1. Seizures in neonates Dr. F. Hemmati neonatologist

2. Paroxysmal involuntary disturbance of brain function that may be manifested as an impairment or loss of consciousness, abnormal motor activity, behavioral abnormalities, sensory disturbance, or autonomic dysfunction. Neonatal seizures are dissimilar from those in a child or adult because generalized tonic-clonic convulsions tend not to occur during the 1 st mo of life

3. Neonates are at particular risk for the development of seizure because metabolic, toxic, structural, and infectious disease are more likely to be manifest. Overestimation and underestimation are reported. Using clinical criteria 0.5% in term infants 22.2% in preterm neonates

4. At least five seizure types are recognizable in newborn infants: Subtle, focal clonic, multifocal clonic, tonic, and myoclonic seizures

5.  Most frequently observed category ( 30%)  Include repetitive buccolingual movements, orbital- ocular movement, unusual bicycling or pedaling movement, excessive salivation, and alterations in respiratory rate including apnea, changes in color, changes in heart rate, blood pressure, oxygenation, or other autonomic sign.  Occur in both full-term and preterm infants.  Usually associated with other seizure type  Only tonic eye deviation is consistently associated with EEG paroxysmal activity.  Despite the “ subtle” expression, these children may have suffered significant brain injury

6.  Focal: Rhythmic movements of muscle groups in a focal distribution that consist of a rapid phase followed by a slow return ( 1 to 3 per second) movement are clonic seizures. Clonic seizures must be distinguished from the symmetric “to end fro” movement of clonus or jitteriness. Clonus can be precipitate or abolished by changes in posture or by stimulation but clonic seizures are not altered. Clonus is ablated by restraining limb movements but in seizure movement, underlying contractions will be felt. Finally facial and ocular movements are present in seizure, but they do not accompany clonus. cont

7.  Focal clonic seizures consist of jerking limited to one or both extremities on the same side of body with or without facial involvements.  Focal clonic seizure is frequent in the newborn and usually denote underlying structural lesion in the cerebral hemispher contralateral to the convulsive activity but can also arise from systemic metabolic disease such as hypoglycemia.  Of all seizure types in neonate, clonic seizures are most consistently associated with epileptiform EEG activity.

8.  Multifocal or migratory clonic activities spread over body parts either in a random or anatomically appropriate fashion.  May alternate from side to side and appear asynchronously between the two halves of body. Upper limb and contralateral lower limb activity is frequently observed.  75% of these seizures occur in infants weighting more than 2500 gr  EEG is usually abnormal.  Neonates with this seizure suffer death or significant neurologic morbidity.

9. Sustained flexion or extension of axial or appendicular muscle groups, and characterized by rigid posturing of the extremities and trunk and sometimes associated with fixed deviation of the eyes. Two types are recognized: generalized and focal. Genteralized tonic seizures mimic the decorticate or decerebrate postures Approximately 70% of these seizures occur in infants weighing less than 2500 gr and 85% inconsistent with EEG change. Focal tonic seizures consist of sustained asymmetric posturing of the trunk or limbs and are consistently with EEG activity.

10. Myoclonic movement are rapid, isolated jerks that can be focal, multifocal, or generalized. focal myoclonus seizures consist of single or multiple rapid contractions of the flexor muscles of an upper extremity, whereas multifocal characterized by asynchronus twitching of several parts of body. Generalized myoclonic seizures consist of massive flexions of the head and trunk in association with flexion or extension of the extremities. They mimic infantile spasm seen in older infants.

11. All three forms of myoclonic seizures can be seen during sleep in premature and full- term infants. that subsides with arousal to the waking state. These episodes typically resolve by 6 months of age. They not associated with underlying structural lesion or metabolic derangement of the brain and EEG is normal during myoclonus and between episodes.

12. Clinical seizure with a consistent EEG events: In focal clonic, focal tonic, and some myoclonic seizure. These seizures are clearly epileptic and are likely to respond to an anticonvulsant Clinical seizure with inconsistent EEG events: In generalized tonic seizures, subtle seizures and some myoclonic seizures. These infants are neurologically depressed or comatose and seizures are nonepileptic and may not respond to anticonvulsant Electrical seizures with absent clinical seizures: May develop in comatose infants who are not on anticonvulsant or in infants with focal tonic or clonic seizures after the introduction of an anticonvulsant.

