Neonatal seizure wachemo university medical note

Medical note

1. Dr Esayas E Neonatal SEIZURES

2. Definitions Seizure (Convulsion): Paroxysmal synchronized discharge of cortical neurons resulting in alteration of function (motor , sensory , cognitive, autonomic). It may or may not be associated with impairment or loss of consciousness .

3. Def n ,….. Seizure disorder is a general term that is usually used to include any 1 of several disorders, including epilepsy, febrile seizures, and possibly single seizures and symptomatic seizures secondary to metabolic, infectious, or other etiologies (e.g., hypocalcemia , meningitis ).

4. Mechanism of seizures : unknown Two hypotheses : 1) Inhibitory neurons are selectively damaged and remaining principal excitatory neurons become hyperexcitable . 2) Aberrant excitatory circuits are formed as part of reorganization after injury . Excitatory neurotransmitters : glutamate , aspartate Inhibitory neurotransmitter : GABA

5. Normal newborns have many repetitive , rhythmic , and jerky movements. Those movements and behaviors provoked by stimulation ,and/or eliminated by passive flexion or soothing touch are unlikely to represent seizures . Neonatal seizures are important marker of neonatal brain injury and may contribute to long-term neurological sequelae .

6. Types 1) Focal seizures - consist of rhythmic twitching of muscle groups e.g. those of the extremities and face. - often associated with localized structural lesions as well as with infections and subarachnoid hemorrhage . 2) Multifocal clonic seizures - convulsions are similar to focal clonic seizures but differ in that many muscle groups are involved, frequently several simultaneously .

7. 3) Tonic seizures - characterized by rigid posturing of the extremities and trunk and are sometimes associated with fixed deviation of the eyes. 4) Myoclonic seizures - brief focal or generalized jerks of the extremities or body that tend to involve distal muscle groups.

8. 5) Subtle seizures - consist of chewing motions, excessive salivation, and alterations in the respiratory rate including apnea , blinking, nystagmus, bicycling or pedaling movements, and changes in color . N.B. Apnea usually associated with tachycardia and pupillary dilatation is a type of subtle seizure .

9. PAROXYSMAL NONEPILEPTIFORM DISORDERS    Jitteriness    Benign neonatal sleep myoclonus N.B. GTC convulsions tend not to occur in the 1st mo of life: - The arborization of axons and dendritic processes as well as myelination is incomplete in the neonatal brain. - A seizure discharge, therefore, cannot readily be propagated throughout the neonatal brain to produce a generalized seizure ( “ reduced connectivity “ ).

10. Fifth-day fits Occur on day 5 of life (4-6 days) in normal appearing neonates . Seizures are multifocal and are present for less than 24 hours The Dx requires exclusion of other causes of seizures The prognosis is good

11. Benign familial neonatal seizures An autosomal dominant condition Begins on the 2 nd -3 rd day of life ,with a seizure frequency of 10-20/day Patients are normal b/n seizures Stops in 1-6 months

12. Pyridoxine dependency A rare disorder Must be considered when generalized clonic seizures begin shortly after birth with signs of fetal distress in utero Seizures are particularly resistant to conventional anticonvulsants ,such as phenobarbital or phenytoin The Hx may suggest that similar seizures ocurred in utero Autosomal recessive inheritance

13. Causes of neonatal seizures AGES 1–4 DAYS    Hypoxic-ischemic encephalopathy    Drug withdrawal, maternal drug use of narcotic or barbiturates    Drug toxicity: lidocaine , penicillin    Intraventricular hemorrhage ( IVH )   Acute metabolic disorders      - Hypocalcemia       - Hypoglycemia - Hypomagnesemia      - Hyponatremia or hypernatremia       Inborn errors of metabolism      Pyridoxine deficiency (must be considered at any age)

14. AGES 4–14 DAYS    Infection    Metabolic disorders    - Hypocalcemia - Hypoglycemia, persistent Drug withdrawal Benign neonatal convulsions ( familial and nonfamilial   ) Kernicterus , hyperbilirubinemia AGES 2–8 WEEKS    Infection      Head injury Inherited disorders of metabolism    Malformations of cortical development      -   Tuberous sclerosis  -  Focal cortical dysplasia -   Lissencephaly - Sturge - Weber syndrome

15. Investigations RBS Serum Electrolytes (Na, Ca , Mg , P ) A lumbar puncture is indicated in virtually all neonates with seizures , unless the cause is obviously related to a metabolic disorder such as hypoglycemia or hypocalcemia . EEG is indicated in all cases , if possible . Neuroimaging ( CT / MRI )

16. EEG Provides direct confirmation that suspicious clinical event represents electroclinical seizures if the event is captured during EEG recording . If suspicious event does not occur during a brief EEG recording : 1) Presence of epileptiform features and/or 2) Focal abnormalities supports the diagnosis of neonatal seizures .

