated Eye Movements,
▪ Change In Color Of Skin (Mottling Or Cyanosis)
▪ Conscious Or Sleeping
▪ Day Of Life
▪ Day 0-3 Perinatal Asphyxia, ICH, Metabolic Causes,
▪ Day 4-7 Sepsis, Meningitis, Metabolic Causes, Developmental
Defects

67. Feeding history
▪ Inborn Errors Of Metabolism
▪ Lethargy, poor activity, drowsiness, and vomiting after
initiation of breast-feeding
▪ Top Feeding With Cow’s Milk
▪ Late onset hypocalcemia considered

68. Examination
Vital signs:
Heart rate, respiration, blood pressure, capillary refill
time and temperature
General examination:
Gestation, birth weight, and weight for age  seizures
in a term ‘well baby’ or in large for date baby may be
different
presence of any obvious malformations or dysmorphic
features.

69. Systemic examination
CNS :
▪ Bulging fontanel  meningitis or intracranial haemorrhage
▪ Neurological examination 
▪ assessment of consciousness (alert/drowsy/comatose)
▪ tone (hypotonia or hypertonia), and
▪ Fundus examination for chorioretinitis.
Other systems
▪ Organomegaly or an abnormal urine odor may be suggestive of IEM
▪ Skin neuro-cutaneous markers (e.g. hypopigmented macules or ash-
leaf spot in Tuberous sclerosis.)

71. Investigations
▪ Essential Investigations
1. Blood sugar,
2. Serum sodium and calcium,
3. Cerebrospinal fluid (csf) examination,
4. Cranial ultrasound (us), and
5. Electroencephalography (eeg).

73. Additional Investigations
▪ Considered in neonates who do not responding to first line
antiepileptics or neonates with specific features.
▪ Neuroimaging (ct, mri),
▪ Screen for congenital infections (TORCH)
▪ Screen for inborn errors of metabolism
▪ An ARTERIAL BLOOD GAS should be performed if IEM is strongly
suspected

74. Neuroimaging
1. NEUROSONOGRAPHY
▪ Excellent bedside tool for detection of intraventricular and
parenchymal hemorrhage. (But not SAH & SDH)
▪ done in all infants with seizures.
2. CT scan
▪ Should generally be avoided
▪ 2nd tier investigation
▪ subarachnoid hemorrhage and developmental malformations

75. ▪ Magnetic resonance imaging (MRI)
▪ all neonates with seizures to evaluate
▪ Useful in hypoxic-ischemic injury, ICH , Stroke, brain malformations.
▪ MR angiography  ischemic stroke or vascular malformation
▪ MR venography  venous sinus thrombosis
▪ MR spectroscopy  evaluate metabolites like
▪ glycine (nonketotic hyperglycinemia),
▪ lactate (mitochondrial disorders), or
▪ loss of creatine (disorder of brain creatine metabolism)

76. EEG
▪ To determine the risk and presence of seizures
▪ Seizure is defined as abnormal EEG pattern which evolves, is of >2
microvolt amplitude, and has a duration of ≥10 seconds
▪ Video EEG monitoring — The gold standard for neonatal seizure
diagnosis is multi-channel video EEG monitoring
▪ EEG should be performed for at least one hour.
▪ Background abnormality in both term and preterm high risk for
neurological sequelae.
▪ emphasis on continuous EEG monitoring to aid in management of
seizures in newborns.

