COVID-19-associated encephalitis: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
* The exact [[pathogenesis]] of [[COVID-19]] [[encephalitis]] is not fully understood. | * The exact [[pathogenesis]] of [[COVID-19]] [[encephalitis]] is not fully understood.<ref name="pmid32266761">{{cite journal| author=Baig AM| title=Neurological manifestations in COVID-19 caused by SARS-CoV-2. | journal=CNS Neurosci Ther | year= 2020 | volume= 26 | issue= 5 | pages= 499-501 | pmid=32266761 | doi=10.1111/cns.13372 | pmc=7163592 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32266761 }}</ref> | ||
* It is thought that this [[viral encephalitis]] is the result of multiple pathophysiologic pathways. | * It is thought that this [[viral encephalitis]] is the result of multiple pathophysiologic pathways. | ||
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* Immune injury: [[Cytokine]] activation and [[vascular]] involvement. | * Immune injury: [[Cytokine]] activation and [[vascular]] involvement. | ||
* Direct injury: Due to hematogenous and [[neuronal]] pathway involvement. | * Direct injury: Due to hematogenous and [[neuronal]] pathway involvement. | ||
*[[Hypoxic]] injury: Due to [[anaerobic metabolism]]. | *[[Hypoxic]] injury: Due to [[anaerobic metabolism]]. | ||
==Causes== | ==Causes== | ||
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==Differentiating COVID-19-associated encephalitis from other Diseases== | ==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 | [[COVID-19]]-associated [[encephalitis]] must be differentiated from other [[diseases]] that cause [[fever]], [[headache]], and [[altered mental status]] with or without [[cough]], such as:<ref name="pmid32251791" /><ref name="pmid32479911">{{cite journal| author=Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K| title=COVID-19-Associated Encephalitis Mimicking Glial Tumor. | journal=World Neurosurg | year= 2020 | volume= 140 | issue= | pages= 46-48 | pmid=32479911 | doi=10.1016/j.wneu.2020.05.194 | pmc=7256557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32479911 }}</ref> | ||
* [[Meningitis]] | * [[Meningitis]] | ||
* Acute [[hypoglycemia]] | * Acute [[hypoglycemia]] | ||
* [[Brain abscess]] | * [[Brain abscess]] | ||
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* [[Tuberculosis]] | * [[Tuberculosis]] | ||
* [[Sepsis]] | * [[Sepsis]] | ||
*[[Glial tumor]] | *[[Glial tumor]] | ||
==Risk Factors== | ==Risk Factors== | ||
* <nowiki/> Common risk factors in the development of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] may be occupational, environmental, and [[genetic]].<ref name="pmid32229625">{{cite journal| author=Nath A| title=Neurologic complications of coronavirus infections. | journal=Neurology | year= 2020 | volume= 94 | issue= 19 | pages= 809-810 | pmid=32229625 | doi=10.1212/WNL.0000000000009455 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32229625 }}</ref> | * <nowiki/> Common [[Risk factor|risk factors]] in the development of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] may be occupational, environmental, and [[genetic]].<ref name="pmid32229625">{{cite journal| author=Nath A| title=Neurologic complications of coronavirus infections. | journal=Neurology | year= 2020 | volume= 94 | issue= 19 | pages= 809-810 | pmid=32229625 | doi=10.1212/WNL.0000000000009455 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32229625 }}</ref> | ||
* [[Risk factors]] for this [[disease]] are the same as for [[COVID-19]]. | * [[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]]. | *[[Auto-immune]] [[syndromes]] might be at higher risk of developing this disease due to [[immunosuppressive therapy]]. | ||
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==Complications== | ==Complications== | ||
* If left untreated, patients with [[COVID-19]]-associated [[encephalitis]] may progress to damage the [[brain]] and cause: | * If left untreated, [[patients]] with [[COVID-19]]-associated [[encephalitis]] may progress to damage the [[brain]] and cause: | ||
{{familytree/start}} | {{familytree/start}} | ||
{{familytree | | | | | | | | | C02| | | |C02=Encephalitis}} | {{familytree | | | | | | | | | C02| | | |C02=Encephalitis}} | ||
