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Key Event Title
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
Key Event Description
Encephalitis by definition is an inflammation of the brain tissue, most commonly caused by viral infections, and in some rare cases it can be caused by bacteria or even fungi. There are two main types of encephalitis: primary and secondary, with primary occurring when a virus directly infects the brain and the spinal cord. On the other hand, secondary encephalitis as a consequence of an infection occurring elsewhere in the body that then spread to the brain (Johnson, 2018).
Several causes may cause encephalitis, but the most common is a viral infection, and can be characterized by mild or severe flu-like symptoms, possibly causing confused thinking, seizures, or problems with movement or with senses, such as sight or hearing. In some cases, encephalitis can be life-threatening, and for this reason timely diagnosis and treatment are essential (Mayo, 2021).
Viral encephalitis refers to inflammatory lesions in the brain parenchyma caused by pathogens, including neuronal damage and nerve tissue lesions. It is characterized by acute onset, and common symptoms include headache, fever (mainly high fever), vomiting, convulsions, and consciousness disorders (Ellul and Solomon, 2018).
Encephalitis in the context of COVID19
Among various neurological adverse outcomes, SARS-CoV and SARS-CoV-2 can cause encephalitis (Moriguchi T et al. 2020; Efe et al. 2020; Najjar et al. 2020; Wu and Tang 2020; Bohmwald K, et al. 2020; Tsai LK et al. 2005; Xiang P. et al., 2020; Pilotto A et al. 2019; Ye M., et al. 2020; Das G, et al. 2020). Indeed, meningitis/meningoencephalitis has been observed in COVID19 patients (Iaconetta G et al. 2020). For instance, Moriguchi et al. have described SARS-CoV-2 encephalitis in a 24-year old man, 10 days after developing COVID19 symptoms, characterized by headache, fatigue, fever, and consciousness disturbance, and with MRI showing hyperintense signal changes in the hippocampus with slight hippocampal atrophy (Moriguchi T et al. 2020).
Early diagnosis of viral encephalitis is critical. In the ongoing pneumonia epidemic, the treatment team of Beijing Ditan Hospital confirmed the presence of SARS-CoV-2 in the cerebrospinal (CSF) fluid of patients with COVID-19 by genome sequencing, thereby clinically verifying viral encephalitis (Xiang et al., 2020). This provided a solid basis for CoV causing encephalitis.
CSF of COVID19 patients with encephalitis/meningoencephalitis often shows pleocytosis and elevated total protein and NfL levels (Espíndola et al. 2020) (Koralnik et al. 2020).
In SARS-CoV-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity (Guilmot et al., 2020).
Intracranial inoculation of murine coronavirus (mouse hepatic virus, MHV), induces optic neuritis and focal encephalitis leading to chronic demyelination in mice (Shindler KS, et al. 2008).
SARS-CoV responsible for the 2002–2004 outbreak was reported to induce encephalitis, along with polyneuropathy and ischemic stroke (Tsai et al. 2005).
Autopsy results of patients with SARS showed ischemic neuronal damage and demyelination. Viral RNA was detected in brain tissue, particularly accumulating in and around the hippocampus (Gu J, et al. 2005).
How It Is Measured or Detected
Encephalitis may be detected through the following diagnostic tests (https://www.columbianeurology.org/neurology/staywell/encephalitis):
- Magnetic resonance imaging (MRI)
- Computed tomography scan (CT or CAT scan)
- Blood tests
- Urine and stool tests
- Electroencephalogram (EEG)
- Spinal tap (lumbar puncture)
- Brain biopsy
- Intracranial pressure monitoring (ICP), measuring the pressure inside the skull. If there is a severe brain injury, head surgery, brain infection, or other problems, the brain may swell.
Domain of Applicability
Regulatory Significance of the Adverse Outcome
Bohmwald K, et al. Neurologic Alterations Due to Respiratory Virus Infections. Front Cell Neurosci. 2018 Oct 26;12:386.
Das G, et al. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020 May 6; 11(9):1206-1209.
Efe et al. COVID-19-Associated Encephalitis Mimicking Glial Tumor. World Neurosurg. 2020 Aug; 140: 46–48.
Ellul M., Solomon T. Acute encephalitis - diagnosis and management. Clin. Med. (Lond) 2018;18(2):155–159.
Encephalitis, available at: https://www.columbianeurology.org/neurology/staywell/encephalitis
Espíndola OM et al. Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid. Int J Infect Dis. 2020 Jul;96:567-569.
Gu J, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202:415–424.
Guilmot A, et al. Immune-mediated neurological syndromes in SARS-CoV-2-infected patients. J Neurol. 2020 Jul 30;1-7.
Iaconetta G et al. Meningoencephalitis Associated with SARS-Coronavirus-2. Transl Med UniSa. 2020 Dec 31;23:42-47.
Johnson S. What is encephalitis? Healthline, 2018 available at https://www.healthline.com/health/encephalitis
Koralnik et al. COVID-19: A Global Threat to the Nervous System. Ann Neurol. 2020 Jul;88(1):1-11.
Mayo Clinic, Encephalitis. 2021, available at https://www.mayoclinic.org/diseases-conditions/encephalitis/symptoms-causes/syc-20356136
Moriguchi T et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;94:55–58.
Najjar et al. Central nervous system complications associated with SARS-CoV-2 infection: integrative concepts of pathophysiology and case reports. J Neuroinflammation. 2020 Aug 6;17(1):231.
Pilotto A et al. Steroid-Responsive Encephalitis in Coronavirus Disease 2019. Ann Neurol. 2020 Aug;88(2):423-427.
Shindler KS, et al. Experimental optic neuritis induced by a demyelinating strain of mouse hepatitis virus. J Virol. 2008 Sep; 82(17):8882-6.
Tsai L.-K., et al. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwanica. 2005;14:113–119
Wu J. and Tang Y. Revisiting the Immune Balance Theory: A Neurological Insight Into the Epidemic of COVID-19 and Its Alike. Front Neurol. 2020 Oct 15;11:566680.
Xiang P., et al. First case of 2019 novel coronavirus disease with Encephalitis. ChinaXiv. 2020;T202003:00015.
Ye M., et al. Encephalitis as a clinical manifestation of COVID-19. Brain, Behavior, and Immunity. 2020 S0889159120304657.