Frontal encephalopathy related to hyperinflammation in COVID-19

Cani, Ilaria; Barone, Valentina; D’Angelo, Roberto; Pisani, Lara; Allegri, Vincenzo; Spinardi, Luca; Malpassi, Paola; Fasano, Luca; Rinaldi, Rita; Fanti, Stefano; Cortelli, Pietro; Guarino, Maria

doi:10.1007/s00415-020-10057-5

Cited by 39 publications

(71 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Aphasia was accompanied by manifestations consistent with dysexecutive syndrome and behavioral symptoms, suggesting a frontal lobe dysfunction. The latter is emerging as a recurrent feature of COVID-19-related encephalopathy (Cani et al, 2020;Helms et al, 2020;Koralnik and Tyler, 2020) and it is possible that the language disturbances observed in our patient as well as in previous reports are secondary to this network's dysfunction. CSF analysis showed a slightly increased cellularity and negative PCR for SARS-CoV-2.…”

Section: Discussionsupporting

confidence: 67%

“…CSF analysis showed a slightly increased cellularity and negative PCR for SARS-CoV-2. Even though these findings cannot rule out CNS viral invasion with certainty, we believe more likely an immuno-mediated para-infectious pathogenic mechanism underlying the neurological manifestations of our patient, also according to the emerging evidence supporting an inflammatory, cytokine-mediated, pathogenesis in a subset of patients with COVID-19-related encephalopathy (Beach et al, 2020;Cani et al, 2020;Muccioli et al, 2020;Pilotto et al, 2020). The relationship between the disclosed oligoclonal bands in the present report and COVID-19 remains unclear.…”

Section: Discussionmentioning

confidence: 49%

“…As COVID-19-related encephalopathy may have a self-limited course even without a specific therapy (Beach et al, 2020;Cani et al, 2020;Bernard-Valnet et al, 2020), it is possible that clinical recovery in our patient occurred spontaneously. However, taking into account the clear relationship in time, neuropsychiatric symptoms may have resolved as a consequence of treatment with tocilizumab.…”

Section: Discussionmentioning

confidence: 92%

See 2 more Smart Citations

COVID-19-related encephalopathy presenting with aphasia resolving following tocilizumab treatment

Muccioli

Pensato

Cani

et al. 2020

Journal of Neuroimmunology

Self Cite

View full text Add to dashboard Cite

Encephalopathy is emerging as a recurrent complication of COVID-19 yet remains poorly characterized. We report the case of a middle-aged woman with COVID-19-related encephalopathy presenting as expressive aphasia and inattentiveness, subsequently progressing to agitation and marked confusion. Brain MRI and CSF analysis were unremarkable, while EEG showed slowing with frontal sharp waves. Neuropsychiatric symptoms resolved following treatment with tocilizumab. CNS involvement in COVID-19 may present as a subacute encephalopathy characterized by prominent frontal lobe dysfunction, with language disturbances as first neurological manifestation. Future studies should further investigate the role of tocilizumab in treating COVID-19-related encephalopathy.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

COVID-19-related encephalopathy presenting with aphasia resolving following tocilizumab treatment

Muccioli

Pensato

Cani

et al. 2020

Journal of Neuroimmunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…An autoantibody-mediated mechanism is unlikely to explain CNS involvement, based on the brief temporal interval between CNS and infection-related symptom onset, negative testing for anti-neuronal antibodies, and the prompt and sustained response to IVIg [15]. Cytokine-mediated neuroinflammation has been implicated in the underlying pathogenic mechanism of COVID-19-associated encephalopathy, and may have contributed to disease course in our patients [5][6][7][8][9][10]. Except the third case, all patients suffered acute respiratory distress secondary to CRS induced by SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 84%

Intravenous immunoglobulin therapy in COVID-19-related encephalopathy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Objective To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. Methods We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. Results Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19–55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1–10 days). No adverse events related to IVIg were observed. Conclusions Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.

show abstract

“…Accordingly, clinical responses observed to various immunomodulatory treatments, such as corticosteroids (13,14) and plasmapheresis (15), suggest an immune-mediated pathogenesis, at least for a subgroup of patients. Recently, cytokine-mediated neuroinflammation has been proposed as the underlying pathogenesis of COVID-19-related encephalopathy/encephalitis (7,13,16), a peculiar pathogenic mechanism also responsible for immune effector cell-associated neurotoxicity syndrome (ICANS) (17)(18)(19)(20). This is a neuropsychiatric complication of chimeric antigen receptor T-cell therapy, which also shares clinical features with encephalopathy related to COVID-19 (20) and is typically associated with cytokine release syndrome (18).…”

Section: Discussionmentioning

confidence: 99%

Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.

show abstract

Frontal encephalopathy related to hyperinflammation in COVID-19

Cited by 39 publications

References 8 publications

COVID-19-related encephalopathy presenting with aphasia resolving following tocilizumab treatment

COVID-19-related encephalopathy presenting with aphasia resolving following tocilizumab treatment

Intravenous immunoglobulin therapy in COVID-19-related encephalopathy

Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke

Contact Info

Product

Resources

About