Neurological symptoms and neuroimaging alterations related with COVID-19 vaccine: Cause or coincidence?

Although vaccination against Coronavirus disease-2019 (COVID-19) is still occurring, several adverse effects temporally related to these vaccines are already being reported, even if through isolated case reports. In the present study, we describe the lesions seen on magnetic resonance imaging (MRI) of three patients who developed neurological symptoms after receiving the ChAdOX1 nCoV-19 vaccine (Oxford/AstraZeneca). The first patient presented with an ischemic stroke in the posterior limb of the left internal capsule, two days after vaccination. The second patient presented with a left facial nerve palsy, seven days after vaccination. The third patient presented with myelitis, eight days after receiving the vaccine. All patients presented the symptoms after the first dose of the vaccine and did not have a history of previous COVID-19. The real incidence of these types of complications is not known yet, but it is important to consider the possibility of COVID-19 vaccine complications, in patients with a recent history of vaccination and recent development of neurological symptoms, even though this association is only casual. Longitudinal studies are necessary to further analyze the incidence of the adverse effects of each vaccine against SARS-CoV-2.

Clinical and radiological features of severe acute respiratory syndrome coronavirus 2 meningo-encephalitis.

BACKGROUND AND PURPOSE: This case illustrates for the first time the clinical and radiological evolution of SARS-CoV-2 meningo-encephalitis. METHODS: A case of a SARS-CoV-2 meningo-encephalitis is reported. RESULTS: A 65-year-old man with COVID-19 presenting with meningo-encephalitis without respiratory involvement is described. He had fever, diarrhea and vomiting, followed by diplopia, urinary retention and sleepiness. Examination disclosed a convergence strabismus and ataxia. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, oligoclonal bands and increased interleukin 6 level. SARS-CoV-2 was detected in the CSF through reverse transcriptase polymerase chain reaction, but not in nasopharyngeal, tracheal secretion and rectal samples. Brain magnetic resonance imaging showed lesions on white matter hemispheres, the body and splenium of the corpus callosum and resembling the projection of corticospinal tract, remarkably on cerebellar peduncles. CONCLUSIONS: This demonstrates the challenges in diagnosing COVID-19 in patients with neurological presentations.

Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019.

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.

Isolated intracranial hypertension associated with COVID-19.

BACKGROUND: Headache is a frequent complaint in COVID-19 patients. However, no detailed information on headache characteristics is provided in these reports. Our objective is to describe the characteristics of headache and the cerebrospinal fluid (CSF) profile in COVID-19 patients, highlighting the cases of isolated intracranial hypertension. METHODS: In this cross-sectional study, we selected COVID-19 patients who underwent lumbar puncture due to neurological complaints from April to May 2020. We reviewed clinical, imaging, and laboratory data of patients with refractory headache in the absence of other encephalitic or meningitic features. CSF opening pressures higher than 250 mmH2O were considered elevated, and from 200 to 250 mmH2O equivocal. RESULTS: Fifty-six COVID-19 patients underwent lumbar puncture for different neurological conditions. A new, persistent headache that prompted a CSF analysis was diagnosed in 13 (23.2%). The pain was throbbing, holocranial or bilateral in the majority of patients. All patients had normal CSF analysis and RT-qPCR for SARS-CoV-2 was negative in all samples. Opening pressure >200 mmH2O was present in 11 patients and, in six of these, > 250 mmH2O. 6/13 patients had complete improvement of the pain, five had partial improvement, and two were left with a daily persistent headache. CONCLUSIONS: In a significant proportion of COVID-19 patients, headache was associated to intracranial hypertension in the absence of meningitic or encephalitic features. Coagulopathy associated with COVID-19 could be an explanation, but further studies including post-mortem analysis of areas of production and CSF absorption (choroid plexuses and arachnoid granulations) are necessary to clarify this issue.

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development.

OBJECTIVES: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. METHODS: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. RESULTS: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. CONCLUSION: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.

Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.

We report that patients with COVID-19 displaying distinct neurological disorders have undetectable or extremely low levels of SARS-CoV-2 RNA in the cerebrospinal fluid, indicating that viral clearance precede the neurological involvement. This finding points to the need for the development of more sensitive molecular tests and the investigation of other neurotropic pathogens to exclude concurrent neuroinfection.