Neonatal seizures

1. NEONATAL SEIZURES Dr. VENKATESH Postgraduate Dept of P ediatrics S V medical college

2. 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 .

3. OVERVIEW DEFINITION OF SEIZURE TYPES OF NEONATAL SEIZURES CAUSES OF NEONATAL SEIZURES SEIZURE MIMICS APPROACH TO NEONATAL SEIZURES DURATION OF ANTICONVULSANT THERAPY GUIDELINES PROGNOSIS

4. 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.

5. 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

6. 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.

7. Why generalised seizures are rare in neonates ? Neonatal brain has reduced connectivity due to incomplete myelination , so electrical discharges spread incompletely.

8. TYPES OF NEONATAL SEIZURES Four types of neonatal seizures 1. Subtle seizures 2. Clonic seizures 3. Tonic seizures 4. Myoclonic seizures

9. 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.

10. 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.

11. 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.

12. 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.

13. Etiology 1.Perinatal events: Hypoxic ischemic encephalopathy Intracranial hemorrhage: Germinal matrix intraventricular hemorrhage, subdural hemorrhage, primary subarachnoid hemorrhage (well baby seizures)

14. 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.

15. Etiology 3.INFECTIONS: Bacterial meningitis Non-bacterial infections: toxoplasmosis, herpes simplex, rubella,cytomegalovirus 4.DEVELOPMENTAL PROBLEMS: Cerebral cortical dysgenesis Neuronal migration disorders Pachygyria , polymicrogyria

16. 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 )

17. 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

18. 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.

19. 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.

20. 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

21. 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 )

22. 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.

23. 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

24. APPROACH TO NEONATAL SEIZURES

25. 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 .

26. 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.

27. 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 .

28. 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 .

29. INVESTIGATIONS Essential - Blood sugar - Serum electrolytes - CSF examination - Cranial ultrasound - EEG

30. 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

31. 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.

32. Acute management of seizures

33. 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

34. 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

35. 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

36. 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.

37. DURATION OF ANTICONVULSANT THERAPY GUIDELINES

38. 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

39. 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.

40. Neurological Disease Normal Development Hypoxic-ischemic encephalopathy 50% Primary subarachnoid hemorrhage 90% Hypocalcemia Early-onset 50% Later-onset 100% Hypoglycemia 50% Bacterial meningitis 50%

41. 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.

42. 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

43. THANK YOU