Neonatal seizures

neonatal pneumonia

1. Neonatal seizures By; Dr Syeda Sumaiya(2019-2022) Pg scholar Dept of OBG NIUM, Bengaluru-91 Under the guidance of: Prof Wajeeha Begum HOD dept of OBG NIUM, Bengaluru-91.

2. Contents Diagnosis Management Prognosis

3. Diagnosis

4. Approach to an infant with neonatal seizures: History: Seizure history: A complete description of the seizure should be obtained from the parents/attendant. History of associated eye movements, restraint of episode by passive flexion of the affected limb, change in color of skin (mottling or cyanosis), autonomic phenomena, and whether the infant was conscious or sleeping at the time of seizure should be elicited. The day of life on which the seizures occurred may provide an important clue to its diagnosis. While seizures occurring on day 0-3 might be related to perinatal asphyxia, intracranial hemorrhage, and metabolic causes, those occurring on day 4-7 may be due to sepsis, meningitis, metabolic causes, and developmental defects. Antenatal history: History suggestive of intrauterine infection, maternal diabetes, and narcotic addiction should be elicited in the antenatal history. A history of sudden increase in fetal movements may be suggestive of intrauterine convulsions.

5. Perinatal history: Perinatal asphyxia is the commonest cause of neonatal seizures and a detailed history including history of fetal distress, decreased fetal movements, instrumental delivery, need for resuscitation in the labor room, Apgar scores, and abnormal cord pH (10 meq /l) should be obtained. Use of a pudendal block for mid-cavity forceps may be associated with accidental injection of the local anesthetic into the fetal scalp. Feeding history: Appearance of clinical features including lethargy, poor activity, drowsiness, and vomiting after initiation of breast-feeding may be suggestive of inborn errors of metabolism. Late onset hypocalcaemia should be considered in the presence of top feeding with cow’s milk. Family history: History of consanguinity in parents, family history of seizures or mental retardation and 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).

6. Examination: Vital signs: Heart rate, respiration, blood pressure, capillary refill time and temperature should be recorded in all infants. General examination: Gestation, birth weight, and weight for age should be recorded as they may provide important clues to the etiology – for example, seizures in a term ‘well baby’ may be due to subarachnoid hemorrhage while seizures in a large for date baby may be secondary to hypoglycemia. The neonate should also be examined for the presence of any obvious malformations or dysmorphic features.

7. CNS examination: Presence of a bulging anterior fontanel may be suggestive of meningitis or intracranial hemorrhage. A detailed neurological examination should include assessment of consciousness (alert/drowsy/comatose), tone ( hypotonia or hypertonia ), and fundus examination for chorioretinitis . Systemic examination: Presence of hepatosplenomegaly or an abnormal urine odor may be suggestive of IEM. The skin should be examined for the presence of any neuro-cutaneous markers. Presence of hypopigmented macules or ash-leaf spot would be suggestive of tuberous sclerosis.

8. Investigations: These are done at the time of convulsions, as the investigations done will help in the immediate management.

9. This is done once the baby has stopped convulsing. This will help to find out the cause

10. These are not always necessary. This is indicated when the convulsions are recurrent, etiology has not been established by routine investigations.

11. Electroencephalogram (EEG) A background abnormality in both term and preterm neonates indicates a high risk for neurological squeal. These changes include burst-suppression pattern, low voltage invariant pattern and electro-cerebral inactivity.

12. Amplitude integrated EEG ( aEEG ) Seizure activity on aEEG is characterized by a rapid rise in both the lower and upper margins of the trace. Some seizures that are focal or relatively brief are, however, missed by this technique.

13. Screen for congenital infections: TORCH screen and VDRL should be considered in the presence of hepatosplenomegaly , thrombocytopenia, intrauterine growth restriction, small for gestational age, and presence of chorioretinitis . Metabolic screen: This includes blood and urine ketones , urine reducing substances, blood ammonia, anion gap, urine and plasma amino acidogram , serum and CSF lactate/ pyruvate ratio.

