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]
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 during this pandemic started in December in Wuhan, China and named as Wuhan coronavirus. 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
- 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.[1][2]
- The association between COVID-19 and encephalitis was made during this pandemic started in December in Wuhan, China and named as Wuhan coronavirus.[3]
- In March 2020, Dr. Ali A. was the first to discover the association between COVID-19 and neurological diseases e.g. encephalitis. He made a clinical diagnosis along with his team and then MRI used to diagnose the disease.[4]
- In January 2020, Chinese doctors confirmed the first case of encephalitis due to COVID-19 in a 56 year old male and they conducted gene sequencing on cerebrospinal fluid (CSF) samples and confirmed the novel virus inside brain, but it was not published.
- There have been several outbreaks of SARS and MERS.
Classification
- There is no established system for the classification of COVID-19 associated encephalitis.
- Based on the duration of symptoms, this disease is classified as acute.
Pathophysiology
- The exact pathogenesis of COVID-19 encephalitis is not fully understood.[5]
- 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 | |||||||||||||||||||||||||||||||||||||||||
- ACE2: Angiotensin converting enzyme receptor 2 is present in multiple organs e.g. lungs, brain, and kidney, etc.
- Hypercoagulability: With elevated D-dimer
- Immune injury: Cytokine activation and vascular involvement.
- Direct injury: Due to hematogenous and neuronal pathway involvement.
- Hypoxic injury: Due to anaerobic metabolism.
Causes
- Coronavirus disease 2019 (COVID-19) associated encephalitis is caused by SARS-CoV-2.
- To read more about this virus, click here.
Differentiating COVID-19-associated encephalitis from other Diseases
COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough, such as:[2][6]
- Meningitis
- Acute hypoglycemia
- Brain abscess
- Herpes simplex encephalitis
- Leptospirosis in humans
- Status epilepticus
- Systemic lupus erythematosus (SLE)
- Cat scratch disease
- Tuberculosis
- Sepsis
- Glial tumor
Risk Factors
- Common risk factors in the development of COVID-19-associated encephalitis may be occupational, environmental, and genetic.[7]
- Risk factors for this disease are the same as for COVID-19.
- Auto-immune syndromes might be at higher risk of developing this disease due to immunosuppressive therapy.
| Autoimmune disease | Immunosuppression |
|---|---|
| Multiple sclerosis | Interferon beta |
| Myasthenia gravis | Corticosteroids |
| Neuromyelitis optica | Monoclonal antibody |
| Sarcoidosis | Corticosteroids |
| Sickle cell disease (SCD) | Crizanlizumab |
Screening
- There is insufficient evidence to recommend routine screening for COVID-19-associated encephalitis.
Complications
- If left untreated, patients with COVID-19-associated encephalitis may progress to damage the brain and cause:
| Encephalitis | |||||||||||||||||||||||||||||||||||||||||
| Memory loss | Epilepsy | Personality changes | Hearing/vision loss | Coma/Death | |||||||||||||||||||||||||||||||||||||
Diagnosis
History and Symptoms
- The majority of patients with COVID-19-associated encephalitis present with respiratory symptoms. e.g. cough, shortness of breath etc.
- Three cases reported till now has specific clinical manifestations:
| Patient No. | Early symptoms | Later presentation | GCS | Lab. Findings | Specific Tests | |
|---|---|---|---|---|---|---|
| CBC | CSF | |||||
| 1. 24-year-old man from Japan[2] | Headache, | 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=320mmH2O Cell count was 12/μL–10 mononuclear and 2 polymorphonuclear cells |
RT-PCR of SARS-CoV-2 RNA was + in CSF |
| 2. 35-year-old woman from Turkey[6] | Flu like symptoms | Headache, nausea, dizziness, and
drug-refractory seizures. |
E4V5M6 | RT-PCR and antibody tests + | ||
| 3. 31-year-old African American woman[8] | SCD patient with dyspnea | Paralysis and sedation (Day 13)
Comatose (Day 15) and death (Day 16) |
E0V0M0 | |||
Physical Examination
- Each patient was presenting with different findings.
- Generalized seizure, headache, abnormal vital signs, neck stiffness, or neurological deficits can suggest this disease.
Treatment
Medical Therapy
The mainstays of medical therapy for viral encephalitis are:[6]
Symptomatic treatments:
- Anti-epileptic drugs like levetiracetam is necessary for seizure management.
- Anti-inflammatory like steroids are also helpful in this disease.
- Severe disease in these patients required intubation and mechanical ventilation.
- Hydorxychloroquine and some antivirals were used in these patients but they did not resolve the condition.
Surgical Therapy
- Focal epilepsy having focal involvement of brain parenchyma can be treated with surgery.
- One of these patients undergone left anterior temporal lobectomy, which improved symptoms completely without any postoperative neurologic deficit.
References
- ↑ 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). - ↑ 2.0 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). - ↑ 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). - ↑ 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). - ↑ 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). - ↑ 6.0 6.1 6.2 Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K (2020). "COVID-19-Associated Encephalitis Mimicking Glial Tumor". World Neurosurg. 140: 46–48. doi:10.1016/j.wneu.2020.05.194. PMC 7256557 Check
|pmc=value (help). PMID 32479911 Check|pmid=value (help). - ↑ Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check
|pmid=value (help). - ↑ 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).