COVID-19-associated encephalitis: Difference between revisions

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'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''.
'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''.
'''For COVID-19 patient information, click [[COVID-19 (patient information)|here]]'''.
__NOTOC__
__NOTOC__
{{SI}}
{{SI}}


{{CMG}}; {{AE}}{{Wd}}
{{CMG}}; {{AE}}{{Wd}}, {{Fs}}, {{MAH}}


{{SK}} Encephalitis covid-19  
{{SK}} Encephalitis covid-19  
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==Overview==
==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]].  
[[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 virus|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==
==Historical Perspective==


* [[COVID-19|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]].<ref name="pmid32052514">{{cite journal| author=Velavan TP, Meyer CG| title=The COVID-19 epidemic. | journal=Trop Med Int Health | year= 2020 | volume= 25 | issue= 3 | pages= 278-280 | pmid=32052514 | doi=10.1111/tmi.13383 | pmc=7169770 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32052514  }}</ref><ref name="pmid32251791">{{cite journal| author=Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J | display-authors=etal| title=A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. | journal=Int J Infect Dis | year= 2020 | volume= 94 | issue=  | pages= 55-58 | pmid=32251791 | doi=10.1016/j.ijid.2020.03.062 | pmc=7195378 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32251791  }}</ref>
*[[COVID-19|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]].<ref name="pmid32052514">{{cite journal| author=Velavan TP, Meyer CG| title=The COVID-19 epidemic. | journal=Trop Med Int Health | year= 2020 | volume= 25 | issue= 3 | pages= 278-280 | pmid=32052514 | doi=10.1111/tmi.13383 | pmc=7169770 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32052514  }}</ref><ref name="pmid32251791">{{cite journal| author=Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J | display-authors=etal| title=A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. | journal=Int J Infect Dis | year= 2020 | volume= 94 | issue=  | pages= 55-58 | pmid=32251791 | doi=10.1016/j.ijid.2020.03.062 | pmc=7195378 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32251791  }}</ref>


* The association between [[COVID-19]] and [[encephalitis]] was made during this [[pandemic]] started in December in [[Wuhan virus|Wuhan]], China and named as [[Wuhan coronavirus]].<ref name="pmid32019669">{{cite journal| author=Riou J, Althaus CL| title=Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. | journal=Euro Surveill | year= 2020 | volume= 25 | issue= 4 | pages=  | pmid=32019669 | doi=10.2807/1560-7917.ES.2020.25.4.2000058 | pmc=7001239 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32019669  }}</ref>
*The association between [[COVID-19]] and [[encephalitis]] was made during this [[pandemic]] started in December in [[Wuhan virus|Wuhan]], China and named as [[Wuhan coronavirus]].<ref name="pmid32019669">{{cite journal| author=Riou J, Althaus CL| title=Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. | journal=Euro Surveill | year= 2020 | volume= 25 | issue= 4 | pages=  | pmid=32019669 | doi=10.2807/1560-7917.ES.2020.25.4.2000058 | pmc=7001239 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32019669  }}</ref>
* In March 2020, Dr. Ali A. was the first to discover the association between [[COVID-19|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]].<ref name="pmid32299017">{{cite journal| author=Asadi-Pooya AA, Simani L| title=Central nervous system manifestations of COVID-19: A systematic review. | journal=J Neurol Sci | year= 2020 | volume= 413 | issue=  | pages= 116832 | pmid=32299017 | doi=10.1016/j.jns.2020.116832 | pmc=7151535 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32299017  }}</ref>
*In March 2020, Dr. Ali A. was the first to discover the association between [[COVID-19|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]].<ref name="pmid32299017">{{cite journal| author=Asadi-Pooya AA, Simani L| title=Central nervous system manifestations of COVID-19: A systematic review. | journal=J Neurol Sci | year= 2020 | volume= 413 | issue=  | pages= 116832 | pmid=32299017 | doi=10.1016/j.jns.2020.116832 | pmc=7151535 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32299017  }}</ref>
*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.
*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 have been several [[outbreaks]] of [[SARS]] and [[MERS]].