14. Management: Initial medical management:

15. Correction of hypoglycemia and hypocalcaemia: If GRBS shows hypoglycemia or if there is no facility to test blood sugar immediately, 2 ml/kg of 10% dextrose should be given as a bolus injection followed by a continuous infusion of 6-8 mg/kg/min. If hypoglycemia has been treated or excluded as a cause of convulsions, the neonate should receive 2 ml/kg of 10% calcium gluconate IV over 10 minutes under strict cardiac monitoring. If serum calcium levels are suggestive of hypocalcaemia, the newborn should receive calcium gluconate at 8 ml/kg/d for 3 days. If seizures continue despite correction of hypocalcaemia, 0.25 ml/kg of 50% magnesium sulfate should be given intramuscularly.

16. Anti-epileptic drug therapy (AED) Phenobarbitone (the WHO guidelines on neonatal seizures recommend phenobarbitone as the first-line agent for management of neonatal seizures) May be diluted to 10 mg/ml in 0.9 % sodium chloride. May be diluted 1:10 with water for injections. Loading dose: 20 mg/kg IV over 15–30 minutes. Maintenance: Commence only if seizures continue after the loading doses. 3–4 mg/kg IV per day. Commence 12–24 hours after loading dose Daily dose (not required) (Controls seizures in 43–85 % of babies ·A second line drug is often required) Side effects include respiratory depression, depressed level of consciousness, hypotension and hypotonia

17. Phenytoin : Second line anticonvulsant for seizures refractory to Phenobarbital. Loading dose: 15–20 mg/kg IV over 30–60 minutes. Maintenance: 5 mg/kg per day58 or 2 mg/kg every 8–12 hours. Administration (loading and maintenance) Dilute to 5 ml with 0.9% sodium chloride and precede and follow injection with 0.9% sodium chloride flush to avoid contact with glucose solution. Administer directly into large peripheral or central vein through large bore catheter Dose related adverse events include nystagmus (level 15–25 mg/ml) and ataxia and mental statues changes (level greater than 30 mg/ml)

18. Midazolam : Based on the available evidence, the WHO guidelines on neonatal seizures recommend either midazolam or lidocaine as the second-line AED in neonatal seizures. Second line anticonvulsant for seizures refractory to Phenobarbital Loading dose: 0.15 mg/kg (150 micrograms/kg) IV over five minutes · Maintenance IV infusion: 60–400 micrograms/kg/hour. Administration (loading and maintenance) Dilute in 0.9% sodium chloride or 5% glucose. Do not administer by rapid infusion as may cause respiratory depression, severe hypotension and seizures. May cause myoclonic jerking, respiratory depression and hypotension when used in conjunction with narcotics

19. Lidocaine : It is usually administered as a bolus dose of 4 mg/kg IV followed by an infusion rate of 2 mg/kg/hr. It is tapered over several days. AE include arrhythmias, hypotension, and seizures. It should not be administered with phenytoin .

20. Paraldehyde: A dose of 0.1-0.2 ml/kg/dose may be given IM or 0.3 ml/kg/dose mixed with coconut oil in 3:1 may be used by per rectal route. Additional doses may be used after 30 minutes and q 4-6 hourly. AE include pulmonary hemorrhage, pulmonary edema, hypotension, and liver injury.

21. Pyridoxine (vitamin B6): Vitamin B6 is a required enzyme in the biosynthesis of dopamine and serotonin. Used to treat inborn error of metabolism due to antiquitin deficiency dehydrogenase deficiency. Consider pyridoxine dependency in any baby with severe seizures even if there is a clear cause (e.g. birth asphyxia). Classic presentation is intractable seizures that appear within hours of birth and are resistant to conventional AEDs Baby responds rapidly to IV pyridoxine · May present with frequent multifocal and erratic or generalized myoclonic jerks.

