Apneic seizures with bradycardia in a newborn

l Epilepsy 1991;4073-180 © 1991 Demos ~ o n s

Apneic Seizures with Bradycardia in a Newborn Sandra L. Helmers, 1Mitchell J. Weiss, and Gregory L. Holmes

A neonate presented in the first week of life with episodes of apnea, cyanosis, and bradycardia in association with feeding. EEG evaluation with polygraphic recording revealed apneic seizures. The initial electroclinical features showed apnea and bradycardia, associated with an isoelectric record. These features have not been described before in association with convulsive apnea. Key Words: Apnea--Neonatal seizures--Isoelectric EEG--Bradycardia.

Apnea in the newborn is a common occurrence. It is associated with many underlying disorders such as metabolic disturbances, sepsis, primary respiratory problems, gastroesophageal reflux, and atypical neonatal seizures. We present the case of a neonate with episodes of convulsive apnea. This patient illustrates the difficulty of establishing the underlying pathophysiology of apnea and the value of EEG with polygraphy. Several features of these apneic seizures are atypical compared to those previously described.

Case Report This infant boy was the 4.3-kg product of an uncomplicated, full-term pregnancy and spontaneous vaginal delivery from a 36-year-old gravida three, para three, white woman. Apgar scores were 9 at 1 min and 9 at 5 min. Analysis of cultured amniotic fluid cells revealed a normal 46 X, Y karyotype. Family history was unremarkable. On the third day of life, he had the first episode of apnea, cyanosis, and grunting with questionable limpness during feeding. PhenoReceived September 17, 1990; accepted May 1, 1991. From the Departments of Neurology and 1Pediatrics, The Children's Hospital, Harvard Medical School, Boston, MA, U.S.A. Address correspondence and reprint requests to Dr. S. L Helmers at Neurophysiology Laboratory, The Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, U.S.A.

barbital was begun for the possibility of seizures. A sepsis workup at this time including cerebrospinal fluid (CSF) examination was negative. A metabolic evaluation included urine and amino acids, blood glucose, and ammonia, all of which were normal. Urinary organic acids were normal except for a mild elevation in beta-hydroxybutyric acid. Cranial ultrasound, computed tomography (CT) of the head without contrast medium, and two EEGs were normal. A gastrointestinal (GI) workup included a barium swallow and upper GI series, both of which were normal. The baby did well for 9 days but was then readmitted to the hospital for further eposides of apnea and abnormal motor activity after feedings. These episodes occurred three to five times per day usually within one hall hour of feeding and lasted up to 30 min. They were characterized by a sudden change in facial expression, stiffening of the body, and deviation of the eyes and head to one side or the other with apnea. Repeat laboratory studies, including serum electrolytes, arterial plasma lactate, amino and organic acids, CSF examination for cells, and glucose and protein, and noncontrast-enhanced head CT were all unremarkable. A pH probe study revealed moderate esophageal reflux, but the spells were not associated with a significant lowering of the esophageal pH. At I month of age, the infant was transferred to our institution for evaluation of these episodes. Weight and head circumference were 90th percentile for age. The neurological examination was normal. Labora] EPILF,PSY, VOL. 4, NO. 3, 1991

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Figure 1. Sixteen-channel EEG with nasal and thoracic respiratory monitoring, lateral eye movement monitors, and EKG channel. A" Onset of a seizure signaled by a cry and sudden stiffening. B" Apnea and bradycardia occur within 3-5 s of the cry. EEG becomes isoelectric during this period. •

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rate slowing from approximately 160 to 60 beats/min. Apneic spells, evidenced by the absence of nasal airflow, were seen at about the same time as the bradycardia. During this period of bradycardia and apnea, the EEG became isoelectric. After 20-30 s the heart rate and respirations returned to baseline. The EEG continued to be very low in amplitude (<20 I~V) for periods up to 20-30 min. The low-voltage EEG was replaced by rhythmic theta activity over the right hemisphere representing an electrographic seizure. Following the end of the episode, the EEG showed a burst-suppression pattern consisting of bursts of high amplitude, sharply contoured delta, and theta activity following periods of background attenuation. After a period of 30-60 min, the EEG returned to a background appropriate for age, both awake and asleep. The baby was diagnosed as having neonatal apneic seizures with associated bradycardia. Phenobarbital was restarted within immediate decrease in the number of seizures. Over the next 7 months, the infant went on to develop generalized tonic, tonic-clonic, and complex partial seizures. The associated apnea and bradycardia gradually ceased. In addition, he has become

Figure 3. Continuation of the same seizure. EEG shows generalW

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tory evaluation was unrevealing. The serum amino acids were mildly and nonspecifically elevated. A serum lactate was 5.4 (0.5-2.2 mmol/L) and pyruvate was 0.41 (0.3-0.7 mg/dl). A repeat arterial plasma lactate was normal. Urine organic acids were normal and CSF studies, including lactate, glycine, and amino acids, were unremarkable. Electron microscopy of a skin biopsy was negative for inclusion bodies. Lysosomal enzymes from skin fibroblast cultures were normal. Brainstem auditory evoked potentials and a magnetic resonance imaging scan of the head were normal. An esophageal pH probe showed mild reflux that occurred after the onset of the spells. A cardiac evaluation that included a cardiology consultation, chest radiographs, and continuous bedside electrocardiographic (EKG) monitoring were unremarkable. Continuous video/EEG monitoring was undertaken, and phenobarbital was discontinued during this procedure. During continuous video/EEG monitoring with EKG, pneumogram, and pH probe, multiple, stereotyped events were recorded. A typical event (see Figs. 1-5) began with a cry and sudden stiffening. Within 3-5 s, bradycardia was noted, with the heart

