Neonatal seizures

Dr. C. Kannan, Resident. MD Peds, MGMCRI

1. THE NICU PROTOCOL FOR NEONATAL SEIZURES Dr. C. Kannan Postgraduate Pediatrics MGMCRI

2. EPIDEMIOLOGY Incidence 10.3/1000 (Term neonates) 20.8/1000 (Preterm neonates) 36.1/1000 (VLBW neonates From NNPD; 2002-03

3. DEFINITIONS Seizures Paroxysmal alteration in neurological function Motor/ behavior /autonomic function Epileptic seizures Clinical seizures corresponding EEG seizure activity Eg. Clonic seizures Non epileptic seizures Clinical seizures without EEG seizure activity Eg. Subtle and generalised tonic seizures EEG seizures Abnormal EEG activity with no clinical correlation

4. ETIOLOGY Hypoxic-ischemic injury Perinatal asphyxia Focal infarction Arterial Venous CNS infection Escherichia coli/GBS/Listeria monocytogenes/HSV Intracranial hemorrhage Intraventricular Parenchymal Subdural Subarachnoid

5. Contd., Inborn errors of metabolism Aminoacidopathies Organic acidurias Peroxisomal diseases Mitochondrial disorders Disorder of glucose transport (GLUT-1 deficiency) Pyridoxine-dependent seizures Folinic acid responsive seizures Acute metabolic disorders Hypoglycemia Hypocalcemia Hypomagnesemia

6. Contd., Malformations and other structural lesions Neuronal migration disorders Cerebral dysgenesis Neurocutaneous disorders, E .g., Sturge-Weber syndrome, tuberous sclerosis Epilepsy syndromes Benign familial syndromes Severe neonatal epileptic encephalopathies E.g., EIEE , Ohtahara syndrome, EME

7. NEUROTRANSMITTERS/RECEPTORS GABA is a Inhibitory neurotransmitter Glutamate is a excitatory neurotransmitter GABA receptors GABA-A/GABA-B(G-Protein coupled receptor)/GABA-C(Retina) GABA-A is a part of GABA-A-BDZ-Cl channel complex GABA binds to GABA-A receptors in brain Increases duration of Cl channel opening Causes CNS depression

8. PATHOPHYSIOLOGY Excitatory and inhibitory processes in immature brain are Unbalanced towards excitatory side Glutaminergic synapses > GABA ergic synapses GABA may temporarily act as an Excitatory neurotransmitter via an Alteration in chloride gradient and transportation These developmental features are etiology for High tendency of seizures in neonates Reduced efficacy of GABA ergic drugs

9. TYPES OF SEIZURES Subtle Clonic Tonic myoclonic

10. SUBTLE SEIZURES Commonest type (50% of all seizures) Mild & often are missed Examples Ocular Tonic horizontal deviation of eyes Sustained eye opening Ocular fixation Cycled fluttering Oral-facial-lingual movements Chewing/tongue-thrusting/lip smacking/etc.,

11. Contd., Limb movements Cycling/paddling/boxing-jabs/etc ., Autonomic phenomena – Tachycardia/bradycardia Apnea Rare manifestation of seizures Apnea due to seizures may have normal or increased HR

12. CLONIC SEIZURES Rhythmic movements of muscle groups Both slow and fast components 1-3 jerks/second Associated with EEG changes Best prognosis

13. TONIC SEIZURES Sustained flexion /extension of Axial or appendicular muscles Focal or generalised May resemble Decerebrate (tonic extension of all limbs) Decorticate posturing (flexion of UL/extension of LL) No EEG changes

14. MYOCLONIC SEIZURES Single/multiple lightening fast jerks of UL/LL How to differentiate from clonic seizures More rapid speed Absence of slow return Predilection for flexor groups EEG changes Burst suppression pattern Focal sharp waves Hypsarrhythmia Worst prognosis (Neurodevelopmental outcome )

15. APPROACH TO SEIZURES History Examination Investigations

16. HISTORY Seizure history Complete description of seizures from parents Eye/limb movements/skin colour change Autonomic phenomena/consciousness Day of life Antenatal history Intrauterine infection/maternal diabetes/narcotic addiction Sudden increase in fetal movements

17. Perinatal history Perinatal asphyxia Fetal distress/reduced fetal movements/instrumental delivery Need for resuscitation/Apgar/cord pH (<7), base deficit (>10) Pudental block for mid cavity forceps Feeding history Lethargy/poor activity/drowsiness/vomiting After initiation of DBF Indicates IEM Late onset hypocalcaemia Due to top feeding with cow’s milk

18. Family history of Consanguinity /seizures / mental retardation Fetal/neonatal deaths – IEM Seizures of either parent or sibling indicates Benign familial neonatal convulsions

19. EXAMINATION Vital signs General examination Gestation / birth weight / weight for age Eg., seizure in a term well baby – SAH Eg., seizure in a LGA baby – Hypoglycemia Malformations / dysmorphic features

20. CNS examination Consciousness – Alert / drowsy / comatose Tone – hypo/hypertonia Bulging anterior fontanel – S/O meningitis / ICH Systemic examination Hepatosplenomegaly / abnormal urine odour S/O IEM Neurocutaneous markers

21. INVESTIGATIONS Essential investigations Blood sugar / sodium / Ca / CSF / Cranial USG / EEG CSF Must in all cases (seizure – may be first sign of meningitis) Even though other etiology is present ( eg ., Hypoglycemia) Can withhold Severe cardiovascular compromise Severe birth asphyxia Do all other investigations Even 1 or 2 were positive - Multiple etiologies may coexist

