Neonatal seizures are a clinical problem frequently encountered by the pediatrician. These convulsions in the newborn period often signify an underlying disease process that may produce irreversible cerebral damage; therefore, it is important to diagnose and treat the underlying cause. Although these seizures should be urgently treated, they often go unrecognized.
Unlike the older child and adult, the neonate rarely has generalized tonic clonic grand mal seizures. In fact, none were encountered in Rose and Lombroso's study' of 137 infants at Boston Children's Hospital. More commonly, the neonate shows "fragmentary" seizures or fragments of a generalized seizure, with migratory clonic movements of first one and then another extremity in a disorderly manner. The various clinical types described also include hemiconvulsions with focal clonic seizures of one side of the body that may alternate sides, tonic seizures with opisthotonic posturing, and myoclonic jerks. There is also a group with changes in respiratory rate, apnea, eye deviations, pedaling movements of the extremities, or repetitive chewing movements as the only manifestation of a seizure. It is in this more subtle group that the electroencephalogram can help document whether an actual clinical seizure has occurred. The clinical clue would be the repetitive, stereotyped nature of these movements.
Although peripheral manifestations are often slight in the neonatal seizure, the EEG changes may be dramatic. Focal seizures in the neonate generally do not signify the presence of an underlying structural lesion.
Why are the clinical seizure patterns in the neonate different from those of the mature person? One must consider the morphologic and physiologic organization of the immature cortex. The newborn nervous system functions at the spinal-cord and brain-stem level. There is little physiologic evidence of higher cortical function. The newborn brain, weighing 350 gm., has its full complement of cortical neurons, but these cells have not yet completed their cytoplasmic differentiation. Dendrites, synaptic connections, and myelinization are all incomplete, and the glial elements have not yet completely formed normal relationships with other neurons.
Experimental evidence suggests that in the kitten the cortical spread of electrical discharges is slow and often limited to one hemisphere. When there is spread to the opposite hemisphere, it is slow and not bilaterally synchronous. Purpura2 showed that in the newborn kitten inhibitory synaptic potentials from the neocortex predominate over excitatory synaptic activities; the latter are more delayed in maturation. Therefore, focal discharges have difficulty in exciting adjacent cortex.
There is greater susceptibility of the subcortical structures and hippocampus to neonatal anoxia.3 This may account for the increased susceptibility of the human newborn to subcortical seizures, such as intermittent rhythmic eye movements, apnea spells, rhythmic chewing, and pedaling motions.
One must have a high index of suspicion when a neonate exhibits bizarre transient events that are periodic. These may represent a seizure manifestation. The EEG is important in the diagnosis during the seizure, since it may give normal results between episodes. Serial EEGs are important to prognosis.
The EEG of the newborn is very different from that of the older child. Just as the neurologic exam can be used to determine the gestational age of the child, so can the EEG. The EEG patterns mature from prematurity to full term. One can date the gestational age of a normal infant. Normals must be recognized at the different ages as well as at what phase of sleep they are in during the recording. There are different patterns for wake and both quiet and paradoxical (rapid eye movement, REM) sleep on the EEG. Also, the EEG recording in the infant who is moving or sucking may have various artifacts that one needs to differentiate from cerebral potentials.
Figure 1 illustrates a normal wake EEG in the neonate. Figure 2 shows multifocal seizure discharges from each hemisphere in a neonate.
Figura 1. Normal wake electroencephalogram of a three-day-old boy.
Figure 2. Electroencephalogram showing multifocal sharp wave-and-sptke discharges from a wake tracing of a three-day-old girl with a history oi neonatal seizures.
The incidence of neonatal seizures varies in different series. One will see a higher percentage in a referral hospital than in a general hospital. Burke's series4 shows a 0.2 per cent incidence, CraigV 0,8 per cent, and Brown's6 1.4 per cent. According to Lombroso, the peak incidence of neonatal seizures is on the second day of life. Intracranial hemorrhage and cerebral contusion can often be implicated. The second highest incidence is on the first day, and that is usually due to perinatal anoxia. In many instances, convulsions can commence unexpectedly even after uneventful progress and discharge from the hospital. In a study in Edinburgh of 142 cases of neonatal seizures,6 43 per cent occurred in the first four days and 57 per cent from the fifth day until the end of the second month. Most convulsions due to brain damage occur in the first three days or after eight days of age. Metabolic seizures often have their onset between the fifth and eighth days. For any infant one cannot depend on the statistics but must properly examine the child to rule out all treatable causes, such as meningitis, sepsis, and metabolic disturbances.