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Figure 4. Continuation of the same seizure. EEG shows a right hemispheric electrographic seizure consisting of rhythmic theta activity. Respiration and heart rate remain at baseline. j EPILEPSY, VOL. 4, NO. 3, 1991

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hypotonic with profound developmental delay. The etiology of his illness remains unclear. Reexamination of his blood and CSF at age 8 months has failed to identify a metabolic basis of his illness. Magnetic resonance imaging of the brain revealed hypomyelination. A follow-up continuous video/EEG study at age 8 months (see Figs. 6-9) showed an initial decremental response with stiffening. This was followed by generalized rhythmic delta and theta activity. This activity was replaced by generalized slow spike-and-wave activity more prominent over the left hemisphere. A burst suppression pattern replaced the slow spikeand-wave activity at the end of the seizure.

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Figure 5. End of the same seizure. EEG shows a burst suppression pattern with the bursts consisting of generalized, high-amplitude, sharply contoured delta and theta activity.

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The etiology of apnea in the newborn can be difficult to ascertain. Polygraphy with EEG can confirm the diagnosis of subtle neonatal seizures as illustrated by this case. This patient demonstrates several atypical features not previously described in neonatal seizures with apnea. First, an isoelectric ictal pattern is unusual. Rhythmic or repetitive epileptiform activity as the initial ictal event on the EEG is more typically observed. Watanabe et al. (1982) reported rhythmic alpha-like

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Figure 9. Continuation of the same seizure. A burst suppression pattern replaces the slow spike-and-wave activity at the cessation of the seizures. J EPILEPSY, VOL. 4, NO. 3, 1991

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activity during apneic seizures in 15 of 21 infants they studied. The other ictal patterns observed were repeated sharp waves, rhythmic theta or delta waves, and repeated, stereotyped, paroxysmal wave complexes. M o n o d et al. (1) reported one case of focal alpha-like activity. One might also argue that the ictal pattern seen in this patient is similar to ictal patterns seen in tonic seizures, namely an electrodecremental pattern. In one aspect, it is similar in that there is a flattening of the background. The flattening in a tonic seizure typically lasts from a few seconds to 1 min. Unlike a tonic seizure, this patient had very prolonged periods of flattening up to 30 min without clinically associated tonic activity. Therefore, this seems unlikely to represent tonic seizures. Second, this patient had a generalized ictal EEG pattern in contrast to most cases of convulsive apnea, which demonstrated focal ictal activity, most commonly in the temporal areas as opposed to central areas in other types of neonatal seizures (2-5). Finally, bradycardia with convulsive apnea is unusual. Navalet et al. (4) described one patient with short episodes of bradycardia (heart rate, 60/min) that occurred a few seconds after the onset of apnea

and a focal ictal EEG discharge. In contrast, Watanabe et al. (2) and Fenichel et al. (6) reported no significant bradycardias in 25 patients with convulsive apnea. Fenichel et al. (6) stated that prolonged convulsive apnea did not occur in conjunction with bradycardia. One could wonder if the apnea, bradycardia, and EEG pattern of our patient represents a secondary response to an autonomic event or cerebral hypoperfusion such as that seen with pallid infantile syncope or ocular compression. In the EEG recording during ocular compression (see Figs. 10-12), bradycardia/ asystole occurs within a few seconds of compression. The EEG does not show flattening until many seconds later and remains fiat for only a few minutes. In our patient, the onset of flattening of the EEG preceded the bradycardia and apnea by 3-5 s (see Fig. 1A). The isoelectric pattern could continue for periods of up to 20-30 min with return of a normal heart rate and respirations well before the EEG returned to baseline. These seizures also occurred spontaneously without any type of autonomic stimulus. Lastly, this patient over the next few months went on to develop clearly epileptic EEG activity at the onset of these spells. In conclusion, this patient illustrates the utility of ] EPILEPSY, VOL. 4, NO. 3, 1991

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EEG and p o l y g r a p h y in establishing the diagnosis of apneic seizures and presents different electrochemical features than previously described. The initial EEG changes in convulsive apnea m a y be very low voltage or isoelectric in a generalized distribution. Bradycardia m a y also be a p r o m i n e n t early component of this seizure.

References 1. Monod N, Peirano P, Plouin P, Sternberg B, Bouille C. Seizure-induced apnea. Ann N Y Acad Sci 1988;533: 411-20.

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2. Watanabe K, Haram K, Miyazaki S, Hakamada S, Kuroyanagi M. Apneic seizures in newborn. Am J Dis Child 1982;136:980-4. 3. Watanabe K, Haram K, Hakamada S, et al. Seizures with apnea in children. Pediatrics 1982;79:87-90. 4. Navelet Y, Wood C, Robieux I, Tardieu M. Seizures presenting as apnea. Arch Dis Child 1989;64:357-9. 5. Navelet Y, Spire JP. Seizures and apnea secondary to neonatal hypoxia. Electroencephalogr Clin Neurophysiol 1975;39:435. 6. Fenichel GM, Olson BJ, Fitzpatrick JE. Heart rate changes in convulsive and nonconvulsive neonatal apnea. Ann Neurol 1979;7:577-82.