22. Additional investigations Who do not respond to Phenobarbitone + phenytoin (or) Earlier in neonates with specific features Neuroimaging Screen for congenital infections (TORCH) Screen for IEM (ABG if strongly suspected) Imaging Cranial USG Detects - IVH / Parenchymal bleed Unable to detect SAH / SDH

23. CT scan Where etiology is not available After first line of investigations Diagnostic in SAH / Developmental malformations MRI Seizures resistant to usual AEDs Diagnostic in Cerebral dysgenesis / lissencephaly / neuronal migration defects

24. EEG Has both diagnostic and prognostic role For all neonates requiring AED therapy Preferably done within first week of seizure Atleast for one hour Ictal EEG – suspected seizures / SZ in mu. r elaxed neonates Inter - I ctal EEG - For long term prognosis

25. Background abnormalities Burst suppression pattern Indicates for high risk for Low voltage invariant pattern Neurological sequelae Electro- cerebral inactivity aEEG New method provides continuous monitoring of Cerebral electrical activity at bedside In critically sick NB

26. Screen for Congenital infections TORCH / VDRL HSM / thrombocytopenia / IUGR / SGA / chorioretinitis Metabolic screen Blood & urine ketones / urine reducing substances / sr. NH3 Anion gap / urine & plasma AAs / Sr & CSF lactate pyruvate ratio

27. MANAGEMENT OF SEIZURES Initial medical management Nurse the baby in thermoneutral environment Ensure TABC Oxygen support / IV access / sampling within 2-5 mins Brief relevant history Quick clinical examination

28. Contd., Correction of hypoglycemia / hypocalcaemia If you suspect hypoglycemia & unable to investigate Give 2 ml/kg of 10% D as bolus F/B 6-8 mg/kg/min as infusion If hypoglycemia is excluded NB should receive 2ml/kg of 10 % Ca IV over 10 mins If hypocalcemia + 8 ml/kg/d for 3 days If SZ persists despite hypocalcemia correction 0.25 ml/kg of 50% MgSO4 IM

29. AED Therapy Even with single clinical seizure SZ after the correction of Ca & sugar Phenobarbitone DOC in NS - Max. dose – 40 mg/kg Loading - 20 mg/kg IV over 20mins (not faster than 1 mg/kg/min) Half loading – 10mg/kg IV over 10 mins If SZ reoccur after completion of loading 2 nd Half loading – 10 mg/kg IV over 10 mins If SZ reoccur after completion of 1 st half loading

30. Maintenance: 3-5mg/kg/day – 2divided doses – 12 hrs after Ld dose MOA of Phenobarbitone Acts by 2 ways Directly binds and activates GABA-A receptors GABA Mimetic Increases b inding of GABA to GABA-A receptors GABA Facilitatory Increases duration of Cl ion channels Causes CNS depression

31. Phenytoin SZ after maximum dose of Phenobarbitone is used Due to adverse effects of Phenobarbitone Loading - 20 mg/kg IV over 20 mins Dilute with normal saline (incompatible with dextrose) Not faster than 1 mg/kg/min Under cardiac monitoring Half loading – 10mg/kg IV over 10 mins If SZ reoccur after completion of loading Maintenance: 3-5mg/kg/day – 2-4 divided doses – 12 hrs after Ld dose

32. MOA of phenytoin Inhibit the sodium channels when they are open Prolong the inactivated stage of sodium channels Na channels are refractory to stimulation Until they reach closed/resting phase Similar action is seen in Carbamazepine Valproate Topiamate Lamotrigine Lacosamide

33. Benzodiazepines Lorazepam & midazolam Diazepam is avoided in neonates Short antiepileptic effect/prolonged sedation Narrow therapeutic index/Na benzoate as preservative Lorazepam (0.05 mg/kg IV bolus over 2-5 mins) longer duration/less adverse effects Midazolam (0.15 mg/kg – bolus F/B infusion 0.1- 0.4 mg/kg/hr) Faster acting than lorazepam More sedation & resp. depression Needs continuous monitoring

34. MOA of benzodiazepine Acts by Binding to BZD receptor ( GABA-A-BDZ-Cl channel complex) Increases binding of GABA to GABA-A receptors GABA Facilitatory Increases frequency of Cl ion channels Causes CNS depression

35. Other AEDs (very rare) Lidocaine Paraldehyde Sodium valproate Vigabatrin Topiramate Other therapies Pyridoxine/Folinic acid Exchange transfusion

36. Neonate with seizure Identify/characterize seizure ABCT secure IV line/sample R/O or treat hypoglycemia/hypocalcemia SZ persisting Phenobarbitone 20 mg/kg IV over 20 mins SZ persisting Repeat Phenobarbitone 10 mg/kg IV over 20 mins SZ persisting Repeat Phenobarbitone 10 mg/kg IV over 20 mins SZ persisting Phenytoin 20 mg/kg over 20 mins with cardiac monitoring SZ persisting Repeat phenytoin 10 mg/kg/dose SZ persisting Lorazepam bolus F/B midazolam infusion, if needed SZ persisting Other AEDs/pyridoxine/exchange transfusion SZ controlled Wean AED slowly to maintenance Phenobarbitone

37. WHEN TO DISCONTINUE AED New born on AED Wean all AED except Phenobarbitone, once seizures controlled Perform neurological examination prior to discharge Normal Abnormal Stop Phenobarbitone continue PBN for 1 month Repeat neurological examination at 1 month Normal Abnormal Taper drugs over 2 wks Evaluate EEG 1. Normal EEG – taper drugs over 2 wks 2. Abnormal EEG continue drug reassess at 3 months

38. THANK YOU