Majid Fotuhi, MD, PhD, on the Neurobiology of COVID-19
Emerging data have shown that coronavirus disease 2019 (COVID-19) is associated with several neurological complications, including stroke, encephalopathy, delirium, and seizures, among others.
According to a new review published in the Journal of Alzheimer’s Disease, research has yet to reveal to what extent neurological complications associated with COVID-19 infection are due to acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19; the cytokine storm triggered by COVID-19; and the subsequent hypercoagulopathy and blood clots that form in blood vessels throughout the brain and the body.
Neurology Consultant spoke with lead author Majid Fotuhi, MD, PhD, a neurologist with the NeuroGrow Brain Fitness Center in McLean, Virginia, and Johns Hopkins Medicine in Baltimore, Maryland, about available data on short-term and long-term neurological complications of COVID-19, as well as the “NeuroCovid” classification scheme he and his colleagues developed in their review.
NEURO CON: How does the cytokine storm triggered by SARS-CoV-2 contribute to the neurological impact of COVID‑19?
Dr Fotuhi: In COVID-19, the cytokine storm, which is a flood of inflammatory markers such as IL‑1, IL‑6, and tumor necrosis factor-α, triggers the formation of blood clots. These blood clots can travel throughout the body to the heart, the liver, and the brain. In the brain, these blood clots can cause small and large strokes. With large strokes, patients experience immediate neurological symptoms, such as loss of control over half of their body, inability to speak, and sudden dizziness, and they are quickly hospitalized.
In more cases, though, patients with COVID-19 have several tiny strokes. These tiny strokes do not cause immediate symptoms, but simply make a person a little slower. For example, someone who has 10 tiny strokes smaller than a grain of rice may have difficulty with word finding, may be a little slower in doing mental math, and may take longer to write an article. Patients with COVID‑19 who are hospitalized and have neurological issues, such as dizziness, headaches, and loss of taste and/or smell may also be having tiny strokes in the brain. Unlike large strokes, which receive immediate attention and treatment, small strokes often go unnoticed.
When patients leave the hospital after recovering from COVID-19, they may feel they are not as sharp as they used to be. This is a problem because they will continue at that level, not knowing that COVID‑19 had impacted their brain. My colleagues and I refer to this as NeuroCovid Stage II, when the blood clots caused by the cytokine storm in turn cause strokes and neurological symptoms. In what my colleagues and I call NeuroCovid Stage III, the cytokine storm is even more pronounced, and it damages the lining of the blood vessels inside the brain. When that happens, the blood content including the cytokines reaches and penetrates the brain. Inside the brain, they cause toxicity, which kills brain cells. When that happens, the patient may experience confusion, encephalopathy, seizures, or coma. Patients who experience this may have long‑term consequences because the virus particles that reach the brain may remain dormant inside brain cells in the short term, but may contribute to conditions such as Parkinson disease or Alzheimer disease in the long term.
NEURO CON: Could you elaborate on the NeuroCOVID staging framework you and your colleagues developed and how the framework could impact clinical practice?
Dr Fotuhi: We have have proposed classifying neurological manifestations of COVID‑19 into 3 stages. NeuroCovid Stage I includes patients who only have issues with taste and smell. At this stage, the virus reaches the nose and mouth, but remains there. There may be some brain involvement or some degree of cytokine storm, but those are minor, and most patients recover within weeks. There are no negative outcomes or long‑term neurological consequences.
In the NeuroCovid Stage II, the cytokine storm is moderate, and blood clots are formed. In NeuroCovid Stage II, blood clots are the dominant issues that need to be addressed. These blood clots cause large or small strokes, and they also cause blood clots in the kidneys, liver, lungs, or heart. There are consequences in different organs, and these consequences can contribute to neurological issues. For example, if a patient has liver damage from COVID-19, this can cause confusion due to hepatic encephalopathy. In addition, antibodies may form, which can cause nerve or muscle damage.
In NeuroCovid Stage III, the cytokine storm is severe. It erodes the blood‑brain barrier, which may allow blood content to reach the brain. At this point, patients may experience confusion, delirium, seizures, coma, or even death. When the virus enters the brain, it can damage parts of the brain stem that control breathing and potentially make a patient stop breathing. Damage to the blood‑brain barrier results in cytokines and viruses reaching the brain parenchyma, which in turn leads to encephalopathy.
NEURO CON: Based on currently available data, could you discuss some of the neurological consequences, especially in the long‑term, that can set in after patients recover from COVID‑19?
Dr Fotuhi: We can say that, based on our experiences with previous epidemics of coronaviruses, patients may have neuropsychiatric symptoms, such as anxiety, depression, insomnia, or even bipolar disorder. They may also have long‑term neurocognitive issues, such as memory issues or dysexecutive function.
NEURO CON: Which patients who recover from COVID‑19 might benefit from seeing a neurologist for evaluation?
Dr Fotuhi: I think that all hospitalized patients with COVID-19 who have neurological symptoms, such as headaches, confusion, seizures, or coma, should undergo a brain MRI to detect any small or large strokes. After they recover from their acute symptoms, they should have a cognitive evaluation to establish where their cognitive abilities stand as compared with other people at their age. In terms of cognitive function, an average person should have scores around the 50th percentile for their age group. If their scores are in the 10th percentile, these patients need follow-up from a neurologist. If they have strokes, seizures, or paralysis, they should clearly follow-up with a neurologist as well.
NEURO CON: What key takeaways do you want to leave with neurologists on this topic?
Dr Fotuhi: I believe we need to emphasize that patients who are hospitalized with COVID‑19 and have neurological issues should undergo a brain MRI in the hospital, and should undergo neurocognitive testing shortly after discharge. The good news is that the brain fog secondary to COVID‑19 issues is treatable. Patients who have small strokes should receive brain rehabilitation. Vigorous exercise, better sleep, improved diet, meditation, and stress reduction can reverse the hypoxia or ischemia caused by COVID‑19. In my practice, at NeuroGrow Brain Fitness Center in Northern Virginia, we typically offer these interventions to patients with age‑related memory loss or concussion and found that more than 80% of such patients have significant improvements in their cognitive scores
—Christina Vogt
Reference:
Fotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheimer Dis. Published online June 8, 2020. doi:10.3233/JAD-200581