COVID-19-associated encephalopathy: Difference between revisions

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


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


{{SK}}Encephalopathy in COVID-19, COVID-19 encephalopathy  
{{SK}}Encephalopathy in COVID-19, COVID-19 encephalopathy  


==Overview==
==Overview==
[[Encephalopathy]] is an alteration of the level or contents of [[consciousness]] due to brain dysfunction and can result from global or focal brain lesions. [[SARS-CoV-2]] which is the member of [[coronavirus]] family has caused many neurological complications including encephalopathy. Acute toxic encephalopathy is caused by [[toxemia]], [[hypoxia]] and metabolic disorders due the systemic viral infection ([[viral sepsis]]).  
[[Encephalopathy]] is an alteration of the level or contents of [[consciousness]] due to brain dysfunction and can result from global or focal brain lesions. [[SARS-CoV-2]] which is the member of [[coronavirus]] family has caused many neurological complications including [[encephalopathy]]. Acute toxic [[encephalopathy]] is caused by [[toxemia]], [[hypoxia]] and metabolic disorders due the systemic viral infection ([[viral sepsis]]).  


==Historical Perspective==
==Historical Perspective==
COVID-19, a disease caused by SARS-CoV-2 first emerged in Wuhan, China in December 2019. It then spread so rapidly that it was declared as pandemic in Feb, 2020. It mostly presents with respiratory symptoms like flue, dry cough, fever, fatigue, dyspnea. Although rare but neurological manifestations have been reported throughout the spectrum of COVID-19 pandemic. These neurological symptoms range from headache, anosmia, meningitis, encephalitis, Guillain Berre Syndrome,and stroke. Encephalopathy is rare and few case has been reported with acute encephalopathy during the severe systemic SARS-CoV-2 infection.
 
* [[COVID-19]], a [[disease]] caused by [[SARS-CoV-2]] first emerged in Wuhan, China in December 2019.  
* It then spread so rapidly that it was declared as pandemic in Feb, 2020.  
* It mostly presents with respiratory symptoms like flue, dry cough, fever, fatigue, dyspnea.  
* Although rare but neurological manifestations have been reported throughout the spectrum of COVID-19 pandemic.  
* These neurological symptoms range from headache, anosmia, meningitis, encephalitis, Guillain Berre Syndrome,and stroke. [[Encephalopathy]] is rare and few case has been reported with acute [[encephalopathy]] during the severe systemic [[SARS-CoV-2]] infection.


==Classification==
==Classification==
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==Differentiating COVID-19-associated encephalopathy from other Diseases==
==Differentiating COVID-19-associated encephalopathy from other Diseases==


* [[COVID-19]]-associated [[encephalopathy]] must be differentiated from other causes of  [[headache]], seizure and loss of consciousness.
* For further information about the differential diagnosis, [[COVID-19-associated encephalopathy differential diagnosis|click here]].
 
* To view the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|click here]].
* The symptoms of encephalopathy may overlap with the symptoms of other diseases:
 
* [[Encephalitis]] which is differentiated from encephalopathy by the presence of [[fever]] and other signs and symptoms of a viral infection.
* [[Meningitis]] which is differentiated from encephalopathy by the presence of [[neck stiffness]], [[headache]], [[meningeal signs]], [[fever]]
 
* [[Postictal state]] which would be differentiated by the presence of [[seizures]]
 
* Intracranial lesions like [[tumors]], masses, [[granulomas]] which are differentiated by the presence of focal neurologic signs and symptoms
 
<br />
{|
|-style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="2" |<small>Diseases</small>
! colspan="4" |<small>Symptoms
! colspan="5" |<small>Physical Examination</small>
! rowspan="2" |<small>Past medical history</small>
! colspan="3" |<small>Diagnostic tests</small>
! rowspan="2" |<small>Other Findings</small>
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!<small>Headache</small>
!↓<small>LOC</small>
!<small>Motor weakness</small>
!<small>Abnormal sensory</small>
!<small>Motor Deficit</small>
!<small>Sensory deficit</small>
!<small>Speech difficulty</small>
!<small>Gait abnormality</small>
!<small>Cranial nerves</small>
!<small>CT /MRI</small>
!<small>CSF Findings</small>
!<small>Gold standard test</small>
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Meningitis]]
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" |History of [[fever]] and [[malaise]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px; text-align:center" |'''↑''' [[Leukocytes]],
 
