COVID-19 in Kids: New Neurologic, Radiographic Findings

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Children with COVID-19-related pediatric multisystem inflammatory syndrome (MIS) may experience neurologic symptoms that involve the central nervous system and the peripheral nervous system, new research suggests.

In a case-series study of 27 children with COVID-19 MIS at a hospital in London, United Kingdom, four presented with new-onset symptoms that included headache, brainstem and cerebellar signs, encephalopathy, muscle weakness, and reduced reflexes.

After the patients were admitted to an intensive care unit, MRI scans showed splenium signal changes in all four patients.

In addition, a "mild excess of slow activity" was found in the three children who underwent electroencephalography, and mild myopathic and neuropathic changes were found in the three who underwent nerve conduction measures and electromyography.

By end of study, all four showed neurologic improvement, and two had made a full recovery.

"Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19," write the investigators, led by Omar Abdel-Mannan, MD, Department of Neurology, Great Ormond Street Hospital for Children, London.

The findings were published online July 1 in JAMA Neurology.

CDC Health Advisory

In May, the Centers for Disease Control and Prevention (CDC) issued a health advisory about MIS associated with COVID-19 in children.

The CDC noted that in April, there were increasing reports in the United Kingdom of "previously healthy children [who] presented with a severe inflammatory syndrome with Kawasaki disease-like features" and who tested positive for SARS-CoV-2.

"Patients presented with a persistent fever and a constellation of symptoms including hypotension, multiorgan (eg, cardiac, gastrointestinal, renal, hematologic, dermatologic and neurologic) involvement, and elevated inflammatory markers. Respiratory symptoms were not present in all cases," the organization wrote in its alert.

Because previous reports have noted cases in which adults with COVID-19 experienced neurologic symptoms, for the current study, investigators wanted to report on these manifestations in children.

Fifty children younger than 18 years presented to the Great Ormond Street Hospital for Children between March 1 and May 8 with SARS-CoV-2 infection, which was confirmed through testing.

Of these, 27 had features consistent with COVID-19-related MIS. Four of those children (14.8%) had neurologic symptoms (median age at symptom onset, 12 years).

All four of the patients had fever, cardiovascular shock, and rash; two also had dyspnea. All needed mechanical ventilation. The median number of days of stay in the ICU was 6.5, and the median number of days of mechanical ventilation was 5.

Signal Changes

Further analyses showed "acellular" cerebrospinal fluid samples in the two children who underwent lumbar punctures. The samples showed normal levels of protein and glucose. Results were negative for oligoclonal bands, bacterial cultures, and viral and bacterial polymerase chain reactions.

Negative results were also found for N-methyl-D-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies for all the children.

MRI results showed that all four patients had signal changes in the splenium of the corpus callosum, and three had T2-hyperintense lesions.

"Nerve conduction studies and electromyography showed mild myopathic and neuropathic changes" in the three children who underwent the tests, the researchers write.

Immunomodulatory therapies were given to three of the patients. Intravenous (IV) methylprednisolone, dexamethasone, anakinra, and IV immunoglobulin were given to two patients, and one received rituximab.

At study end, two of the patients had been discharged from the hospital, one at 11 days and one at 18 days. Although the other two had been discharged from the ICU, they remained inpatients and wheelchair bound because of lower-limb muscle weakness.

Surveillance Needed

The investigators note that the sample size is a "key" study limitation.

"Further studies are now required to confirm our observation and evaluate the mechanism of disease in this distinct syndrome," they write.

They note that respiratory symptoms were uncommon "and, when present, were mild and easily missed."

Because of this, "SARS-CoV-2 should be considered in pediatric patients presenting with primary neurologic symptoms without systemic involvement," the researchers write.

"Close neurodevelopmental surveillance is required to assess the neurological and cognitive outcomes in these patients," they conclude.

Abdel-Mannan has reported no relevant financial relationships. Disclosures for the other investigators are listed in the original article.

JAMA Neurol. Published online July 1, 2020. Full article

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