Encephalopathy, other neurologic manifestations occur frequently in COVID-19

Neurologic manifestations occurred often in a large cohort of patients with COVID-19, regardless of respiratory disease severity, according to a retrospective analysis conducted in the Chicago area during the early months of the pandemic.

The analysis found that encephalopathy — the third most frequently observed neurological manifestation — correlated independently with worse functional outcomes and greater mortality. Researchers published their findings in Annals of Clinical and Translational Neurology.

Igor J. Koralnik

“Encephalopathy, which is characterized by altered mental function ranging from mild confusion to coma, is the most severe neurologic manifestation of COVID-19,” Igor J. Koralnik, MD, FAAN, FANA, chief of neuro-infectious diseases and global neurology and Archibald Church professor of neurology at Northwestern University’s Feinberg School of Medicine, told Healio Neurology. “The frequency and magnitude of the problem was surprising compared to two similar studies that found neurologic manifestations in 36% of hospitalized patients in China and 57% in Spain. This may be caused by ethnic differences between the populations or potentially variations in the virus that are occurring over time.”

Koralnik, along with Eric M. Liotta, MD, MS, assistant professor of neurology (stroke and neurocritical care) and surgery (organ transplantation) at Northwestern University’s Feinberg School of Medicine, and colleagues gathered data on the first consecutive patients with COVID-19 admitted to Northwestern Medicine Healthcare, which includes one academic medical center and nine other hospitals in the Chicago area, between March 5, 2020, and April 6, 2020.

The day data collection began, March 5, the Illinois Department of Public Health announced the fifth confirmed positive case of COVID-19 in the state. Four days after researchers began collecting data, on March 9, Gov. J. B. Pritzker, D-Ill., declared a state of disaster in Illinois. Later that month, on March 20, Pritzker announced that COVID-19 had “rapidly spread throughout Illinois” in an executive order that enacted a stay-at-home order, social distancing guidelines and a moratorium of non-essential business operations, public or private gatherings and evictions.

Liotta and colleagues’ retrospective analysis compared COVID-19 severity and outcomes in patients who had neurologic manifestations and in patients who did not. The researchers used Northwestern Medicine Healthcare’s integrated templates that were instituted as part of the COVID-19 response to identify neurologic manifestations and dates of onset for those manifestations, as well as COVID-19 symptoms.

The final study population included 509 patients. Patients had a mean age of 58.51, 55.2% were men and 26.3% had a history of a neurological disorder.

Most patients (n = 419; 82.3%) experienced a neurologic manifestation at some point while infected with COVID-19 and 134 (26.3%) required mechanical ventilation. The most common neurological manifestations included myalgias (n = 228; 44.8%), headaches (n = 192; 37.7%), encephalopathy (n = 162; 31.8%), dizziness (n = 151; 29.7%), dysgeusia (n = 81; 15.9%) and anosmia (n = 58; 11.4%). Other neurological pathologies, including ischemic and hemorrhagic stroke, movement disorders, focal motor and sensory deficits, ataxia and seizures, were not common. These issues affected only 0.2% to 1.4% of the study population, according to the researchers. Koralnik and colleagues reported no cases of Guillain-Barre syndrome or acute demyelinating encephalomyelitis.

Patients with neurologic manifestations went to the hospital more days after symptom onset (7 vs. 5 days; P = .003) and were younger (57.53 vs. 62.98 years; P = .005) compared with patients who had no neurologic manifestations. Researchers wrote that the greater likelihood for neurologic manifestations among younger patients was “surprising” and said it could be due to “greater clinical emphasis on the risk [for] respiratory failure than other symptoms in older patients” or that neurologic manifestations may have prompted younger patients to seek medical care earlier.

However, patients with encephalopathy were older than those without this neurological condition (65.51 vs. 55.22 years; P < .001) and went to the hospital fewer days after symptom onset (6 vs. 7 days; P = .014). Patients with severe COVID-19 more frequently had encephalopathy (84.3% vs 13.1%; P < .001) and neurologic manifestations overall (92.5% vs. 78.9%; P = .001).

Pandemic-related restrictions prevented extensive diagnostic testing for most patients in the study, according to the researchers, but “the most likely etiology of encephalopathy in patients with COVID-19 is multifactorial, including systemic disease and inammation, coagulopathy, direct neuroinvasion by the virus, endotheliitis and possibly post-infectious auto-immune mechanisms.”

The long-term effect of COVID-19 on the nervous system “remains uncertain” 9 months into the pandemic, Koralnik and colleagues wrote. “Our results suggest that, of all neurologic manifestations, encephalopathy is associated with a worse functional outcome in hospitalized patients with COVID-19 and may have lasting effects.”

Koralnik, who leads the Neurology COVID-19 clinic team at Northwestern Memorial Hospital, and his colleagues are studying those potential lasting effects.

“We are now looking to characterize the long-term neurologic effects of COVID-19 and the cognitive outcomes in patients with COVID-19-associated encephalopathy,” he told Healio Neurology. “We’re studying this in patients who are discharged from the hospital, as well as in COVID-19 ‘long-haulers,’ who have never been hospitalized but also suffer from a similar range of neurological problems, including brain fog.”

References:

• Illinois Department of Public Health (2020). Public health officials announce fifth case of coronavirus disease in Illinois. Accessed Oct. 20, 2020. http://www.dph.illinois.gov/news/public-health-officials-announce-fifth-case-coronavirus-disease-illinois.
• State of Illinois (2020). Gubernatorial disaster proclamation. Accessed Oct. 20, 2020. https://www2.illinois.gov/sites/gov/Documents/CoronavirusDisasterProc-3-12-2020.pdf.
• State of Illinois (2020). Executive order in response to COVID-19 (COVID-19 executive order no. 8). Accessed Oct. 20, 2020. https://www2.illinois.gov/pages/executive-orders/executiveorder2020-10.aspx.