Neonatal Seizures

Seizures are a common manifestation of serious CNS disease in the newborn, and Indicate serious underlying disease (90%-95% of cases).

85% of neonatal seizure occurs in the first two weeks of life 65% occurs between 2-5 days after birth 25% in NICU in preterm neonates. And 0.8% In term infant.

Neonatal seizures may have a deleterious effect on the developing brain by depleting cerebral glucose levels, which, in turn, may interfere with deoxyribonucleic acid (DNA) synthesis and myelination.

Seizures also causes to deficiency in cell brain numbers and repeated seizures causes brain Injery.

ETLOGY OF NEONATAL SEIZURES Gestational Age Time of onset (days of age) EtiologyPrematureTerm Hypoxic-ischemic encephalopathy intracranial hemorrhage +++ Intraventricular hemorrhage +-+ Subarachnoid hemorrhage -++ Hypoglycemia +++

Gestational Age Time of onset (days of age) Etiology Premature Term Infection + ++ Developmental Anomalies + ++ Hypocalcemia Early onset + ++ Late onset - ++ cont

Seizure typeMajor clinical Manifestations Subtle Repetitive blinking, eye deviation, staring Repetitive mouth or tongue movements apnea Tonic (i.e. generalized or focal) Bicycing movements’ tonic extension of limb or limbs’ tonic flexion of upper limbs’ extension of lower limbs

Clonic (i.e. multifocal or focal) Multifocal, synchronous or asynchronous limb movements Repetitive, jerky limb movements nonordered progression Localized repetitive clonic limb movements with preservation of consciousness Myoclonic (i.e. generalized, focal, multifocal ) Single or several flexion jerks of upper limbs(common) and lower limbs (rare) cont.

JITTERINESS VERSUS SEIZURE CLINCAL FEATURE JITTERINESSSEIZURE Abnormality of gaze or eye movement 0+ Movements exquisitely stimulus sensitive +0 Predominant movement Tremor Clonic jerking movemnts cease with passive flexion +0 Autonomic changes 0+

Movement Description Benign neonatal sleep myoclonus Bilateral or unilateral jerking during sleep Occurs during active sleep Not stimulus sensitive Often involve upper> lower trunk

CAUSES OF NEONATAL JITTERINESS Metabolic Disorders Hypoglycemia Hypocalcemia Hypomagnesemia CNS Disorders Hemorrhage Hypoxia

(cont.) Congenital abnormality Hyperviscosity (high hematocrit)syndorme Drug Withdrawal Heroin Methadone Barbiturates Idiopathic Prefeeding Others

Clinical features  Neonatal seizures differ considerably from seizures observed in older children, because the immature brain is less capable of propagating generalized electrical discharges, so primary generalized seizures are very rare in the newborn.

Diagnosis: 1. Maternalal History : A. History of drug abuse B. History of intrauterine infection C. History of Genetic or metabolic conditions D. Use of local anesthetic drugs during labour. E. History of previous child with seizures

2. Nconatal Ph ex: - General ex - Neurological ex - Retinal ex - Skin ex

3- Laboratory testes: Evaluation of metabolic diseases (Bs- ca p-Mg) evaluation of Infectious diseases (BC-LP-Torch) Evaluation of Electrolit disorders (Na- K)

4- Neuroimaging studies Scalp sonography (I.V. H. …) Ct scan or MRI (focal seizures) EEG Monitoring (for prognosis & duration of therapy.

ACUTE THERAPY OF NEONATAL SEIZUES HYPOGLYCEMIA Glucose 10% solution: 2 ml/kg. I.V. NO HYPOGLYCEMIA Phenobarbital: 20 Mg/kg (10-15 min) If necessary additional Phenobarbital: 5mg /kg(10-15 min) I.V. to a maximum of 20 mg/kg (consider omission of this additional Phenobarbital if infant is severely “asphyxiated”)

*Phenytoin: 20 mg/kg. I.V. (1 mg/kg/min) lorazepam: mg/kg. I.V. *Fosphenytoin: my be a preferred form of phenytion

Cont. OTHER (AS INDICATED) Caicium gluconate, 5% solution: 4 ml/kg, I.V. Magnesium sulfate, 50%solution: 0.2ml/kg, I.M. Pyridoxine: mg, I.V.

EXPECTED RESPONSE OF NEONATAL SEIZURES TO SEQUENCE OF THERAPY ANTICONVULSANT DRUG (CUMULATVE DOSE) CESSATION OF SEIZURES (CUMULATIVE%) Phenobarbital, 20mg/kg40% Phenobarbital,40mg/kg70% Phenytion, 20mg/kg85% Lorazepam, mg/kg95-100%

Maintenance Therapy of Neonatal Seizures Glucose: as high as 8mg/kg/min,IV Phenobarbital: 3-4 mg/kg/24hr, IV, IM, or PO Pheyntoin: 3-4mg/kg/24hr IV Calcum gluconate: 500mg/kg/24hr, Po Magnesium sulfate (50%):0.2 ml/kg/24hr, IM

Determinants of duration of Anticonvulsant Drug therapy for Neonatal seizures

If neonatal neurological examination is persistently abnormal, consider etiology and obtain electroencephalogram (EEG) Continue Phenobarbital Discontinue phenytoin Reevaluate in 1 month

ONE MONTH AFTER DISCHARGE If neurologic examination has become normal, discontinue phenobarbital

Porognosis Dependent to three major predictors: 1. the underlying aetiology 2. EEG features 3. Gestational age

Other useful predictors: a- neurologic examination b- neuroimaging finding

Normal EEG  neurological sequelae  10% Moderate abnormal EEG  Neurological sequelae = 50% Severe abnormal EEG  Neurological sequelae ≥ 90% cont

The inedience of neurological sequelae (mental retardation – motor deficits – epilepsy)=25%- 35%) M.R, Motor deficits (C.P) are more common than Epilepsy=15%-20%

cnot Neanatal seizures in infants <32 weeks  high mortality (80%)& higher risk of adverse neurological outcome Overall, presentation of seizures at the first hours of life & prolonged seizures that do not respond to therapy  have worse prognosis

Prognosis of Neonatal seizures by etiology Normal outcome(%)Etiology 50Hypoxia-ischemia 50Meningitis 50Hypoglycemia 90Subarachnoid hemorrhage 50Early hypocalcemia 100Late hypocalcemia 10Intraventricular hemorrhage 0Dysgenesis 75Unknown

Other anticonvulsant drugs for treatment of refractory neonatal seizures: 1. Diazepam drip (continuous infusion) mg/kg/hour 2. Midazolam drip (continuous infusion) mg/kg/hour 3. Carbamazepine  10mg/kg.NG No adverse effects, but more data are needed

cont 4. Valproic Acid  Hepatotoxic 5. Lidocain  Iv infusion 4-6mg/kg/hour  cardiac toxicity-BP  6. Thiopental  BP  (more data are needed) 7. Paraldehyde  0.3ml/kg/dose / PR  BP  respiratory disturbance 8. Primidone  ( more data are needed) 9. Lamotrigine & topiramate  (more data are needed)