About half of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) have new-onset neurologic symptoms, research shows.
These symptoms involve the central and peripheral nervous systems but do not always affect the respiratory system. In addition, neurologic symptoms appear to be more common in severe presentations of this syndrome.
“These new data consolidate the initial findings in our JAMA Neurology publication on the neurological problems that children with PIMS-TS can present with, even in the absence of respiratory systems,” study investigator Omar Abdel-Mannan, MD, clinical research fellow at University College London Institute of Neurology and senior resident at Great Ormond Street Hospital for children in London, said in an interview.
He added that the findings are in keeping with other recent research studies on PIMS-TS, which is known more commonly in the United States as multisystem inflammatory syndrome in children (MIS-C).
The findings will be presented April 18 at the American Academy of Neurology (AAN) 2021 Annual Meeting.
Neurologic manifestations common
Many children and adults with COVID-19 have developed neurologic manifestations. PIMS-TS is a severe, postinfectious, immune-mediated disorder characterized by persistent fever and extreme inflammation.
Patients may have acute diarrhea or vomiting, rash or bilateral conjunctivitis, and low blood pressure. They should be examined by a pediatric specialist, and most children with this disorder need intensive care.
To report the neurologic manifestations in children with PIMS-TS, the researchers retrospectively examined data for children and adolescents younger than 18 years who had the disorder and presented to a single center between April 4, 2020, and Sept. 1, 2020.
Forty-six patients (median age, 10.2 years) were included in the analysis. Thirty (65.2%) were male, and 37 (80.4%) were of non-White ethnicities.
Twenty-four (52.2%) patients had new-onset neurologic symptoms, which included headache (n = 24), encephalopathy (n = 14 patients), dysarthria/dysphonia (n = 6), hallucinations (n = 6), ataxia (n = 4), peripheral nerve involvement (n = 3), and seizures (n=1).
Laboratory and imaging results provided further information. One patient had 118 leukocytes in cerebrospinal fluid. Children with neurologic involvement had higher levels of peak inflammatory markers and were more likely to be ventilated and require inotropic support in the PICU (P < .05).
Four of 16 patients who underwent brain MRI had splenium signal changes. Of 15 patients who underwent electroencephalogram (EEG), 14 had an excess of slow activity. Four of 7 patients who underwent nerve conduction studies and electromyography (EMG) had myopathic and neuropathic changes.
Response to SARS-CoV-2
Central neurologic problems of the brain and peripheral nerve involvement rarely occur at the same time in children.
“This makes it highly possible that the syndrome is secondary to cytokine release in response to the SARS-CoV-2 virus, as there is significant clinical overlap with both genetic and acquired forms of another immune-mediated condition known as hemophagocytic lymphohistiocytosis,” said Dr. Abdel-Mannan.
The researchers found no demographic differences between children with neurologic involvement at presentation and those without.
“However, the numbers are small given the rarity of this condition, which makes it difficult to extrapolate associations and differences between the two groups, and will require future collaborative larger scale studies to look at what potentially makes some children more susceptible to neurologic involvement than others,” said Dr. Abdel-Mannan.
Excluding potential causes of the symptoms other than COVID-19 also is important, he added.
The preponderance of ethnic minorities in the current study population mirrors that in other PIMS-TS cohorts in other countries, said Dr. Abdel-Mannan. It reflects the higher incidence of COVID-19 in ethnic minority groups. However, presentation, investigations, and management did not differ between White and non-White children in the current study.
“Although PIMS-TS patients with neurologic involvement are initially sicker, our center’s preliminary follow-up data up to 6 months post discharge from hospital demonstrates that most of these children make an almost complete functional recovery, which is reassuring,” said Dr. Abdel-Mannan.
The data underscore how important it is that clinicians be aware that children with PIMS-TS can present with neurologic symptoms, even in the absence of respiratory involvement, he added.
The researchers will soon begin a multicenter research study that will involve longitudinal clinical and cognitive assessments and advanced neuroimaging. The objective will be to determine whether all children with PIMS-TS, or only those with neurologic symptoms, are at risk of chronic longer-term neurocognitive and psychiatric outcomes.