'''↑''' Protein
 
↓ Glucose
| style="background: #F5F5F5; padding: 5px;" |[[CSF analysis]]<ref name="pmid19398286">{{cite journal| author=Carbonnelle E| title=[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]. | journal=Med Mal Infect | year= 2009 | volume= 39 | issue= 7-8 | pages= 581-605 | pmid=19398286 | doi=10.1016/j.medmal.2009.02.017 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19398286  }}</ref>
| style="background: #F5F5F5; padding: 5px;" |[[Fever]], [[Neck rigidity|neck]]
[[Neck rigidity|rigidity]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Encephalitis]]
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" | +/-
| style="background: #F5F5F5; padding: 5px text-align:center" | +/-
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" | +/-
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" |History of [[fever]] and [[malaise]]
| style="background: #F5F5F5; padding: 5px text-align:center" | +
| style="background: #F5F5F5; padding: 5px text-align:center" |'''↑''' [[Leukocytes]], ↓ Glucose
| style="background: #F5F5F5; padding: 5px text-align:center" |CSF [[PCR]]
| style="background: #F5F5F5; padding: 5px text-align:center" |[[Fever]], [[Seizure|seizures]], [[Focal neurologic signs|focal neurologic abnormalities]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" | [[Brain tumor]]<ref name="pmid10582668">{{cite journal| author=Morgenstern LB, Frankowski RF| title=Brain tumor masquerading as stroke. | journal=J Neurooncol | year= 1999 | volume= 44 | issue= 1 | pages= 47-52 | pmid=10582668 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10582668  }} </ref>
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" |[[Weight loss]], [[fatigue]]
|style="background: #F5F5F5; padding: 5px; text-align:center"| +
|style="background: #F5F5F5; padding: 5px text-align:center" |Cancer cells<ref name="pmid21371327">{{cite journal| author=Weston CL, Glantz MJ, Connor JR| title=Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. | journal=Fluids Barriers CNS | year= 2011 | volume= 8 | issue= 1 | pages= 14 | pmid=21371327 | doi=10.1186/2045-8118-8-14 | pmc=3059292 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21371327  }}</ref>
|style="background: #F5F5F5; padding: 5px;" |MRI
|style="background: #F5F5F5; padding: 5px;" |[[Cachexia]], gradual progression of symptoms
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Hemorrhagic stroke]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" |[[Hypertension]]
|style="background: #F5F5F5; padding: 5px; text-align:center" | +
| style="background: #F5F5F5; padding: 5px;" | -
|style="background: #F5F5F5; padding: 5px;" |CT scan  without contrast<ref name="pmid21694755">{{cite journal| author=Birenbaum D, Bancroft LW, Felsberg GJ| title=Imaging in acute stroke. | journal=West J Emerg Med | year= 2011 | volume= 12 | issue= 1 | pages= 67-76 | pmid=21694755 | doi= | pmc=3088377 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694755  }}</ref><ref name="pmid21807345">{{cite journal| author=DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF et al.| title=ACR Appropriateness Criteria® on cerebrovascular disease. | journal=J Am Coll Radiol | year= 2011 | volume= 8 | issue= 8 | pages= 532-8 | pmid=21807345 | doi=10.1016/j.jacr.2011.05.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21807345  }}</ref>
|style="background: #F5F5F5; padding: 5px;" |[[Neck stiffness]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" | [[Subdural hematoma|Subdural hemorrhage]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" |[[Trauma]], fall
|style="background: #F5F5F5; padding: 5px; text-align:center" | +
|style="background: #F5F5F5; padding: 5px;" |Xanthochromia<ref name="pmid1198628">{{cite journal| author=Lee MC, Heaney LM, Jacobson RL, Klassen AC| title=Cerebrospinal fluid in cerebral hemorrhage and infarction. | journal=Stroke | year= 1975 | volume= 6 | issue= 6 | pages= 638-41 | pmid=1198628 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1198628  }}</ref>
|style="background: #F5F5F5; padding: 5px;" |CT scan  without contrast<ref name="pmid21694755">{{cite journal| author=Birenbaum D, Bancroft LW, Felsberg GJ| title=Imaging in acute stroke. | journal=West J Emerg Med | year= 2011 | volume= 12 | issue= 1 | pages= 67-76 | pmid=21694755 | doi= | pmc=3088377 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694755  }}</ref><ref name="pmid21807345">{{cite journal| author=DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF et al.| title=ACR Appropriateness Criteria® on cerebrovascular disease. | journal=J Am Coll Radiol | year= 2011 | volume= 8 | issue= 8 | pages= 532-8 | pmid=21807345 | doi=10.1016/j.jacr.2011.05.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21807345  }}</ref>
|style="background: #F5F5F5; padding: 5px;" |[[Confusion]], [[dizziness]], [[nausea]], [[vomiting]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Neurosyphilis]]<ref name="pmid22482824">{{cite journal| author=Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG et al.| title=Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients. | journal=J Neurol Sci | year= 2012 | volume= 317 | issue= 1-2 | pages= 35-9 | pmid=22482824 | doi=10.1016/j.jns.2012.03.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22482824  }} </ref><ref name="pmid24365430">{{cite journal |vauthors=Berger JR, Dean D |title=Neurosyphilis |journal=Handb Clin Neurol |volume=121 |issue= |pages=1461–72 |year=2014 |pmid=24365430 |doi=10.1016/B978-0-7020-4088-7.00098-5 |url=}}</ref>
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" |[[Sexually transmitted disease|STI]]<nowiki/>s
|style="background: #F5F5F5; padding: 5px; text-align:center" | +
|style="background: #F5F5F5; padding: 5px;" |'''↑''' [[Leukocytes]] and [[protein]]
|style="background: #F5F5F5; padding: 5px;" |CSF [[VDRL]]-specifc
CSF FTA-Ab -sensitive<ref name="pmid22421697">{{cite journal| author=Ho EL, Marra CM| title=Treponemal tests for neurosyphilis--less accurate than what we thought? | journal=Sex Transm Dis | year= 2012 | volume= 39 | issue= 4 | pages= 298-9 | pmid=22421697 | doi=10.1097/OLQ.0b013e31824ee574 | pmc=3746559 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22421697  }}</ref>
|style="background: #F5F5F5; padding: 5px;" |[[Blindness]], [[confusion]], [[depression]],
 
