The case-based reports ultimately suggest that more data collection is required, but highlight the observations of more than 60 patients, including a 5-patient cohort with Guillain-Barré syndrome.
Sabrina Ravaglia, MD, PhD, IRCCS Casimiro Mondino National Neurological Institute Foundation
Sabrina Ravaglia, MD, PhD
Two new case-based reports describing the neurologic features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 have been published in the New England Journal of Medicine, one of which centered around individuals with Guillain-Barré syndrome.1,2
The first reported on the more general neurologic features of 58 patients admitted to the hospital in France from March 3 to April 3, 2020, with acute respiratory distress syndrome (ARDS) due to COVID-19. The data were collected by Ferhat Meziani, MD, PhD, and colleagues from the University of Strasbourg.1
Meziani et al. noted that ARDS due to SARS-CoV-2 infection was observed to be linked with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. These findings were recorded in 14% (n = 8) of the patients upon ICU admission prior to treatment, and in 67% (n = 39) of the cohort when sedation and a neuromuscular blocker were withheld. Additionally, of the 13 patients who underwent brain MRI underwent due to unexplained encephalopathic features, 15.3% (n = 2) had single acute ischemic strokes.
“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,” they concluded.
The cohort was a median age of 63 years old with a median Simplified Acute Physiology Score II of 52 (interquartile range [IQR], 37—65). Of the 58 patients, 7 had a prior neurologic disorder, including transient ischemic attack, partial epilepsy, and mild cognitive impairment (MCI). All 58 patients had positive reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples for SARS-CoV-2, while assays of cerebrospinal fluid (CSF) samples were negative in all 7 patients with samples available.
The CSF samples from 7 of the patients showed no cells, 2 showed oligoclonal bands with an identical electrophoretic pattern in serum, and 1 showed elevated protein and Immunoglobulin G levels. In total, 8 patients underwent electroencephalography (EEG), though only nonspecific changes were observed, with a single patient having diffuse bifrontal slowing that is consistent with encephalopathy.
When the neuromuscular blockade was halted, agitation occurred in 69% (n = 40) of patients, and of those, 26 experienced confusion. Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were reported in 67% (n = 39) of the cohort. At the time of the data analysis, 45 patients had been discharged and 33% (n = 15) of those had dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to commands.
Additionally, the MRI data revealed that 8 of the 13 patients had enhancement in leptomeningeal spaces, while every patient who underwent perfusion (n = 11) reported bilateral frontotemporal hypoperfusion. Meziani et al. wrote that pair of patients who were asymptomatic had “small acute ischemic stroke with focal hyperintensity on diffusion-weighted imaging and an overlapping decreased apparent diffusion coefficient,” and another had a “subacute ischemic stroke with superimposed increased diffusion-weighted imaging and apparent diffusion coefficient signals.”
The second case-based report included 5 patients with Guillain-Barré syndrome who were admitted to hospitals in Italy from February 28 to March 21, 2020, and noted that Guillain-Barré syndrome with COVID-19 should be distinguishable from the late-stage critical illness neuropathy and myopathy.2
This assessment, conducted by Sabrina Ravaglia, MD, PhD, and colleagues at the IRCCS Casimiro Mondino National Neurological Institute Foundation, included 4 patients with a positive nasopharyngeal swab for SARS-CoV-2 at the onset of the neurologic syndrome, and 1 with a negative nasopharyngeal swab and negative bronchoalveolar lavage, though that patient had a positive serologic test for the virus. Analysis of CSF via real-time polymerase-chain-reaction assay was negative for SARS-CoV-2 for all 5 patients.
“On the basis of this observational series involving 5 patients, it is not possible to determine whether severe deficits and axonal involvement are typical features of COVID-19—associated Guillain-Barré syndrome,” Ravaglia and colleagues detailed. “We could not determine the effect of reduced vital capacity due to neuromuscular failure from Guillain-Barré syndrome in these patients, but such an effect might be considered if findings on chest imaging are not commensurate with the severity of respiratory insufficiency.”
Generalized, flaccid tetraparesis or tetraplegia evolved over a range of 36 hours to 4 days in 4 of the patients, of which 3 received mechanical ventilation. None of the patients had dysautonomic features.
The interval between COVID-19 symptoms and symptoms of Guillain-Barré syndrome ranged from 5 to 10 days, which Ravaglia et al, noted is similar to what is seen with Guillain-Barré syndrome that occurs during or after other infections. “Although many infectious agents have been associated with Guillain—Barré syndrome, there may be a propensity for preceding infection with Campylobacter jejuni, Epstein-Barr virus, cytomegalovirus, and Zika virus. There have been reports of an association between Guillain—Barré syndrome and coronavirus infections,” the group wrote.
The CSF analysis of these 5 patients revealed normal protein levels for 2 patients and a white-cell count of <5 per mm3. Antiganglioside antibodies were absent in the three patients who were tested. For 4 patients in the cohort, the first symptoms of their Guillain-Barré syndrome were lower-limb weakness and paresthesia, while 1 experienced facial diplegia followed by ataxia and paresthesia. MRI showed enhancement of the caudal nerve roots in 2 patients, enhancement of the facial nerve in 1 patient, and no signal changes in nerves in 2 patients.
Electrophysiological assessments revealed that compound muscle action potential amplitudes were low but were able to be collected and showed that 2 patients had prolonged motor distal latencies. Electromyography showed fibrillation potentials in 3 patients initially and in another after 12 days. These findings, the authors wrote, were consistent with a Guillain-Barré syndrome variant for 3 patients and a demyelinating process for 2 patients.
Recently, NeurologyLive spoke with Jennifer Frontera, MD, professor of neurology, NYU Langone, who is among many doctors in New York City dedicating their time to care for patients with COVID-19 who also have preexisting neurologic conditions. Watch her share her insight from that experience below.
1. Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. Published online April 15, 2020. doi: 10.1056/NEJMc2008597
2. Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. Published online April 17, 2020. doi: 10.1056/NEJMc2009191