Is SARS-CoV-2 Infection a Risk for Potentiation of Epileptic Seizures in Children With Pre-existing Epilepsy?

Published reports describing the neurological manifestations in children with COVID-19 are expanding the COVID-19 phenotype.¹ Whether seizure exacerbation might be an issue for children with pre-existing epilepsy and SARS-CoV-2 infection is unknown. We describe two children with reappearance of seizures during a COVID-19 infection after a long seizure-free period.

The first child is a five-year-old girl who had experienced a perinatal ischemic stroke. Her focal epilepsy had been fully controlled by levetiracetam, but after four years without seizures, she developed focal motor status epilepticus that resolved following intravenous midazolam. She had a two-day history of fever and rhinitis. Her electroencephalography showed postictal focal slowing, and her magnetic resonance imaging was unchanged.

The second child is an 11-year-old girl with fragile X syndrome and recurrent status epilepticus usually triggered by febrile episodes. She had been seizure-free for six years with levetiracetam. After two days of fever she developed prolonged focal seizures requiring intravenous midazolam. Blood examinations detected transient respiratory acidosis. Her electroencephalography showed an irregular background activity and rare sharp abnormalities.

Polymerase chain reaction testing for COVID-19 was positive in both girls. Both children were discharged after six days with no need for respiratory support, no seizure recurrence, and no increase in their antiepileptic drug dosing.

So far, there is no clear evidence that COVID-19 triggers seizure relapses in epileptic patients. Considering the extreme ratio between reported COVID-19 cases with seizures and the overall increasing number of reported COVID-19 cases, as well as the high prevalence of epilepsy, this association could be merely a coincidence.

The occurrence of seizures during febrile illnesses in children with epilepsy is well-known, and we cannot be certain that SARS-CoV-2 merely triggered the seizures in the same fashion as other pathogens. Hypoxia, sepsis or direct brain infection is unlikely in our patients. Other mechanisms have been hypothesized, such as the up-regulation of components of the renin-angiotensin system, mediating proinflammatory and vasoconstrictive effects, or the increase in pro-inflammatory cytokine levels such as interleukin-6.²

A seizure recurrence risk in patients with pre-existing epilepsy should be considered in children with mild COVID-19, especially after a long seizure-free period, due to possible lowering of the seizure threshold. The epileptogenic effect of SARS-CoV-2 requires further confirmations.