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Functional MRI Detects Intact Brain Network in Patient Unresponsive After COVID-19

Key findings

  • A 47-year-old man who survived critical illness with COVID-19 fluctuated between coma and a minimally conscious state for several weeks after being weaned from mechanical ventilation
  • The studies typically used for neuroprognostication were either equivocal (electroencephalography) or concerning (structural brain MRI)
  • However, resting state functional MRI showed intact brain network connectivity
  • In discussions with families of patients with COVID-19 who have prolonged disorders of consciousness, clinicians should acknowledge uncertainty about neurologic prognosis

Many patients who survive severe COVID-19 experience a prolonged disorder of consciousness. Brain lesions have been found on structural MRI in less than half of such patients, and their impact on brain function and neurologic recovery are unknown. Thus, the utility of structural neuroimaging for predicting neurologic outcomes in COVID-19 is unclear.

In post-anoxic patients and survivors of cardiac arrest, resting state functional MRI (rs-fMRI) has proven more effective than structural neuroimaging for neuroprognostication. In the Annals of Neurology, David Fischer, MD, neurologist, and Brian L. Edlow, MD, associate director of the Center for Neurotechnology and Neurorecovery at the Department of Neurology at Massachusetts General Hospital, and colleagues report similar findings in a critically ill patient with severe COVID-19 and prolonged unresponsiveness.

Introduction to the Case

On day 1 of hospitalization for COVID-19, a 47-year-old man developed progressive respiratory failure and was transferred to the ICU. He required mechanical ventilation for over 40 days and developed shock, renal failure and pneumomediastinum.

The patient was weaned from sedation on hospital day 20, but for the next several weeks he fluctuated between coma and a minimally conscious state. He intermittently visually tracked an examiner but otherwise did not demonstrate purposeful behaviors. The clinician's noted:

  • Electroencephalography on day 39 was equivocal; it showed disorganized delta–theta slowing but no evidence of seizures or epileptiform discharges
  • Structural brain MRI on day 40 was concerning; it showed symmetric T2 hyperintensity of the bilateral basal ganglia, medial thalami and parahippocampal gyri, as well as diffusion restriction of the basal ganglia

Functional Neuroimaging

As part of a clinical MRI protocol, the authors used rs-fMRI to evaluate the patient's default mode network (DMN), a functional brain network thought to be involved in human consciousness. Unexpectedly, rs-fMRI revealed robust functional connectivity within the four DMN nodes studied—the medial prefrontal cortex, posterior cingulate cortex and bilateral inferior parietal lobules.

In fact, DMN connectivity was comparable between the patient and five healthy controls. In another unresponsive individual, scanned with identical rs-fMRI parameters, diminished DMN connectivity was observed, illustrating that DMN connectivity is not necessarily present in patients with disorders of consciousness.

When presented with the discordant prognostic data, the patient's family chose to have life-sustaining treatment continued. By hospital day 61, his level of consciousness had improved to the point of following commands, and by day 66 he consistently demonstrated gaze tracking to visual and auditory stimuli.

Applying Findings to Practice

Patients with disorders of consciousness after severe COVID-19 may have intact functional brain networks despite structural brain injury. Clinicians should exercise caution before presuming a poor neurologic outcome based on EEG or structural MRI and acknowledge uncertainty about neurologic prognosis during discussions with families.

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In six patients who recovered from COVID-19 respiratory failure, Massachusetts General Hospital researchers found MRI evidence of white matter–specific injury, which may have been due to the sequela of profound hypoxemia.