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===History and Symptoms=== | ===History and Symptoms=== | ||
* The majority of patients with [[COVID-19]]-associated [[encephalitis]] present with [[respiratory]] symptoms. ''e.g.'' [[cough]], [[shortness of breath]] ''etc''. | * 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: | ||
{| class="wikitable" | {| class="wikitable" | ||
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! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CSF</small> | ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CSF</small> | ||
|- | |- | ||
|1. 24-year-old man from ''' | |1. 24-year-old man from Japan'''<ref name="pmid32251791" />''' | ||
|[[Headache]], | |[[Headache]], | ||
[[Fever]], | [[Fever]], | ||
| Line 150: | Line 150: | ||
Pressure=320mmH<sub>2</sub>O | Pressure=320mmH<sub>2</sub>O | ||
Cell count was 12/μL–10 mononuclear and 2 polymorphonuclear cells | Cell count was 12/μL–10 [[Mononuclear cells|mononuclear]] and 2 [[polymorphonuclear cells]] | ||
|RT-PCR of [[SARS-CoV-2]] [[RNA]] was + in [[CSF]] | |[[RT-PCR]] of [[SARS-CoV-2]] [[RNA]] was + in [[CSF]] | ||
|- | |- | ||
|2. 35-year-old woman from | |2. 35-year-old woman from Turkey<ref name="pmid32479911" /> | ||
|[[Flu like]] | |[[Flu]] like [[Symptom|symptoms]] | ||
|[[Headache]], [[nausea]], [[dizziness]], and | |[[Headache]], [[nausea]], [[dizziness]], and | ||
drug-[[refractory]] [[seizure]]<nowiki/>s. | drug-[[refractory]] [[seizure]]<nowiki/>s. | ||
| Line 160: | Line 160: | ||
| | | | ||
| | | | ||
|RT-PCR and antibody tests + | |[[RT-PCR]] and [[antibody tests]] + | ||
|- | |- | ||
|3. 31-year-old | |3. 31-year-old African American woman<ref name="pmid32487282">{{cite journal| author=Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T | display-authors=etal| title=Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020. | journal=Emerg Infect Dis | year= 2020 | volume= 26 | issue= 9 | pages= | pmid=32487282 | doi=10.3201/eid2609.202122 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32487282 }}</ref> | ||
|[[SCD]] patient with [[dyspnea]] | |[[SCD]] patient with [[dyspnea]] | ||
|[[Paralysis]] and [[sedation]] (Day 13) | |[[Paralysis]] and [[sedation]] (Day 13) | ||
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===Physical Examination=== | ===Physical Examination=== | ||
*Each patient was presenting with different findings. | *Each [[patient]] was presenting with different findings. | ||
*<nowiki/><nowiki/>[[Generalized seizure]], [[headache]], abnormal [[vital signs]], [[neck stiffness]], or [[neurological]] deficits can suggest this [[disease]]. | *<nowiki/><nowiki/>[[Generalized seizure]], [[headache]], abnormal [[vital signs]], [[neck stiffness]], or [[neurological]] deficits can suggest this [[disease]]. | ||
==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" />''' | ||
===== Symptomatic treatments: ===== | ===== Symptomatic treatments: ===== | ||
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* [[Anti-inflammatory]] like [[steroids]] are also helpful in this [[disease]]. | * [[Anti-inflammatory]] like [[steroids]] 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]]. | ||
=== Surgical Therapy === | === Surgical Therapy === | ||
* [[Focal Epilepsy|Focal epilepsy]] having focal involvement of [[brain]] [[parenchyma]] can be treated with [[surgery]]. | * [[Focal Epilepsy|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. | * One of these [[Patient|patients]] undergone left [[anterior]] [[temporal]] [[lobectomy]], which improved [[symptoms]] completely without any postoperative [[neurologic]] deficit. | ||
==References== | ==References== | ||
Revision as of 00:28, 10 July 2020
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COVID-19-associated encephalitis On the Web |
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American Roentgen Ray Society Images of COVID-19-associated encephalitis |
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Risk calculators and risk factors for COVID-19-associated encephalitis |
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).