The aim of the pediatrician should be to quickly rule out all remediable causes, such as hypoglycemia or meningitis, that can lead to irreversible brain damage if not corrected. Table 1 lists major causes to be considered in the differential diagnosis of neonatal seizures.
The clinical symptoms of neonatal neurologic illness are not specific. There may be episodes of tremors, cyanosis, convulsions, apnea, irregular respiration, apathy, high-pitched or weak cry, limpness, refusal to eat, or eye rolling. There is really no pathognomonic picture for any of the causes mentioned.
Specific causes. Hypocalcemia, hypoglycemia, intracranial birth injuries, perinatal anoxia, and congenital malformations are more common causes of neonatal seizures than aminoaciduria and pyridoxine dependency. In the Boston Children's Hospital series of neonatal seizures, 27 per cent were due to metabolic disturbances, 14.6 per cent to intracranial birth injuries, and 9.5 per cent to prenatal or postnatal infections, while congenital malformations and anoxic brain damage each accounted for 7 to 8 per cent of the patients. One must search for treatable causes first.
Hypoglycemia. In the full-term neonate, hypoglycemia is defined as less than 30 mg./100 ml. of glucose during the first 72 hours and less than 40 mg./lOO ml. thereafter.7 Glucose diffuses transplacentally via the umbilical vein. Cord blood glucose is generally 70 to 80 per cent of maternal blood glucose. Neonatal glucose decreases in the first four to six hours after birth and usually stabilizes at 50-60 mg./lOO ml. at full term. The factors that affect blood sugar in the infant include the time of the mother's last meal, the duration of her labor, whether the mother is receiving intravenous glucose, and lowering of the infant's body temperature.
Conditions predisposing to neonatal hypoglycemia include a diabetic or a toxemic mother, a small-for-dates baby with low glycogen stores, and an infant with intracranial bleeding or meningitis. In these conditions, hypoglycemia is usually transient. When it is persistent, one must consider galactosemia, leucine sensitivity, islet cell tumor, glycogen storage disease, and idiopathic hypoglycemia.
The examination of a child with hypoglycemia should include serial blood sugars, glucose tolerance test, urine test for reducing substance, galactose-1 -phosphate uridyl transferase assay of the blood, and, in persistent cases, insulin level, growth hormone level, catecholamines, 17-hydroxysteroids, and a glucagon stimulation test, as well as a leucine tolerance test when indicated.
Therapy includes immediate intravenous administration of glucose, followed by supplementary glucose feedings and, in some intractable cases, steroids to maintain the blood glucose.
Hypocalcemia. Hypocalcemia in the newborn may be defined as a serum calcium level below 7-8 mg./lOO ml.8 Neonatal hypocalcemia as a cause of seizures can be divided into two major groups, complicated and uncomplicated. ' Uncomplicated hypocalcemia classically refers to neonatal tetany. These infants are fed cow's milk, which has a 1:1 ratio of calcium to phosphorus - unlike mother's milk and many of the proprietary formulas, which have a 2:1 calcium-to-phosphorus ratio. The relative phosphate load in the newborn, with his immature parathyroid and renal function, can cause hyperphosphatemia with hypocalcemia, resulting in tetany or neonatal seizures. Serum phosphorus is almost always elevated to above 7 mg./100 ml. A formula with supplementary calcium is used as treatment. This hypocalcemia is usually a transient problem with a good prognosis.
ETIOLOGY OF NEONATAL SEIZURES
Complicated hypocalcemic seizures are defined as convulsions associated with a calcium of less than 7-8 mg./100 ml. and a major complication of pregnancy, labor, or delivery. The seizures may become apparent within the first 24 to 48 hours.8 Predisposing factors include prematurity, low birth weight, maternal diabetes, and toxemia.
