- An acute or subacute derangement in consciousness and/or cognition
- Limited data exist on neurologic complications of COVID-19, but one study of 214 patients with confirmed diagnosis at three hospitals in Wuhan, China, found that 14.8% of those with severe disease and 2.4% of those without severe disease were found to have impaired consciousness 
- Those affected were more likely to be older, with comorbidities including hypertension
- Other coronavirus infections have been linked to acute disseminated encephalomyelitis (ADEM) in children 
- Direct CNS involvement by the virus, possibly via hematogenous or lymphatic dissemination or through invasion of peripheral nerve terminals with subsequent trans-synaptic transfer .
- Secondary toxic/metabolic encephalopathy as a consequence of metabolic derangements or medications.
- Para-infectious or inflammatory processes, e.g. ADEM.
- Other indirect mechanisms, including subclinical seizure: 10 percent of critically ill patients with sepsis may be experiencing subclinical seizures .
- Although rare, cases in the literature describe encephalitis or meningoencephalitis in association with COVID-19 [5-8]
- In one of 4 cases, nasopharyngeal SARS-CoV-2 testing resulted negative,5 and in a second case, there were no preceding respiratory symptoms 
- In case with associated respiratory symptoms, onset of encephalopathy ranged from concomitant with respiratory symptoms to day 9 after the onset of respiratory symptoms [7,8]
- Symptomatology: decreased level of consciousness, generalized tonic-clonic seizures, confusion, photophobia.
- Physical examination features: nuchal rigidity, hyperreflexia.
- Imaging findings: head CT may be normal; MRI may show a range of findings, including diffusion-restriction or FLAIR hyperintensity involving the ventricles, temporal lobes or bilateral thalami, as well as hemorrhagic lesions in rare cases; in cases of meningitis, imaging may reveal meningeal enhancement.
- Cerebrospinal fluid findings: basic studies range from normal to lymphocytic pleocytosis with elevated protein; SARS-CoV-2 PCR may be positive in CSF if tested, though the CSF titer may also be undetectable or extremely low.
Evaluation and Management:
- Evaluate for metabolic etiologies of encephalopathy with complete blood count, coagulation studies, electrolyte panel, and examination of calcium, magnesium, phosphate, glucose, blood urea nitrogen, creatinine, bilirubin, liver enzymes, ammonia, serum osmolality, and arterial blood gases, as metabolic derangements may be common in SARS-CoV2 infected patients
- Review medication list for benzodiazepines, opiates, cephalosporins, and other potential etiologies of toxic encephalopathy
- Telephone consult to neurology for any of the following: focal deficits, including focal weakness, gaze deviation, cranial nerve abnormality, or language deficit; acute change in level of consciousness or mental status without alternative explanation; persistently depressed level of consciousness without explanatory metabolic derangement
- Neurology consult attending may choose to evaluate over video or, for selected cases, in person
- Routine EEG, head CT, MRI, or LP may be considered for patients with the above deficits at the discretion of the neurology consultant
- Treatment options may include correction of metabolic derangements, medication simplification, antiepileptic therapy, or immunomodulatory therapy depending on findings
- For management of seizures, please refer to the Seizures and EEGs section
- Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv 2020.
- Yeh EA, Collins A, Cohen ME, et al. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 2004.
- Li Y-C, Bai W-Z, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J. Med. Virol. 2020.
- Oddo M, Carrera E, Claassen J, et al. Continuous electroencephalography in the medical intensive care unit. Crit. Care Med. 2009.
- Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. International Journal of Infectious Diseases. 2020;94:55–58.
- Duong L, Xu P, Liu A. Meningoencephalitis without Respiratory Failure in a Young Female Patient with COVID-19 Infection in Downtown Los Angeles, Early April 2020. Brain, Behavior, and Immunity. Epub 2020 Apr.:S0889159120305092.
- Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology. Epub 2020 Mar 31.:201187.
- Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain, Behavior, and Immunity. Epub 2020 Apr.