COVID-19-associated encephalitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Wajeeha Aiman, M.D.[2], Fahimeh Shojaei, M.D.

Synonyms and Keywords: Encephalitis covid-19

Overview

Encephalitis is inflammation of the brain parenchyma and it is commonly caused by viruses. COVID-19 is a virus related to the severe acute respiratory syndrome coronavirus (SARS-CoV) group and named as SARS-CoV-2. COVID-19 associated encephalitis was first discovered by Moriguchi T. et al. a Japanese critical care physician in late February 2020 during the pandemic of SARS-Coronavirus-2: SARS-CoV-2. The association between COVID-19 and encephalitis was made early in the pandemic in the Wuhan province of China. There is no established system for the classification of COVID-19 associated encephalitis. The exact pathogenesis of COVID-19 encephalitis is not fully understood. COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough.

Historical Perspective

Classification

Pathophysiology

  • It is thought that this viral encephalitis is the result of multiple pathophysiologic pathways.


 
 
 
 
 
 
 
 
SARS-CoV-2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACE2
 
Direct Injury due to Infection
 
Immune Injury
 
Hypoxic Injury
 
Hypercoagulability
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral Encephalitis
 
 
 
 
 


Causes

  • To read more about this virus, click here.
Case courtesy of Dr. Daniel J Bell, Radiopaedia.org, rID: 74536

Differentiating COVID-19-associated encephalitis from other Diseases

  • For further information about the differential diagnosis, click here.
  • To view the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

Risk Factors

Risk factors for COVID-19-associated encephalitis
Autoimmune disease Immunosuppression
Multiple sclerosis Interferon beta

Glatiramer

Corticosteroids

Myasthenia gravis Corticosteroids
Neuromyelitis optica Monoclonal antibody
Sarcoidosis Corticosteroids

Methotrexate

Azathioprine

Sickle cell disease (SCD) Crizanlizumab

Screening

Natural History, Complications, and Prognosis


 
 
 
 
 
 
 
 
Encephalitis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memory loss
 
Epilepsy
 
Personality changes
 
Hearing/vision loss
 
Coma/Death


Diagnosis

Diagnostic Study of Choice

History and Symptoms

Common Symptoms

Less Common Symptoms

  • Clinical manifestation of 3 cases of COVID-19 associated encephalitis are shown below:
Patient No. Early symptoms Later presentation GCS Lab. Findings Specific Tests Imaging studies
CBC CSF MRI/CT scan
24-year-old man from Japan[2] Headache,

Fever,

Fatigue

Worsening headache, Sore throat. (Day 5)

Impaired consciousness and transient generalized seizure, (Day 9)

E4V1M1 WBCs and neutrophils
lymphocytes

CRP

Clear and colorless fluid,

Pressure=320 mmH2O,

Cell count was 12/μL–10

mononuclear and 2 polymorphonuclear cells

RT-PCR of SARS-CoV-2 RNA was positive in CSF Brain MRI:

Hyperintensity in the right lateral ventricle's inferior horn along the wall,

pan-paranasal sinusitis.

35-year-old woman from Turkey[9] Flu like symptoms Headache, nausea, dizziness, and

drug-refractory seizures.

E4V5M6 NA NA RT-PCR and antibody tests positive Brain MRI: Hyperintensity in the left temporal lobe.

MR Spectroscopy: Decrease N-acetyl aspartate peak along with a marked elevated choline peak.

31-year-old African American woman[10] SCD patient with dyspnea Paralysis and sedation (Day 13)

Comatose (Day 15) and death (Day 16)

E0V0M0 NA Pressure=30cmH2O

115 nucleated cell /ml

7374 erythrocytes

/ml

Protein> 200mg/dl

RT=PCR for SARS-CoV-2 was positive in nasopharyngeal swab Brain MRI: Nonenhancing cerebral edema and restricted diffusion in the right cerebral hemisphere with brain herniation.

Physical Examination

Neuromuscular

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT scan

MRI

Other Diagnostic Studies

Treatment

Medical Therapy

The mainstays of medical therapy for viral encephalitis are:[9][11][2][12]

Symptomatic treatments:

Surgery

Primary Prevention

Secondary Prevention

References

  1. Velavan TP, Meyer CG (2020). "The COVID-19 epidemic". Trop Med Int Health. 25 (3): 278–280. doi:10.1111/tmi.13383. PMC 7169770 Check |pmc= value (help). PMID 32052514 Check |pmid= value (help).
  2. 2.0 2.1 2.2 Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).
  3. Riou J, Althaus CL (2020). "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020". Euro Surveill. 25 (4). doi:10.2807/1560-7917.ES.2020.25.4.2000058. PMC 7001239 Check |pmc= value (help). PMID 32019669 Check |pmid= value (help).
  4. Asadi-Pooya AA, Simani L (2020). "Central nervous system manifestations of COVID-19: A systematic review". J Neurol Sci. 413: 116832. doi:10.1016/j.jns.2020.116832. PMC 7151535 Check |pmc= value (help). PMID 32299017 Check |pmid= value (help).
  5. Baig AM (2020). "Neurological manifestations in COVID-19 caused by SARS-CoV-2". CNS Neurosci Ther. 26 (5): 499–501. doi:10.1111/cns.13372. PMC 7163592 Check |pmc= value (help). PMID 32266761 Check |pmid= value (help).
  6. Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK; et al. (2017). "Middle East Respiratory Syndrome". N Engl J Med. 376 (6): 584–594. doi:10.1056/NEJMsr1408795. PMC 5362064. PMID 28177862.
  7. Tsai LK, Hsieh ST, Chang YC (2005). "Neurological manifestations in severe acute respiratory syndrome". Acta Neurol Taiwan. 14 (3): 113–9. PMID 16252612.
  8. Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check |pmid= value (help).
  9. 9.0 9.1 9.2 9.3
  10. Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T; et al. (2020). "Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020". Emerg Infect Dis. 26 (9). doi:10.3201/eid2609.202122. PMID 32487282 Check |pmid= value (help).
  11. Ueda R, Saito Y, Ohno K, Maruta K, Matsunami K, Saiki Y, Sokota T, Sugihara S, Nishimura Y, Tamasaki A, Narita A, Imamura A, Maegaki Y (May 2015). "Effect of levetiracetam in acute encephalitis with refractory, repetitive partial seizures during acute and chronic phase". Brain Dev. 37 (5): 471–7. doi:10.1016/j.braindev.2014.08.003. PMID 25174548.
  12. Nakano A, Yamasaki R, Miyazaki S, Horiuchi N, Kunishige M, Mitsui T (2003). "Beneficial effect of steroid pulse therapy on acute viral encephalitis". Eur. Neurol. 50 (4): 225–9. doi:10.1159/000073864. PMID 14634267.