Severe renal anomalies and exchange transfusions with citrated blood without supplementary calcium can also cause hypocalcemic seizures in the newborn. In the rare case of a mother who has latent hyperparathyroidism, the infant may have hypocalcemia and tetany from suppression of the fetal parathyroid glands during life in utero. In unexplained hypocalcemia, the mother's calcium and phosphorus should be drawn as well.8 Another rare cause of hypocalcemia in the newborn is hy popara thy roidism due to parathyroid agenesis.1,8
If hypocalcemia is intractable, one must also consider hypomagnesemia," which can accompany hypocalcemia. In such cases, magnesium is needed in addition to the calcium for therapy.
When an infant is examined for hypocalcemia, serum protein and globulin ratios should be recorded. The serum protein determines the amount of ionized and nonionized calcium. With hypoproteinemia, there may be low serum calcium without seizures or tetany, since it is the unbound calcium that is related to neuromuscular and cerebral irritability.
Pyridoxine dependency. Pyridoxine dependency, a rare autosomalrecessive defect, can be responsible for neonatal and even intrauterine seizures that are resistant to anticonvulsants. Usually the clue is a history of previous siblings' having had intractable seizures or intrauterine convulsions.10 It is felt that pyridoxine is important in the brain as part of the coenzyme pyridoxal phosphate, which mediates the reaction of an enzyme, glutamic carboxylase, in forming the compound -y-aminobutyric acid. The absence of this compound, a presumed central nervous system inhibitor, may cause convulsions. One can test for this metabolic error by assessing tryptophan metabolism and giving an increased tryptophan load. There should be an increase in xanthenuric acid. The best way to determine this in the acute situation is to inject intravenous pyridoxine into the child with convulsions; this should stop the seizures immediately and change the EEG to normal within minutes.
Aminoaciduria. After the first few days of life, when the child has been given a milk load, aminoaciduria becomes apparent. In some cases, the presence of amino acid in the mother during pregnancy has effects on the fetus. Other infants may appear normal until feedings have been started. With the protein load and its amino acids, various symptoms may ensue. Seizures become apparent from the fifth to the 10th day of life. Maple syrup urine disease, for example, is a defect in decarboxylation of the three ketoaminoacids that build up, resulting in seizures and abnormal liver function. If untreated, these babies die in the neonatal period. Another well-known example is the absence of phenylalanine hydroxylase, causing phenylketonuria. There are metabolic cliseases, such as hyperglycinemia and methylmalonic acidemia, that also include seizures among their clinical manifestations. A metabolic screening test of the urine is of utmost importance in these infants.
Hypo- and hypernatremia. Generally, abnormalities in sodium metabolism are iatrogenic. The baby may receive too much hypotonie fluid if treated intravenously after surgery or from poor feeding. Accidental hypernatremia has occurred when salt instead of sugar has been put in formulas. Adrenogenital syndrome, a rare disease, can also cause metabolic sodium imbalance.
Drug addiction and withdrawal. With the higher incidence of drug use under the age of 20 and throughout the reproductive period, the question of withdrawal seizures in the neonate becomes very important to consider in the differential diagnosis. Often the mother is malnourished, has received poor prenatal care, and may have other underlying illnesses. Infants can have withdrawal syndromes from heroin and methadone up to the fourth day and even longer with barbiturates. Between 76 and 91 per cent of infants born to actively addicted mothers manifest withdrawal symptoms, most of them displaying symptoms within the first 48 hours.11 The mortality may be high if these infants are untreated. There is a correlation between the amount of narcotic taken and the severity of the withdrawal reaction. The timing of the last dose before delivery is important.
