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Neonatal
Seizures
• Dr.C.S.N.Vittal
DEFINITIONS
SEIZURE:
• A seizure is a paroxysmal behavior caused by hypersynchronous discharge of a
group of neurons.
NEONATAL SEIZURE:
• Neonatal seizures may be defined more aptly as paroxysmal
alterations in neurologic function (eg, behavioral, motor, or autonomic
function).
Neonatal seizures are the most common overt manifestation of neurological dysfunction in the newborn.
Pathophysiology
• Immature brain has many differences from the mature brain that
render it more excitable and more likely to develop seizures.
• Delay in Na+ , K+ -adenosine triphosphatase maturation and
increased NMDA and α-amino-3-hydroxy-5-methylisoxazole-4-
propionate (AMPA) receptor density.
• Delay in the development of inhibitory GABAergic transmission
• GABA in the immature brain has an excitatory function
CAUSES OF NEONATAL SEIZURES
Presentation Time Aetiology of Seizures
< 4 days • Hypoxic-ischaemic encephalopathy
• Acute metabolic disorders
• Intra cranial haemorrhage
• Acute metabolic disorders
• Hypoglycemia, Hypoelectrolytemia
• Congenital Viral infections
• Pyridoxine dependency
• Non-ketotic Hyperglycemia
• Urea cycle disorder
• Sepsis
CAUSES OF NEONATAL SEIZURES
Presentation Time Aetiology of Seizures
4-14 days • Infection
• Meningitis (bacterial)
• Encephalitis (enteroviral, herpes simplex)
• Metabolic disorders
• Hypocalcemia related to diet, milk formula
• Hypoglycemia, persistent
• Inherited disorders of metabolism
• Galactosemia, Fructosemia
• Drug withdrawal : Eg. Methadone
• Kernicterus
CAUSES OF NEONATAL SEIZURES
Presentation Time Aetiology of Seizures
2-8 weeks • Infection
• Herpes simplex or enteroviral encephalitis
• Bacterial meningitis
• Head injury
• Subdural hematoma
• Child abuse
• Inherited disorders of metabolism
• Aminoacidurias
• Urea cycle defects
• Organic acidurias
• Malformations of cortical development
Etiology
Hypoxic-Ischemic
Encephalopathy
Brain
Malformations
Infarction &
Hemorrhage
Genetic Metabolic
Infections
HIE (35 - 45%)
Infarction & Hemorrhage (20-30%)
Brain Malformations (5-10%)
Infections (5-20%)
Metabolic (7-20%)
Genetic (6-10%)
Unknown/ Other (10%)
05
04
Neonatal Seizures - Types
01
02
03
Subtle
Clonic
Tonic
Spasms
Myoclonic
1 Subtle Seizures
• Transient eye deviations, nystagmus, blinking, mouthing,
• Abnormal extremity movements (rowing, swimming,
bicycling, pedalling, and Stepping),
• Fluctuations in heart rate, hypertension episodes, and
• Apnea.
• More commonly in premature
01
2 Clonic Seizures
• Focal:
• Involve face upper + /- lower extremities on
• one site “axial structures (neck / trunk)
• Usually associated with neuropathology (i.e. Cerebral infarction and intra
cerebral haemorrhage)
• Multi focal:
• Involve several body parts and often
• migrate in a non-jacksonian (random) manner may also involve the face.
• Consider the neonatal equivalent of generalized tonic – clonic seizures.
02
3 Tonic Seizures
• Focal :
• Sustained posturing of a limb or
• Asymmetric posturing of the trunk and / or neck
• Generalized :
• Decerebrate posturing
• Decorticate posturing
• Usually associated with apnoea and upward gaze of eyes
• Most common in preemies and usually
• indicates structural brain damage and IVH
03
4 Spasms
• Spasms are sudden generalized jerks lasting 1-2 sec
• May be flexor or extensor or mixed
• Shorter duration
• Cannot be provoked by stimulation or suppressed by restraint
• Usually associated with a single, very brief, generalized discharge
• Epileptic in nature
04
5 Myoclonic seizures
Characteristics: Rapidity of the jerks (<50 msec) and by their lack of rhythmicity
• Focal : Mostly flexors of upper limbs
• Multifocal:
• Asynchronous twitching of several parts of body.
• Generalized:
• Bilateral jerks of upper and some times lower limbs
• Rapid movements of distal flexors
• All 3 types of may occur during sleep in the new born.