Abnormal [[gait]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |Complex or atypical [[migraine]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" |Family history of [[migraine]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
|style="background: #F5F5F5; padding: 5px;" |Clinical assesment
|style="background: #F5F5F5; padding: 5px;" |Presence of aura, [[nausea]], [[vomiting]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Hypertensive encephalopathy]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" |[[Hypertension]]
|style="background: #F5F5F5; padding: 5px;" | +
|style="background: #F5F5F5; padding: 5px;" | -
|style="background: #F5F5F5; padding: 5px;" |Clinical assesment
|style="background: #F5F5F5; padding: 5px;" |[[Delirium]], [[cortical blindness]], [[cerebral edema]], [[seizure]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Wernicke's encephalopathy|Wernicke’s encephalopathy]]
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" |History of alcohal abuse
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |Clinical assesment and lab findings
|style="background: #F5F5F5; padding: 5px;" |[[Ophthalmoplegia]], [[confusion]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Brain abscess|CNS abscess]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" |History of [[drug abuse]], [[endocarditis]], [[immunosupression]]
|style="background: #F5F5F5; padding: 5px;" | +
|style="background: #F5F5F5; padding: 5px;" |'''↑''' leukocytes, '''↓''' glucose and '''↑''' protien
|style="background: #F5F5F5; padding: 5px;" |MRI is more sensitive and specific
|style="background: #F5F5F5; padding: 5px;" |High grade [[fever]], [[fatigue]],[[nausea]], [[vomiting]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Drug toxicity]]
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |Drug screen test
|style="background: #F5F5F5; padding: 5px;" |[[Lithium]], [[Sedatives]], [[phenytoin]], [[carbamazepine]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Conversion disorder]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
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|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" |
|style="background: #F5F5F5; padding: 5px text-align:center" |History of [[emotional stress]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
|style="background: #F5F5F5; padding: 5px;" |Diagnosis of exclusion
|style="background: #F5F5F5; padding: 5px;" |[[Tremor|Tremors]], [[blindness]], difficulty [[swallowing]]
|-
|style="background: #DCDCDC; padding: 5px; text-align: center;" |Metabolic disturbances ([[electrolyte imbalance]], [[hypoglycemia]])
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |[[Hypoglycemia]], [[Hyponatremia|hypo]] and [[hypernatremia]], [[Hypokalemia|hypo]] and [[hyperkalemia]]
|style="background: #F5F5F5; padding: 5px;" |Depends on the cause
| style="background: #F5F5F5; padding: 5px;" |[[Confusion]], [[seizure]], [[Palpitation|palpitations]], [[sweating]], [[dizziness]], [[hypoglycemia]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Multiple sclerosis]] exacerbation
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" |History of relapses and remissions
| style="background: #F5F5F5; padding: 5px; text-align:center" | +
| style="background: #F5F5F5; padding: 5px; text-align:center" |'''↑'''  CSF IgG levels
(monoclonal bands)
| style="background: #F5F5F5; padding: 5px;" |Clinical assesment and [[MRI]] <ref name="pmid8274111">{{cite journal| author=Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH et al.| title=Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group. | journal=Arch Neurol | year= 1994 | volume= 51 | issue= 1 | pages= 61-6 | pmid=8274111 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8274111  }}</ref>
| style="background: #F5F5F5; padding: 5px;" |[[Blurred vision|Blurry vision]], [[urinary incontinence]], [[fatigue]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Seizure]]
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | -
|style="background: #F5F5F5; padding: 5px text-align:center" | +
|style="background: #F5F5F5; padding: 5px text-align:center" |Previous history of [[seizures]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |Mass lesion
| style="background: #F5F5F5; padding: 5px;" |Clinical assesment and [[EEG]] <ref name="pmid11385043">{{cite journal| author=Manford M| title=Assessment and investigation of possible epileptic seizures. | journal=J Neurol Neurosurg Psychiatry | year= 2001 | volume= 70 Suppl 2 | issue=  | pages= II3-8 | pmid=11385043 | doi= | pmc=1765557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11385043  }}</ref>
| style="background: #F5F5F5; padding: 5px;" |[[Confusion]], [[apathy]], [[irritability]],
|}
===Other differentials===
