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EEG Monitoring of the Epileptic Newborn

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EEG Monitoring of the Epileptic Newborn Current Neurology and Neuroscience Reports (2020) 20:6 https://doi.org/10.1007/s11910-020-1027-7 PEDIATRIC NEUROLOGY (WE KAUFMANN, SECTION EDITOR) EEG Monitoring of the Epileptic Newborn Francesco Pisani1 & Carlotta Spagnoli2 & Carlo Fusco2 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Purpose of Review Although differentiating neonatal-onset epilepsies from acute symptomatic neonatal seizures has been increasingly recognized as crucial, existing guidelines, and recommendations on EEG monitoring are mainly based on acute symptomatic seizures, especially secondary to hypoxic-ischemic encephalopathy. We aimed to narratively review current knowl- edge on neonatal-onset epilepsies of genetic, metabolic, and structural non-acquired origin, with special emphasis on EEG features and monitoring. Recent Findings A wide range of rare conditions are increasingly described, reducing undiagnosed cases. Although distinguishing features are identifiable in some, how to best monitor and detect less described etiologies is still an issue. A comprehensive approach considering onset, seizure evolution, ictal semiology, clinical, laboratory, EEG, and neuroimaging data is key to diagnosis. Summary Phenotypic variability prevents precise recommendations, but a solid, consistent method moving from existing pub- lished guidelines helps in correctly assessing these newborns in order to provide better care, especially in view of expanding precision therapies. Keywords Neonatal seizures . Newborn . Epilepsy, . EEG, . Monitoring Introduction The most prevalent etiologies include hypoxic- ischemic encephalopathy (HIE) in the full-term and Distinction between Acute Symptomatic Neonatal near-term newborn, and intraventricular hemorrhage Seizures and Neonatal-Onset Epilepsies (IVH) in preterm infants. Full-term and near-term new- borns can also suffer from seizures secondary of perinatal The majority of neonatal seizures are of acute symptom- ischemic stroke. Additional, less frequent causes include atic origin [1]. They have a significant incidence [2•]and infections and transient metabolic derangements [3]. are associated with a worsening in neurological and sur- Acute symptomatic seizures typically tend to decline spon- vival outcome [1]. taneously after a high seizure burden period, which tends to be concentrated in the first days of life [4], but can be followed by This article is part of the Topical Collection on Pediatric Neurology the development of spontaneous seizures (epilepsy) later in life in a substantial proportion of cases [5]. This typical time * Carlotta Spagnoli course has been a cornerstone for the development of recom- [email protected] mendations for EEG monitoring in newborn patients [6]. Neonatal-onset epilepsies, on the contrary, are sustained by Francesco Pisani structural, genetically-driven or non-acquired, metabolic, or [email protected] genetic etiologies [7]. Historically, well-described Carlo Fusco electroclinical syndromes of early-onset have included [email protected] Ohtahara syndrome, early-onset metabolic encephalopathy, and benign (familial) neonatal-onset epilepsy, which have def- 1 Child Neuropsychiatry Unit, Medicine & Surgery Department, Neuroscience Division, University of Parma, Parma, Italy inite clinical and EEG diagnostic criteria. However, increasing availability of genetic testing has resulted in a complete para- 2 Child Neurology Unit, Presidio Ospedaliero Provinciale Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, viale Risorgimento 80, digmatic shift, and now the literature is moving towards ge- 42123 Reggio Emilia, Italy netically based or pathophysiological mechanisms-based 6 Page 2 of 17 Curr Neurol Neurosci Rep (2020) 20:6 classifications [8•, 9]. Nonetheless, precise phenotypic de- risk for neonatal seizures in the following 18–24 h, depending scription is mandatory in order to correctly interpret the huge on the background activity [17]. The rewarming phase should amounts of data coming from next generation DNA sequenc- also be monitored in hypoxic newborns undergoing therapeu- ing investigations. tic hypothermia, as it is accompanied by an increased risk of It has long been acknowledged that etiology is the most seizure recurrence [18, 19]. important determinant of outcome following neonatal seizures Recording EEG should be considered in the presence of [10] and, therefore, there is an urgent need to construct seizure risk factors, among others: fetal distress, central ner- etiology-specific clinical studies on patients, as previous study vous system infection, HIE, preterm birth, intracranial hemor- designs did not use to distinguish between these patients. In rhage, and cardiac surgery [6, 14, 20–22]. As only a small some instances, for example, KCNQ2 encephalopathy, it has percentage of neonatal seizures have a clinical correlate (es- been possible to delineate specific electroclinical phenotypes pecially in HIE) [23], video-EEG monitoring is recommended based on etiology [11]. It is becoming increasingly clear that [14]. As per American Clinical Neurophysiology Society’s these conditions have disease-specific developmental and sei- recommendations, this should be performed for 24 h [6], al- zure outcomes and therefore need to be considered as a sepa- though according to some research the increased risk period is rate group. Significantly, the International League Against extended to the first 24–36 h [17, 24, 25]. Epilepsy (ILAE) classification of the epilepsies has incorpo- EEG can be critical for differentiating seizures from parox- rated the etiologic dimension in every step of the diagnostic ysmal, abnormal non epileptic events [26]. When this is the definition [12], and this approach should apply to the neonatal indication for EEG, its duration should be guided by the abil- period as well. ity to detect multiple typical events [6]. However, treatment strategies for neonatal seizures have After seizures are diagnosed, prolonged, or continuous remained substantially unchanged due to lack of high- monitoring is used to correctly estimate the “seizure burden” quality evidence [13]. Importantly for everyday clinical prac- and to diagnose neonatal status epilepticus (NSE). This has tice, the distinction between epilepsies and acute seizures is relevant practical implications, in guiding treatment decisions now necessary from the beginning, because of the existence of [6] as NSE has been linked to worse neurological and survival disease-specific therapies (precision medicine), which in a few outcome and to later development of epilepsy [1]. conditions are already established as current clinical practice, EEG is then mandatory for evaluating response to an- and in many additional conditions are either under way or ticonvulsant medications. To this end, EEG monitoring might become available in the future based on clinical obser- should continue for at least 24 h after seizure freedom is vation or basic science studies. gained, and seizure recurrence should be checked during and after drug discontinuation [6]. What is Already Known on EEG Monitoring in Newborns with Seizures Structural, Genetically Caused Brain EEG monitoring in intensive care units is performed through Abnormalities two different methods: conventional EEG (c-EEG) and amplitude-integrated EEG (aEEG). In real-world clinical prac- Tuberous Sclerosis Complex tice, c-EEG is recorded as serial standard EEG or as continu- ous EEG. Conventional EEG is recognized as gold standard Epilepsy associated with tuberous sclerosis complex (TSC) for seizure diagnosis and quantification, as it allows demon- usually begins in infancy, while onset in the neonatal period stration of the seizure onset focus and propagation [6] and can is rare [27]. Resective surgery is indicated in refractory cases, provide detailed information on brain maturation, ongoing or but typically not until the early-infantile period. As TSC1/ previous brain injury, and subsequent outcome. Simultaneous TSC2 gene products act as regulators of the PI3K-AKT- videorecordingisstandardofcareinmanyinstitutions mTOR pathway, rapalogs have been evaluated as targeted [14]. Many neonatal units, however, routinely use trend therapies of TSC-related epilepsy [28]. analysis, especially a-EEG, which allows rating of back- ground activity and degree of HIE, and prognostication Malformations of Cortical Development [15], although it has to be considered as a complimentary, “screening” tool [16] for seizure evaluation. aEEG’s eas- These include disorders of cell proliferation and apopto- iness of use and readiness of interpretation can assist real- sis, disorders of cell migration, and disorders of post- time decision-making on a 24-h basis by neonatology migrational development. Early-onset refractory epilepsy staff, which can be followed by c-EEG confirmation. is common, and neonatal onset has been described in all. In newborns with hypoxic-ischemic encephalopathy, even Examples include the well-known ARX (X-linked short standard EEGs can be useful in predicting short-term aristaless-related homeobox gene) which can often be Curr Neurol Neurosci Rep (2020) 20:6 Page 3 of 17 6 present in the neonatal period, and give rise to different KCNQ2 Encephalopathy phenotypes, including severe hydrocephalus, agenesis of the corpus callosum, malformations of cortical develop- De novo mutations in KCNQ2 are associated with a neonatal- ment, but also non malformation-related phenotypes [29]. onset developmental encephalopathy, referred to as “KCNQ2
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