22. May also present with tonic seizures, spasms, abnormal eye movements, grimacing or irritability. Seizures may occur without ictal changes on the EEG. Maternal history may report sensation of sustained hammering lasting 15– 20 minutes by fetus in- utero . Used for diagnosis and treatment of pyridoxine dependent seizures. 50–100 mg IV injection, over 20 minutes or IM If required may be repeated after 10 minutes up to a total maximum dose of 500 mg. If responsive then administer 50–100 mg orally, once per day.

23. Treatment for refractory seizures : If the seizures are refractory, 40mg/kg of initial dose of phenorbarbitone , then phenytoin at the dose of 20mg/kg is administered. Then if the seizures remain unresponsive, benzodiazepine (diazepam, lorazepam ) or paraldehyde is used. Simultaneous EEG should be performed to document cessation of seizures activity. Magnesium sulphate at the dose of 0.2 ml/kg/dose of 50 % solution can be used. Pyridoxine is also tried at the dose of 50-100 mg IV. If the convulsions are intractable and baby is in states convulsions, clonazepam 50 µg/kg IV slowly for 2-3 min is given. Alternatively clonazepam 100-200 µg/kg can be given IV over 30 sec. Benzodiazepam can be repeated as and when needed. Midazolam 0.05-0.15 mg/kg/ dose is effective when given IM.

24. Follow up of anticonvulsant therapy: All the medications which are used to control the seizures can be stopped. The only maintenance dose of Phenobarbitone is continued. (indications for stopping anticonvulsants are: normal examination findings, absence of recurrent and nonepileptiform seizures.) The duration of therapy is guided by neurological status of the infant, cause of the seizures and EEG findings. The infant is evaluated at 6-8 wks. If there is no recurrence of seizures, CNS examination and EEG is normal, the Phenobarbitone is stopped. When the Phenobarbitone is continued the child is evaluated at the age of 6 months. The infant is treated like the case of epilepsy if the seizures are recurrent or if there are any evidence of neurological disabilities.

25. Prognosis: Neonatal seizures can cause both acute effects and long term sequelae . Acute and long term adverse effects result from energy failure, excitotoxicity , neuronal death, apoptosis and status epilepticus . These all contribute to cognitive, motor and behavioral problems. Normal outcome: 56% Neurological sequelae : 30-40 % Death: 15-25% Chronic seizure disorder: 15-20 %

26. Outcome depends on : Level of maturity Etiology Neurological examination EEG/ imaging studies   Good prognosis: Uncomplicated hypoglycemia Narcotic withdrawal SAH

27. Poor prognostic factors: Apgar score- less than 6 at 5 minutes 5 minutes IPPV following birth Early onset of seizure Seizures lasting more than 30 minutes Hypotonia at 5 minutes following birth Uncontrolled seizures for 3 or more days Presence of tonic or myoclonic seizures.

28. References: 1.Glass HC, Shellhaas RA. Acute Symptomatic Seizures in Neonates. Semin Pediatr Neurol 2019;32:100768. 2. Soul JS. Acute symptomatic seizures in term neonates: Etiologies and treatments. Semin Fetal Neonatal Med 2018;23:183-90. 3. Kang SK, Kadam SD. Neonatal Seizures: Impact on Neurodevelopmental Outcomes. Front Pediatr 2015;3:101. 4. Kaushal S, Tamer Z, Opoku F, Forcelli PA. Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia 2016;57:727-34. 5.Tekgul H, Gauvreau K, Soul J, Murphy L, Robertson R, Stewart J, et al. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics 2006;117:1270-80. 2. 6. National Neonatal Perinatal Database. Report for the year 2002–03. http://www.newbornwhocc.org/pdf/nnpd_report_2002-03.PDF (accessed Jan 8, 2012). 7.Ghai O. P. Ghai Essential Pediatrics : Disease of neurological disorder 8 th edition Delhi-92 CSB Publ : 2009. p. 260-269. 8.Care of the newborn. Singh M ( ed ), 9 th edition, New delhi sagar publication : (2010)