Task force gives guidance on classifying neonatal seizures - An ILAE podcast

Reported and produced by Nancy Volkers, ILAE communications officer

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There are many types of seizures, and many types of epilepsy. ILAE has published guidelines on classifying seizures and epilepsies, but those classifications didn’t account for seizures in newborn babies. Called neonatal seizures, these rare events occur soon after birth, usually within the first week of life. They’re different in many ways from seizures in older children and adults.

Two ILAE task forces spent several years on a position paper that modifies the seizure and epilepsy classifications for neonatal seizures. ILAE spoke with Dr. Ronit Pressler, who chaired the first task force and is first author on the paper, The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate, published in February 2021 in the journal Epilepsia.

Pressler explained the importance of classifying neonatal seizures.

Ronit Pressler: Neonatal seizures are treated by different people – neonatologists, neurologists, geneticists, neurophysiologists, metabolic people – you have a variety of different specialties treating these babies. So it’s a multidisciplinary team and you need to speak the same language. Classification gives you a language to talk, so everyone speaks about the same thing.

It took a long time, but I think it was worth the effort – we have a classification that’s acceptable for neonatologists and neurologists, and in different regions.

ILAE: Unlike seizures in older children and adults, multiple seizures in a neonate does not indicate epilepsy.

Pressler: Neonates have acute provoked seizures – they have a stroke, they have hypoxia, and for three or four days after the brain insult, the brain responds with seizures, but the baby doesn’t have epilepsy. After those three or four days, the seizures stop. The baby may develop epilepsy later, or may not. But what the baby has in those first few days is not epilepsy, it’s acute provoked seizures.

So they don’t have epilepsy and they don’t necessarily need long-term treatment, they need acute treatment and acute management, but not treatment for weeks and months and years.

ILAE: Neonatal seizures also are more subtle than seizures in older people. In many cases, the seizures are clinically invisible: the baby doesn’t look as if it’s having a seizure, but an EEG shows seizure activity. The paper also addressed what a neonatal seizure looks like on EEG.

Pressler: We also discussed in the paper how to define seizures – the definition of a seizure in adults is a clinical seizure. You need a seizure manifestation, signs and symptoms, due to abnormal neuronal firing. But 50% of seizures in babies have no clinical signs; they are purely electrographic. We and others, the ACNS (American Clinical Neurophysiology Society) for example, have identified electrographic seizures as a seizure on EEG lasting more than 10 seconds. The definition is different than the definition in older patients, because we define a seizure according to EEG and not clinical manifestations.

And this so-called 10-second rule is slightly difficult. Why is something that lasts 11 seconds a seizure, and something that looks the same but lasts 9 seconds is not a seizure? There’s no solution yet. Sometimes the 9-second run is just as much a seizure as the 11-second run, but if we call everything a seizure there will be overtreatment and that’s dangerous too, because we know that if you treat a baby who doesn’t need the medication, then that might affect long-term outcome. Clearly if you have seizures it’s better to treat, but if there are just a few sharp waves and you don’t apply the 10-second rule there’s a risk that anything sharp in the EEG is treated, and you don’t want that either.

ILAE: While EEG is the gold standard for diagnosing neonatal seizures, most neonatal care units don’t have access to it.

Pressler: In the paper we talk about EEG and aEEG. The gold standard is full EEG, but full EEG is not available in many neonatal units across the world. The US probably has the most, but even in the UK very few neonatal units have access to full EEG 24/7. They can get a one-hour EEG during working hours, but that’s it. There are maybe three or four neonatal units that have access to continuous EEG monitoring in the UK. In the United States there are far more units so it’s better; in Europe it’s mixed; and in Asia and Africa there is little to no EEG at all for neonates.

So what neonatologists use is what we call aEEG, amplitude integrated EEG. Instead of 10 to 20 electrodes you use 2 or 4 electrodes, and you measure from just 1 or 2 channels. That is a very good method to diagnose seizures, though it’s not as good as continuous EEG. But it’s cheaper, more widely available and it doesn’t require specialist input – the neonatologist can diagnose seizures; they don’t need a neurologist or neurophysiologist. That’s far more available in the UK – 90% of neonatal units have aEEG.

But in some regions outside Europe, even aEEG is not widely available. Without aEEG, we show this in the paper in a flowchart: Only focal clonic and focal tonic seizures can be diagnosed with what we call probable diagnostic certainty. If you have any other seizure types, those are possible seizures; you can’t diagnose the other seizure types. Depending on where you are, people will have to manage seizures in neonates without EEG, but it’s important to be aware that you can only diagnose focal clonic and focal tonic seizures in those cases, and the others you cannot.

ILAE: The position paper includes guidelines for evaluating and diagnosing neonatal seizures. Early diagnosis is important.

We are hoping that it helps people diagnose seizures and understand how to approach them. There’s a diagnostic flowchart in there. We say if you have a baby at high risk or with possible seizures, you need to do an EEG to make sure if it’s a seizure or not. And then take it further and differentiate into clinical and subclinical or electrographic-only seizures.

We also found evidence in the literature and from our own experience that the different seizures types can give you indications of the etiology of the seizures. So if you have a certain seizure type, this can indicate why the baby is having seizures. When neonates have seizures you need to treat them straight away – unlike in adults you don’t have weeks and months to come up with a diagnosis. If you have a baby having seizures that day, many of those etiologies need treatment straight away. You have a baby who has seizures that day, and many of those etiologies need treatment that day. So the etiology is one of the most important things in the management of seizures in neonates. For example, clonic seizures are an indication that the baby very likely had a stroke. Or myoclonic seizures indicate it’s very likely to be an inborn error of metabolism.

In the past, people just said this baby is having seizures and that’s as far as it went. But now we are starting to say okay, let’s look at the kind of seizure it is, and take it further. You can use the information you get from the seizure type to find the etiology and then target your treatment.

There is evidence that a high seizure burden can have long term effects on neurodevelopmental outcome. In the past people thought well maybe seizures in babies don’t really matter. But now there is evidence from animal and clinical studies that shows that the longer it takes for the seizures to be treated, the more difficult it becomes to treat them, and the higher the seizure burden is, the more likely there is poor outcome. So if a baby has a high seizure burden, more than 13 minutes of seizures per hour is associated with a poor neurodevelopmental outcome. The quicker you treat, the easier it is to treat and the less likely you’ll have a higher seizure burden. Therefore a quick diagnosis and timely treatment are important.

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

Read more about neonatal seizures: Neonatal seizures: Closing the knowledge and treatment gap