The medical community continues to wrestle with the full implications of the COVID-19 pandemic. Data is surfacing daily based on the experiences of physicians working on the frontlines.

Now we must sort out this information to develop a more complete understanding of what it means. We also need to figure out how – or if – it should change the approach to caring for patients infected by the novel coronavirus. This is certainly true for neurologists as case information trickles in about neurologic signs and symptoms.

A recent case report in JAMA outlined the clinical course of an elderly patient with COVID-19 who developed encephalopathy. The authors of the paper mentioned other potential neurologic complications of the disease, including acute stroke, impaired consciousness, and skeletal muscle injury.

Another case study published in The Lancet on April 1 reports the first known presentation of Guillain-Barré syndrome in a patient with COVID-19. Other reports include trigeminal neuralgia, ataxia, and seizures.

Too Much Information?

But what is a neurologist supposed to do with this information? Case studies can’t offer the evidence needed to determine whether a causal relationship exists. Has COVID-19 caused some or all of these disorders? Or has it just hit so many people at once that a certain number are statistically going to have other coincidental health concerns?

Dr. Brad Klein

Dr. Brad Klein, who practices neurology in Pennsylvania, says that as more literature gets published he’s come to believe COVID-19 “can have a significant effect on the nervous system.” He cited a retrospective case series of patients with COVID-19 in Wuhan, China, as evidence.

The case series examined the clinical course of 214 patients with COVID-19. Of those patients, 146 had non-severe infections and 88 had severe infections. The study found that those with severe infection had more neurological manifestations. Patients with central nervous system (CNS) symptoms had “lower lymphocyte levels, platelet counts, and higher blood urea nitrogen levels compared with those without CNS symptoms.”

Similar observations were detailed in a follow-up response letter from France. Of the 64 patients admitted to two intensive care units for acute respiratory distress syndrome (ARDS) due to COVID-19, 58 (90.5 percent) had neurological manifestations.

Warning Signs

Klein outlines several possible mechanisms for these neurological effects. They include the potential ability of SARS-CoV-2 to use the ACE2 receptor to penetrate the nervous system in much the same way SARS-CoV does. There’s also concern that COVID-19 puts the patient in a hypercoagulable state, raising the risk for issues such as microemboli and stroke.

In fact, the authors of the JAMA study reported that rapid clinical deterioration from COVID-19 “could be associated with a neurologic event such as stroke, which would contribute to its high mortality rate.” While “could be associated” is far from definitive clinical fact, the findings of this case series do make two points clear:

  1. Neurologists should consider acute neurologic disease as a potential warning for an underlying COVID-19 infection. This should prompt appropriate treatment and measures to prevent transmission even when typical symptoms are absent, according to Klein. “Some patients may first experience symptoms from loss of smell, taste, headache, myalgia, or more severe symptoms like stroke or impaired consciousness early in the course of the disease,” he says. “As a result, providers should presume the patient has COVID-19 until proven otherwise. While we still need to consider the full differential diagnosis associated with a patient presenting with mental status change, we should now include encephalopathy due to COVID-19 on our short list.”
  2. Appropriate surveillance of those with severe COVID-19 disease should be standard. The implications of COVID-19 on neurological health appear to be real and significant, if not fully elucidated. Again, Klein emphasizes this point: “There are a number of different coronaviruses, and each has a number of reports and papers revealing varying neurological manifestations, including severe acute disseminated encephalomyelitis, vasculopathy, and Guillain-Barré syndrome. While these diseases appear relatively rare, we need to appreciate that we don’t yet have the full breadth of knowledge as to what COVID-19 can do to a person.”

Having the Scientific Wherewithal

We are just beginning our understanding of SARS-CoV-2 and COVID-19. Sadly, though, there is no orientation period for a pandemic. Klein, however, offers some hope and a charge for moving forward.

“As the dust settles, and clinicians and scientists have the time to digest the enormous amount of data created within hospitals and large health systems, we should be able to better understand the probability of neurological comorbidities across the board,” he says.

Watchfulness will give us our best opportunity to understand future viruses and keep ourselves from being caught off guard when they arise. Another key will be continuing to share clinical experience.

“While we will overcome this challenge, I hope this event proffers a productive, future discussion and reflection within the governments of the world to better remember and appreciate the value in communication, collaboration, and having the scientific wherewithal available to prevent any similar calamities,” Klein adds. “Time will tell.”

Brad Klein, MD, MBA practices neurology with Abington Neurological Associates in the Philadelphia area. You can connect with him on LinkedIn.