77. ▪ excess of sharp waves nonspecific indicator of encephalopathy.
▪ Bursts of repetitive or short, stereotyped evolving rhythmic bursts
of sharp waves  increased seizure risk
▪ Evolving rhythmic discharges longer than 10 seconds seizures

78. Amplitude-integrated EEG (aEEG)
▪ widespread use at the bedside
▪ reduced number of electrodes single channel (2 electrodes) or
dual-channel (4 electrodes) EEG tracing
▪ Final display showing several hours of aEEG data on a single
screen generated.
▪ Electrographic seizures are characterized
▪ by upward arches

79. Management
▪ Who to treat
▪ Identify first  gold standard, conventional video EEG, or, limited
channel aEEG
▪ potential adverse effects of seizures on ventilatory function, circulation,
cerebral metabolism, and subsequent brain development, considered
▪ repeated seizures should be stopped
▪ World Health Organization recommended treatment of all clinical and
electrographic seizures
▪ goal of therapy is the elimination of electrical seizure activity

80. Stabilization
1. Thermoneutral environment
2. ensure airway, breathing, and circulation (TABC).
3. Oxygen should be started, IV access should be secured, and
blood should be collected for glucose and other investigations.
4. A brief relevant history should be obtained and quick clinical
examination should be performed.
5. All this should not require more than 2-5 minutes

81. Easily correctable causes
▪ Correction of hypoglycemia hypocalcemia and hypomagnesemia :
▪ Hypoglycemia
▪ 2 mL/kg of 10% dextrose bolus injection followed by a continuous
infusion
▪ hypoglycemia - treated / excluded
▪ Give 2 mL/kg of 10% calcium gluconate IV over 10 minutes under
strict cardiac monitoring.
▪ If hypocalcemia
▪ Give additional calcium gluconate at 8 mL/kg/d for 3 days.
▪ If seizures continue despite hypocalcemia, 0.25 mL/kg of 50%
magnesium sulfate should be given intramuscularly.

82. Ref.Uptodate 2021

83. Anti-epileptic drug therapy (AED)
▪ Even in a single clinical seizure and facilities for continuous EEG
monitoring not available.
▪ Eliminating all electrical seizure activity should be the goal of AED
therapy
▪ seizures persist even after metabolic correction

84. PHENOBARBITONE
▪ Drug of choice in neonatal seizures
▪ Loading -20 mg/kg/IV slowly over 20 minutes
▪ seizures persist additional doses of phenobarbitone 10 mg/kg every
20-30 minutes until a total dose of 40 mg/kg
▪ maintenance dose - 3-5 mg/kg/day in 1-2 divided doses, started 12 hours
after the loading dose.

85. PHENYTOIN
▪ maximal dose of phenobarbitone failed
▪ or appearance of adverse effects like respiratory
depression, hypotension, Bradycardia
▪ Loading Dose is 20 mg/kg IV
▪ Only NS dilution
▪ refractory seizures  repeat dose 10 mg/kg
▪ maintenance dose 3-5 mg/kg/d in 2-4 divided doses.

86. BENZODIAZEPINES
▪ may be required in up to 15-20% of neonatal seizures.
▪ lorazepam and midazolam.
▪ Diazepam - prolonged sedative effect, narrow therapeutic
index, sodium benzoate as a preservative.
▪ Lorazepam - longer duration of action and less adverse effects
▪ Midazolam is faster acting than lorazepam and may be
administered as an infusion.
▪ It causes less respiratory depression and sedation than
lorazepam.

87. ▪ The doses of these drugs are given below:
▪ 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 0.1 to 0.4mg/kg/hour.

88. LEVETIRACETAM
▪ Benign side effect profile, and limited interactions
▪ Loading doses vary from 10 to 20 mg/kg to as high as 40 to 50 mg/kg.
▪ Maintenance doses 10 to 80 mg/kg/day with most providers starting at 20
mg/kg/day, whereas others suggest 40 mg/kg/day.
▪ Although twice daily dosing is usual, three-times daily dosing has been
suggested.

89. Antiepileptic drugs for refractory seizures
LIDOCAINE:
▪ It is usually administered as a bolus dose of 4 mg/kg IV followed by an infusion
rate of 2 mg/kg/hr.
▪ Adverse effects include arrhythmias, hypotension, and seizures.
▪ It should not be administered with phenytoin.
PARALDEHYDE:
▪ A dose of 0.1-0.2 mL/kg/dose may be given IM
▪ 0.3 mL/kg/dose mixed with coconut oil in 3:1 may be used by per rectal route
▪ pulmonary hemorrhage, pulmonary edema, hypotension, and liver injury.