Infants born to addicts are usually of low birth weight, often less than 2,500 gm. Clinical signs include tremors, irritability, hyperactivity, vomiting, poor feecling, high-pitched cry, diarrhea, and fever. Twitching, cyanosis, yawning, sneezing, depressed respiration, convulsions, apnea, nasal stuffiness, lacrimation, hypohidrosis, respiratory difficulties, and death have been reported in other infants. In infants of heroin addicts, the incidence of seizures is generally reported as 4 per cent, whereas those of mothers who were on methadone have a 10 per cent incidence of withdrawal seizures.11 Therapy with paregoric, barbiturates, chlorpromazine, or diazepam has been used. Patients are considered under control when body temperature is normal and the infant is seizure free and is not tremulous when dosage of the narcotic is tapered. The EEG is often normal in the routine tracing, but the sleep patterns are disturbed and paradoxical sleep and quiet sleep patterns are often not well delineated.
Kernicterus. Hyperbilirubinemia should generally be vigorously treated as needed with exchange transfusions and phototherapy. In recent years it has been rare to find a baby opisthotonic and convulsing with hyperbilirubinemia related to kernicterus in the United States, but this should still be considered in the differential diagnosis. If hyperbilirubinemia is found, its cause should be vigorously sought.
It is important to establish diagnoses for perinatal and postnatal infections.
Among prenatal infections, intrauterine rubella, toxoplasmosis, cytomegalic inclusion disease, and herpes simplex all may exhibit encephalitis and neonatal seizures. Often microcephaly, jaundice, chorioretinitis, petechiae, hepatomegaly, and intracranial calcification accompany the seizures. It is important to make the diagnosis, since in some cases therapy is available.
One of the most crucial diagnoses to establish is neonatal meningitis, which must be treated immediately. The most common organism in the neonate is E. colt. The index of suspicion for neonatal meningitis in any infant with seizures must be foremost. The cerebrospinal fluid must be examined at any sign of a seizure to rule out meningitis. One cannot wait for the usual signs - stiff neck, irritability, and tense fontanel. Poor feeding or a seizure may be the only manifestation at the onset of meningitis. Immediate treatment is essential. Sequelae of meningitis, especially if it is not treated early, are residual brain damage and hydrocephalus. Hydrocephalus occurs because, with thick purulent exudative meningitis, there is obstruction to absorption of spinal fluid by the arachnoid granulations and obstruction to flow via the incisura, resulting in communicating hydrocephalus. With neonatal bacterial meningitis, there is often a ventriculitis with glial scarring of the aqueduct that can cause an obstructive hydrocephalus. Even with prompt treatment, one must follow these babies, once the acute infection is cured, with serial head circumference and neurologic exams for evidence of neurologic damage.
A high incidence of maternal perinatal infection was proved by Berman and Banker,12 who cultured the identical organism from the mother and infant in a series of 29 infants who had meningitis in the first month. Postmortems were obtained on 25 infants. They showed inflammation with lymphocytes and plasma cells, related to immature defense mechanisms. Cortical vein thrombosis and arteritis can complicate the picture. In one-third of infants with neonatal sepsis, meningitis is a concomitant.13 In some series, up to 10 white blood cells are accepted as normal if they are lymphocytes. Polymorphs are abnormal. Cerebrospinal fluid sugar of less than half the blood sugar and any organism on smear are very suggestive evidence of meningitis even without positive cultures.
A major cause of neonatal convulsions is perinatal anoxia. Unless there is a clear-cut difficulty in delivery or fetal distress in utero, it is difficult to establish perinatal anoxia as a primary problem. It is well known that infants with neurologic damage have apnea spells more often than normal infants. Frequent apnea spells from underlying central nervous system disease can cause further damage. Anoxia is a very common problem, and the implications may not be apparent until the child is older. Certain parts of the brain, such as the hippocampus in the temporal lobe and the nuclei of the basal ganglia, are particularly vulnerable to cerebral anoxia. If seizures do not occur acutely, they may occur as a sequela in later childhood. Such temporal-lobe seizures may accompany a history of cerebral anoxia.
