Encephalopathy, agitation with confusion, and corticospinal signs were associated with severe COVID-19 in a case series from France.
In addition, three patients showed cerebral ischemic stroke on MRI, reported Ferhat Meziani, MD, PhD, of Strasbourg University Hospital, and co-authors, in a letter to the .
The study included 64 consecutive patients with COVID-19 and acute respiratory distress syndrome (ARDS) seen in two Strasbourg intensive care units (ICUs) from March 3 to April 3, 2020. Six patients were excluded because they had paralytic neuromuscular blockade when data were collected, or because they had died without a neurologic exam.
In the remaining 58 patients, COVID-19 was diagnosed by detecting the SARS-CoV-2 virus in reverse transcriptase-polymerase chain reaction (RT-PCR) assays of nasopharyngeal samples. Neurologic findings were seen in 14% (8 patients) on ICU admission and in 67% (39 patients) when sedation and a neuromuscular blocker were withheld.
Patients had a median age of 63 and a median Simplified Acute Physiology Score II () of 52, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness. Seven patients had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment.
When neuromuscular blockade was discontinued, 69% (40 patients) had agitation. A total of 26 of 40 patients had confusion according to the Confusion Assessment Method for the ICU algorithm.
"Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command," Meziani and co-authors noted.
Two-thirds of the sample (39 patients) had diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes.
Thirteen patients underwent MRI for nonfocal encephalopathy; two patients had small acute ischemic stroke and one had subacute ischemic stroke. In eight patients, leptomeningeal enhancement was seen. All 11 patients who underwent perfusion imaging showed bilateral frontotemporal hypoperfusion.
Eight patients underwent electroencephalography and showed nonspecific changes.
Cerebrospinal fluid (CSF) samples were available for seven patients. Oligoclonal bands were present in two patients with the same electrophoretic pattern in serum. CSF protein and IgG levels were elevated in one patient. For all seven patients, RT-PCR assays of CSF samples were negative for SARS-CoV-2.
Acute cerebrovascular events, impaired consciousness, and muscle injury also were reported in patients with severe COVID-19 infection in a small study in Wuhan, China recently.
In both reports, questions of causality remain unanswered. "Data are lacking to determine which of these features were due to critical illness-related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection," Meziani and colleagues wrote.
Disclosures
Researchers reported relationships with Johnson & Johnson, Actelion Pharmaceuticals, Teva, UCB, AbbVie, Aguettant, LVL, and Canon Medical Systems Europe.
Primary Source
New England Journal of Medicine
Helms J, et al "Neurologic features in severe SARS-CoV-2 infection" N Engl J Med 2020; DOI: 10.1056/NEJMc2008597.