Toxic encephalopathy must also be differentiated from other diseases that cause [[personality changes]], altered level of [[consciousness]] and hand [[tremors]] ([[asterixis]]). The differentials include the following:<ref name="pmid20495225">{{cite journal| author=Meparidze MM, Kodua TE, Lashkhi KS| title=[Speech impairment predisposes to cognitive deterioration in hepatic encephalopathy]. | journal=Georgian Med News | year= 2010 | volume=  | issue= 181 | pages= 43-9 | pmid=20495225 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20495225  }} </ref><ref name="pmid25013309">{{cite journal| author=Kattimani S, Bharadwaj B| title=Clinical management of alcohol withdrawal: A systematic review. | journal=Ind Psychiatry J | year= 2013 | volume= 22 | issue= 2 | pages= 100-8 | pmid=25013309 | doi=10.4103/0972-6748.132914 | pmc=4085800 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25013309  }} </ref><ref name="pmid12813481">{{cite journal| author=Roldán J, Frauca C, Dueñas A| title=[Alcohol intoxication]. | journal=An Sist Sanit Navar | year= 2003 | volume= 26 Suppl 1 | issue=  | pages= 129-39 | pmid=12813481 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12813481  }} </ref><ref name="pmid21590619">{{cite journal| author=Seifter JL, Samuels MA| title=Uremic encephalopathy and other brain disorders associated with renal failure. | journal=Semin Neurol | year= 2011 | volume= 31 | issue= 2 | pages= 139-43 | pmid=21590619 | doi=10.1055/s-0031-1277984 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21590619  }} </ref><ref name="pmid6864698">{{cite journal| author=Handler CE, Perkin GD| title=Wernicke's encephalopathy. | journal=J R Soc Med | year= 1983 | volume= 76 | issue= 5 | pages= 339-42 | pmid=6864698 | doi= | pmc=1439130 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6864698  }} </ref><ref name="pmid23251840">{{cite journal| author=Kim Y, Kim JW| title=Toxic encephalopathy. | journal=Saf Health Work | year= 2012 | volume= 3 | issue= 4 | pages= 243-56 | pmid=23251840 | doi=10.5491/SHAW.2012.3.4.243 | pmc=3521923 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23251840  }} </ref><ref name="pmid2497395">{{cite journal| author=Hartmann A, Buttinger C, Rommel T, Czernicki Z, Trtinjiak F| title=Alteration of intracranial pressure, cerebral blood flow, autoregulation and carbondioxide-reactivity by hypotensive agents in baboons with intracranial hypertension. | journal=Neurochirurgia (Stuttg) | year= 1989 | volume= 32 | issue= 2 | pages= 37-43 | pmid=2497395 | doi=10.1055/s-2008-1053998 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2497395  }} </ref><ref name="pmid21590622">{{cite journal| author=Kumar N| title=Acute and subacute encephalopathies: deficiency states (nutritional). | journal=Semin Neurol | year= 2011 | volume= 31 | issue= 2 | pages= 169-83 | pmid=21590622 | doi=10.1055/s-0031-1277986 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21590622  }} </ref><ref name="pmid23035103">{{cite journal| author=Chiu GS, Chatterjee D, Darmody PT, Walsh JP, Meling DD, Johnson RW et al.| title=Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1. | journal=J Neurosci | year= 2012 | volume= 32 | issue= 40 | pages= 13945-55 | pmid=23035103 | doi=10.1523/JNEUROSCI.0704-12.2012 | pmc=3476834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23035103  }} </ref><ref name="pmid15284663">{{cite journal| author=Peate I| title=An overview of meningitis: signs, symptoms, treatment and support. | journal=Br J Nurs | year= 2004 | volume= 13 | issue= 13 | pages= 796-801 | pmid=15284663 | doi=10.12968/bjon.2004.13.13.13501 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15284663  }} </ref><ref name="pmid25821643">{{cite journal| author=Abdelhafiz AH, Rodríguez-Mañas L, Morley JE, Sinclair AJ| title=Hypoglycemia in older people - a less well recognized risk factor for frailty. | journal=Aging Dis | year= 2015 | volume= 6 | issue= 2 | pages= 156-67 | pmid=25821643 | doi=10.14336/AD.2014.0330 | pmc=4365959 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25821643  }} </ref>
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="2" |Diseases
! colspan="3" |History and Symptoms
! colspan="4" |Physical Examination
! colspan="3" |Laboratory Findings
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!Personality changes
!Altered level of consciousness
!Hand tremors (asterixis)
!Slurred speech
!Writing disturbances
!Voice monotonous
!Impaired '''memory'''
!Elevated blood ammonia
!Hyponatremia
!hypokalemia
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''Hepatic encephalopathy'''
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
| style="background: #F5F5F5; padding: 5px;" | <nowiki>++</nowiki>
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Alcohol intoxication]]'''
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Alcohol withdrawal]]'''
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Uremia]]'''
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" |[[Hyperkalemia]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Wernicke encephalopathy]]'''
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | ++
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Toxic encephalopathy]] from drugs'''
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''Altered [[intracranial pressure]]'''
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''Intoxication by chemical agents'''
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Malnutrition]]'''
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Hypoxic brain injury]]'''
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Meningitis]] and [[encephalitis]]'''
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''[[Hypoglycemia]]'''
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -/+
| style="background: #F5F5F5; padding: 5px;" | -/+
|}


