Apneic Seizures Research Articles

GABRB1-related early onset developmental and epileptic encephalopathy: Clinical trajectory and novel de novo mutation.

Developmental and epileptic encephalopathy 45 (DEE45) is a neurogenetic disorder caused by heterozygous pathogenic variants of GABRB1, encoding the beta1 subunit of the GABA type A receptor. Only three infants with DEE45 have been reported so far, and a detailed description of the disease history of these patients is still lacking. We describe the clinical and genetic findings of a 21-year-old woman with DEE45 carrying a novel de novo GABRB1 mutation (c.841A>G, p.T281A). The patient presented at birth with hypotonia and focal apneic seizures evolving in a phenotype of epilepsy of infancy with migrating focal seizures that were refractory to antiseizure medications. Epileptic spasms partially responsive to steroid therapy appeared in the second year of life. Acquired microcephaly, profound mental retardation, and tetraparesis became evident with development. During childhood and adolescence, the epileptic phenotype evolved toward a Lennox-Gastaut Syndrome. Atypical absence status and clusters of tonic seizures occurred, often triggered by respiratory infections. The main strengths of this work are the identification of a novel pathogenic GABRB1 variant localized in the same transmembrane domain of a previously described mutation and the detailed description of the clinical trajectory of GABRB1-related encephalopathy along 21 years of disease history.

Joubert Sendromu ve Biot Solunumunun Epilepsi Olarak Yanlış Teşhisi

Joubert syndrome (JS) is a rare ciliopathy characterized by neurodevelopmental delay and irregular breathing patterns. Here we present a patient with JS, who was misdiagnosed as having epilepsy. A five year-old girl with JS was referred due to excessive daytime sleepiness. She was diagnosed as having apneic seizures, and given antiseizure medications with no benefit. Apneas were present during wakefulness lasting for more than one minute, with sudden myoclonic jerks characterized by the extension of the body and the flexion of the limbs at the resume of respiration with paradoxical breathing, hyperventilation and tachypnea. A full-night polysomnography (PSG) revealed pediatric obstructive and central sleep apnea syndromes. The patient was effectively treated by adaptive servo ventilation therapy. Respiratory control disturbances are commonly encountered in the children with JS. Although routine electroencephalography may be helpful in differentiation of the apneas of epileptic origin, polygraphic recordings and/or PSG better delineate the pathophysiology.

Prolonged Video-EEG and Heart Rate Variability can Elucidate Autonomic Dysregulation in Infantile Apneic Seizures

BackgroundInfantile apneic seizures (IASs) are unexpected life-threatening events. We aimed to determine the utility of prolonged video-electroencephalography (vEEG) and heart rate variability (HRV) in IAS. MethodsThe study included seven infants with apneic seizures captured by vEEG, percutaneous oxygen saturation (SpO2), and electrocardiography (ECG). Interictal, preictal, and postictal HRV of patients and N2 sleep HRV of 10 age-matched controls were determined. ResultsWe analyzed seven vEEGs (duration = 17 to 87 hours) of seven patients aged three to 13 months (mean onset age of apneic event = 6.3 months). Fifteen apneic seizures (one to five per infant) were captured. The initial apneic seizure was captured at 7.5 to 76 hours (mean = 36.6 hours) after vEEG initiation. Ictal rhythmic delta/theta/fast waves were seen over temporal (five patients), central (one), and diffuse areas (one). Ictal SpO2 decreased between 1.5% and 90% (mean = 47.9%). Ictal decreased heart rate (HR) (six seizures) and ictal increased HR (14) was detected. Both decreased and increased HR was observed (five). The preictal low-frequency (LF)/high-frequency (HF) ratio was significantly higher than the interictal LF/HF ratio (P = 0.048). Preictal (P = 0.048), and postictal (P = 0.019) root mean square of successive differences (RMSSDs) of patients were lower than the sleep RMSSD of controls. These results indicated dominant sympathetic activity. RMSSD from interictal to preictal periods tended to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.066). The postictal RMSSD showed tendency to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.088). The decreased HR and increased RMSSD suggested not only sympathetic activity but also escalated parasympathetic activity in IAS. ConclusionsInfants with unexpected apneic events should be monitored with prolonged vEEG, SpO2, and ECG. Abnormal HRV in infants with apneic seizures might indicate additional autonomic dysregulation in IAS.

Apneic Seizures in a Child with Achondroplasia.

Apneic Seizures in a Child with Achondroplasia.

