1. DR. MUSTAFA BERBER ÇOCUK SAĞLIĞI VE HASTALIKLARI A.D. NEONATOLOJİ B.D.
NEONATAL CONVULSIONS
DR. MUSTAFA BERBER
ÇOCUK SAĞLIĞI VE HASTALIKLARI A.D.
NEONATOLOJİ B.D.

2. Neonatal seizures (NS) are the most frequent and distinctive clinical manifestation of neurological dysfunction in the newborn infant.
Neonatal period limited to :
- first 28 days for term infants
- 44 weeks gestational age for pre-term
First sign of neurological dysfunction
Powerful predictors of long-term cognitive and developmental impairment

3. Definition:
A seizure is defined clinically as a paroxysmal alteration in neurologic function, i.e. motor, behavior and/or autonomic function.
Epileptic seizures: phenomena associated with
corresponding EEG seizure activity e.g. clonic seizures.
2. Non-epileptic seizures: Clinical seizures without corresponding EEG correlate e.g. subtle and generalized tonic seizures.
3. EEG seizures: abnormal EEG activity with no clinical correlation.

4. Pathophysiology
Abnormal synchronous depolarization from large group of neurons
Excessive excitatory amino acid release (glutamate)
Lack of inhibitory systems (GABA)
Depolarization results from Na influx into cells; repolarization from outflux of K+
Disruption of Na/K ATP pump

5. Basic Mechanisms of Seizures
Abnormal energy production (hypoxemia, hypoglycemia)
Alteration in neuronal membrane (hypocalcemia, hypomagnesemia)
Relative excess of excitatory versus inhibitory neurotransmitters (GABA)

6. Do Seizures Harm the Developing Brain?
Animal studies:
Persistent neonatal seizures in rats induce neuronal death and changes in hippocampus
Chronic seizures in adults associated with memory impairment and poor psychosocial outcome
Permanent reduction in seizure threshold associated with significant deficits in learning and memory

7. Biochemical Changes with Seizures
↓ ATP
↓ phosphocreatine
Pyruvate converted to lactate
↓ brain glucose
Increased production of pyruvate from ADP

9. Adverse Effects of Seizures
Cell division and migration
Formation and expression of receptors
Synaptogenesis and apotosis
Long term effects: seizure threshold, learning, and cognition

10. Incidence Higher in neonates than any other age group
Incidence(overall):2 in 1000 to 14 in 1000 live births
Most frequent in the first 10 days of life

11. Etiology Convulsion Metabolic: Neurological: Hypoglycemia HİE
Hypocalcemia
Hyponatremia
Hypernatremia
Hypomagnesemia
Neurological:
HİE
ICH
CNS infection
Epileptic syndroms
Infarction
Malformation

12. ETIOLOGY HIE (45-50%) Intracranial hemorrhage (17%)
CNS infection (10%)
Infarction (7%)
Metabolic disorders (5%)
Inborn errors (3%)
Unknown (10%)
Drug withdrawal (1%)

13. ETIOLOGY Hypoxic-ischemic encephalopathy Intracranial Hemorrhage
subarachnoid haemorrhage
germinal matrix –intraventricular haemorrhage
subdural hemorrhage
Metabolic disorders(hypoglycemia/ hypocalcemia /hypomagnesemia/hyponatremia)

14. Intracranial infections TORCH infections Pyridoxine dependency
bacterial meningitis
TORCH infections
Pyridoxine dependency
Benign neonatal seizures

15. Etyoloji-4 Time relation Convulsion time 1-2 days 3-7 days 7-10 days
ICH X
HIE
Hypoglycemi a
Hypocalcemia
X (early)
X (late)
Inborn error of met.
CNS inf.
Malformation
Epileptic syndromes

16. Classification: Subtle seizures:
They are the most common type. More common in premature infants. Typically have no electrographic correlate, are likely primarily subcortical
1. Ocular - Tonic horizontal deviation of eyes or sustained eye opening with ocular fixation or cycled fluttering
2. Oral–facial–lingual movements - Chewing, tongue- thrusting, lip-smacking, etc.

17. Limb movements - Cycling, paddling, boxing-jabs, etc
Autonomic phenomena - Tachycardia or bradycardia
Apnea may be a rare manifestation of seizures. Apnea due to seizure activity has an accelerated or a normal heart rate when evaluated 20 seconds after onset.

18. Clonic seizures: Primarily in term. Signals focal cerebral injury
Focal or multifocal, rhythmic movements with slow return movement
rhythmic movements of muscle groups.
May be associated with generalized or focal brain abnormality
Most commonly associated with electrographic seizures
occur with a frequency of jerks per second

19. Tonic seizures: Primarily in Preterm
Sustained flexion or extension of one extremity or the whole body
Extensive neocortical damage with uninhibited subcortically generated movements
May or may not have electrographic correlate
Signals severe ICH in preterm infants Generally poor prognosis

20. Myoclonic seizures: Rare Focal, multifocal or generalized
Lightning fast contractions-like jerks of extremities
(upper > lower)
Signify diffuse –serious brain injury Rapid, isolated jerks which lacks the slow return phase of clonic movements
Myoclonic movements may be normal in preterm or term infants

21. Myoclonic seizures carry the worst prognosis in terms of neuro-developmental outcome and seizure recurrence.
Focal clonic seizures have the best prognosis.