13. Hypoxic- ischemic encephalopathy is the most common cause. Both the timing of the seizure onset and the type of seizure can be important clues in differential diagnosis. At least as important as the seizures themselves are the underlying factors that herald their onset, because these predisposing factors primarily determine neurology outcome

14.  Major cause of seizure within the first 72 hours after birth.  Most within first 24 hours.  Most asphyxia insult occurred before or during labor.  Associated metabolic abnormalities include hypoglycemia, hypocalcemia, and hyponatremia (SIADH)

15. Hypoglycemia Glucose levels of 35 to 40 mg/dl Vulnerability of brain to ischemic insult is enhanced by concomitant hypoglycemia. hypocalcemia Total serum calcium levels below 7 to 8 mg/dl The ionized fraction is a more sensitive indicator of seizure vulnerability. Mother’s calcium status should be evaluated Hyponatremia and hypernatremia Hyponatremia with SIADH Hypernatremia with dehydration or iatrogenic

16.  Hemorrhagic or ischemic lesions.  On either an arterial or venous basis.  Intraventricular or periventricular hemorrhage is the most common hemorrhage in preterm newborns.  Subarachnoid hemorrhage in full term infants has favorable outcome. Most commonly there are no clinical signs but on occasion, develop seizure on the second or third day of life and have a benign course, with no apparent sequellae.  Subdural hemorrhage is rare when focal trauma to face, scalp or head has occurred, should be considered.  Cerebral infarction typically present with focal and multifocal clonic seizure combined with hypotonia especially of the upper extremity. cont

17.  CNS infection during antepartum or postnatal period.  Congenital infections (TORCH) can produce severe encephalopathic damage.  Other congenital infections includes enteroviruses and parvoviruses.  Bacterial meningitis acquired in utero or postnatally from either gram-negative or gram positive organisms can produce seizure.

18.  5% to 10% of all seizures occurring in the first week of postnatal life.  May be phenotypically with multiple congenital anomaly or appear entirely normal despite major cerebral malformations. So must be evaluate all neonates with persistent seizures.  May occur as a result of either genetic causes or acquired defects during the first half of gestations.

19. Inherited biochemical abnormalities are rare causes of neonatal seizures. Pregnancy, labor, and delivery histories are commonly uneventful. Food intolerance as well as increasing lethargy, stupor, coma, and seizure is an early indication May initially present as neurologically depressed and hypotonic child with asphyxia and seizures. Vitamin B6 or pyridoxine deficiency is a rare cause of neonatal seizures within first days of postnatal life. Pyridoxine acts as cofactor in GABA synthesis, and its absence produce seizures. Disorders of CHO metabolism with coincident hypoglycemia, are rare causes of seizure

20. Newborns born to mother who engaged in prenatal substance use or abuse. Exposure to barbiturates, alcohol, heroin, cocaine, or methadone commonly present with tremors and irritability and seizures tend to occur late ( 4-6 week after birth) Short acting barbiturates may be associated with seizures within first several days of life. Seizures may occur directly after substance withdrawal, or associated with longer standing uteroplacental insufficiency

21.  Direct injection of local anesthetic into the fetus can occur during paracervical, epidural and pudendal anesthesia.  Patients present during the first 6 to 8 hours of life with apnea, bradycardia, and hypotonia, and are comatose, without brain stem reflexes.  Frequently mistaken as complications of asphyxia they have widely dilated, fixed pupils with absent oculocephalic doll’s eye) reflex  Diagnosis: with detection of puncture marks in child’s scalp or body and determination of plasma levels of the drugs  Treatment: ventilatory support, therapeutic diuresis, acidification of the urine, or exchange transfusion. Antiepileptic drugs are rarely indicated.

