Children may develop neurological complications of COVID-19 ranging from mild to severe, a large brain-imaging study confirms.

“Different recognizable patterns of brain, cranial nerve, and spinal cord involvement were identified, including multifocal T2 bright lesions in brain white matter, vasculitic patterns with ischemic lesions, enhancing neuritis or polyradiculitis, venous thrombosis, splenial lesions of the corpus callosum, longitudinally extensive myelitis, and myositis,” the study team reports in The Lancet Child and Adolescent Health.

“These findings should be recognized and investigated for possible SARS-CoV-2 infection as the underlying etiological factor,” Dr. Susan Palasis of Robert H. Lurie Children’s Hospital of Chicago and colleagues suggest.

The cohort included 38 children with encephalopathy from eight countries with SARS-CoV-2 infection (representing the acute, subacute and postinfectious phases) and abnormal neuroimaging findings on magnetic resonance imaging or computed tomography.

Throughout all phases and presentations of COVID-19, the most common neuroimaging manifestations resembled an immune-mediated parainfectious pattern of disease involving the brain, spine, cranial nerves and nerve roots, the researchers found.

Brain manifestations were most commonly acute disseminated encephalomyelitis (ADEM)-like in appearance, with “patchy or confluent areas of T2 hyperintensity in the grey and white matter, with or without reduced diffusion or enhancement.” The exact pathophysiology of these abnormalities remains to be clarified, the researchers say.

There were two atypical cases of severe myelitis, both seen in the acute phase of the disease. One involved a child with no pre-existing conditions or other comorbidities who developed a clinically catastrophic myelitis, resulting in permanent quadriplegia. The other case of severe myelitis involved a child who died from SARS-CoV-2-related encephalitis and fulminant tuberculosis.

Neuritis, marked by enhancement of cranial and spinal nerves or the cauda equina, was seen in 12 (32 percent) children. Similar cranial nerve abnormalities have been observed in adults with acute COVID-19. However, an “important observation” is that cranial nerve enhancement can occur in the absence of corresponding neurological symptoms, the researchers say.

Loss of taste and smell is well documented in adults with COVID-19, with similar case reports in children. In the current cohort, however, anosmia was reported in only one child and signal abnormalities or enhancement of the olfactory nerves or surrounding tissues were not seen on imaging.

In the 11 children with multisystem inflammatory syndrome, splenial lesions and myositis of the face and neck were the predominant findings.

Seven (18 percent) children had findings that could be characterized as thromboembolic or vasculitic and often manifesting in the setting of confounding comorbid conditions such as co-infections.

Regarding outcomes for the entire cohort, none of the children had significant pre-existing conditions and most fared well with COVID-19 and were either normal or had some mild residual neurological deficits at last follow-up, the researchers report.

However, four previously healthy children developed atypical central nervous system (CNS) co-infections, leading to death despite aggressive treatment.

Two of these four children developed fulminant Mycobacterium tuberculosis infections of the CNS and had no known tuberculosis exposure. The third case involved a child who was co-infected with methicillin-resistant Staph aureus (MRSA) and varicella zoster virus. The fourth case involved a child co-infected with Fusobacterium necrophorum and Streptococcus constellatus who developed meningitis and vasculitis and died from multifocal cerebral infarctions.

“These four cases emphasise the potential for SARS-CoV-2 to impede the host’s normal immune responses such that co-infections can work synergistically, contributing to a more severe clinical evolution of infection,” the researchers caution.

Summing up, they say, “Knowledge of the neuroimaging patterns of COVID-19 is important, as these patterns could be the first indication of SARS-CoV-2 infection in children with neurological abnormalities.”