Intracranial Hemorrhage resulting in Apneic Seizures in a Full-term infant: A Case Report and Review of Literature

Symptomatic spontaneous intracranial hemorrhage is rare in term neonates and the literature available on this subject is limited. In this case report, we present the clinical presentation, imaging findings and clinical course of a term neonate with neonatal seizures who was found to have intracranial hemorrhage. The available literature on this has been briefly reviewed and imaging findings and management of these newborns has been discussed in brief.

Amygdala and hippocampus are symptomatogenic zones for central apneic seizures.

To identify limbic sites of respiratory control in the human brain, and by extension, the symptomatogenic zone for central apnea. We used direct stimulation of anatomically, precisely placed stereotactic EEG electrodes to analyze breathing responses. We prospectively studied 3 patients who were explored with stereotactically implanted depth electrodes. The amygdala and hippocampus, as well as extralimbic sites (orbitofrontal, temporal tip, and temporal neocortex), were investigated. Individual stimulation of the amygdala and hippocampal head consistently elicited central apnea in the expiratory phase, as did exquisitely focal hippocampal seizures. These findings confirm that hippocampus and amygdala are limbic breathing control sites in humans, as well as the symptomatogenic zone for central apneic seizures.

The Puzzle of Apparent Life-Threatening Events in a Healthy Newborn

Apneic neonatal seizures can present as apparent life-threatening events. We report a newborn with unexplained episodes of apnea associated with cyanosis and desaturation, starting on the first day postpartum. Biochemical tests were normal. Central nervous system infections as well as abnormalities of upper airways and cardiovascular system were excluded. Brain monitoring using amplitude-integrated electroencephalography (aEEG) was inconclusive. Continuous monitoring using video EEG revealed epileptic seizures originating from the left temporal region as the cause of the apneas. Magnetic resonance imaging (MRI) of the brain showed a developmental malformation of the left frontal and temporal lobes. The patient became seizure free after treatment with antiepileptic medication. This report illustrates that brain monitoring using amplitude-integrated EEG alone could miss focal neonatal seizures. When clinical suspicion of apneic seizures is high in infants with apparent life threatening events, multichannel polygraphic video-EEG monitoring is indicated. Prompt diagnosis and treatment can be life saving.

Intracranial hemorrhage in full-term newborns: a hospital-based cohort study

IntroductionIn recent years, intracranial hemorrhage (ICH) with parenchymal involvement has been diagnosed more often in full-term neonates due to improved neuroimaging techniques. The aim of this study is to describe clinical and neuroimaging data in the neonatal period and relate imaging findings to outcome in a hospital-based population admitted to a level 3 neonatal intensive care unit (NICU).MethodsFrom our neuroimaging database, we retrospectively retrieved records and images of 53 term infants (1991–2008) in whom an imaging diagnosis of ICH with parenchymal involvement was made. Clinical data, including mode of delivery, clinical manifestations, neurological symptoms, extent and site of hemorrhage, neurosurgical intervention, and neurodevelopmental outcomes, were recorded.ResultsSeventeen of the 53 term infants had infratentorial ICH, 20 had supratentorial ICH, and 16 had a combination of the two. Seizures were the most common presenting symptom (71.7%), another ten infants (18.9%) presented with apneic seizures, and five infants had no clinical signs but were admitted to our NICU because of perinatal asphyxia (n = 2), respiratory distress (n = 2), and development of posthemorrhagic ventricular dilatation (n = 1). Continuous amplitude-integrated electroencephalography recordings were performed in all infants. Clinical or subclinical seizures were seen in 48/53 (90.6%) infants; all received anti-epileptic drugs. Thirteen of all 53 (24.5%) infants died. The lowest mortality rate was seen in infants with supratentorial ICH (10%). Three infants with a midline shift required craniotomy, six infants needed a subcutaneous reservoir due to outflow obstruction, and three subsequently required a ventriculoperitoneal shunt. The group with poor outcome (death or developmental quotient (DQ) <85) had a significantly lower 5-min Apgar score (p = .006). Follow-up data were available for 37/40 survivors aged at least 15 months. Patients were assessed with the Griffiths Mental Developmental Scales, and the mean DQ of all survivors was 97 (SD = 12). Six infants (17%) had a DQ below 85 [two of them had cerebral palsy (CP)]. Three infants developed CP (8.6%); one had cerebellar ataxia, and two had hemiplegia.ConclusionICH with parenchymal involvement carries a risk of adverse neurological sequelae with a mortality of 24.5% and development of CP in 8.6%. The high mortality rate could partly be explained by associated perinatal asphyxia. Infants with supratentorial ICH had a lower, although not significant, mortality rate compared with infants with infratentorial ICH and infants with a combination of supratentorial ICH and infratentorial ICH. In spite of often large intraparenchymal lesions, 30 of the 34 survivors without CP (88.2%) had normal neurodevelopmental outcome at 15 months.