22. for example neurofibromatosis, tuberous sclerosis, and sturge Weber syndrome  Predominantly of the focal or multifocal clonic seizure  Seizure are early manifestations of hamartomas, neurofibromas or vascular malformation.  A thorough examination for the presence of cafe au lait spots or lisch nodules, depigmented skin lesion and facial portwine stain aids in the diagnosis

23. Familial seizures  Autosomally dominant inherited seizures  Seizure occur between the second and third days of postnatal life  Frequent clonic activity occasionally with apnea  EEG is normal between seizure  Seizure is self-limited and generally disappear within 2 to 4 week  Benign and affected infant develops normally but nonfebrile seizures occur in 15% of affected newborn

24. Nonfamilial seizures ( Fifth day fits)  Occur typically in the later part of the first week of postnatal life  Seizures are clonic, generally multifocal, occasionally lasting several hours  EEG can be abnormal between seizures  Episodes usually diminish within 24 hours of onset and followed by normal development  Etiology remain obscure

25. Begins with a detailed review of the medical histories of the mother, fetus, and newborn. Any of the following factors in the history are important: 1-PROM,chorioamnionitis, maternal fever, or other evidence of systemic infection 2-Difficult labor and delivery and evidence of fetal distress 3-F.HX of seizures 4-Maternal HX of diabetes, parathyroid disease; or maternal drug addiction cont

26. Careful physical examination including neurologic examination to determine the functional status of the CNS and to uncover any focal abnormalities. In addition, examination of retina that may show chorioretinitis suggesting of TORCH infections. Inspection of the skin may show hypopigmented lesions of tuberous sclerosis or the typical crusted vesicular lesions of incontinentia pigments. An unusual body odor suggests an inborn error of metabolism cont

27. Laboratory investigations should follow a logical approach to the differential diagnosis. Blood should be obtained for determinations of glucose, calcium, magnesium, electrolytes, BUN, ABG,CBC and blood culture. A lumbar puncture is indicated in all neonate with seizures, unless the cause is obviously metabolic disorder. EEG is indicated in all seizures. With clinical suspicion of specific disease, additional investigations must be done:  TORCH antibody titers and viral cultures.  Blood and urine metabolic studies ( bilirubin, ammonia, reducing substance, blood and urine amino acid)  CT or ultrasound scan

28. Rapid infusion of glucose with4 cc/kg of a 10% dextrose solution followed by infusion of 8-10 mg/kg/min of glucose should be initiated before antiepileptic medications. Hypocalcemia- induced seizures should be treated with an IV infusion of 2cc/kg of 10% calcium gluconate and repeated every 6 hours to maintain serum calcium above 7 to 8 Hypomagnesemia ( serum Mg< 1.5): 0.2 cc/kg of a 50% solution Of Mgso 4 that should be given by IM injection. Disorders of serum sodium treated by either fluid restriction or replacement with hypotonic solutions. Pyridoxine dependency requires the injection of 50 to 100 mg of pyridoxine with coincident EEG monitoring cont

29. Anticonvulsant drugs must be used when a metabolic derangement is not contributing to seizure activity in a newborn Phenobarbital : initial loading dose at 20 mg/kg IV followed by 3 to 5 mg/kg/day. Additional doses of 10mg/kg ( up to 40 mg/kg /day total) may be needed. Therapeutic levels are 20-40 µg/ml. phenytoin : loading dose 15 to 20 mg/kg followed by 5 mg/kg/day Diazepam : 0.3- 0.5 mg/kg followed by 0.1 mg/kg/hr Lorazepam :0.05mg/kg repeated every 10 to 15 minutes to a total dose of 0.2 mg/kg. Paraldehyde :0.1 mg/kg diluted 1:10 in mineral oil given rectally. Contraindicated with active pulmonary disease Lidocaine : continous infusion of 4 mg/kg/hr mixed with saline.

30. Prognosis of neonatal seizures depends on the underlying disease: Neurologic disease normal development(%) HIE 50 Intracerebral hemorrhage <10 Primary subarachnoid hemorrhage 90 Hypocalcemia Early onset 50 Late onset 100 hypoglycemia 50 Bacterial meningitis 50 CNS malformation 0

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