Neurologic Symptoms and COVID-19:
What's Known, What Isn't

Damian McNamara

April 05, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's  Coronavirus Resource Center.

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus' prodromal symptoms and severe respiratory effects.  

However, US neurologists are now reporting that COVID-19 symptoms may also could include encephalopathy, ataxia, and other neurologic signs. 

"I am hearing about strokes, ataxia, myelitis, etc," Stephan Mayer, MD, a neurointensivist in Troy, Michigan, posted on Twitter on March 26.

Other possible signs and symptoms include subtle neurologic deficits, severe fatigue, trigeminal neuralgia, complete/severe anosmia, and myalgia as reported by clinicians who responded to the tweet.

Last week, as reported by by Medscape Medical News, the first presumptive case of encephalitis linked to COVID-19 was documented in a 58-year-old woman treated at Henry Ford Health System in Detroit.

Physicians who reported the acute necrotizing hemorrhagic encephalopathy case in the journal Radiology counseled neurologists to suspect the virus in patients presenting with altered levels of consciousness.

Researchers in China also reported the first presumptive case of Guillain-Barre syndrome associated with COVID-19. A 61-year-old woman initially presented with signs of the autoimmune neuropathy GBS, including leg weakness, and severe fatigue after returning from Wuhan, China. She did not initially present with the common COVID-19 symptoms of fever, cough, or chest pain.

Her muscle weakness and distal areflexia progressed over time. On day 8, the patient developed more characteristic COVID-19 signs, including 'ground glass' lung opacities, dry cough, and fever. She was treated with antivirals, immunoglobulins, and supportive care, recovering slowly until discharge on day 30.

"Our single-case report only suggests a possible association between GBS and SARS-CoV-2 infection. It may or may not have causal relationship. More cases with epidemiological data are necessary," senior author Sheng Chen, MD, PhD, told Medscape Medical News.

However, "we still suggest physicians who encounter acute GBS patients from pandemic areas protect themselves carefully and test for the virus on admission. If the results are positive, the patient needs to be isolated," added Chen, a neurologist at Shanghai Ruijin Hospital and Shanghai Jiao Tong University School of Medicine in China.

Neurologic presentations of COVID-19 "are not common, but could happen," Chen added. Headache, muscle weakness and myalgias have been documented in other patients in China, he said.

We know almost nothing about the potential interactions between COVID-19 and the nervous system. Dr Robert Stevens, Johns Hopkins School of Medicine, Baltimore

Early Days

Despite this growing number of anecdotal reports and observational data documenting neurologic effects, the majority of patients with COVID-19 do not present with such symptoms.

"Most COVID-19 patients we have seen have a normal neurological presentation. Abnormal neurological findings we have seen include loss of smell and taste sensation, and states of altered mental status including confusion, lethargy, and coma," Robert Stevens, MD, who focuses on neuroscience critical care at the Johns Hopkins School of Medicine in Baltimore, Maryland, told Medscape Medical News.

Other groups are reporting seizures, spinal cord disease, and brain stem disease. It has been suggested that brain stem dysfunction may account for the loss of hypoxic respiratory drive seen in a subset of patients with severe COVID-19 disease, he added.  

However, Stevens, who plans to track neurologic outcomes in COVID-19 patients, also cautioned that it's still early and these case reports are preliminary.  

"An important caveat is that our knowledge of the different neurological presentations reported in association with COVID-19 is purely descriptive. We know almost nothing about the potential interactions between COVID-19 and the nervous system," he noted.

He added it's likely that some of the neurologic phenomena in COVID-19 are not causally related to the virus.

"This is why we have decided to establish a multisite neuro-COVID-19 data registry, so that we can gain epidemiological and mechanistic insight on these phenomena," he said.

Nevertheless, in an online report February 27 in the Journal of Medical Virology, Yan-Chao Li, MD, and colleagues write that "increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system, inducing neurological diseases."

Li is affiliated with the Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, China.

A Global View

Scientists observed SARS-CoV in the brains of infected people and animals, particularly the brainstem, they note. Given the similarity of SARS-CoV to SARS-CoV2, also known as COVID-19, the researchers suggest a similar invasive mechanism could be occurring in some patients.

Although it hasn't been proven, Li and colleagues suggest COVID-19 could act beyond receptors in the lungs, traveling via "a synapse‐connected route to the medullary cardiorespiratory center" in the brain. This action, in turn, could add to the acute respiratory failure observed in many people with COVID-19.

Other neurologists tracking and monitoring case reports of neurologic symptoms potentially related to COVID-19 include Mayer and Amelia Boehme, PhD, MSPH, an epidemiologist at Columbia University specializing in stroke and cardiovascular disease.

Boehme suggested on Twitter that the neurology community conduct a multicenter study to examine the relationship between the virus and neurologic symptoms/sequelae.  

Medscape Medical News interviewed Michel Dib, MD, a neurologist at the Pitié Salpêtrière hospital in Paris, who said primary neurologic presentations of COVID-19 occur rarely — and primarily in older adults. As other clinicians note, these include confusion and disorientation.  He also reports cases of encephalitis and one patient who initially presented with epilepsy.

Initial reports also came from neurologists in countries where COVID-19 struck first. For example, stroke, delirium, epileptic seizures and more are being treated by neurologists at the University of Brescia in Italy in a dedicated unit designed to treat both COVID-19 and neurologic syndromes, Alessandro Pezzini, MD, reported in Neurology Today, a publication of the American Academy of Neurology.

Pezzini notes that the mechanisms behind the observed increase in vascular complications warrant further investigation. He and colleagues are planning a multicenter study in Italy to dive deeper into the central nervous system effects of COVID-19 infection.

Clinicians in China also report neurologic symptoms in some patients. A study of 221 consecutive COVID-19 patients in Wuhan revealed 11 patients developed acute ischemic stroke, one experienced cerebral venous sinus thrombosis, and another experienced cerebral hemorrhage.

Older age and more severe disease were associated with a greater likelihood for cerebrovascular disease, the authors report.

Chen and Li have disclosed no relevant financial relationships.

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