==Classification==
==Classification==


* There is no established system for the [[classification]] of [[COVID-19]] associated [[encephalitis]].
*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]].
*Based on the duration of [[symptoms]], this disease is classified as [[acute]].


==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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* ACE2: [[Angiotensin-converting enzyme|Angiotensin converting enzyme]] receptor 2 is present in multiple organs ''e.g.'' [[lungs]], [[brain]], and [[kidney]], ''etc''.
*ACE2: [[Angiotensin-converting enzyme|Angiotensin converting enzyme]] receptor 2 is present in multiple organs ''e.g.'' [[lungs]], [[brain]], and [[kidney]], ''etc''.
*[[Hypercoagulability]]: With elevated [[D-dimer]]
*[[Hypercoagulability]]: With elevated [[D-dimer]]
* 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]].<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>
*[[Hypoxic]] injury: Due to [[anaerobic metabolism]].


==Causes==
==Causes==


* Coronavirus disease 2019 ([[COVID-19]]) associated [[encephalitis]] is caused by [[SARS-CoV-2]].
*Coronavirus disease 2019 ([[COVID-19]]) associated [[encephalitis]] is caused by [[SARS-CoV-2]].
 
*To read more about this virus, click [[COVID-19 causes#Overview|here]].


* To read more about this virus, click [[COVID-19 causes#Overview|here]].
[[File:SARS-CoV-2 49534865371.jpg|center|300px|thumb|Case courtesy of Dr. Daniel J Bell, Radiopaedia.org, rID: 74536]]


==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


* [[Meningitis]]<ref name="pmid32251791" />
*For further information about the differential diagnosis, [[COVID-19-associated encephalitis differential diagnosis|click here]].
* Acute [[hypoglycemia]]
*To view the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|click here]].
* [[Brain abscess]]
 
* [[Herpes simplex encephalitis]]
==Epidemiology and Demographics==
* [[Leptospirosis]] in [[humans]]
* [[Status epilepticus]]
* [[Systemic lupus erythematosus]] ([[SLE]])
* [[Cat scratch disease]]
* [[Tuberculosis]]
* [[Sepsis]]
*[[Glial tumor]]<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>


[[File:SARS-CoV-2 49534865371.jpg|thumb|Case courtesy of Dr. Daniel J Bell, Radiopaedia.org, rID: 74536]]
*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]]
*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==
==Risk Factors==


Common risk factors in the development of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] may be occupational, environmental, and [[genetic]].
*<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]].
*To view the risk factors of COVID-19, [[COVID-19 risk factors|click here]].
*[[Auto-immune]] [[syndromes]] might be at higher risk of developing this disease due to [[immunosuppressive therapy]].<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>
*[[Auto-immune]] [[syndromes]] might be at higher risk of developing this disease due to [[immunosuppressive therapy]].


{| class="wikitable"
{| class="wikitable"
|+Risk factors for COVID-19-associated encephalitis
|+Risk factors for COVID-19-associated encephalitis
!Autoimmune disease          
!Autoimmune disease
!Immunosuppression  
!Immunosuppression
|-
|-
|[[Multiple sclerosis]]
|[[Multiple sclerosis]]
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==Screening==
==Screening==


* There is insufficient [[evidence]] to recommend routine [[screening]] for [[COVID-19|COVID-19-]]<nowiki/>associated [[Encephalitis|encephalitis.]]
*There is insufficient [[evidence]] to recommend routine [[screening]] for [[COVID-19|COVID-19-]]<nowiki/>associated [[Encephalitis|encephalitis.]]
*To view screening for [[COVID-19]], [[COVID-19 screening|click here]].
 