Birth trauma is a possible cause of neonatal seizures because the baby has been subject to the mother's labor and its complications. Even after a cesarean section, head trauma is possible, especially if cephalopelvic disproportion in the mother necessitated the surgery. Ten to 14 per cent of neonates born by vaginal delivery have some blood in the cerebrospinal fluid in the form of a few red cells or xanthochromic fluid.14 Forty per cent of newborn infants bom by vaginal delivery have been shown to have retinal hemorrhage.15
Extradural bleeding is very rare in the neonate. Subdurai hematoma is an important consideration, because in large babies and in infants born of primiparas it is twice as common as in the infants of multiparas. Subdurai hematomas are much more common with breech presentation. Most of these infants had a difficult instrument delivery, and very often the subdurals are bilateral. Seizures related to subdural hematomas usually become manifest after the first week of life. Retinal hemorrhage and progressive head enlargement - often with poor feeding, focal neurologic signs, and neonatal seizures - suggest the presence of subdural hematomas. Although transillumination may be negative, subdural taps should be performed. Subarachnoid hemorrhage can occur after uncomplicated pregnancies and, more frequently, after complicated labor. Spells of apnea and poor color may be the manifestations, along with seizures, in infants with subarachnoid hemorrhage. Gross intracerebral hemorrhage, which is less common, is more likely in the fullterm infant with prolonged labor. Intraventricular hemorrhage is much more common in the premature infant. It may be due to venous congestion and anoxia and rupture of veins in the periventricular region, which can lead to periventricular leukomalacia and brain damage. Sequelae of hemorrhage, like meningitis, include hydrocephalus.
Congenital anomalies are a cause of neonatal seizures and should be sought once remediable, metabolic, infectious, and traumatic causes have been ruled out by appropriate tests.
In the examination of an infant with neonatal seizures (Table 2)16 the history is very important, and one should determine whether there was premature rupture of the membranes predisposing to infection, a difficult delivery and birth suggesting head trauma, and a family history of metabolic dysfunction, as well as whether the mother was diabetic or a drug addict. Physical examination may show petechiae if there is any hemorrhagic tendency; hematomas on the head with a traumatic delivery; and chore o re tini ti s, hepatosplenomegaly, microcephaly, or macrocephaly if there was an intrauterine infection. Transillumination can be helpful if there are subdural effusions or hematomas. Chronically, they may transilluminate; acutely, they may not. A cyst or a malformation of the brain might show up on one side by asymmetric transillumination. Blood counts and serial hematocrits are important to document hemorrhage. Urinary sis and reducing substance in the urine once the baby has been fed, and ferric chloride and 2,4-dinitrophenylhydrazine while the amino acid chromatography is pending, are useful tests. Glucose, calcium, phosphorus, total protein with albumin -globulin ratio, magnesium, electrolytes, and blood urea nitrogen are important screening tests. A lumbar puncture is mandatory for cells, protein, sugar, smear, and culture. Cultures for sepsis are vital, since one-third of the patients with sepsis have meningitis. Skull x-rays are helpful in showing inrracranial calcification or skull fracture. The EEG can determine whether an atypical stereotyped activity is a seizure, and serial tracings can help in determining prognosis. If lack of pyridoxine caused the seizures, monitoring the EEG during pyridoxine infusions will show disappearance of the epileptiform activity. Subdural taps are particularly important if delivery was traumatic. If there is respiratory distress or evidence of cardiac anomalies, chest x-ray is indicated. ECG monitoring for bradycardia is essential during calcium infusion. Other diagnostic tests would be screening for intrauterine infection and blood and urine amino acids.
EVALUATION OF AN INFANT WITH NEONATAL SEIZURES
EMERGENCY DIAGNOSIS AND TREATMENT OF STATUS EPILEPTICUS IN NEONATES
EMERGENCY TREATMENT OF STATUS EPILEPTICUS
The emergency treatment of status epilepticus in the newborn (Table 3)16 includes the immediate determination of blood sugar, calcium, phosphorus, blood urea nitrogen, magnesium, total protein, albuminglobulin ratio, and electrolytes. A lumbar puncture should be done immediately, to make sure there is no meningitis. If there is no evidence of meningitis or hemorrhage to explain the seizures, one should give diagnostic infusions and, if possible, monitor with EEG. An intravenous should be running, and one should immediately inject glucose (5-10 cc. of 20 to 30 per cent solution) and observe the baby's response. If this is effective, seizures will stop within two to five minutes. If there is no improvement within 10 minutes, 25-50 mg. of pyridoxine can be injected intravenously. If the pyridoxine produces no change, with ECG monitoring for bradycardia, a 2.5 per cent solution of calcium gluconate in a dose of 2-6 cc. should be slowly injected intravenously, to avoid infiltration. If this infusion does not stop the seizures, 2 to 3 per cent magnesium sulfate in a dose of 2-6 cc. can be given intravenously. If none of these measures work, one can slowly inject 0.2-1.0 mg. of diazepam* (Valium®) intravenously, watching respiration and heart rate. Always, when one is treating status epilepticus, one must be ready to intubate and resuscitate. A total of 2-3 mg. of diazepam may be given in successive doses; this may be repeated later if seizures recur. Respiratory and cardiac rates must be watched closely.