• Presence suggests severe diffuse brain damage
05
Differentiation of Seizures from Nonconvulsive Movements
• Jitteriness – Tremor
• No associated ocular movements or autonomic phenomena,
• Stimulus sensitivity,
• Tremor that is suppressed by flexing the limb.
• Benign neonatal sleep myoclonus
• Occurs in healthy newborns
• Only during sleep. Jerking ceases on wakening
• Apnea of prematurity
• In Preterms, apnea and bradycardia
Diagnosis
- History: Maternal drug abuse, Intrauterine infection, metabolic disease,
natal history, etc.
- Complete Hemogram
- Blood : Sugar, Calcium, Magnesium, Na+, K+ & HCO3 , Elevated
Ammonia, Lactate Levels, Culture & Sensitivity, plasma
aminoacids, drugs
- CSF :Analysis, Biochemical & C/s.
- Cranial U/s. : hemorrhage, cysts, abnormal ventricles
- EEG :Plays an important role
Diagnosis - EEG
• Continuous electroencephalogram (cEEG): >3 hours of monitoring is
gold standard for the diagnosis of neonatal seizures
• Including video analysis can be very helpful
• Routine neonatal EEG recording, typically of 1 hour duration, allows
assessment of background activity, including cycling state change,
developmental maturity, and sometimes, epileptic potential.
• Amplitude-integrated electroencephalogram (aiEEG): a bedside
technique increasingly being used by neonatologists for
neuromonitoring
MANAGEMENT OF NEONATAL SEIZURES - ACUTE PHASE
• GENERAL MEASURES :
• OPTIMISE:Ventilation, Circulation, Electrolytes, Acid-Base Balance
• NONEPILEPTIC EVENTS : Associated with No EEG Seizure Activity.
• These Types of Neonatal Seizures Should not be Treated.
• EPILEPTIC EVENTS: Associated with EEG Seizure Activity
Aim: prevent brain injury
MANAGEMENT: - Correct metabolic disturbances.
Hypoglycemia:
• (10% glucose in water) 2 mL/kg IV (0.2 g/kg) as bolus .
Follow with continuous infusion at up to 8 mg/kg/min IV
MANAGEMENT: - Correct metabolic disturbances.
Hypocalcemia:
• Calcium gluconate 10%: 100 mg/kg IV mixed with equal amount
of 10% dextrose given by slow I.V. over 1 to 3 minutes
• Note: Monitor cardiac rhythm for bradycardia
• Follow with maintenance of 500 mg/kg/24 hrs IV or PO
Hypomagnesemia:
• Magnesium sulfate - 25-250 mg/kg/dose IV/IM (50% magnesium
sulphate 0.2 ml/kg)
Management: - Anticonvulsant therapy.
1.Phenobarbital: 20 mg/kg IV. If necessary, additional 10-20 mg/kg IV in 10 mg/kg aliquots
Maintenance: 4–6 mg/kg/24 hrs IV/PO
If 40 mg/kg of Phenobarbital is not effective, >>
2. Lorazepam: 0.05 mg/kg to 0.10 mg/kg IV in 0.05 mg/kg increments over several minutes.
• (Inj. Clonzepam Loading dose of 0.25 mg/kg followed by 0.01 to 0.03 mg/kg/orally given (or)
• Inj. Midazolam 0.02 to 0.1 mg/kg - I.V. can be given )
3. Phenytoin: 20 mg/kg IV (diluted in 0.9% NaCl) (Maximal rate: 1 mg/kg/min.
Monitor cardiac rate and rhythm). Maintenance 5–10 mg/kg/24h IV
5. Fourth line anticonvulsants include Paraldehyde
DIAZEPAM : Not safe in neonates as it interferes with vital functions its
sedative effect half life exceeds 24 hours
Management of Pyridoxin Dependent Epilepsy
• Failure of conventional AEDs
• Pyridoxine 100 mg iv
• Caution: May cause severe hypotonia, bradycardia, apnea
• Treat with daily B6, 200 mg/ day
• B6 withdrawal challenge to confirm dx
• If seizure recur in 7 days to 3 weeks - restart B6
DURATION OF TREATMENT
• Determined by the underlying cause (i.e., related to risk of
recurrence), the physical examination and the EEG
• When seizures have stopped and if the neurological examination is
normal, consider stopping Phenobarbital.
• If the neurological examination remains abnormal, then consider
stopping medication if the EEG is normal.
• Make this evaluation prior to discharge and then frequently after
discharge, if the child has been discharged on Phenobarbital.
