Table 1.

COVID 19 encephalopathy: pathogenetic hypotheses

	Clinical features	Mechanism	Course	Management	Outcome	Putative neuropathological findings
Secondary CNS damage	Not specific: fever, consciousness disorder, delirium	Indirect effect (fever, hypoxia, ischemia/hemorrhage, metabolic derangement, sepsis, toxins, concurrent conditions)	Acute/subacute	General measures: ventilatory support, O2, sedation, antibiotics, etc	Variable	Hypoxic and ischemic injuries
Direct CNS invasion	Not specific: confusion to coma, headache, seizures	Direct invasion of the CNS by SARS-CoV-2	Acute	Symptomatic therapy: steroids, antiepileptics, etc	Unknown (few reports)	SARS-CoV-2 RNA and proteins (rare) not associated with the severity of neuropathological changes
Immunomediate reaction to the virus	Prevalent “Frontal” symptoms and language impairment	Cytokine-mediated neuroinflammatory process	Few days	Immunotherapy	Reversal/attenuation	Mild abnormalities with inflammation by diffuse astrocytes and microglia activation and infiltration of cytotoxic T lymphocytes