To present five patients with neurological complications following COVID-19 infection or vaccination that were initially misdiagnosed as multiple sclerosis (MS).

COVID-19 is a relatively novel disease, therefore its interaction with the immune system is not yet fully understood. MS is an autoimmune disease of unknown cause that is characterized by inflammatory demyelination of the central nervous system (CNS). This study examines cases in which an unexpected immune response to COVID-19 or to COVID-19 vaccination presented with neurological manifestations that led to a diagnosis of MS. 

Five patients were referred to the treating neurologist for a second opinion as possible cases of MS. All the patients presented within 2-8 weeks post-COVID-19 vaccination (N=4) or one patient after contracting a COVID-19 infection. Clinical neurological examinations, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) and serum analysis were performed.

These patients presented with acute onset of neurological manifestations including weakness, sensory complaints, and brainstem or cerebellar dysfunction within a few weeks of receiving vaccination for COVID-19 or getting a COVID-19 infection. MRI imaging showed white matter lesions in the brain or spinal cord with or without contrast enhancement. CSF enzyme-linked immunosorbent assay (ELISA) studies showed highly elevated immunoglobulin G (IgG) levels against the spike protein receptor binding domain (S1-RBD) of the coronavirus. Some patients also had CSF oligoclonal bands. The patients were all followed for at least a year post-presentation. 

MS should be diagnosed with caution in patients with recent COVID-19 vaccination or infection. The presence of CSF antibodies to the S1-RBD suggests an immune response to COVID-19 in the CNS as the likely cause of these neurological complications. In patients developing acute neurological complaints in the period following COVID-19 infection or vaccination, CSF should be analyzed for reactivity against the S1-RBD.