COVID-19-associated encephalitis: Difference between revisions

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==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 the [[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.<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>
*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]].
*[[Hypoxic]] injury: Due to [[anaerobic metabolism]].


==Causes==
==Causes==
* 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]].
*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]].
 
[[File:SARS-CoV-2 49534865371.jpg|center|300px|thumb|Case courtesy of Dr. Daniel J Bell, Radiopaedia.org, rID: 74536]]
[[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==


* For further information about the differential diagnosis, [[COVID-19-associated encephalitis differential diagnosis|click here]].
*For further information about the differential diagnosis, [[COVID-19-associated encephalitis differential diagnosis|click here]].
* To view the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|click here]].
*To view the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|click here]].


== 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.<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>
*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.
*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.
* There is no racial predilection to [[COVID-19]]-associated [[encephalitis]] but more cases were present in African Americans.
*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.
*[[COVID-19]]-associated  [[encephalitis]] affects men and women equally.


==Risk Factors==
==Risk Factors==


* <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>
*<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]].
*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]].
*[[Auto-immune]] [[syndromes]] might be at higher risk of developing this disease due to [[immunosuppressive therapy]].
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{| 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]].
*To view screening for [[COVID-19]], [[COVID-19 screening|click here]].


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==


* To view Natural History for [[COVID-19]], [[COVID-19 natural history, complications and prognosis|click here]].
*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 ===
===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]].
*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|COVID-19-]]<nowiki/>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.


==== Common Symptoms ====
====Common Symptoms====


*The common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
*The common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
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**Impaired [[consciousness]]
**Impaired [[consciousness]]


==== Less Common Symptoms ====
====Less Common Symptoms====


*Less common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:  
*Less common symptoms of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:  
** Tran<nowiki/>sient [[generalized seizure]]
**Tran<nowiki/>sient [[generalized seizure]]
**[[Dizziness]],
**[[Dizziness]],
**[[Paralysis]]
**[[Paralysis]]
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**[[Comatose|Coma]]
**[[Comatose|Coma]]


* Clinical manifestation of 3 cases of COVID-19 associated encephalitis are shown below:
*Clinical manifestation of 3 cases of COVID-19 associated encephalitis are shown below:


{| class="wikitable"
{| class="wikitable"
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pan-[[Paranasal sinus|paranasal]] [[sinusitis]].
pan-[[Paranasal sinus|paranasal]] [[sinusitis]].
|-
|-
|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 [[Symptom|symptoms]]
|[[Flu]] like [[Symptom|symptoms]]
|[[Headache]], [[nausea]], [[dizziness]], and
|[[Headache]], [[nausea]], [[dizziness]], and
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*<nowiki/>Common physical examination findings of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include
*<nowiki/>Common physical examination findings of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include


==== Neuromuscular ====
====Neuromuscular====


*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>[[Generalized seizure]]
*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>[[Generalized seizure]]
*<nowiki/><nowiki/>[[Headache]]  
*<nowiki/><nowiki/>[[Headache]]
*<nowiki/><nowiki/>[[Neck stiffness]]
*<nowiki/><nowiki/>[[Neck stiffness]]
*<nowiki/><nowiki/>Focal [[neurological]] deficits can be present in this [[disease]].
*<nowiki/><nowiki/>Focal [[neurological]] deficits can be present in this [[disease]].


=== Laboratory Findings ===
===Laboratory Findings===


* Positive [[RT-PCR]] in [[CSF]] or nasopharyngeal swab is diagnostic of  [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]].
*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.
*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]].
*[[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]].
*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 ===
===Electrocardiogram===


* There are no [[ECG]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>a<nowiki/>ssociated [[encephalitis]].
*There are no [[ECG]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>a<nowiki/>ssociated [[encephalitis]].


=== X-ray ===
===X-ray===


* There are no [[X-rays|x-ray]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]].
*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.
*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 ===
===Echocardiography or Ultrasound===


* There are no [[echocardiography]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>associated <nowiki/>[[encephalitis|e]]<nowiki/>[[encephalitis|ncephalitis]].
*There are no [[echocardiography]] findings associated with [[COVID-19|COVID-19-]]<nowiki/>associated <nowiki/>[[encephalitis|e]]<nowiki/>[[encephalitis|ncephalitis]].