Apneic Seizures: A Sign of Temporal Lobe Hemorrhage in Full-Term Neonates

Intracranial hemorrhage is a common cause of neonatal seizures in full-term infants. However, only some infants with intracranial hemorrhage come to clinical attention. A right temporal lobe hemorrhage with resulting apneic seizures was described previously in one neonate. In this case report, we review three full-term male neonates with no significant perinatal complications who presented with apneic events and temporal lobe hemorrhage. One neonate had apnea as the sole manifestation of a seizure that was confirmed electrographically. One neonate had motor manifestations of seizures, in addition to apnea, that were confirmed as seizures electrographically. The third neonate had pure apneic events before initiation of electroencephalogram monitoring which were presumed to be seizures, because the electroencephalogram demonstrated epileptiform abnormalities. At follow-up, all three children were neurodevelopmentally normal. This case report emphasizes that, although uncommon, full-term neonates may present with apnea as the initial manifestation of temporal lobe hemorrhage. Because apnea could be a manifestation of a seizure, continuous electroencephalogram monitoring should be considered in a full-term neonate with unexplained apnea.

Partial Epilepsy Presenting as Apneic Seizures Without Posturing

Apnea is a symptom present in many conditions. During the neonatal period, apnea has been associated with epileptiform activity in the absence of posturing. However, the occurrence of apneic seizures without posturing beyond the neonatal period is an uncommon presentation for partial epilepsy. The aim of this case report is to present a rarely documented cause of apnea and desaturation in an otherwise healthy 24-month-old child. Further investigations revealed that the etiology of the spells was partial seizures originating in the right anterior midtemporal region. Polysomnography with extended electroencephalography and video is the gold standard tool to evaluate patients with apnea due to suspected seizures.

Apparent life-threatening episodes as the first manifestation of epilepsy

Nunes ML, Appel CC, da Costa JC (Hospital São Lucas, Porto Alegre, Brazil) An apparent life-threatening episode (ALTE) is characterized by some combination of apnea, color alteration (usually pallid), a change in muscle tone (usually marked limpness), choking, or gagging. In young children, an ALTE may be an unrecognized initial manifestation of an epileptic seizure. Six cases are reviewed in which children seen between the ages of 2 months and 30 months with ALTEs were subsequently found to have epilepsy. A 4-month-old girl was admitted for cardiorespiratory monitoring after experiencing apnea, pallor, and staring. An uncle and a cousin of the child (both on the father's side) had epilepsy. Neurologic examination findings, neuropsychomotor development, and the results of an ECG, an electroencephalogram (EEG), and a brain computed tomographic (CT) scan were all normal. Treatment for mild gastroesophageal reflux was started based on results of a polysomnographic recording with esophageal pH monitoring. The spells recurred during hospitalization, however, and an ictal seizure was eventually noted when the child underwent a second polysomnographic recording. Another EEG 2 months later showed focal spikes in the left temporal region. Valproate controlled seizures for 2 years, but the seizures reappeared 3 months after the drug was discontinued. The parents refused further studies, but the child has remained seizure free for more than 1 year with normal development. Approximately 50% of infants with an ALTE receive a specific diagnosis, but the cause of the episode is unknown in the remaining 50%. Because a normal-appearing EEG does not exclude epileptic seizures, epilepsy as a manifestation of ALTE can be a diagnostic challenge. An apneic spell may be the only indication of apneic seizures or partial seizures. ALTE is considered any episode that is characterized by apnea, color changes, marked change in muscle tone, choking, or gagging. Any infant presenting to the emergency department with such symptoms is concerning enough to warrant observation and workup. It is not uncommon to find that gastroesophageal reflux is the only significant finding in the workup. This article discussed several cases in which the cause of ALTE was epilepsy. This is a diagnostic challenge because the apneic spell may be the only sign of apneic or partial seizures. Still, our emergency department management remains the same, although seizures could be higher in our differential diagnosis.

Apneic seizures in infants: role of continuous EEG monitoring.

