Half of kids with MIS-C experience neurological symptoms
Preliminary research suggested half of children at a London hospital who developed a multisystem inflammatory syndrome associated with COVID-19 experienced neurological symptoms, such as headache, encephalopathy and hallucinations.
Omar Abdel-Mannan, MD, of University College London, and colleagues presented their findings at the American Academy of Neurology annual meeting, which is being held virtually. They reviewed the patient records of all children aged 18 years or younger who were admitted to the Great Ormond Street Hospital in London between April 4 and Sept. 1, 2020, and met the criteria for what they called pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, or PIMS-TS.
In the United States, the condition is termed multisystem inflammatory syndrome in children (MIS-C). According to the CDC, the case definition for MIS-C includes any patient aged younger than 21 years who presents with fever, laboratory evidence of inflammation, evidence of clinically severe illness requiring hospitalization, with two or more organs involved, who has no alternative plausible diagnosis and has tested positive for current or recent SARS-CoV-2 infection, or reports exposure to a suspected or confirmed case of COVID-19.
Although rare, MIS-C can emerge weeks after infection with SARS-CoV-2, according to the CDC, and a similar syndrome — MIS-A — has been documented in adults with COVID-19.
The report by Abdel-Mannan and colleagues focused on 46 patients who presented during the study period. The average age of patients was 10 years, 65.2% were boys and 80.4% were of nonwhite ethnicities. New-onset neurological symptoms were reported in 52.2% of the children, including headache (n = 24), encephalopathy (n = 14), dysarthria/dysphonia (n = 6), hallucinations (n = 6), ataxia (n = 4), peripheral nerve involvement (n = 3) and seizures (n = 1).
“With this new inflammatory syndrome that develops after children are infected with the coronavirus, we are still learning how the syndrome affects children and what we need to watch out for,” Abdel-Mannan said in a press release. “We found that many children experienced neurologic symptoms involving both the central and peripheral nervous systems.”
The researchers also found that children who experienced neurological symptoms were more likely to need ventilation and inotropic agents in the pediatric ICU (P < .005).
A case series published in JAMA in February that included more than 1,100 pediatric patients showed that cardiac involvement, as well age and race — specifically, those aged 6 to 12 years and Black children — are all factors that could help differentiate MIS-C from severe COVID-19.
These latest results suggest that children who develop MIS-C should be evaluated for neurological symptoms and longer term cognitive outcomes, according to Abdel-Mannan.
“More studies are needed involving more children and following children to see how this condition changes over time and if there are any longer term neurocognitive effects,” he said.
References:
Abdel-Mannan O, et al. Neurologic and radiographic findings associated with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children. Presented at: American Academy of Neurology Annual Meeting; April 17-22, 2021 (virtual meeting).
CDC. Case definition for MIS-C. https://www.cdc.gov/mis-c/hcp/. Accessed April 12, 2021.
Feldstein LR, et al. JAMA. 2021;doi:10.1001/jama.2021.2091.
Perspective
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When COVID-19 started to appear, there was a sense of relief that perhaps children were largely spared — and maybe even in some cases people thought they were completely spared — some of the severe manifestations. We quickly learned that wasn’t true. One of the interesting complications that emerged was the so-called multisystem inflammatory syndrome in children, or MIS-C. A lot of the initial reports discussed non-neurologic complications of that disorder — everything from pulmonary to cardiac to hemodynamic to skin complications. There were clear mentions of neurological syndromes, but they probably weren’t at the forefront.
The first thing that was impressive to me was that this was a reasonably sized study, with 46 kids, and about half of them experienced new neurologic signs or symptoms, which is a much higher percentage than what most of us might have said based on earlier literature. One of the take-home messages is the prevalence of neurological signs or symptoms in this disorder, and some of the more important of these are headache and encephalopathy.
This study was done in the United Kingdom, and the dominant circulating strain of SARS-CoV-2 there is B.1.1.7 (the ‘British variant’), which is likely now the major strain circulating in the U.S. as well. It remains to be seen if different SARS-CoV-2 ‘variants of concern’ have differing rates of MIS-C or of neurological complications in those who develop MIS-C.
The second take-home message is a reminder that, as we’ve seen in previous descriptions of MIS-C, this can be the presenting manifestation of COVID-19, meaning that many of these children don’t have a dramatic prior history of respiratory or other symptoms that might make you think, ‘Oh, we need to look for COVID-19.’ One of the other messages here is that if you have children presenting with some of these symptoms — and of course, these are general symptoms — it’s important to be aware that these can be part of this larger syndrome, and it should encourage physicians to think of COVID-19 as a possible trigger and then test for it. We think this is part of the post-infectious, immune-mediated process, so you can be in that window of time in which testing by PCR or nucleic acid may be negative, and you may need to do antibody testing to show that a patient has been previously exposed to COVID-19.
The third take-home message is that the authors of the study found that children with neurological symptoms were more likely to need a ventilator and hemodynamic stabilization if you compared them with children with MIS-C without neurologic complications. So, it does seem like the neurology is linked to more severe disease. If there’s a bright note in this study at all, it’s that the authors didn’t find differences in short-term outcomes between children with neurologic symptoms vs. those without neurologic symptoms, but they also mentioned as a cautionary note that it will be important to follow up with these children to see what the recovery trajectory is and if there any long-term neurologic effects.
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Abdel-Mannan O, et al. Neurologic and radiographic findings associated with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children. Presented at: American Academy of Neurology Annual Meeting; April 17-22, 2021 (virtual meeting).