• Stop Phenytoin when IV therapy is stopped as this drug is very
difficult to maintain PO.
• Dr.C.S.N.Vittal

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Neonatal seizures

  • 2. DEFINITIONS SEIZURE: • A seizure is a paroxysmal behavior caused by hypersynchronous discharge of a group of neurons. NEONATAL SEIZURE: • Neonatal seizures may be defined more aptly as paroxysmal alterations in neurologic function (eg, behavioral, motor, or autonomic function). Neonatal seizures are the most common overt manifestation of neurological dysfunction in the newborn.
  • 3. Pathophysiology • Immature brain has many differences from the mature brain that render it more excitable and more likely to develop seizures. • Delay in Na+ , K+ -adenosine triphosphatase maturation and increased NMDA and α-amino-3-hydroxy-5-methylisoxazole-4- propionate (AMPA) receptor density. • Delay in the development of inhibitory GABAergic transmission • GABA in the immature brain has an excitatory function
  • 4. CAUSES OF NEONATAL SEIZURES Presentation Time Aetiology of Seizures < 4 days • Hypoxic-ischaemic encephalopathy • Acute metabolic disorders • Intra cranial haemorrhage • Acute metabolic disorders • Hypoglycemia, Hypoelectrolytemia • Congenital Viral infections • Pyridoxine dependency • Non-ketotic Hyperglycemia • Urea cycle disorder • Sepsis
  • 5. CAUSES OF NEONATAL SEIZURES Presentation Time Aetiology of Seizures 4-14 days • Infection • Meningitis (bacterial) • Encephalitis (enteroviral, herpes simplex) • Metabolic disorders • Hypocalcemia related to diet, milk formula • Hypoglycemia, persistent • Inherited disorders of metabolism • Galactosemia, Fructosemia • Drug withdrawal : Eg. Methadone • Kernicterus
  • 6. CAUSES OF NEONATAL SEIZURES Presentation Time Aetiology of Seizures 2-8 weeks • Infection • Herpes simplex or enteroviral encephalitis • Bacterial meningitis • Head injury • Subdural hematoma • Child abuse • Inherited disorders of metabolism • Aminoacidurias • Urea cycle defects • Organic acidurias • Malformations of cortical development
  • 7. Etiology Hypoxic-Ischemic Encephalopathy Brain Malformations Infarction & Hemorrhage Genetic Metabolic Infections HIE (35 - 45%) Infarction & Hemorrhage (20-30%) Brain Malformations (5-10%) Infections (5-20%) Metabolic (7-20%) Genetic (6-10%) Unknown/ Other (10%)
  • 8. 05 04 Neonatal Seizures - Types 01 02 03 Subtle Clonic Tonic Spasms Myoclonic
  • 9. 1 Subtle Seizures • Transient eye deviations, nystagmus, blinking, mouthing, • Abnormal extremity movements (rowing, swimming, bicycling, pedalling, and Stepping), • Fluctuations in heart rate, hypertension episodes, and • Apnea. • More commonly in premature 01
  • 10. 2 Clonic Seizures • Focal: • Involve face upper + /- lower extremities on • one site “axial structures (neck / trunk) • Usually associated with neuropathology (i.e. Cerebral infarction and intra cerebral haemorrhage) • Multi focal: • Involve several body parts and often • migrate in a non-jacksonian (random) manner may also involve the face. • Consider the neonatal equivalent of generalized tonic – clonic seizures. 02
  • 11. 3 Tonic Seizures • Focal : • Sustained posturing of a limb or • Asymmetric posturing of the trunk and / or neck • Generalized : • Decerebrate posturing • Decorticate posturing • Usually associated with apnoea and upward gaze of eyes • Most common in preemies and usually • indicates structural brain damage and IVH 03
  • 12. 4 Spasms • Spasms are sudden generalized jerks lasting 1-2 sec • May be flexor or extensor or mixed • Shorter duration • Cannot be provoked by stimulation or suppressed by restraint • Usually associated with a single, very brief, generalized discharge • Epileptic in nature 04
  • 13. 5 Myoclonic seizures Characteristics: Rapidity of the jerks (<50 msec) and by their lack of rhythmicity • Focal : Mostly flexors of upper limbs • Multifocal: • Asynchronous twitching of several parts of body. • Generalized: • Bilateral jerks of upper and some times lower limbs • Rapid movements of distal flexors • All 3 types of may occur during sleep in the new born. • Presence suggests severe diffuse brain damage 05
