Q&A: Small neuroimaging study shows ‘markedly distinct’ findings in patients with COVID-19

Research into the neurological manifestations of COVID-19 continues as investigators also examine the impact of COVID-19 on comorbid neurological diseases, including MS and epilepsy.

Findings presented at MSVirtual2020 demonstrated that Expanded Disability Scale Status and age served as independent risk factors for severe COVID-19 infection in patients with MS. Another study showed that, for patients with epilepsy, negative effects of the COVID-19 pandemic included heightened seizure frequency and an increase in comorbid psychiatric disorders, among other concerns.

Regarding the neurological manifestations of COVID-19, one study demonstrated that SARS-CoV-2 spike proteins have a “direct impact” on endothelial cells in the brain. That study offered a “plausible explanation” for the neurological manifestations seen with the disease, according to the researchers. Another retrospective analysis conducted during the early months of the pandemic showed that these neurological symptoms occured frequently in patients with COVID-19, regardless of respiratory disease severity.

A new study in American Journal of Neuroradiology used magnetic resonance spectroscopy to image the brains of three patients with COVID-19, including one patient with COVID-19-associated necrotizing leukoencephalopathy, another patient who had a recent pulseless electrical activity cardiac arrest with subtle white matter changes and a patient without frank encephalopathy or a recent severe hypoxic episode. Healio Neurology spoke with Eva-Maria Ratai, PhD, associate professor of radiology at Harvard Medical School and assistant in neuroscience at Massachusetts General Hospital, about the potential implications of the small study.

Q: Why did you choose to use 3 - Tesla Magnetic Resonance Spectroscopy specifically for this study?

A: While standard MRI shows structural abnormalities in the brain (eg, white matter lesions), magnetic resonance spectroscopy (MRS) is able to measure neurochemical abnormalities in the brain. MRS may provide valuable information for clinicians to find out if SARS-CoV-2 produces neuronal injury, demyelination, neuroinflammation or hypoxia.

Q: What were the primary findings?

A: The three consecutive patients with COVID-19 presented markedly distinct MRI and MRS findings. The most severe metabolic abnormalities were seen in an intubated patient who was treated in our ICU. He showed several white matter lesions — so-called necrotizing encephalopathy. This patient’s MRS showed reductions in N-Acetyl-aspartate, indicating neuronal injury/loss, as well as choline and myo-inositol elevation, indicating demyelination and neuroinflammation, respectively. In addition, we saw a pronounced lactate elevation consistent with silent hypoxia. Interestingly, this spectral pattern has been previously reported in the setting of delayed post-hypoxic leukoencephalopathy following carbon monoxide poisoning or medication overdose.

Q: How do these results inform our understanding of neurological complications of COVID-19?

A: Understanding metabolic abnormalities helps inform us of the underlying pathologic mechanisms associated with central nervous system consequences of COVID-19. Thus, insights gained by neuroimaging studies, including MR Spectroscopy, will be critical for developing disease-modifying therapies.

Q: What are the next steps for this research?

A: Most neuroimaging studies have been performed during the acute phase of COVID-19 infection. Following the acute phase, approximately 10% of patients experience prolonged illness, during which neurological symptoms (headaches, ‘brain fog’ and fatigue) are among the top 10 symptoms reported by COVID-19 survivors. The underlying biology of these prolonged symptoms is unknown; therefore, prospective studies to systematically investigate the pathophysiology of such sequelae are urgently needed.

Researcher at Massachusetts General Hospital, together with five other institutions — the University of Minnesota, Mayo Clinic Rochester, Johns Hopkins University, Houston Methodist Research Institute and the Laboratory of Neuro Imaging at the University of Southern California — formed the COVID BRain Advanced Imaging Network (COVID-BRAIN) Consortium and have applied for NIH funding to systematically elucidate the long-term CNS pathophysiology of COVID-19 using advanced MRI/MRS technology in conjunction with standardized neurological and neuropsychological evaluation.