=== CT scan ===
===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.
*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 ===
===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:  
*[[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 right lateral [[Ventricle|ventricle's]] inferior horn along the wall and pan-[[Paranasal sinus|paranasal]] [[sinusitis]].
** Hyper-intensity in the left [[temporal lobe]].
**Hyper-intensity in the left [[temporal lobe]].
** MR [[Spectroscopy]]: Decrease [[N-acetyl aspartate]] peak along with a marked elevated [[choline]] peak.
**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]].
**Non-enhancing [[cerebral edema]] and restricted [[diffusion]] in the right [[cerebral hemisphere]] with [[brain herniation]].


=== Other Diagnostic Studies ===
===Other Diagnostic Studies===


* <nowiki/> Other diagnostic studies for  [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalitis]] include:
*<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,
**[[RT-PCR]] of [[SARS-CoV-2]] [[RNA]] positive in [[CSF]] and [[nasopharyngeal]] swab,
**[[Antibody]] [[IgM]] for [[acute]] [[infection]], and
**[[Antibody]] [[IgM]] for [[acute]] [[infection]], and
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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>
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-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]].
*[[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===


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


=== Primary Prevention ===
===Primary Prevention===


* There are no established measures for the [[primary prevention]] of [[COVID-19]] associated [[encephalitis]].
*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.
*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]].
*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]].
*To view primary prevention for COVID-19 [[COVID-19 primary prevention|click here]].


=== Secondary Prevention ===
===Secondary Prevention===


* There are no established measures for the [[secondary prevention]] of [[COVID-19]] associated [[encephalitis]].
*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]].
*To view secondary prevention for COVID-19 [[COVID-19 secondary prevention|click here]].



Revision as of 23:12, 30 August 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.


WikiDoc Resources for COVID-19-associated encephalitis

Articles

Most recent articles on COVID-19-associated encephalitis

Most cited articles on COVID-19-associated encephalitis

Review articles on COVID-19-associated encephalitis

Articles on COVID-19-associated encephalitis in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on COVID-19-associated encephalitis

Images of COVID-19-associated encephalitis

Photos of COVID-19-associated encephalitis

Podcasts & MP3s on COVID-19-associated encephalitis

Videos on COVID-19-associated encephalitis

Evidence Based Medicine

Cochrane Collaboration on COVID-19-associated encephalitis

Bandolier on COVID-19-associated encephalitis

TRIP on COVID-19-associated encephalitis

Clinical Trials

Ongoing Trials on COVID-19-associated encephalitis at Clinical Trials.gov

Trial results on COVID-19-associated encephalitis

Clinical Trials on COVID-19-associated encephalitis at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on COVID-19-associated encephalitis

NICE Guidance on COVID-19-associated encephalitis

NHS PRODIGY Guidance

FDA on COVID-19-associated encephalitis

CDC on COVID-19-associated encephalitis

Books

Books on COVID-19-associated encephalitis

News

COVID-19-associated encephalitis in the news

Be alerted to news on COVID-19-associated encephalitis

News trends on COVID-19-associated encephalitis

Commentary

Blogs on COVID-19-associated encephalitis

Definitions

Definitions of COVID-19-associated encephalitis

Patient Resources / Community

Patient resources on COVID-19-associated encephalitis

Discussion groups on COVID-19-associated encephalitis

Patient Handouts on COVID-19-associated encephalitis

Directions to Hospitals Treating COVID-19-associated encephalitis

Risk calculators and risk factors for COVID-19-associated encephalitis

Healthcare Provider Resources

Symptoms of COVID-19-associated encephalitis

Causes & Risk Factors for COVID-19-associated encephalitis

Diagnostic studies for COVID-19-associated encephalitis

Treatment of COVID-19-associated encephalitis

Continuing Medical Education (CME)

CME Programs on COVID-19-associated encephalitis

International

COVID-19-associated encephalitis en Espanol

COVID-19-associated encephalitis en Francais

Business

COVID-19-associated encephalitis in the Marketplace

Patents on COVID-19-associated encephalitis

Experimental / Informatics

List of terms related to 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], 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 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.

35-year-old woman from Turkey[9][10] 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[11] 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:[9][12][2][13]

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. 9.0 9.1 9.2 9.3
  10. 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).
  11. 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).
  12. 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.
  13. 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.


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