One may use phenobarbital instead of diazepam; it should be slowly injected intravenously in doses of 5-15 mg./kg. over several minutes, again monitoring respiration. Diazepam and phenobarbital should not be given together intravenously, since they can synergistically depress respiration.
PROGNOSIS IN NEONATAL SEIZURES
Data are very meager on the outcome for children who have had neonatal seizures. Although there are studies showing percentages of normal or abnormal children, most of mese children are followed only for the first few years before school age. In earlier studies, moreover, no effort was made to divide the outcome according to etiology. Knowing the cause of the seizures really tells a great deal about the prognosis. For example, the child who has had neonatal hemorrhage or meningitis does poorly compared with one who had transient neonatal hypocalcemia.
The neurologic exam is not very helpful in predicting neurologic deficits in the neonate. In fact, in the first four months of life, a hydranencephalic infant may appear normal at neurologic examination, since one is testing only brain-stem function. Even signs of depressed neonatal reflexes can be progrvostically unreliable, because the child may do well in spite of examination results.
Prolonged, therapeurically resistant seizures are usually related to significant cerebral dysfunction if metabolic and other remedial causes have been eliminated. This resistant group generally has a more unfavorable outlook.
Recently, Lombroso stated that the EEG is very helpful in determining prognosis. A French group, Dreyfus-Brisac and Monod/7 have also confirmed the use of the EEG as a prognostic tool. Prichard,18 too, has shown a strong correlation between EEG and results. The EEG during the episode may be abnormal, and thus helpful in documenting a seizure, but the interictal EEG is also valuable in helping to predict results on a statistical basis.
In Rose and Lombroso's study, it was found that if an infant had a normal EEG between seizures in the first week of life, he had an 86 per cent chance of being normal and having no seizure disorder at age four years. If the EEG was grossly abnormal, multifocal, periodic, or flat, the child had only a 7 per cent chance of being nonnal and without seizures at the age of four years. One must not depend solely upon the EEG, however, for prognosis in any given patient. It is more reliable to take serial EEGs than to be completely influenced by one tracing.
In general, when reviewing the literature, one must evaluate the studies of neonatal seizures and look for the varying proportion of prematures - which, if high, will skew the study toward poor prognosis. Assessing the length of follow-up is also difficult. It is important to know about follow-up once the child has achieved school age. Will such children have "minimal brain dysfunction," which may not show up until school age? Is the study prospective or retrospective? Also, was the study done after new techniques of resuscitation and drug therapy were instituted? There may be more survivors now, since more marginally functional babies can be helped. Will these babies have residual brain damage or, with newer methods and earlier diagnosis, will more of them have normal function? Also, the criteria for the EEG in earlier studies often specified only normal or abnormal function, with very vague descriptions. The more recent studies from France and the United States specify classification of the EEG by the abnormality.
In Rose and Lombroso's study of 137 full-term neonates with seizures, 50 per cent were normal, 30 per cent had serious neurologic deficits, and 20 per cent had died by the age of four years.
In the infant with neonatal seizures, one must not rely upon statistics but, rather, should examine that infant immediately for any remediable cause of the seizures. Prompt therapy may make the difference between a retarded, brain-damaged, epileptic child and a normally functioning child, particularly in the cases of neonatal hypoglycemia and neonatal meningitis.
Neonatal seizures differ from convulsions in the older child and adult in five major respects.
