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Neurologic findings in adult COVID-19 patients were also observed in some pediatric inflammatory multisystem syndrome (PIMS) cases that follow exposure to the virus, with brain imaging showing the impact, researchers reported.

New-onset neurological symptoms turned up in four of 27 (14.8%) previously healthy children in a case series reported by Yael Hacohen, MD, PhD, of University College London, and colleagues in .

Those symptoms included encephalopathy and global muscle weakness in all four children along with:

• Headache in three children
• Brainstem signs with dysarthria or dysphagia in two children
• Reduced reflexes in two children
• Meningism in one child
• Cerebellar ataxia in one child

Those findings affirm what "we have heard and seen of the lethargy, headache and confusion as part of the presenting symptom complex in many patients," commented Kevin Friedman, MD, who has treated such patients at Boston Children's Hospital.

Among the 186 cases in 26 states with targeted surveillance by the national Overcoming COVID-19 study reported earlier this week in the New England Journal of Medicine, neurologic involvement in cases defined by the was seen in 5% of those age 12 and younger and in 11% of those ages 13 to 20.

Among the 99 MIS-C cases reported to the New York State Department of Health active mandatory surveillance by May 10 and published alongside the national data in NEJM, neurologic symptoms (predominantly headache) occurred in 13% of patients age 5 and younger and 38% of those ages 13 to 20.

In adults, a Chinese study documented neurologic findings in 36.4% of patients, most commonly dizziness and headache but also impaired consciousness, acute cerebrovascular disease, ataxia, and seizures.

The London study, though, may be first to describe brain imaging in such children.

Neuroimaging showed region of the brain in all four PIMS patients with neurological symptoms. While T2-hyperintense lesions associated with restricted diffusion were seen in three, the fourth patient had a splenial lesion on CT that subsequent MRI didn't show as restricted diffusion.

"Reversible lesions of the SCC are rare but have been previously reported in patients with encephalopathies and are thought to represent focal intramyelin edema secondary to inflammation," the researchers noted.

A transient lesion in the SCC, "either in isolation or with more extensive brain involvement, has also been reported in children with Kawasaki disease," they added. Kawasaki disease overlaps with PIMS or MIS-C in a number of cases.

While the imaging finding has been seen with other viral infections, "clinicians should be adding SARS-CoV-2 to their differential diagnosis for children presenting with new neurologic symptoms and this imaging finding while still exploring other possible causes," Hacohen's group argued.

"Furthermore, because respiratory symptoms were uncommon in this cohort and, when present, were mild and easily missed, and because reports are growing of children carrying COVID-19 infection without symptoms (with this condition likely presenting late), SARS-CoV-2 should also be considered in pediatric patients presenting with primary neurologic symptoms without systemic involvement."

One child in Hacohen's retrospective study with repeated MRI on day 5 showed resolution of diffusion restriction in the SCC and centrum semiovale.

"It is unclear what, if any, medium- and long-term implications the neurologic findings have," added Friedman, who is a member of the American Heart Association's Young Hearts Council and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. "Most patients are returning to normal mental status and having resolution of headache fairly quickly after treatment, but long-term follow-up will be needed to see if there are ongoing implications."

The researchers also called for further surveillance of these children.

The study included all patients under age 18 who presented with new-onset neurological symptoms to a single children's hospital in London from March 1 through May 8, 2020, and who had SARS-CoV-2 infection confirmed by nasopharyngeal swab PCR assay or a positive serum immunoglobulin G antibody test.

Lumbar punctures done for two of the children turned up nothing unusual.

"The phenotype of our cohort raises the possibility of a virus-specific immunological syndrome," the researchers concluded. "A plausible mechanism would be exposure of the immune system to new CNS [central nervous system] antigens as a result of blood-brain barrier damage from SARS-CoV-2, which causes endotheliopathy and leads to an immune-directed attack on the CNS."

"The combinations of both CNS and peripheral nervous system symptom profiles are rare in pediatrics but can be seen in children with hemophagocytic lymphohistiocytosis," they noted. "This condition, which can be either genetic or acquired, is traditionally characterized by a cytokine storm with multiorgan dysfunction."

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