COVID-19-associated encephalitis: Difference between revisions
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== Epidemiology and Demographics == | == Epidemiology and Demographics == | ||
* There are approximately 50 cases of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] reported in the first six months of the pandemic. | * There are approximately 50 cases of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] reported in the first six months of the pandemic.<ref name="pmid28177862">{{cite journal| author=Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK | display-authors=etal| title=Middle East Respiratory Syndrome. | journal=N Engl J Med | year= 2017 | volume= 376 | issue= 6 | pages= 584-594 | pmid=28177862 | doi=10.1056/NEJMsr1408795 | pmc=5362064 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28177862 }}</ref><ref name="pmid16252612">{{cite journal| author=Tsai LK, Hsieh ST, Chang YC| title=Neurological manifestations in severe acute respiratory syndrome. | journal=Acta Neurol Taiwan | year= 2005 | volume= 14 | issue= 3 | pages= 113-9 | pmid=16252612 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16252612 }}</ref> | ||
* 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]] | * 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. | * The incidence of [[COVID-19]]-associated [[encephalitis]] increases with age; the median age at [[diagnosis]] is 54 years. | ||
| Line 139: | Line 139: | ||
==== Common Symptoms ==== | ==== Common Symptoms ==== | ||
*The common symptoms | *The common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include: | ||
**[[Cough]], | **[[Cough]], | ||
**[[Shortness of breath]] | **[[Shortness of breath]] | ||
| Line 149: | Line 149: | ||
==== Less Common Symptoms ==== | ==== Less Common Symptoms ==== | ||
* | *Less common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include: | ||
** | ** Tran<nowiki/>sient [[generalized seizure]] | ||
**[[Dizziness]], | **[[Dizziness]], | ||
**[[Paralysis]] | **[[Paralysis]] | ||
| Line 156: | Line 156: | ||
**[[Comatose|Coma]] | **[[Comatose|Coma]] | ||
* Clinical manifestation of | * Clinical manifestation of 3 cases of COVID-19 associated encephalitis are shown below: | ||
{| class="wikitable" | {| class="wikitable" | ||
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==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
The mainstays of [[medical]] [[therapy]] for [[viral encephalitis]] are: | The mainstays of [[medical]] [[therapy]] for [[viral encephalitis]] are:<ref name="pmid32479911" /><ref name="pmid25174548">{{cite journal |vauthors=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 |title=Effect of levetiracetam in acute encephalitis with refractory, repetitive partial seizures during acute and chronic phase |journal=Brain Dev. |volume=37 |issue=5 |pages=471–7 |date=May 2015 |pmid=25174548 |doi=10.1016/j.braindev.2014.08.003 |url=}}</ref><ref name="pmid32251791" /><ref name="pmid14634267">{{cite journal |vauthors=Nakano A, Yamasaki R, Miyazaki S, Horiuchi N, Kunishige M, Mitsui T |title=Beneficial effect of steroid pulse therapy on acute viral encephalitis |journal=Eur. Neurol. |volume=50 |issue=4 |pages=225–9 |date=2003 |pmid=14634267 |doi=10.1159/000073864 |url=}}</ref> | ||
===== Symptomatic treatments: ===== | ===== Symptomatic treatments: ===== | ||
* [[Anti-epileptic drugs]] like [[levetiracetam]] (50-60 mg/kg/day) | * [[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) | * [[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]] | * Severe disease in these [[patients]] required [[intubation]] and [[mechanical ventilation]]. | ||
* [[Hydroxychloroquine|Hydorxychloroquine]] and some [[antivirals]] were used in these [[patients]] but they did not resolve the [[condition]] | * [[Hydroxychloroquine|Hydorxychloroquine]] and some [[antivirals]] were used in these [[patients]] but they did not resolve the [[condition]]. | ||
=== Surgery === | === Surgery === | ||
Revision as of 12:50, 21 July 2020
For COVID-19 frequently asked outpatient questions, click here.
For COVID-19 frequently asked inpatient questions, click here.
For COVID-19 patient information, click here.
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 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
- 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.[6][7]
- 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.
Risk Factors
- Common risk factors in the development of COVID-19-associated encephalitis may be occupational, environmental, and genetic.[8]
- 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.
| 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.
- 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:
| Encephalitis | |||||||||||||||||||||||||||||||||||||||||
| Memory loss | Epilepsy | Personality changes | Hearing/vision loss | Coma/Death | |||||||||||||||||||||||||||||||||||||
Diagnosis
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.
Common Symptoms
- The common symptoms of COVID-19-associated encephalitis include:
- Cough,
- Shortness of breath
- Headache,
- Fever
- Fatigue
- Impaired consciousness
Less Common Symptoms
- Less common symptoms of COVID-19-associated encephalitis include:
- Transient generalized seizure
- Dizziness,
- Paralysis
- Sedation
- Coma
- 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, | 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 |
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, |
| 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
- Common physical examination findings of COVID-19-associated encephalitis include
- Generalized seizure
- Headache
- Abnormal vital signs
- Neck stiffness
- Neurological deficits can be present in this disease.
Laboratory Findings
- Positive RT-PCR in CSF or nasopharyngeal swab is diagnostic of COVID-19-associated encephalitis.
- 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.
Electrocardiogram
- There are no ECG findings associated with COVID-19-associated encephalitis.
X-ray
- 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
- There are no echocardiography findings associated with COVID-19-associated encephalitis.
CT scan
- The findings on the CT scans associated with COVID-19-associated encephalitis are similar to MRI which is the preferred modality.
MRI
- 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:
Treatment
Medical Therapy
The mainstays of medical therapy for viral encephalitis are:[9][11][2][12]
Symptomatic treatments:
- 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.
- Hydorxychloroquine and some antivirals were used in these patients but they did not resolve the condition.
Surgery
- Focal epilepsy having focal involvement of brain parenchyma can be treated with surgery[9].
- One of these patients undergone left anterior temporal lobectomy, which improved symptoms completely without any postoperative neurologic deficit[9].
Primary Prevention
- 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.
Secondary Prevention
- There are no established measures for the secondary prevention of COVID-19 associated encephalitis.
- To view secondary prevention for COVID-19 click here.
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). - ↑ 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.
- ↑ Tsai LK, Hsieh ST, Chang YC (2005). "Neurological manifestations in severe acute respiratory syndrome". Acta Neurol Taiwan. 14 (3): 113–9. PMID 16252612.
- ↑ Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check
|pmid=value (help). - ↑ 9.0 9.1 9.2 9.3
- ↑ 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). - ↑ 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.
- ↑ 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.