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.


OR
* The incidence of [[COVID-19]]-associated [[encephalopathy]] is approximately 93 patients worldwide.
* In July 2020, the incidence of [[COVID-19]]-associated [[encephalopathy]] is approximately 93 cases with 69% of the patients in [[intensive care unit]].
* Patients of all age groups may develop [[COVID-19]]-associated [[encephalopathy]].
* The incidence of [[COVID-19]]-associated [[encephalopathy]] increases with age; the median age at [[diagnosis]] is 54 years.
* There is no racial predilection to [[COVID-19]]-associated [[encephalopathy]] but more cases were present in African Americans.
* [[COVID-19]]-associated [[encephalopathy]] affects men and women equally.


In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
==Risk Factors==


OR
* There are no established risk factors for [[COVID-19]]-associated [[encephalopathy]].
*To view the risk factors of COVID-19, [[COVID-19 risk factors|click here]].


In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
==Screening==
 
 
 
Patients of all age groups may develop [disease name].
 
OR
 
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
 
OR
 
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
 
OR
 
[Chronic disease name] is usually first diagnosed among [age group].
 
OR
 
[Acute disease name] commonly affects [age group].
 
 
 
There is no racial predilection to [disease name].


OR
* There is insufficient evidence to recommend routine screening for [[COVID-19]]-associated [[encephalopathy]].  
 
*To view screening for COVID-19, [[COVID-19 screening|click here]].
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
 
 
 
[Disease name] affects men and women equally.
 
OR
 
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
 
 
 
The majority of [disease name] cases are reported in [geographical region].
 
OR
 
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
 
==Risk Factors==
There are no established risk factors for COVID-19-associated encephalopathy.
 
==Screening==
There is insufficient evidence to recommend routine screening for COVID-19-associated encephalopathy.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].


OR
*If left untreated, COVID-19-associated [[encephalopathy]] may cause long term [[neurological]] [[Complication (medicine)|complications]].
*To view Natural History for COVID-19, [[COVID-19 natural history, complications and prognosis|click here]].


Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
==== Complications ====


OR
*Long term [[neurological]] [[Complication (medicine)|complications]] can develop according to the involved [[brain]] [[parenchymal]] area.


Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
<br />{{familytree/start}}
{{familytree | | | | | | | | | C02| | | |C02=Encephalopathy}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| | }}
{{familytree | |!| | | |!| | | |!| | | |!| | | |!| | | }}
{{familytree | D01 | | D02 | | D03 | | D04 | | D05 |D01=Memory loss|D02=Epilepsy|D03=Personality changes|D04=Hearing/vision loss|D05=Coma/Death}}
{{familytree/end}}


==Diagnosis==
==Diagnosis==
Line 581: Line 105:


* There are no established criteria for the diagnosis of [[COVID-19]]-associated [[encephalopathy]].
* There are no established criteria for the diagnosis of [[COVID-19]]-associated [[encephalopathy]].
* The diagnostic study of choice for [[COVID-19]]-associated [[encephalopathy]] is [[CSF]] [[analysis]] along with [[RT-PCR]] for [[SARS-CoV-2]] positive on nasopharyngeal swab or on [[CSF]].
* The diagnostic study of choice for [[COVID-19]]-associated [[encephalopathy]] is [[CSF]] [[analysis]] along with [[RT-PCR]] for [[SARS-CoV-2]] positive on [[nasopharyngeal]] swab or on [[CSF]].


