Most deaths among children with epilepsy due to infection

Most children with epilepsy who die succumb to an infection during the winter months, preliminary results of a new UK study show.

The study also found that most of the mortality was among those who were male and aged 11 to 15 years.

Because previous studies of mortality in children with epilepsy had design problems, "we wanted to provide some sort of evidence-based information for clinicians and families," said Omar Abdel-Mannan, a pediatric neurology trainee in Great Ormond Street Hospital for Children, London, United Kingdom.

The study was presented at the Congress of the European Academy of Neurology (EAN) 2018.

Epilepsy is the most common long-term disabling central nervous system condition, affecting over 6000 people in the United Kingdom, Abdel-Mannan told meeting delegates.

Children — and adults — with epilepsy face higher risk for premature death from multiple causes, including seizure complications (such as aspiration, suffocation, injury, and status epilepticus), underlying conditions (such as brain tumors), suicide, and sudden unexpected death in epilepsy (SUDEP).

Previous studies have shown serious deficiencies in care, but researchers believe this didn't accurately reflect the picture of mortality among kids with epilepsy.

"We felt that a prospective active surveillance system was needed to estimate epilepsy mortality," said Abdel-Mannan.

The researchers aimed to gather information across the United Kingdom over a 1-year period — from November 2016 to October 2017.

They used information from the British Pediatric Surveillance Unit (BPSU), a research unit that is part of UK Royal College of Pediatrics. Its case reporting system involves contacting every pediatrician in the United Kingdom and inquiring about various conditions, in this case mortality.

When clinicians report cases, the BPSU gets in touch with researchers, who then contact pediatricians to get information on individual patients through questionnaires.

The response rate from clinicians is about 94% to 95%, so the reporting system is highly reliable, said Abdel-Mannan.

For this study, pediatric mortality was defined as children dying between age 1 month and their 16th birthday, who were diagnosed with epilepsy, and had seizures or were receiving antiseizure medication during the last 5 years.

Although there were 131 case notifications, 20 were lost to follow-up, 14 were duplicates, and 9 didn't meet inclusion criteria. This left 88 confirmed cases that were included in the analysis.

The deaths occurred throughout the year, with the greatest number in January and the fewest in August.

Almost 90% of reported cases came from England, with a handful from Wales, Ireland, and Scotland. But Abdel-Mannan believes some Scottish cases may have been missed "as the study was not fully rolled out" in that country.

The greatest proportion of children who died (46%) were aged 11 to 15 years. About 66% were male, and 70% were white, with South Asians representing the next biggest racial group. 

The most common cause of death was pneumonia or lower respiratory tract infection (14%) and sepsis (10%), which together made up a quarter of all cases. This, said Abdel-Mannan, "might explain the winter spike in deaths."

Of the 72 cases with relevant information, just over a third of deaths were due to Dravet syndrome, Lennox-Gastaut syndrome, or other epilepsy syndrome.

Almost 90% of children had some developmental delay, and more than half (52%) experienced generalized tonic-clonic seizures.

"More interestingly," said Abdel-Mannan, was that 23% of the children had no seizures at the time of death.

There were 10 cases of probable or definite SUDEP, although the true number may be higher, said Abdel-Mannan. "We think there may have been a few more among the large number of 'unknown' deaths."

Sodium valproate and levetiracetam were the most frequently prescribed antiepileptic drugs (AEDs). About 90% of the children were receiving at least one AED, although 10% died not taking any medication, said Abdel-Mannan.

Discussions with the family around the issues of death or SUDEP had taken place in more than half the cases.

Only 36% of the children had a pediatric neurologist actively involved in their care, although about half had a general pediatrician with an interest in neurology managing their care.

Gathering mortality data for children with epilepsy is challenging, noted Abdel-Mannan. "As you can imagine, there is a lot of sensitivity around this topic."

He noted that reporting is often delayed. Sometimes the reporting clinician is not the one looking after the charts, "so we have to sort of go find the primary clinician to get the information."

As well, postmortem results are often not available at the time of reporting, and death certificate information may be missing, he said.

Session co-chair Ivan Rektor, MD, professor of neurology, Masaryk University Brno, Czech Republic, commented that 24% "is an unusually high number" of children who died of sepsis or pneumonia.

Abdel-Mannan explained that these are complex epileptic patients with multiple comorbidities. "They are not a cohort of healthy children."

Rektor also wondered if the same high risk for sepsis occurred in adolescents as in younger kids.

The lowest number of deaths was in patients younger than 1 year, and the rate among those 5 to 10 and 11 to 15 years "was not that different," said Abdel-Mannan.

"It would be interesting to go back and look to see if this was correlated with sepsis and pneumonia cases."

Asked to provide more details on the SUDEP cases, Abdel-Mannan said most of these deaths occurred at home or in a hospice and were unwitnessed. As well, most involved patients with one of the underlying syndromes, such as Dravet.

When asked if he has any suggestions for prevention measures, Abdel-Mannan said that "there is talk in the pediatric literature" about devices that capture seizures, as well as recommendations to sleep next to a partner.

"This is something we want to look at in future," said Abdel-Mannan.

The study received funding from SUDEP Action. 

Congress of the European Academy of Neurology (EAN) 2018. Oral session O212. Presented June 17, 2018.

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