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Synonyms and keywords: Encephalitis covid-19
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.
- 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.
- 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.
- 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 the brain, but it was not published.
- There have been several outbreaks of SARS and MERS.
- 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.
- It is thought that this viral encephalitis is the result of multiple pathophysiologic pathways.
|ACE2||Direct Injury due to Infection||Immune Injury||Hypoxic Injury||Hypercoagulability|
- 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.
- To read more about this virus, click here.
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
- There are approximately 50 cases of COVID-19-associated encephalitis reported in the first six months of the pandemic.
- MERS and SARS-CoV had neurologic manifestation like encephalitis at the time of outbreaks.
- Patients of all age groups may develop COVID-19-associated encephalitis
- The incidence of COVID-19-associated encephalitis increases with age; the median age at diagnosis is 54 years.
- There is no racial predilection to COVID-19-associated encephalitis but more cases were present in African Americans.
- COVID-19-associated encephalitis affects men and women equally.
- Common risk factors in the development of COVID-19-associated encephalitis may be occupational, environmental, and genetic.
- Risk factors for this disease are the same as for COVID-19.
- To view the risk factors of COVID-19, click here.
- Auto-immune syndromes might be at higher risk of developing this disease due to immunosuppressive therapy.
|Multiple sclerosis||Interferon beta|
|Neuromyelitis optica||Monoclonal antibody|
|Sickle cell disease (SCD)||Crizanlizumab|
- There is insufficient evidence to recommend routine screening for COVID-19-associated encephalitis.
- To view screening for COVID-19, click here.
Natural History, Complications, and Prognosis
- To view Natural History for COVID-19, click here.
- If left untreated, patients with COVID-19-associated encephalitis may progress to damage the brain and cause:
|Memory loss||Epilepsy||Personality changes||Hearing/vision loss||Coma/Death|
Diagnostic Study of Choice
- The diagnostic study of choice for COVID-19-associated encephalitis is CSF analysis for ruling out other viral and bacterial panels with the help of RT-PCR.
History and Symptoms
- The majority of patients with COVID-19-associated encephalitis present with respiratory symptoms. e.g. cough, shortness of breath etc.
- The common symptoms of COVID-19-associated encephalitis include:
Less Common Symptoms
- Less common symptoms of COVID-19-associated encephalitis include:
- 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|
|24-year-old man from Japan||Headache,||Worsening headache, Sore throat. (Day 5)||E4V1M1||↑WBCs and neutrophils
|Clear and colorless fluid,
Cell count was 12/μL–10
|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,
|In Wuhan, in a letter to editor, Ye M et.al, reported COVID-19 associated encephalitis case in a male with laboratory finding ||Fever
|Confusion||NA||WBC count (3.3 × 109/L) and lymphopenia (0.8 × 109/L)||Pressure=220 mmg
WBC (0.001 × 109/L)
protein (0.27 g/L)
sugar (3.14 mmol/L)
|SARS-CoV-2 was positive on nasopharyngeal swab but negative on CSF testing
All other bacterial and viral causes of encephlitis were negative
|35-year-old woman from Turkey whose COVID-19 associated encephalitis mimicking as glial tumor of CNS||Flu like symptoms||Headache, nausea, dizziness, and||E4V5M6||NA||NA||RT-PCR and antibody tests positive||Brain MRI: Hyperintensity in the left temporal lobe.|
|31-year-old African American woman||SCD patient with dyspnea||Paralysis and sedation (Day 13)
Comatose (Day 15) and death (Day 16)
115 nucleated cell /ml
|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.|
- Generalized seizure
- Neck stiffness
- Focal neurological deficits can be present in this disease.
- Laboratory findings consistent with the diagnosis of COVID-19-associated encephalitis include CSF analysis, RT-PCR and brain MRI.
- D-dimer or white blood cells can be normal among patients with COVID-19-associated encephalitis.
- Some patients with COVID-19-associated encephalitis may have elevated erythrocytes in CSF which is usually suggestive of COVID-19-associated encephalitis.
- There are no x-ray findings associated with COVID-19-associated encephalitis.
- However, an x-ray chest may be helpful in the diagnosis of COVID-19-associated respiratory disease.
Echocardiography or Ultrasound
- The findings on the CT scans associated with COVID-19-associated encephalitis are similar to MRI which is the preferred modality.
- Brain MRI may be helpful in the diagnosis of COVID-19 associated encephalitis. Findings on MRI suggestive of COVID-19-associated encephalitis include:
- Hyper-intensity in the right lateral ventricle's inferior horn along the wall and pan-paranasal sinusitis.
- Hyper-intensity in the left temporal lobe.
- MR Spectroscopy: Decrease N-acetyl aspartate peak along with a marked elevated choline peak.
- Non-enhancing cerebral edema and restricted diffusion in the right cerebral hemisphere with brain herniation.
Other Diagnostic Studies
- Other diagnostic studies for COVID-19-associated encephalitis include:
- Anti-epileptic drugs like levetiracetam (50-60 mg/kg/day) is necessary for seizure management.
- Anti-inflammatory like pulse steroids (methylprednisolone 1,000 mg/day) are also helpful in this disease.
- Severe disease in these patients required intubation and mechanical ventilation.
- IVIG can be administrated in severe cases.
- Hydorxychloroquine and some antivirals were used in these patients but they did not resolve the condition.
- 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.
- There are no established measures for the primary prevention of COVID-19 associated encephalitis.
- Effective measure for the primary prevention of COVID-19 associated encephalitis. include social distancing and avoidance behaviors.
- There are no available vaccines against COVID-19 associated encephalitis. Multiple trials are under process for vaccinations.
- To view primary prevention for COVID-19 click here.
- There are no established measures for the secondary prevention of COVID-19 associated encephalitis.
- To view secondary prevention for COVID-19 click here.
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