===Signs and symptoms===
===Signs and symptoms===
Line 597: Line 121:
==== Less Common Symptoms ====
==== Less Common Symptoms ====


* There are few [[symptoms]] which are not present in all patients with [[COVID-19]]-associated [[encephalopathy]]
* There are few [[symptoms]] which are not present in all patients with [[COVID-19]]-associated [[encephalopathy]]:
** Transient [[generalized seizure]],
** Transient [[generalized seizure]],
** Absent [[brain]] [[reflexes]],
** Absent [[brain]] [[reflexes]],
Line 608: Line 132:
** [[Comatose|Coma]].
** [[Comatose|Coma]].


The [[COVID-19]]-associated [[encephalopathy]] cases have been analyzed in the table below:
13 cases of [[COVID-19]]-associated [[encephalopathy]] cases have been analyzed in the table below:
{| class="wikitable"
{| class="wikitable"
|-  
|-  
Line 614: Line 138:
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Early symptoms</small>
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Early symptoms</small>
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Later presentation</small>
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Later presentation</small>
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>GCS</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Lab. Findings</small>
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Lab. Findings</small>
! colspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Specific Tests</small>
! colspan="4" 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>Imaging studies</small>
|-  
|-
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CBC</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CSF</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>CSF</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>bacterial panel</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>bacterial panel</small>
Line 636: Line 158:


|altered mentation
|altered mentation
|NA
|NA
|Not possible due to traumatic rupture
|Not possible due to traumatic rupture
|Negative
|Negative
Line 655: Line 175:


altered mentationn
altered mentationn
|NA
|NA
|
|
* WBCs =4
* WBCs =4
Line 681: Line 199:


<br />
<br />
|GCS 11 which fell to 5 after admission
|NA
|
|
* CSF opening pressure = 28 cm water
* CSF opening pressure = 28 cm water
Line 701: Line 217:
* Comatosed post intubation
* Comatosed post intubation
* absent brain reflexes
* absent brain reflexes
|NA
|NA
|
|
* CSF opening pressure= 30 cm water
* CSF opening pressure= 30 cm water
Line 724: Line 238:
* absent corneal and gag reflexes
* absent corneal and gag reflexes
* comatosed
* comatosed
|NA
|NA
|
|
* CSF opening pressure= 48 cm of water
* CSF opening pressure= 48 cm of water
Line 749: Line 261:
* myoclonus
* myoclonus
* absent deep tendon reflexes
* absent deep tendon reflexes
|NA
|NA
|Normal
|Normal
|Negative
|Negative
Line 767: Line 277:
* no response to painful stimuli
* no response to painful stimuli
* decreased activity of brain on EEG
* decreased activity of brain on EEG
|NA
|NA
|WBCs =2 cells
|WBCs =2 cells


Line 786: Line 294:
* agitation
* agitation
* choreiform movements of upper extremities
* choreiform movements of upper extremities
|NA
|NA
|CSF findings negative for bacterial or viral meningitis/encephalitis
|CSF findings negative for bacterial or viral meningitis/encephalitis
|Negative
|Negative
Line 805: Line 311:
* left nasolabial fold was reduced
* left nasolabial fold was reduced
* reduced reflexes
* reduced reflexes
|NA
|NA
|CSF negative for bacterial or viral findings
|CSF negative for bacterial or viral findings
|Negative
|Negative
Line 824: Line 328:
* altered mentation
* altered mentation
* ARDS
* ARDS
|NA
|NA
|NA
|NA
|Negative
|Negative
Line 833: Line 335:
|MRI showed vasogenic edema in the posterior parieto-occipital regions with subacute blood products suggestive of hemorrhagic posterior reversible encephalopathy syndrome (PRES)
|MRI showed vasogenic edema in the posterior parieto-occipital regions with subacute blood products suggestive of hemorrhagic posterior reversible encephalopathy syndrome (PRES)
|-
|-
|11. Hayashi et.al reported first case of COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion in 75 year old male<ref name="pmid32474220">{{cite journal| author=Hayashi M, Sahashi Y, Baba Y, Okura H, Shimohata T| title=COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion. | journal=J Neurol Sci | year= 2020 | volume= 415 | issue=  | pages= 116941 | pmid=32474220 | doi=10.1016/j.jns.2020.116941 | pmc=7251406 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32474220  }}</ref>
|11. Hayashi et.al reported the first case of COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion in 75-year-old male<ref name="pmid32474220">{{cite journal| author=Hayashi M, Sahashi Y, Baba Y, Okura H, Shimohata T| title=COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion. | journal=J Neurol Sci | year= 2020 | volume= 415 | issue=  | pages= 116941 | pmid=32474220 | doi=10.1016/j.jns.2020.116941 | pmc=7251406 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32474220  }}</ref>
|
|
* Left dominant kinetic tremors
* Left dominant kinetic tremors
Line 841: Line 343:
* fever day 2
* fever day 2
* Hypoxemia
* Hypoxemia
|NA
|NA
|NA
|NA
|negative
|negative
Line 850: Line 350:
|(MRI) of the brain revealed an abnormal hyperintensity in the splenium of corpus callosum (SCC),  suspicious for clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS)
|(MRI) of the brain revealed an abnormal hyperintensity in the splenium of corpus callosum (SCC),  suspicious for clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS)
|-
|-
|12. Cani et. al reported Frontal encephalopathy related to hyperinflammation in 77 year old female with COVID-19<ref name="pmid32654063">{{cite journal| author=Cani I, Barone V, D'Angelo R, Pisani L, Allegri V, Spinardi L | display-authors=etal| title=Frontal encephalopathy related to hyperinflammation in COVID-19. | journal=J Neurol | year= 2020 | volume=  | issue=  | pages=  | pmid=32654063 | doi=10.1007/s00415-020-10057-5 | pmc=7353824 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32654063  }}</ref>
|12. Cani et. al reported Frontal encephalopathy related to hyperinflammation in 77-year-old female with COVID-19<ref name="pmid32654063">{{cite journal| author=Cani I, Barone V, D'Angelo R, Pisani L, Allegri V, Spinardi L | display-authors=etal| title=Frontal encephalopathy related to hyperinflammation in COVID-19. | journal=J Neurol | year= 2020 | volume=  | issue=  | pages=  | pmid=32654063 | doi=10.1007/s00415-020-10057-5 | pmc=7353824 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32654063  }}</ref>
|fever
|fever