==Natural History, Complications, and Prognosis==


==Complications==
*To view Natural History for [[COVID-19]], [[COVID-19 natural history, complications and prognosis|click here]].
*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:
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==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
*The diagnostic study of choice for [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] is [[CSF]] [[analysis]] for ruling out other [[viral]] and [[bacterial]] panels with the help of [[RT-PCR]].
===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|COVID-19-]]<nowiki/>associated [[encephalitis]] present with [[respiratory]] [[symptoms]]. e.g. [[cough]], [[shortness of breath]] etc.
* '''Three''' '''cases''' reported till now has specific [[clinical]] manifestations:
 
====Common Symptoms====
 
*The common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
**[[Cough]],
**[[Shortness of breath]]
**[[Headache]],
**[[Fever]]
**[[Fatigue]]
**Impaired [[consciousness]]
 
====Less Common Symptoms====
 
*Less common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
**Tran<nowiki/>sient [[generalized seizure]]
**[[Dizziness]],
**[[Paralysis]]
**[[Sedation]]
**[[Comatose|Coma]]
 
*Clinical manifestation of 3 cases of COVID-19 associated encephalitis are shown below:


{| class="wikitable"
{| class="wikitable"
|-  
|-  
! style="background: #4479BA; color: #FFFFFF; text-align: center;" rowspan="2" |<small>Patient No.</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Patient No.</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" rowspan="2" |<small>Early symptoms</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Early symptoms</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" rowspan="2" |<small>Later presentation</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Later presentation</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" rowspan="2" |<small>GCS</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>GCS</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" colspan="2" |<small>Lab. Findings</small>
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Lab. Findings</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" rowspan="2" |<small>Specific Tests</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Specific Tests</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Imaging studies</small>
|-  
|-  
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CBC</small>  
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CBC</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CSF</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CSF</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>MRI/CT scan</small>
|-
|-
|1. 24-year-old man from '''Japan<ref name="pmid32251791" />'''
|24-year-old man from Japan'''<ref name="pmid32251791" />'''
|[[Headache]],
|[[Headache]],
[[Fever]],
[[Fever]],
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Impaired [[consciousness]] and transient [[generalized seizure]], (Day 9)
Impaired [[consciousness]] and transient [[generalized seizure]], (Day 9)
|E4V1M1
|E4V1M1
|↑[[WBC|WBCs]] and [[neutrophils]]<br />↓[[lymphocytes]]
|↑[[WBC|WBCs]] and [[neutrophils]]<br />↓[[lymphocytes]]
↑ [[CRP]]
↑ [[CRP]]
|Clear and colorless fluid,
|Clear and colorless fluid,


Pressure=320mmH<sub>2</sub>O
[[Pressure]]=320 mmH<sub>2</sub>O,
 
[[Cell]] count was 12/μL–10
 
[[Mononuclear cells|mononuclear]] and 2 [[polymorphonuclear cells]]
|[[RT-PCR]] of [[SARS-CoV-2]] [[RNA]] was positive in [[CSF]]
|Brain [[MRI]]:
Hyperintensity in the right lateral [[Ventricle|ventricle's]] inferior horn along the wall,
 
pan-[[Paranasal sinus|paranasal]] [[sinusitis]].
|-
|In Wuhan, in a letter to editor, Ye M et.al, reported COVID-19 associated encephalitis case in a male with laboratory finding <ref name="pmid32283294">{{cite journal| author=Ye M, Ren Y, Lv T| title=Encephalitis as a clinical manifestation of COVID-19. | journal=Brain Behav Immun | year= 2020 | volume= 88 | issue=  | pages= 945-946 | pmid=32283294 | doi=10.1016/j.bbi.2020.04.017 | pmc=7146652 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32283294  }}</ref>
|Fever
SOB
 
[[Myalgia]]
|[[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)


