Neonatal Seizures n Seizures are a common manifestation

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Neonatal Seizures

Neonatal Seizures

n Seizures are a common manifestation of serious CNS disease in the newborn, and

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

n 85% of neonatal seizure occurs in the first two weeks of life 65%

n 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.

n Neonatal seizures may have a deleterious effect on the developing brain by depleting

n 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

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

ETLOGY OF NEONATAL SEIZURES Etiology Hypoxic-ischemic encephalopathy intracranial hemorrhage Intraventricular hemorrhage Subarachnoid hemorrhage Hypoglycemia

ETLOGY OF NEONATAL SEIZURES Etiology Hypoxic-ischemic encephalopathy intracranial hemorrhage Intraventricular hemorrhage Subarachnoid hemorrhage Hypoglycemia Gestational Age Premature Term Time of onset (days of age) 0 -3 4 -10 + + - + + +

cont Etiology Infection Developmental Anomalies Hypocalcemia Early onset Late onset Gestational Age Premature Term

cont Etiology Infection Developmental Anomalies Hypocalcemia Early onset Late onset Gestational Age Premature Term + + + - + + Time of onset (days of age) 0 -3 4 -10 + +

Seizure type Major clinical Manifestations Subtle Tonic (i. e. generalized or focal) Repetitive blinking,

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

cont. Multifocal, synchronous or asynchronous limb movements Clonic (i. e. multifocal Repetitive , jerky

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

JITTERINESS VERSUS SEIZURE CLINCAL FEATURE JITTERINESS SEIZURE Abnormality of gaze or eye movement 0

JITTERINESS VERSUS SEIZURE CLINCAL FEATURE JITTERINESS SEIZURE 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 Bilateral or unilateral jerking during sleep Occurs during active sleep Benign neonatal

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

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

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

(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 ,

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: Maternalal History : 1. A. B. C. D. E. History of drug abuse

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

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

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

3 - Laboratory testes: n Evaluation of metabolic diseases (Bs- ca p-Mg) n evaluation

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

4 - Neuroimaging studies n Scalp sonography (I. V. H. …) n Ct scan

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

ACUTE THERAPY OF NEONATAL SEIZUES HYPOGLYCEMIA n Glucose 10% solution: 2 ml/kg. I. V.

ACUTE THERAPY OF NEONATAL SEIZUES HYPOGLYCEMIA n Glucose 10% solution: 2 ml/kg. I. V. n NO HYPOGLYCEMIA n n n Phenobarbital: 20 Mg/kg (10 -15 min) If necessary additional Phenobarbital: 5 mg /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: 0. 05 -0. 10 mg/kg.

* Phenytoin: 20 mg/kg. I. V. (1 mg/kg/min) lorazepam: 0. 05 -0. 10 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. n Magnesium

Cont. OTHER (AS INDICATED) Caicium gluconate, 5% solution: 4 ml/kg, I. V. n Magnesium sulfate, 50%solution: 0. 2 ml/kg, I. M. n Pyridoxine: 50 -100 mg, I. V. n

EXPECTED RESPONSE OF NEONATAL SEIZURES TO SEQUENCE OF THERAPY ANTICONVULSANT DRUG (CUMULATVE DOSE) Phenobarbital,

EXPECTED RESPONSE OF NEONATAL SEIZURES TO SEQUENCE OF THERAPY ANTICONVULSANT DRUG (CUMULATVE DOSE) Phenobarbital, 20 mg/kg CESSATION OF SEIZURES (CUMULATIVE%) 40% Phenobarbital , 40 mg/kg 70% Phenytion, 20 mg/kg 85% Lorazepam, 0. 05 -0. 10 mg/kg 95 -100%

Maintenance Therapy of Neonatal Seizures Glucose: as high as 8 mg/kg/min, IV Phenobarbital: 3

Maintenance Therapy of Neonatal Seizures Glucose: as high as 8 mg/kg/min, IV Phenobarbital: 3 -4 mg/kg/24 hr , IV, IM, or PO Pheyntoin: 3 -4 mg/kg/24 hr IV Calcum gluconate: 500 mg/kg/24 hr, Po Magnesium sulfate (50%): 0. 2 ml/kg/24 hr, IM

Determinants of duration of Anticonvulsant Drug therapy for Neonatal seizures

Determinants of duration of Anticonvulsant Drug therapy for Neonatal seizures

n If neonatal neurological examination is persistently abnormal, consider etiology and obtain electroencephalogram (EEG)

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

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

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

Porognosis n 1. 2. 3. Dependent to three major predictors: the underlying aetiology EEG

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

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

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

cont Normal EEG neurological sequelae 10% Moderate abnormal EEG Neurological sequelae = 50% Severe

cont 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.

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

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

Prognosis of Neonatal seizures by etiology Etiology Normal outcome(%) Hypoxia-ischemia 50 Meningitis 50 Hypoglycemia

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

Other anticonvulsant drugs for treatment of refractory neonatal seizures: 1. 2. 3. Diazepam drip

Other anticonvulsant drugs for treatment of refractory neonatal seizures: 1. 2. 3. Diazepam drip (continuous infusion) 0. 1 -0. 3 mg/kg/hour Midazolam drip (continuous infusion) 0. 06 -0. 4 mg/kg/hour Carbamazepine 10 mg/kg. NG No adverse effects , but more data are needed

cont 4. 5. 6. 7. 8. 9. Valproic Acid Hepatotoxic Lidocain Iv infusion 4

cont 4. 5. 6. 7. 8. 9. Valproic Acid Hepatotoxic Lidocain Iv infusion 4 -6 mg/kg/hour cardiac toxicity-BP Thiopental BP (more data are needed) Paraldehyde 0. 3 ml/kg/dose / PR BP respiratory disturbance Primidone ( more data are needed) Lamotrigine & topiramate (more data are needed)