Neugeborenenanfälle

Epileptische Anfälle kommen mit einer Inzidenz von 1 bis 3 pro 1000 Lebendgeborenen und 1–13 % derer mit sehr niedrigem Geburtsgewicht in dieser Lebensphase wesentlich häufiger vor als zu irgendeinem anderen Zeitpunkt im Leben. Die meisten neonatalen Anfälle sind akut symptomatisch. Bei Reifgeborenen stellt die hypoxisch-ischämische Enzephalopathie, die typischerweise in den ersten 24 Lebensstunden beginnt, die häufigste Ursache dar. Andere Ätiologien sind Schlaganfall, Blutungen, Infektionen und metabolische Erkrankungen. Die Epilepsiesyndrome mit Beginn im Neugeborenenalter schließen die selbstlimitierenden familiären und sporadischen Neugeborenenanfälle, die frühe myoklonische Enzephalopathie und die frühinfantile epileptische Enzephalopathie mit Suppression-Burst (Ohtahara-Syndrom) ein. Wegen der breiten Differenzialdiagnose sollten die initialen diagnostischen Schritte auf die häufigen Ursachen, die eine sofortige Behandlung erfordern, konzentriert sein (Blutzucker, Elektrolyte, Blutgasanalyse, Infektionsabklärung, zerebraler Ultraschall und EEG [Elektroenzephalogramm]). Neonatale Anfälle lassen sich klinisch nicht sicher diagnostizieren, und etwa 50–70 % der Anfälle stellen sich ausschließlich elektrographisch dar. Das bedeutet, dass in dieser Situation ein EEG zur Bestätigung der Diagnose bei suspekten klinischen Zeichen und zur Feststellung elektrographischer Anfälle absolut notwendig ist, zudem korreliert es mit der Prognose. Phenobarbital ist bei Neugeborenenanfällen weiterhin das Medikament der Wahl und kann die klinischen Anfälle bei etwa 40–60 % der Kinder kontrollieren. Empfehlungen bezüglich der Antiepileptika der zweiten Wahl variieren erheblich und schließen Levetiracetam, Phenytoin, Midazolam und Lidocain ein. Allerdings begünstigen Phenobarbital und Phenytoin die elektroklinische Dissoziation. Bei fehlendem Ansprechen auf die Therapie oder suspekter abnormer EEG-Hintergrundaktivität ist ein früher Behandlungsversuch mit Vitamin B6, Pyridoxalphosphat und Folinsäure indiziert. Die Prognose neonataler Anfälle wird v. a. durch die Ätiologie bestimmt. Dabei gibt es eine zunehmende Evidenz, dass sich elektroklinische und rein elektrographische Anfälle gleichermaßen negativ auf das neurologische Outcome und die Entwicklung auswirken

Sleep architecture in neonatal and infantile onset epilepsies in the first six months of life: A scoping review

AIM: Epilepsy occurs in approximately 80 per 100,000 infants in the first year of life, ranging in severity from self-limited and likely to spontaneously resolve, to severe developmental and epileptic encephalopathies. Sleep plays a key role in early brain development and the reciprocal relationship between sleep and seizures is not yet fully understood, particularly in young children. We conducted a Scoping Review to synthesise current knowledge of sleep architecture in neonates and infants with epilepsy. METHODS: Peer-reviewed publications from 2005 to 2022 describing sleep architecture in infants up to six months of age with unprovoked seizures were included. The analysis set was derived from EMBASE, Web of Science and PubMED using key terms “sleep, epilepsy and infant” and related descriptors. Inclusion criteria were prospectively described in a Scoping Review protocol. Sleep architecture was assessed as macro- and micro-structural elements. RESULTS: 21 publications were included in the qualitative analysis. In self-limited familial and genetic epilepsy, sleep macrostructure was generally preserved. In DEEs and in epileptic encephalopathies of genetic or structural aetiology, sleep architecture was significantly disrupted. INTERPRETATION: Early identification of infants with epilepsy is important to ensure early and effective treatment. In the DEE spectrum, sleep architecture is significantly impacted, and abnormal sleep architecture may be associated with compromised developmental outcome. Further research is needed to identify the sequence of events in abnormal brain development, epilepsy and sleep disruption and potentially help to predict the course of epilepsy towards a self-limited epilepsy versus a DEE