Cell count was 12/μL–10 mononuclear and 2 polymorphonuclear cells
sugar (3.14 mmol/L)
|RT-PCR of SARS-CoV-2 RNA was + in CSF
|SARS-CoV-2 was positive on nasopharyngeal swab but negative on CSF testing
All other bacterial and viral causes of encephlitis were negative
|
*skull CT was normal
*chest CT showed multiple subpleural ground glass opacities
|-
|-
|2. 35-year-old woman from '''Turkey<ref name="pmid32479911" />'''
|35-year-old woman from Turkey<ref name="pmid32479911" /><ref name="pmid324799112">{{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> whose COVID-19 associated encephalitis mimicking as [[glial tumor]] of CNS
|[[Flu like]] symptoms
|[[Flu]] like [[Symptom|symptoms]]
|[[Headache]], [[nausea]], [[dizziness]], and
|[[Headache]], [[nausea]], [[dizziness]], and
drug-[[refractory]] [[seizure]]<nowiki/>s.
drug-[[refractory]] [[seizure]]<nowiki/>s.
|E4V5M6
|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.
|-
|-
|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>
|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)
[[Comatose]] (Day 15) and death (Day 16)
[[Comatose]] (Day 15) and death (Day 16)
|E0V0M0
|E0V0M0
|
|NA
|
|[[Pressure]]=30cmH<sub>2</sub>O
|
 
|-
115 nucleated cell /ml
 
7374 [[erythrocytes]]
 
/ml
 
[[Protein]]> 200mg/dl
<br />
|[[Reverse transcriptase PCR|RT=PCR]] for [[SARS-CoV-2]] was positive in [[Nasopharyngeal|nasopharyngea]]<nowiki/>l [[Swabbing|swab]]
|Brain [[MRI]]: Nonenhancing [[cerebral edema]] and restricted [[diffusion]] in the right [[cerebral hemisphere]] with [[brain herniation]].
|}
|}


===Physical Examination===
===Physical Examination===


* Each patient was presenting with different findings.
*<nowiki/>Common physical examination findings of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include
*<nowiki/><nowiki/>[[Generalized seizure]], [[headache]], abnormal [[vital signs]], [[neck stiffness]], or [[neurological]] deficits can suggest this [[disease]].  
 
====Neuromuscular====
 
*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>[[Generalized seizure]]
*<nowiki/><nowiki/>[[Headache]]
*<nowiki/><nowiki/>[[Neck stiffness]]
*<nowiki/><nowiki/>Focal [[neurological]] deficits can be present in this [[disease]].
 
===Laboratory Findings===
 
*Positive [[RT-PCR]] in [[CSF]] or nasopharyngeal swab is diagnostic of  [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]].
 
*Laboratory findings consistent with the diagnosis of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include [[CSF analysis]], [[RT-PCR]] and brain MRI.
 
*[[D-dimer]] or [[white blood cells]] can be normal among patients with [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]].
*Some patients with [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] may have elevated [[erythrocytes]] in [[CSF]] which is usually suggestive of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]].
 
===Electrocardiogram===
 
*There are no [[ECG]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>a<nowiki/>ssociated [[encephalitis]].
 
===X-ray===
 
*There are no [[X-rays|x-ray]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]].
*However, an [[X-rays|x-ray]] chest may be helpful in the diagnos<nowiki/>is of [[COVID-19|COV]]<nowiki/>[[COVID-19|ID-19-]]<nowiki/>associated respiratory disease.
 
===Echocardiography or Ultrasound===
 
*There are no [[echocardiography]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>associated <nowiki/>[[encephalitis|e]]<nowiki/>[[encephalitis|ncephalitis]].
 
===CT scan===
 
*The findings on the [[CT scans]] associated with [[COVID-19|COVID-19-]]<nowiki/>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|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
**Hyper-intensity in the right lateral [[Ventricle|ventricle's]] inferior horn along the wall and pan-[[Paranasal sinus|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===
 
*<nowiki/> Other diagnostic studies for  [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
**[[RT-PCR]] of [[SARS-CoV-2]] [[RNA]] positive in [[CSF]] and [[nasopharyngeal]] swab,
**[[Antibody]] [[IgM]] for [[acute]] [[infection]], and
**[[Antibody]] [[IgG]] for resolved or [[chronic]] [[infection]].


