Neurologic Aspects of Coronavirus Disease of 2019 Infection

Catherine E. Hassett; Jennifer A. Frontera


Curr Opin Infect Dis. 2021;34(3):217-227. 

In This Article

Postinfectious Neurologic Complications

Guillain-Barré Syndrome

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most common variant of Guillain-Barré Syndrome, is an autoimmune demyelinating disorder of the peripheral nervous system usually following an antecedent infection.[68] Molecular mimicry may occur between epitopes of COVID-19 spike bearing gangliosides and peripheral nerve glycolipids, similar to the well-established cross-reactivity described in Campylobacter jejuni and Zika virus infections.[68] There are several cases of patients developing axonal and demyelinating AIDP variants, including Miller Fisher Syndrome, pharyngeal–cervical–brachial and polyneuritis cranialis after the onset of COVID-19 symptoms.[27,68–71] One of the earliest case series in the pandemic reported five patients presenting with paraplegia, facial muscle weakness, and areflexia 5–10 days after COVID-19 symptom onset.[70] Three patients had the pathognomonic CSF findings of albuminocytologic dissociation consistent with Guillain-Barre[Combining Acute Accent] Syndrome, but all tested negative for SARS-CoV-2 using PCR of the CSF. All patients were treated with intravenous immunoglobulin, but only two patients had clinical improvement at the time of publication.

Postinfectious Encephalitis

In acute viral encephalitis, viral replication occurs in the brain tissue leading to significant CNS insults.[72] In vivo studies of human coronavirus-OC43 infected mice have shown that human coronaviruses can infect neurons and subsequently cause persistent infection in human neural-cell lines.[9,10] Encephalitis has been proposed in COVID-19 patients to explain a wide variety of neurologic manifestations including headache, irritability, confusion, psychotic symptoms, and neck stiffness, however, definitive clinical evidence of primary SARS-CoV-2 encephalitis remains elusive. More data exists supporting the possibility of postinfectious or autoimmune encephalitis following SARS-CoV-2 infection. Rare cases of probable acute disseminated encephalomyelitis (ADEM) and acute necrotizing encephalitis have been reported in SARS-CoV-2.[72–74] CSF SARS-CoV-2 PCR has been negative in these reported cases. Patients have been treated with intravenous immunoglobulin or intravenous methylprednisolone with neurologic improvement. Despite multiple case reports, these postinfectious COVID-19 complications appear to be exceedingly rare.