Early serial EEG in hypoxic ischaemic encephalopathy

Objectives: To perform early serial EEGs in infants with hypoxic ischaemic encephalopathy (HIE) and compare the findings with neurodevelopmental outcome.// Methods: Nine full-term neonates with HIE had simultaneous video-EEG polygraphic studies within 8 h of birth. The EEG was repeated at 12–24 h intervals. All surviving infants had a neurodevelopmental assessment at 1 year.// Results: Two infants had a normal or mildly abnormal EEG within 8 h of birth and neurodevelopmental outcome was normal. Seven infants had severely depressed background activity in the first 8 h of life. In 3 infants the EEG activity recovered within 12–24 h showing continuous activity with no or only minor abnormalities. All these infants had a normal outcome. The remaining 4 infants, who also had an initially inactive recording, subsequently developed severe background abnormalities. At follow-up, two infants had died and the remainder developed major neurological sequelae.// Conclusions: Early EEG is an excellent prognostic indicator for a favourable outcome if normal within the first 8 h of life and for a poor outcome if the background activity continues to be inactive or grossly abnormal beyond 8–12 h of life. However, an inactive or very depressed EEG within the first 8 h of life can be associated with good outcome if the EEG activity recovers within 12 h

Effect of lamotrigine on cognition in children with epilepsy

Background: Lamotrigine does not affect cognition in healthy adult volunteers or adult patients with epilepsy, but its effect on cognition in children is uncertain.// Objective: To compare the effect of lamotrigine and placebo on cognition in children with well-controlled or mild epilepsy.// Method: In a double-blind, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Each treatment phase was 9 weeks, the crossover period 5 weeks. A neuropsychological test battery was performed during EEG monitoring at baseline and at the end of placebo and drug phases. The paired Student’ t test was used for statistical analysis for neuropsychological data (two tailed) with a p value of 0.01 considered significant. Carryover and period effect were analyzed with generalized linear modeling (SPSS 10).// Results: Forty-eight children completed the study. Seizure frequency was similar during both treatment phases. No significant difference was found in continuous performance, binary choice reaction time, verbal and nonverbal recognition, computerized visual searching task, verbal and spatial delayed recognition, and verbal and nonverbal working memory between placebo and lamotrigine treatment phase. There was no significant carryover and period effect when corrected for randomization.// Conclusion: Lamotrigine exhibits no clinically significant cognitive effects in adjunctive therapy for children with epilepsy

Neonatal Seizures—Perspective in Low-and Middle-Income Countries

Neonatal seizures are the commonest neurological emergency and are associated with poor neurodevelopmental outcome. While they are generally difficult to diagnose and treat, they pose a significant clinical challenge for physicians in low- and middle-income countries (LMIC). They are mostly provoked seizures caused by an acute brain insult such as hypoxic–ischemic encephalopathy (HIE), ischemic stroke, intracranial hemorrhage, infections of the central nervous system, or acute metabolic disturbances. Early onset epilepsy syndromes are less common. Clinical diagnosis of seizures in the neonatal period are frequently inaccurate, as clinical manifestations are difficult to distinguish from nonseizure behavior. Additionally, a high proportion of seizures are electrographic-only without any clinical manifestations, making diagnosis with EEG or aEEG a necessity. Only focal clonic and focal tonic seizures can be diagnosed clinically with adequate diagnostic certainty. Prompt diagnosis and timely treatment are important, with evidence suggesting that early treatment improves the response to antiseizure medication. The vast majority of published studies are from high-income countries, making extrapolation to LMIC impossible, thus highlighting the urgent need for a better understanding of the etiologies, comorbidities, and drug trials evaluating safety and efficacy in LMIC. In this review paper, the authors present the latest data on etiology, diagnosis, classification, and guidelines for the management of neonates with the emphasis on low-resource settings

Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia

OBJECTIVE: To investigate the role of EEG background activity, electrographic seizure burden, and MRI in predicting neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy (HIE) in the era of therapeutic hypothermia. METHODS: Twenty-six full-term infants with HIE (September 2011-September 2012), who had video-EEG monitoring during the first 72 h, an MRI performed within the first two weeks and neurodevelopmental assessment at two years were evaluated. EEG background activity at age 24, 36 and 48 h, seizure burden, and severity of brain injury on MRI, were compared and related to neurodevelopmental outcome. RESULTS: EEG background activity was significantly associated with neurodevelopmental outcome at 36 h (p = 0.009) and 48 h after birth (p = 0.029) and with severity of brain injury on MRI at 36 h (p = 0.002) and 48 h (p = 0.018). All infants with a high seizure burden and moderate-severe injury on MRI had an abnormal outcome. The positive predictive value (PPV) of EEG for abnormal outcome was 100% at 36 h and 48 h and the negative predictive value (NPV) was 75% at 36 h and 69% at 48 h. The PPV of MRI was 100% and the NPV 85%. The PPV of seizure burden was 78% and the NPV 71%. CONCLUSION: Severely abnormal EEG background activity at 36 h and 48 h after birth was associated with severe injury on MRI and abnormal neurodevelopmental outcome. High seizure burden was only associated with abnormal outcome in combination with moderate-severe injury on MRI

Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children

BACKGROUND: Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the "resting state"; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work's motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population. METHODS: Forty-six children with focal epilepsy and 20 controls (6-18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies ("rest sessions"), for another two sessions, subjects watched a child friendly stimulation i.e. movie ("movie sessions"). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject. FINDINGS: Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance. CONCLUSIONS: A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without sedation. Our data suggest that ~20 minutes is the optimal length of scanning for EEG-fMRI studies in children with frequent IED. The efficiency of the fMRI design derived from spontaneous IED generation is an important factor for producing concordant results

The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group

Neonatal Seizure Management – Is the Timing of Treatment Critical?

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden; secondary aim was to describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks' gestation) requiring electroencephalographic (EEG) monitoring recruited to two multicentre European studies were included. Infants who received anti-seizure medication exclusively after electrographic seizure onset, were grouped based on time to treatment of the first seizure: ASM within 1-hour, ASM between 1-2 hours and ASM after 2-hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures and ASM dose over 24-hours following seizure onset. RESULTS: Out of 472 newborns recruited, 154(32.6%) infants had confirmed electrographic seizures. Sixty-nine infants were exclusively treated after onset of electrographic seizures: 21 infants received ASM within 1 hour, 15 infants between 1-2 hours and 33 infants after 2 hours of seizure onset. Significantly lower seizure burden and less seizures were noted in infants treated with ASM within 1 hour from seizure onset (p value=0.029 and 0.035, respectively). Overall, 258/472(54.7%) infants received ASM throughout the study period, of which 40 infants without electrographic seizures had treatment during EEG monitoring and 11 infants with electrographic seizures had no treatment. CONCLUSION: Treatment of neonatal seizures may be time-critical, but more research is required to confirm this. We also need to improve neonatal seizure diagnosis and treatment

Current practice and recommendations in UK epilepsy monitoring units. Report of a national survey and workshop

PURPOSE: Inpatient video-EEG monitoring (VEM) is an important investigation in patients with seizures or blackouts, and in the pre-surgical workup of patients with epilepsy. There has been an expansion in the number of Epilepsy Monitoring Units (EMU) in the UK offering VEM with a necessary increase in attention on quality and safety. Previous surveys have shown variation across centres on issues including consent and patient monitoring. METHOD: In an effort to bring together healthcare professionals in the UK managing patients on EMU, we conducted an online survey of current VEM practice and held a one-day workshop convened under the auspices of the British Chapter of the ILAE. The survey and workshop aimed to cover all aspects of VEM, including pre-admission, consent procedures, patient safety, drug reduction and reinstatement, seizure management, staffing levels, ictal testing and good data recording practice. RESULTS: This paper reports on the findings of the survey, the workshop presentations and workshop discussions. 32 centres took part in the survey and there were representatives from 22 centres at the workshop. There was variation in protocols, procedures and consent processes between units, and levels of observation of monitored patients. Nevertheless, the workshop discussion found broad areas of agreement on points. CONCLUSION: A survey and workshop of UK epilepsy monitoring units found that some variability in practice is inevitable due to different local arrangements and patient groups under investigation. However, there were areas of clear consensus particularly in relation to consent and patient safety that can be applied to most units and form a basis for setting minimum standards