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.

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

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.

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

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

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

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

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

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

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

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

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

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

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

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.

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.

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 1-3 jerks per second

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

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

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

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

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

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

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

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.

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).

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

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…)

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

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

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

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,

IV lorazepam 0.05 mg/kg every 4-8 hourly IV phenytoin 15-20 mg/kg diluted in equal volume of normal saline at a maximum rate of 1mg/kg/min over 35-40 minutes IV lorazepam 0.05 mg/kg every 4-8 hourly IV midazolam as a continuous infusion (as initial IV bolus of 0.05-0.1mg/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.

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

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

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

Prognosis

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

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

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

Prognoz

Burst-suppression pattern

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