22. Nonepileptic movements
Benign sleep myoclonus
jitteriness
Stimulus evoked myoclonus from metabolic encephalopathies, CNS malformation
Apnoea

23. Benign Sleep Myoclonus
Onset 1st week of life
Synchronous jerks of upper and lower extremities during sleep
No EEG correlate
Ceases upon arousal
Resolves by 2 months
Good prognosis

24. Jitteriness vs. Seizures
No ocular phenomena
Stimulus sensitive
Tremor
Movements cease with passive flexion

25. DIAGNOSIS Seizure history Antenatal history eye movements
restraint of episode by passive flexion of the affected limb
The day of life on which the seizure occurred
Antenatal history
Intruterine infection, maternal diabetes and narcotic addiction

26. Perinatal history Perinatal asphyxia fetal distress
Need for resuscitation in the labor room, low Apgar scores (<3 at 1 and/ or 5 minutes) and
abnormal cord pH (≤7) and base deficit (> 10 mEq/L) should be obtained.

27. Feeding history: Family history
Appearance of clinical features AFTER initiation of breast-feeding may be suggestive of inborn errors of metabolism.
Late onset hypocalcemia should be considered in the presence of top feeding with cows’ milk.
Family history
consanguinity in parents,
family history of seizures or mental retardation
early fetal/neonatal deaths would be suggestive of inborn errors of metabolism.
History of seizures in either parent or sib(s) in the neonatal period may suggest benign familial neonatal convulsions (BFNC).

28. GENERAL EXAMINATION
CNS EXAMINATION
BLOOD INVESTIGATIONS
ULTRASOUND CRANIUM
EEG (ELECTROENCEPHALOGRAPHY)
SPECIFIC INVESTIGATIONS
CT SCAN OR MRI

29. INVESTIGATIONS:
Lab studies -Blood count -Blood, urine & CSF culture -Blood biochem.->evaluation of Glu, Ca, Mg, electrolytes Blood gas levels to detect acidosis AND hypoxia Serum IgM & IgG-specific TORCH titres
-METABOLİC EVALUATİON (AMMONİA,LACTATE…)

30. EEG: Ultrasonography and CT scan of head:
Main tool for diagnosis It is useful to confirm a clinically doubtful
convulsion , to locate an epileptic focus and
and to determine its anatomical basis
Ultrasonography and CT scan of head:
To detect subarachnoid /intraventricular hemorrhage

31. Treatment More difficult to suppress than in older children
Treatment is worthwhile because seizures:
May cause hemodynamic or respiratory compromise
Disrupt cerebral autoregulation
May result in cerebral energy failure and further injury

32. Treatment Stabilize vital signs and treat underlying hypotension
Correct transient metabolic disturbances
Phenobarbital is first line agent

33. Nelson Protocol: Maintain ABC and temperature Check blood glucose
Correct glucose and calcium
Administer IV, phenobarbitone 20mg/kg
Repeat in 5 -10mg/kg boluses till a maximum of 40 mg/kg,

34. IV lorazepam 0.05 mg/kg every 4-8 hourly
IV phenytoin mg/kg diluted in equal volume of normal saline at a maximum rate of 1mg/kg/min over minutes
IV lorazepam mg/kg every 4-8 hourly
IV midazolam as a continuous infusion (as initial IV bolus of mg/kg, followed by continuous infusion (0.5-1ug/kg/min ) increasing by 2 ug/kg/min every 5 minutes to achieve seizure control
Primidone, lidocaine, carbamazepine, valproate, lamotrigine,
topiramate, and levetiracetam have been used.

35. Weaning of anticonvulsant therapy
Newborn on anticonvulsant therapy
Wean all antiepileptic drugs except phenobarbitone once seizure controlled
Perform neurological examination prior to discharge
normal
Abnormal

36. Stop phenobarbitone prior to discharge
Continue phenobarbitone for 1 month
Repeat neurological examination at 1 month of age
Normal examination
Abnormal examination

37. Taper drugs over 2 week
Evaluate EEG
Normal EEG
Taper drug over 2 weeks
Abnormal EEG
Continue drug
Reassess at 3 months

38. Prognosis

39. Prognosis based on etiology
Cerebral dysgenesis has grave prognosis, almost none are normal
Prematurity and seizures associated with high risk of death or very poor outcome

40. Prognosis based on type
Subtle Depends on cause,
other seizure types
Clonic Better prognosis
Generalized Tonic Poor
Myoclonic Poor

41. Prognosis by EEG
Severe inter-ictal EEG background associated with adverse outcome
Normal EEG background at presentation associated with good outcome
Ictal features less reliable
Better outcome when clinical and EEG seizures correlate
Increased number and frequency may relate to worse outcome

42. Prognoz

43. Burst-suppression pattern