Neonatal Seizures DR. MAHMOUD MOHAMED OSMAN MBBCh, MSc (Pedia), MRCPCH (UK), FRCP (Edinburgh) Consultant Pediatrician & Neonatologist Al Yammamah Hospital , MOH

LEARNING OBJECTIVES OF NEONATAL SEIZURES: Hypoxic-Ischemic Encephalopathy………….. LEARNING OBJECTIVES OF NEONATAL SEIZURES: Introduction Definition Diagnosis Common clinical patterns Major causes Pathogenesis Investigations Managament Prognosis Review cases

1. INTRODUCTION: DEFINITION: A seizure is a paroxysmal behavior caused by hypersynchronous discharge of a group of neurons. Seizures may be symptomatic of an underlying disorder or due to a primary epileptic condition. In neonates, the vast majority of seizures are symptomatic of underlying disorders. The occurrence of seizure may be the first clinical indication of neurologic disorder. INCIDENCE : The incidence of neonatal seizures range from 1.0 to 3.5 per 1,000 live births

PATHOGENESIS: Seizures may interfere with cardiorespiratory function and with nutrition and may have detrimental long-term effects on cerebral development. Potential mechanisms of brain injury with repeated neonatal seizures include: Hypoventilation/apnea causing hypoxia (leading to cardiovascular collapse). Elevated blood pressure increases CBF and risk of ICH. Increased glycolysis leading to hypoglycemia which exacerbates seizure induced brain injury. Excitatory amino acids (increased release) resulting in excitotoxic brain injury. Most of these can be prevented with good intensive care and control of the seizures.

2. DIAGNOSIS: Early diagnosis of neonatal seizures is important to: Identification and treatment of underlying disorders Prevent additional seizures and seizure-related systemic effects, such as hypoxemia and hypertension Prevent seizure-related neuronal injury Diagnosis of seizures in the neonate requires: 1. Knowledge of the clinical patterns associated with electrographic seizures at this age and 2. Confirmation of the abnormal electrical discharge this may be recorded by electroencephalography (EEG).

1. Common clinical seizure patterns: 1.Subtle seizure Eye deviation - Blinking, fixed stare Repetitive mouth & tongue movements Apnea Pedaling, tonic posturing of limbs 2. Tonic seizure (focal or generalized) Tonic extension or flexion of limbs (severe ICH in preterm) 3. Clonic seizure (focal or multifocal) Clonic limb movements (synchronous or asynchronous) Consciousness may be preserved 4. Myoclonic seizure (focal, multifocal, or generalized) Lightning-like jerks of extremities (upper>lower)

Many newborns may have more than one seizure type In premature infants, a wider range of clinical behaviors can be associated with electrographic seizure patterns; for instance: Self-limited short periods of otherwise unexplained tachypnea, tachycardia, and other autonomic changes may represent seizures. As may chewing, sucking, and cycling movements. Many newborns may have more than one seizure type

2. EEG diagnosis 1. Routine neonatal EEG recording: Typically of 1 hour duration, allows assessment of background activity, developmental maturity, and epileptic potential. 2. Video telemetry: Is very helpful in neonates to clarify the nature of nonepileptic behaviors and also to avoid misinterpretation of artifactual EEG patterns.

Electrographic seizure begins in the left parasagittal area (open arrow), and 12 seconds later, focal clonus of the right foot is noted.

3. Amplitude-integrated EEG (aEEG): It is a bedside technique increasingly being used by neonatologists for neuromonitoring. This technique allows the neonatologist to continually assess the background EEG characteristics, and thereby judge the severity of encephalopathy, the improvement or deterioration over time, and response to therapies.

Amplitude integrated EEG

MAJOR CAUSES OF NEONATAL SEIZURES: Hypoxic-Ischemic Encephalopathy Acute Metabolic Disorders. Hypoglycemia Hypocalcemia Hypomagnesemia Hyper/Hyponatremia Congenital CNS Abnormalities Inherited Metabolic Disorders. Amino Acid, Organic Acid Urea Cycle Disorders Drug Withdrawal Pyridoxine Dependency (Vitamin B6)

Intracranial infection Bacterial meningitis (E. coli, Group B Strep, Listeria) Viral Encephalitis (Herpes Simplex, Enterovirus) Intrauterine Infection (CMV, Toxoplasm., HIV, Rubella, Syphilis) Cerebral Vascular Hemorrhages (Intraventricular, Subarachnoid, Subdural, Epidural) Focal Ischemic Necrosis (Stroke) Developmental defects Neurocutaneous Disorders (Tuberous Sclerosis). Epilepsy Syndromes Epileptic Encephalopathies (Early Myoclonic Encephalopathy) Benign Familial Neonatal Convulsions

Seizures versus non-convulsive movements: Jitteriness is distinguished from clonic seizures by: No associated ocular movements or autonomic phenomena. Stimulus sensitivity. Tremor that is suppressed by flexing the limb. Benign neonatal sleep myoclonus (occurs in healthy newborns); Distinguished from myoclonic seizures.

4. INVESTIGATIONS. The approach to investigations should be individualized with an emphasis on early identification of correctable disorders. EEG confirmation of seizures if available, and with anticonvulsant treatment of ongoing seizures. Sepsis work up (include lumbar puncture ) should be considered and the approach modified by the individual case history. General metabolic screening Screening for inborn errors of metabolism. Neuro-imaging should be considered. Cranial ultrasound: may identify intracranial hemorrhage. Head CT, and brain MRI, are more helpful to confirm these disorders. However, usually require transportation, with the risk of destabilization of ill infants.

1. Ensure adequate ventilation and perfusion. MANAGEMENT: Give anticonvulsant medication only after adequate ventilation and perfusion have been established and the blood glucose concentration has been measured. 1. Ensure adequate ventilation and perfusion. 2. Correct metabolic disturbances. Hypoglycemia: (10% glucose in water) 2 mL/kg IV as bolus. Follow with continuous infusion at up to 8 mg/kg/min IV. Hypocalcemia: (calcium gluconate 10%) 100 mg/kg IV over 1 to 3 minutes (Monitor cardiac rhythm for bradycardia) Follow with maintenance of 500 mg/kg/24 hrs IV or PO. Hypomagnesemia: (magnesium sulfate 10%) 25-250 mg/kg/dose IV. 3. Begin anticonvulsant therapy.

Anticonvulsant Drug Doses for Initial Management of Neonatal Seizures 4. Pyridoxine deficiency is a rare cause of neonatal seizures and should be considered in any newborn with intractable seizures. The diagnosis is made by pyridoxine IV with concurrent EEG.

6. PROGNOSIS. Advances in obstetric management and in neonatal intensive care have yielded a reduction in mortality in infants with neonatal seizures from about 40% to <20%, with <10% mortality in term infants in one recent series. Morbidity rates have changed less, partly due to increased numbers of survivors among ill, premature newborns, who have a greater risk of neurologic sequelae. Long-term sequelae, including cerebral palsy and intellectual disabilities, still occur at a high rate.

The most important factor affecting outcome for infants with neonatal seizures is the underlying etiology. Normal development can be expected in infants with benign idiopathic neonatal seizures. Whereas only 50% of those with HIE. Gestational age is also an important factor with increasing mortality and morbidity with increasing immaturity. Useful clinical indicators for a good outcome include a normal neonatal neurologic exam, normal or mildly abnormal neonatal EEG background activity, and normal neuro-imaging.

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