1. Clinical pattern
2. Most common causes
3. EEG correlates
4. Mode of therapy
Seizures are difficult to diagnose in the neonate because one observes fragmentary seizures. One must learn to look for parts of a seizure and repetitive, stereotyped movements. Metabolic and infectious diseases and trauma are remediable causes that must be considered. Focal seizures are usually a sign of metabolic or diffuse brain damage, rather than a focal lesion. The EEG findings in normal wake and sleep states, and even some of the seizure patterns, are different in the neonate from those in the more mature individual. One approaches status epilepticus in the neonate by trying to rule out meningitis and metabolic defects by spinal tap and diagnostic metabolic infusions initially, rather than by drug therapy. The prognosis differs, depending mainly upon the cause of the seizures.
1. Rose, A.L. andLombroso, C.T. Neonatal seizure states. Pediatrics 45 (1970), 404.
2. Purpura, D.B. Stability and seizure susceptibility of immature brain. In Jasper. H.H., Ward, A.A., and Pope, A. eds.}. Basic Mechanisms ot the Epilepsies. Boston: Little, Brown & Company, 1969, p. 517.
3. Freeman. J.M. Neonatal seizures - Diagnosis and management. J. Pediatr. 77 (1970). 701.
4. Burke, J, B. The prognostic significance of neonatal convulsions. Arch. Dis. Child. 29 (1954), 342.
5. Craig. W.S. Convulsive movements occurring in the first 10 days of life. Arch. Dis. Child. 35 (1960), 336.
6. Srawn, J.K., Cockbum, F.. and Forfar, J.O. Clinical and chemical correlates in convulsions of the newborn. Lancef I (1972), 135.
7. Comblath, M. , and Schwartz, R. Disorders of Carbohydrate Metabolism in Infants, Volume III: Major Problems in Clinical Pediatrics. Philadelphia and London: W.B. Saunders Company, 1966.
8. Mizrachi, A., London, D., and Gribetz, D. Neonatal hypocalcémie; its causes and treatment. N. Engl. J. Med. 278 (1968), 1163.
9. Davis, J.A., Harvey, D.R., and Yu, J,S. Neonatal fits associated with hypomagnesemia. Arch. Dis. Child. 40(1965). 286.
10. Bejsovec, M., Kulenda, Z., and Ponco. E. Familial intrauterine convulsions in pyridoxine dependency. Arch. Dis. Child. 42 (1967), 201.
11. Zelson. C, Sook, J. L.. and Casalino, M. Neonatal narcotic addiction; Comparative effects of maternal intake of heroin and methadone. N. Engl. J. Med. 289 (1973). 1216.
12. Berman, P.M., and Banker, B.O. Neonatal meningitis. Pediatrics 38 (1966), 6.
13. Gotoff, S.P., and Behrman, R.E. Neonatal septicemia. J. Pediatr. 76 (1970). 142-153.
14. Ford, F.R. Diseases of the Nervous System in Infancy, Childhood and Adolescence. Springfield, III.: Charles C Thomas, 1966, p. 1030.
15. Grossman, M. The newborn infant. In Bamett, H.L. (ed.). Pediatrics. New York: Appleton-CenturyCrofts, 1972, p. 80.
16. Solomon, G.E., and Plum. F. Clinical Management of Seizures: A Guide for the Physician. Philadelphia; W.B. Saunders Company (in press).
17. Dreyfus-Brisac. C.. and Monod, N. Electroclinical studies o( status epilepticus and convulsions in the newborn. In Kellaway, P,, and Petersen, I. (eds,), Neurological and Electroencephalographic Correlative Studies in Infancy. New York; Grune & Stratton, 1964. p. 250.
18. Prichard. J. S. The character and significance of epileptic seizures in infancy, in Kellaway, P., and Petersen. I. (eds.). Neurological and Electroencephalographic Correlative Studies in Infancy. New York: Grune & Stratton, 1964. p. 273.
ETIOLOGY OF NEONATAL SEIZURES
EVALUATION OF AN INFANT WITH NEONATAL SEIZURES
EMERGENCY DIAGNOSIS AND TREATMENT OF STATUS EPILEPTICUS IN NEONATES