  • 14. Differentiation of Seizures from Nonconvulsive Movements • Jitteriness – Tremor • No associated ocular movements or autonomic phenomena, • Stimulus sensitivity, • Tremor that is suppressed by flexing the limb. • Benign neonatal sleep myoclonus • Occurs in healthy newborns • Only during sleep. Jerking ceases on wakening • Apnea of prematurity • In Preterms, apnea and bradycardia
  • 15. Diagnosis - History: Maternal drug abuse, Intrauterine infection, metabolic disease, natal history, etc. - Complete Hemogram - Blood : Sugar, Calcium, Magnesium, Na+, K+ & HCO3 , Elevated Ammonia, Lactate Levels, Culture & Sensitivity, plasma aminoacids, drugs - CSF :Analysis, Biochemical & C/s. - Cranial U/s. : hemorrhage, cysts, abnormal ventricles - EEG :Plays an important role
  • 16. Diagnosis - EEG • Continuous electroencephalogram (cEEG): >3 hours of monitoring is gold standard for the diagnosis of neonatal seizures • Including video analysis can be very helpful • Routine neonatal EEG recording, typically of 1 hour duration, allows assessment of background activity, including cycling state change, developmental maturity, and sometimes, epileptic potential. • Amplitude-integrated electroencephalogram (aiEEG): a bedside technique increasingly being used by neonatologists for neuromonitoring
  • 17. MANAGEMENT OF NEONATAL SEIZURES - ACUTE PHASE • GENERAL MEASURES : • OPTIMISE:Ventilation, Circulation, Electrolytes, Acid-Base Balance • NONEPILEPTIC EVENTS : Associated with No EEG Seizure Activity. • These Types of Neonatal Seizures Should not be Treated. • EPILEPTIC EVENTS: Associated with EEG Seizure Activity Aim: prevent brain injury
  • 18. MANAGEMENT: - Correct metabolic disturbances. Hypoglycemia: • (10% glucose in water) 2 mL/kg IV (0.2 g/kg) as bolus . Follow with continuous infusion at up to 8 mg/kg/min IV
  • 19. MANAGEMENT: - Correct metabolic disturbances. Hypocalcemia: • Calcium gluconate 10%: 100 mg/kg IV mixed with equal amount of 10% dextrose given by slow I.V. over 1 to 3 minutes • Note: Monitor cardiac rhythm for bradycardia • Follow with maintenance of 500 mg/kg/24 hrs IV or PO Hypomagnesemia: • Magnesium sulfate - 25-250 mg/kg/dose IV/IM (50% magnesium sulphate 0.2 ml/kg)
  • 20. Management: - Anticonvulsant therapy. 1.Phenobarbital: 20 mg/kg IV. If necessary, additional 10-20 mg/kg IV in 10 mg/kg aliquots Maintenance: 4–6 mg/kg/24 hrs IV/PO If 40 mg/kg of Phenobarbital is not effective, >> 2. Lorazepam: 0.05 mg/kg to 0.10 mg/kg IV in 0.05 mg/kg increments over several minutes. • (Inj. Clonzepam Loading dose of 0.25 mg/kg followed by 0.01 to 0.03 mg/kg/orally given (or) • Inj. Midazolam 0.02 to 0.1 mg/kg - I.V. can be given ) 3. Phenytoin: 20 mg/kg IV (diluted in 0.9% NaCl) (Maximal rate: 1 mg/kg/min. Monitor cardiac rate and rhythm). Maintenance 5–10 mg/kg/24h IV 5. Fourth line anticonvulsants include Paraldehyde DIAZEPAM : Not safe in neonates as it interferes with vital functions its sedative effect half life exceeds 24 hours
  • 21. Management of Pyridoxin Dependent Epilepsy • Failure of conventional AEDs • Pyridoxine 100 mg iv • Caution: May cause severe hypotonia, bradycardia, apnea • Treat with daily B6, 200 mg/ day • B6 withdrawal challenge to confirm dx • If seizure recur in 7 days to 3 weeks - restart B6
  • 22. DURATION OF TREATMENT • Determined by the underlying cause (i.e., related to risk of recurrence), the physical examination and the EEG • When seizures have stopped and if the neurological examination is normal, consider stopping Phenobarbital. • If the neurological examination remains abnormal, then consider stopping medication if the EEG is normal. • Make this evaluation prior to discharge and then frequently after discharge, if the child has been discharged on Phenobarbital. • Stop Phenytoin when IV therapy is stopped as this drug is very difficult to maintain PO.