Line 859: Line 359:
* myoclonus
* myoclonus
* positive primitive reflexes
* positive primitive reflexes
|NA
|NA
|normal
|normal
|negative
|negative
Line 867: Line 365:
|Negative
|Negative
|MRI displayed diffuse white-matter lesions consistent with chronic small vessel disease without contrast enhancement
|MRI displayed diffuse white-matter lesions consistent with chronic small vessel disease without contrast enhancement
|-
|13. Encephalopathy and seizure activity in a 41-year-old COVID-19 well-controlled HIV patient was reported by Haddad S et.al<ref name="pmid32426230">{{cite journal| author=Haddad S, Tayyar R, Risch L, Churchill G, Fares E, Choe M | display-authors=etal| title=Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient. | journal=IDCases | year= 2020 | volume=  | issue=  | pages= e00814 | pmid=32426230 | doi=10.1016/j.idcr.2020.e00814 | pmc=7228895 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32426230  }}</ref>
|Fever
fatigue
chills
cough
|
* confusion
* agitation
* seizure
* EEG showed evidence of diffuse slowing but no epileptiform activity.
|WBCs = 0
RBCs = 5 cells
Proteins = 102
Glucose = 81
|Negative
|negative
|SARS-CoV-2 positive on RT-PCR
|neagtive
|NA
|}
|}


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


* Patients with [[COVID-19]]-associated [[encephalopathy]] usually appear [[Confusion|confused]].
* Physical examination of COVID-19 associated encephalopathy is usually difficult to perform as patients are confused and non cooperative.
* Physical examination of patients with [[COVID-19]]-associated [[encephalopathy]] is usually remarkable for [[altered mentation]], [[speech]] arrest, [[seizure]], and [[neurological illness]].
* So, clinicians usually do focused examinations in encephalopathic patients.
* The presence of [[seizures]], [[confusion]], and [[Neurological illness|neurological illnesses]] on [[physical examination]] is highly suggestive of [[COVID-19]]-associated [[encephalopathy]].
 
==== Appearance of the patient ====
 
* Generally, the patients with COVID-19 associated encephalopathy are not oriented to time, place and persons.
* Patients are usually agitated and sedated medically sometimes.
* Patients have dusky appearance usually due to concurrent pulmonary disease in most cases of COVID-19 associated encephalopathy.
 
==== Vital signs ====
 
* Usually, patients with COVID-19 associated encephalopathy have high grade fever.
* Autonomic instability with [[tachycarida]]/[[bradycardia]], [[hypotnesion]]/hypertension
 
==== Neurological examination ====
Common findings in COVID-19 associated neurological examinations are:
 
* Inattention
* Altered mentation
* [[speech]] arrest
* Multifocal [[myoclonus]]
* Postural action tremors
* flapping motions of an outstretched, dorsiflexed hand ([[asterixis]])
* reduced reflexes


===Laboratory Findings===
===Laboratory Findings===
Line 889: Line 432:
* There are no [[x-ray]] findings associated with [[COVID-19]]-associated [[encephalopathy]].
* There are no [[x-ray]] findings associated with [[COVID-19]]-associated [[encephalopathy]].