Respiratory compromise is not uncommon in epileptic seizures. However, pure apneic seizures are rare. In this study, we report 10 children who presented with pure apneic seizures. All the children were admitted because of apneic events. Seizures were also considered in the differential diagnosis. Six patients had nonspecific findings consisting of multifocal interictal epileptiform activity with no event correlation. Continuous 24-72 hours electroencephalogram (EEG) was performed in all patients to rule out apneic seizures. Ictal EEG showed high correlation with the apneic episodes, confirming the diagnosis of apneic seizures. Our study suggests that continuous EEG monitoring is essential in the diagnosis and treatment of apneic seizures.

A Case of Alternating Hemiplegia of Childhood With Cerebellar Atrophy

A case of alternating hemiplegia of childhood is reported. Tonic fits and generalized tonic-clonic seizures developed during her infancy. Frequent twitching and apneic seizures appeared at 16 years of age. Zonisamide transiently suppressed the tonic, twitching and apneic seizures, as well as the facial and neck dystonia. Cranial computed tomography and magnetic resonance imaging revealed progressive vermian atrophy. Cerebellar dysfunction may play a role in the clinical features of some patients with alternating hemiplegia of childhood.

Apneic seizures with EEG decrement and bradycardia in an infant

A 5-month-old infant presented with episodes of apnea, cyanosis, and bradycardia. Initial investigations showed signs of esophageal reflux without interictal EEG abnormalities. Symptoms continued to recur despite treatment of the reflux. Continuous video/EEG monitoring revealed apneic seizures that were different from those previously described.

Apneic seizures in newborns

Apneic seizures in newborns

Diagnostic and prognostic value of polysomnography in term and preterm newborns following apneic seizures : J.C. Costa, M.L. Nunes, D.B. Nora, J. Becker and K.K. Lopes (Hospital São Lucas, School of Medicine, PUCRS)

We examined the relationship between MRI lesions and electro-clinical findings with special attention to the localising value of aura sensations and the sides of interictal epileptiform discharges in 327 patients with symptomatic localisation-related epilepsy. As a result, while autonomic as well as psychic auras were correlated with temporal lesions, simple motor seizures were associated with extra-temporal ones. Within the group of patients with temporal lobe epilepsy, autonomic but not psychic auras concurred significantly more often with medial temporal structural lesions. Furthermore, there was a significant difference between concordance rates between sides of MRI lesions and EEG foci as a function of laterality: while the right-sided MRI lesions constantly showed ipsilateral EEG foci, EEG foci concurring with the left-sided MRI lesions proved to be often falsely lateralising. From these results, we assumed that lateral as well as medial temporal involvement is needed in the genesis of the psychic aura in contrast to the autonomic aura, which could be induced without lateral temporal involvement, and lesions in the left hemisphere are more apt to induce secondarily epileptogenic than those in the right hemisphere.

Apneic seizures in newborns: a prospective clinical investigation : J.C. Costa, M.L. Nunes, D.B. Nora, J. Becker and D.K. Lopes (Hospital São Lucas, School of Medicine, PUCRS)

Apneic seizures in newborns: a prospective clinical investigation : J.C. Costa, M.L. Nunes, D.B. Nora, J. Becker and D.K. Lopes (Hospital São Lucas, School of Medicine, PUCRS)

Apneic seizures with bradycardia in a newborn

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.

Cassette electroencephalographic recording of neonates with apneic episodes

To evaluate the practical importance of seizures as a cause of neonatal apnea, we obtained extended cassette electroencephalographic recording for periods as long as 24 hours from 50 neonates experiencing apneic episodes unassociated with clinical seizure activity. Electroencephalographic recording through definite apneic episodes was obtained in 37 neonates; a total of 153 episodes were detected. None was associated with electroencephalographic seizure activity, although one term neonate without documented apneic episodes had seizure activity detected by cassette electroencephalography and may have had apneic seizures. The episodic apnea and bradycardia commonly encountered in preterm neonates is unlikely to be a manifestation of seizure activity, and extended electroencephlographic monitoring of such patients is of low yield.

The prognostic value of EEG in neonatal meningitis.

EEG recordings were made polygraphically in 29 newborn infants with meningitis. Visual and auditory evoked potentials, and CT scans were also obtained in some of them. The neonatal findings of these examinations were well correlated with the clinical outcome. Background EEG activity was a good prognostic tool but could not indicate the type of complications, although persistent abnormality correlated with severe brain damage or development of complications. The polygraphically recorded EEG was of great value to diagnose the apneic seizures often encountered in neonatal meningitis.