==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) 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.<ref name="pmid32454137">{{cite journal| author=Panariello A, Bassetti R, Radice A, Rossotti R, Puoti M, Corradin M | display-authors=etal| title=Anti-NMDA receptor encephalitis in a psychiatric Covid-19 patient: A case report. | journal=Brain Behav Immun | year= 2020 | volume= 87 | issue=  | pages= 179-181 | pmid=32454137 | doi=10.1016/j.bbi.2020.05.054 | pmc=7255176 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32454137  }}</ref><ref name="pmid32389697">{{cite journal| author=Dogan L, Kaya D, Sarikaya T, Zengin R, Dincer A, Akinci IO | display-authors=etal| title=Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series. | journal=Brain Behav Immun | year= 2020 | volume= 87 | issue=  | pages= 155-158 | pmid=32389697 | doi=10.1016/j.bbi.2020.05.022 | pmc=7204750 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32389697  }}</ref>
*[[Hydroxychloroquine|Hydorxychloroquine]] and some [[antivirals]] were used in these [[patients]] but they did not resolve the [[condition]].


* [[Anti-epileptic drugs]] like [[levetiracetam]] is necessary for [[seizure]] management.
<br />
* [[Anti-inflammatory]] like [[steroids]] are also helpful in this [[disease]].
===Surgery===
* 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]].


=== Surgical Therapy ===
*[[Focal Epilepsy|Focal epilepsy]] having focal involvement of [[brain]] [[parenchyma]] can be treated with [[surgery]]<ref name="pmid32479911" />.
*One of these [[Patient|patients]] undergone left [[anterior]] [[temporal]] [[lobectomy]], which improved [[symptoms]] completely without any postoperative [[neurologic]] deficit<ref name="pmid32479911" />.


* [[Focal Epilepsy|Focal epilepsy]] having focal involvement of [[brain]] [[parenchyma]] can be treated with [[surgery]].
===Primary Prevention===
* One of these patients undergone left [[anterior]] [[temporal]] [[lobectomy]], which improved [[symptoms]] completely without any postoperative [[neurologic]] deficit.'''<ref name="pmid32479911" />'''
 
*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 [[COVID-19 primary prevention|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 [[COVID-19 secondary prevention|click here]].


==References==
==References==
{{reflist|2}}
{{reflist|2}}
[[Category:Up-To-Date]]


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Latest revision as of 01:59, 31 August 2020

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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., Muhammad Adnan Haider, M.B.B.S.[3]

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.

In Wuhan, in a letter to editor, Ye M et.al, reported COVID-19 associated encephalitis case in a male with laboratory finding [9] Fever

SOB

Myalgia

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

  • skull CT was normal
  • chest CT showed multiple subpleural ground glass opacities
35-year-old woman from Turkey[10][11] whose COVID-19 associated encephalitis mimicking as glial tumor of CNS 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[12] 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:[10][13][2][14]

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. Ye M, Ren Y, Lv T (2020). "Encephalitis as a clinical manifestation of COVID-19". Brain Behav Immun. 88: 945–946. doi:10.1016/j.bbi.2020.04.017. PMC 7146652 Check |pmc= value (help). PMID 32283294 Check |pmid= value (help).
  10. 10.0 10.1 10.2 10.3
  11. 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).
  12. 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).
  13. 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.
  14. 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.
  15. Panariello A, Bassetti R, Radice A, Rossotti R, Puoti M, Corradin M; et al. (2020). "Anti-NMDA receptor encephalitis in a psychiatric Covid-19 patient: A case report". Brain Behav Immun. 87: 179–181. doi:10.1016/j.bbi.2020.05.054. PMC 7255176 Check |pmc= value (help). PMID 32454137 Check |pmid= value (help).
  16. Dogan L, Kaya D, Sarikaya T, Zengin R, Dincer A, Akinci IO; et al. (2020). "Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series". Brain Behav Immun. 87: 155–158. doi:10.1016/j.bbi.2020.05.022. PMC 7204750 Check |pmc= value (help). PMID 32389697 Check |pmid= value (help).


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