Case reports underscore risk of cerebral edema, AFCE in children with COVID-19

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.