17. Neuroimaging The goal of neuroimaging is identification of : - Intracranial hemorrhage - Focal or diffuse parenchymal injury - Structural developmental abnormalities m

18. Cranial ultrasound Can be performed at the bedside Effective in identifying : - Intraventricular hemorrhages - Many parenchymal hemorrhages Has limitations in its ability to detect : - Focal infarcts - developmental abnormalities - Cerebral convexity hemorrhages

19. CT or MRI Yields more information than cranial U/S Requires skilled transportation from neonatal ICU to the radiology suite . May be deferred ,at least initially , until the infant is stabilized .

20. Treatment 1) General supportive measures 2) Management of any underlying disorder 3) Anticonvulsant medication

21. Goals of clinical management Correct identification of suspicious clinical events EEG confirmation Immediate supportive therapy Correction of reversible precipitating conditions Accurate diagnosis of the underlying etiology Anticonvulsant therapy

22. 1) General supportive measures Seizures themselves and treatment with anticonvulsant medication may impair respiratory drive and the ability to maintain adequate circulation . Supportive management to ensure maintenance of adequate ventilation and perfusion is necessary.

23. 2) Management of any underlying disorder Acute treatment of the most common acute reversible metabolic abnormalities : - Hypoglycemia - Hyponatremia - Hypocalcemia - Hypernatremia - Hypomagnesemia Pyridoxine-dependent seizures HIE IVH Sepsis-meningitis

24. Hypocalcemia Occurs in isolation or in association with hypomagnesemia Risk factors: - CNS insult in the perinatal period e.g. PNA - birth trauma - Maternal diabetes(IDM) - Prematurity - DiGeorge syndrome - High-phosphate feedings

25. Etiology-specific therapy for neonatal seizures of metabolic origin 1) Glucose 10% solution 4ml/kg 2) Calcium gluconate 10% solution 2 ml/kg IV over 10 min 3) ) Magnesium sulfate 0.25 ml/kg IM 4) Pyridoxine - 100 mg IV

26. 3) Anticonvulsant drugs (ACDs) Anticonvulsant therapy is appropriate in many,but not necessarily all cases . Decisions regarding initiation and duration of therapy should be individualized . Phenytoin and phenobarbitone are equally but incompletely effective as anti - convulsants in neonates , controlling seizures in less than 50% of cases . Neuroprotection and/or antiepileptogenic effect

27. Indication for ACDs Decision to Rx neonatal seizures with ACDs depends on : 1) Risk of acute seizure related respiratory or cardiac decompensation in a critically ill newborn 2) The potential for long-term seizure-related neurological injury 3) The potential adverse effects of anticonvulsant medications

28. ACDs A ) First-line drugs - Benzodiazepines (diazepam , lorazepam ) - Phenobarbital - Most commonly used drug as first-line therapy . - Phenytoin ( its prodrug fosphenytoin ) N.B. More than 90% of neonatal seizures are controlled by combined use of the above ACDs.

29. B ) Second line drugs : 1) For acute therapy (IV) - Midazolam - Paraldehyde - Clonazepam 2) For refractory seizures ( PO ) ( Adjunctive therapy) - Carbamazepine - Vigabatrin - Primidone - Lamotrigine - Valproate

30. Response to Rx (ACDs) Treatment with anticonvulsant medication is often associated with resolution of clinical seizures. From 30% - 80% of newborns may continue to have electrographic seizures , with out clinical seizure , after ACDs are initiated. Continuous or serial EEG recordings should be strongly considered .

31. Duration of ACD Rx No guideline exists as to appropriate duration of ACDs treatment for newborns with seizures . 1 week – 12 months after the last seizure ( usually 2 wks after the last seizure ) Preferably do EEG before D/C of AEDs .

32. The trend is toward shorter therapy , taking into account : - Short-lived nature of precipitating causes - Recovery from acute HIE in many instances - Possible detrimental effects of ACDs on the immature brain .

33. Indications for long-term treatment Persistent , difficult to control seizures Persistently abnormal EEG Persistently abnormal neurological examination

34. Prognosis Depends on :1) Primary cause of the disorder 2) Severity of brain injury at the time of seizure disorder Excellent prognosis - Hypoglycemia in IDM - Hypocalcemia b/c of excess phosphate feeding

35. Poor prognosis - Severe HIE - Cytoarchitectural abnormality of the brain ( Lissencephaly or schizencephaly ) Mortality associated with neonatal seizures is 20% or less ( decreased) Morbidity changed less b/c of surviving ill preterm newborns with greater neurological sequelae .

36. Risk of abnormal neurological outcome ( motor and/or cognitive abnormality ) is approximately 25-35 % . The likelihood of postneonatal epilepsy is15-20% . The role of neonatal seizures in generating brain injury and long-term sequelae remains controversial .

37. The role of clinically silent electrographic seizures is controversial. The immature brain appears to be more resistant to seizure - related excitotoxicity than the mature brain BUT It is more susceptible for developmental effects of anticonvulsant drugs b/c many physiologic processes are immature .

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