90. ▪ SODIUM VALPROATE:
▪ Per rectal or IV route may be used in acute condition.
▪ The dose is 20-25 mg/kg/d followed by 5-10 mg/kg every 12 hours.
▪ Used with caution in newborns given the uncertain risk of hepatotoxicity
following its use.
▪ VIGABATRIN:
▪ It has been used in neonates with infantile spasms.
▪ The dose is 50mg/kg/day.

91. ▪ TOPIRAMATE:
▪ potential neuroprotective effect against injury caused by seizures.
▪ For refractory infantile spasms in infants.
▪ initial and maintenance doses of approximately 3 mg/kg

92. Other therapies
▪ PYRIDOXINE:
▪ A therapeutic trial of pyridoxine is reserved as a last resort in refractory seizures.
▪ Intravenous route is the preferred method
▪ intramuscular (IM) route be used
▪ hypotension and apnea can occur.

94. ▪ EXCHANGE TRANSFUSION:
▪ Indicated in
▪ life-threatening metabolic disorders,
▪ accidental injection of local anesthetic,
▪ trans-placental transfer of maternal drugs (e.g. chlorpropamide)
▪ bilirubin encephalopathy.

95. Maintenance anti-epileptic therapy
▪ Monotherapy is the most appropriate strategy to control seizures.
▪ Attempts should be made to stop all anti-epileptic drugs and wean
the baby to only phenobarbitone at 3-5 mg/kg/day.
▪ If seizures are uncontrolled or if clinical toxicity appears, a second
AED may be added.

96. When to discontinue AED
▪ no specific guidelines
▪ Discontinue phenobarbitone as early as possible
▪ try to discontinue all medications at discharge if clinical examination is normal, irrespective
of etiology and EEG
▪ If neurological examination is persistently abnormal at discharge, AED is continued and the
baby is reassessed at one month.
▪ If the baby is normal on examination and seizure free at 1 month, phenobarbitone is
discontinued over 2 weeks.
▪ If neurological assessment is not normal, an EEG is obtained. If EEG is not overtly
paroxysmal, phenobarbitone is tapered and stopped.
▪ If EEG is overtly abnormal, the infant is reassessed in the same manner at 3 months and
then 3 monthly till 1 year of age

97. Take home message
▪ Neonatal seizures are common in both the preterm and term born infant.
▪ • Electroencephalography is essential to diagnose and treat neonatal seizures
because of the frequency with which clinical signs are misinterpreted as
seizures OR seizures or status epilepticus can be clinically silent.
▪ • Seizures are a sign of neurologic dysfunction from a variety of etiologies,
including hypoxic ischemia, such as stroke, and metabolic and infectious
etiologies. Investigation to determine the etiology of neonatal seizures is
necessary and often requires blood and cerebrospinal fluid sampling,
electroencephalography, and magnetic resonance imaging.
▪ • Therapy for neonatal seizures is important to limit both the short-term
physiologic impact of the seizures and the potential contribution to long-term
outcomes. Phenobarbitol remains first-line anticonvulsant therapy.
▪ • Length of time with anticonvulsant therapy for neonatal seizures remains
unknown, although more recent trends are to minimize exposure to
anticonvulsants unless a protracted risk for seizures persists

98. REFERENCES
1. Cloherty and starks manual of neonatal care 8th edition.
2. Aiims protocols in neonatology
3. Avery’s diseases of the newborn. -- 9th ed. / [Edited by] christine
A. Gleason, sherin U. Devask
4. Fanaroff and martin’s neonatal-perinatal medicine : diseases of
the fetus and infant / [edited by] richard J. Martin, avroy A.
Fanaroff, michele C. Walsh.—10th edition.

99. Thank You