ABSTRACT
OBJECTIVE: Encephalopathy is a major neurological complication of severe Coronavirus Disease 2019 (COVID-19), but has not been fully defined yet. Further, it remains unclear whether neurological manifestations are primarily due to neurotropism of the virus, or indirect effects, like cerebral hypoxia. METHODS: We analysed the electroencephalograms (EEGs) of 19 consecutive patients with laboratory-confirmed COVID-19, performed at peak disease severity as part of their clinical management. Disease severity, respiratory failure, immune and metabolic dysfunction, sedation status, and neurological examination on the day of the EEG were noted. RESULTS: Severe encephalopathy was confirmed in 13 patients, all with severe COVID-19; 10 remained comatose off sedation, and five of them had alpha coma (AC). Disease severity, sedation, immune and metabolic dysfunction were not different between those with AC and those without. CONCLUSIONS: Severe COVID-19 encephalopathy is a principal cause of persisting coma after sedation withdrawal. The relatively high incidence of the rare AC pattern may reflect direct SARS-CoV-2 neurotropism with a predilection for the brainstem ascending reticular system. SIGNIFICANCE: Systematic early EEG detection of encephalopathy related to severe COVID-19 is important for the acute care and the management of long-term neurological and cognitive sequelae, and may help our better understanding of its pathophysiology.
Subject(s)
Brain Diseases/physiopathology , Brain/physiopathology , COVID-19/physiopathology , Coma/physiopathology , Adult , Aged , Aged, 80 and over , Brain Diseases/etiology , COVID-19/complications , Coma/etiology , Electroencephalography , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache "personal protection equipment-related headache" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barré syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.
Subject(s)
Ageusia/physiopathology , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Encephalitis/physiopathology , Guillain-Barre Syndrome/physiopathology , Headache/physiopathology , Olfaction Disorders/physiopathology , Pneumonia, Viral/physiopathology , Stroke/physiopathology , Ageusia/etiology , Betacoronavirus , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , Blood-Brain Barrier , Brain Ischemia/blood , Brain Ischemia/etiology , Brain Ischemia/immunology , Brain Ischemia/physiopathology , COVID-19 , Coma/etiology , Coma/physiopathology , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/immunology , Delirium/etiology , Delirium/physiopathology , Encephalitis/etiology , Encephalitis/immunology , Encephalomyelitis, Acute Disseminated/etiology , Encephalomyelitis, Acute Disseminated/immunology , Encephalomyelitis, Acute Disseminated/physiopathology , Fatigue/etiology , Fatigue/physiopathology , Guillain-Barre Syndrome/etiology , Headache/etiology , Humans , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/physiopathology , Leukoencephalitis, Acute Hemorrhagic/etiology , Leukoencephalitis, Acute Hemorrhagic/immunology , Leukoencephalitis, Acute Hemorrhagic/physiopathology , Myalgia/etiology , Myalgia/physiopathology , Olfaction Disorders/etiology , Pandemics , Personal Protective Equipment/adverse effects , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , SARS-CoV-2 , Stroke/blood , Stroke/etiology , Stroke/immunologyABSTRACT
Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness. ANN NEUROL 2020;88:851-854.