1. Neonatal Seizures DR. MAHMOUD MOHAMED OSMAN MBBCh, MSc (Pedia), MRCPCH (UK), FRCP (Edinburgh) Consultant Pediatrician & Neonatologist Al Yammamah Hospital, MOH 1 16-09-2015

2. 2 Learning Objectives of Neonatal Seizures  Introduction  Major causes of neonatal seizures  Diagnosis  Common clinical seizure patterns  Investigations  Managament  Prognosis

3. 1. INTRODUCTION: A.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. B.INCIDENCE :  The incidence of neonatal seizures range from 1.0 to 3.5 per 1,000 live births

4. C.PATHOGENESIS:  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.  Seizures may interfere with cardiorespiratory function and with nutrition and may have detrimental long-term effects on cerebral development.

5. 2. MAJOR CAUSES OF NEONATAL SEIZURES:  ypoxic-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)

6.  Intracranial infection  Bacterial meningitis (E. coli, Group B Strep, Listeria)  Viral Encephalitis (Herpes Simplex, Enterovirus)  Intrauterine Infection (CMV, Toxoplasm., HIV, Rubella, Syphilis)  Cerebral Vascular Accidents  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

7. 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.

8. 3. DIAGNOSIS: 3. 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. 2. Confirmation of the abnormal electrical discharge this may be recorded by electroencephalography (EEG).

9. 1. 1. Common clinical seizure patterns: 1.Subtle seizure Eye deviation - Blinking, fixed stare Repetitive mouth & tongue movements Pedaling, tonic posturing of limbs Apnea 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)

10.  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 be chewing, sucking, and cycling movements.  Many newborns may have more than one seizure type.

11. 2. EEG diagnosis 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 non- epileptic behaviors and also to avoid misinterpretation of artifactual EEG patterns.

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

13. 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,  The response to therapies.

14. Amplitude integrated EEG

15. 4. INVESTIGATIONS.  The approach to investigations should be modified by the individual case history, with an emphasis on early identification of correctable disorders.  Sepsis work up (include lumbar puncture ) should be considered.  General metabolic screening  Screening for inborn errors of metabolism.  EEG confirmation of seizures if available, and with anticonvulsant treatment of ongoing seizures.  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.

16. 5. MANAGEMENT: 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 baradycardia) 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. NB: Giving anticonvulsant medications only after adequate ventilation and perfusion have been established and the blood glucose concentration has been measured.

17. 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.

18. 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%.  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.

19.  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.