* A Chest [[x-ray]] may be helpful in the diagnosis of [[COVID-19]]-associated respiratory disease.
* A Chest [[x-ray]] may be helpful in the diagnosis of [[COVID-19]]-associated respiratory disease.


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
Line 897: Line 440:


===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


OR
* Head CT scan may be helpful in the diagnosis of [[COVID-19]]-associated [[encephalopathy]].
 
* Findings on head CT scan suggestive of [[COVID-19]]-associated [[encephalopathy]] include:
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
** Noncontrast head CT images demonstrated symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram,
** Hemorrhagic Posterior Reversible Encephalopathy Syndrome.


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR


There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
*[[Brain]] [[MRI]] is helpful in the [[diagnosis]] of [[COVID-19]]-associated [[encephalopathy]].
* Findings on [[brain]] [[MRI]]  suggestive of [[COVID-19]]-associated [[encephalopathy]] include:
**[[Hemorrhagic]] rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions,
** Diffuse swelling and hemorrhage in the brain stem and both amygdalae,
** Nonenhancing cerebral edema and diffusion weighted imaging abnormalities,
** Brain herniation
** Nonenhancing hyperintense lesion.


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
Other imaging studies may be helpful in the diagnosis of [[COVID-19]]-associated [[encephalopathy]] include:
 
OR


[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
* MR [[spectroscopy]],
*[[CT angiography|CT angiogram]] and
*[[CT]] [[venogram]] may be helpful in the [[diagnosis]] of [[COVID-19]]-associated [[encephalopathy]].


===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
Other diagnostic studies for [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]] include:


OR
* [[Antibody]] [[IgM]] for [[acute]] [[infection]], and
 
* [[Antibody]] [[IgG]] for resolved or [[chronic]] [[infection]].
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
* [[RT-PCR]] of [[SARS-CoV-2]] [[RNA]] positive in [[CSF]] or [[nasopharyngeal]] swab.
 
OR
 
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
The mainstay of [[medical]] [[therapy]] for [[viral encephalitis]] are:
 
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR


The mainstay of treatment for [disease name] is [therapy].
==== Symptomatic Treatment ====


OR
* There is no specific treatment for [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]]; the mainstay of therapy is supportive care.<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><ref name="pmid32654063" /><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="pmid32620554">{{cite journal| author=Johnson RM, Vinetz JM| title=Dexamethasone in the management of covid -19. | journal=BMJ | year= 2020 | volume= 370 | issue=  | pages= m2648 | pmid=32620554 | doi=10.1136/bmj.m2648 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32620554  }}</ref><ref name="pmid322344672">{{cite journal| author=Zhang C, Wu Z, Li JW, Zhao H, Wang GQ| title=Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. | journal=Int J Antimicrob Agents | year= 2020 | volume= 55 | issue= 5 | pages= 105954 | pmid=32234467 | doi=10.1016/j.ijantimicag.2020.105954 | pmc=7118634 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32234467 }}</ref><ref name="urlA Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia - Full Text View - ClinicalTrials.gov">{{cite web |url=+https://clinicaltrials.gov/ct2/show/NCT04372186 |title=A Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia - Full Text View - ClinicalTrials.gov |format= |work= |accessdate=}}</ref>
   
* Supportive therapy for [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]] includes corticosteroids, anti-epileptic drugs, and treating underlying condition.
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
* [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]] can present in a medical emergency and requires prompt treatment.
 
*Severe di<nowiki/>sease require [[intubation]] and [[mechanical ventilation]].
OR
*[[Anti-inflammatory]] medicines like pulse [[steroids]] ([[methylprednisolone]] 1,000 mg/day) are helpful in this [[disease]], some patients improved even with a very low dose (60mg/day). Dexamthasone is  helpful in COVID-19 who are oxygen dependent and hospitalized.
 
* [[Anti-epileptic drugs]] like [[levetiracetam]] (50-60 mg/kg/day) is necessary for [[seizure]] management in patients with refractory seizures.
[Therapy] is recommended among all patients who develop [disease name].
*[[Tocilizumab]] (8mg/kg/dose) is IL-6 anatgonist, that reduces cytokine storm syndrome responsible for neurological manifestations in a COVID-19 patient.
 
*To see treatment protocol to manage the underlying cause i.e., COVID-19, [[COVID-19 medical therapy|click here]]
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of [disease name].


OR
* Surgical intervention is not recommended for the management of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]].
 
* [[Focal Epilepsy|Focal epileptic]] involvement of brain [[parenchyma]] can be treated with [[resection]] of the area.
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].


OR
* There are no established measures for the primary prevention of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]].
 
* To view primary prevention for COVID-19 [[COVID-19 primary prevention|click here]].
There are no available vaccines against [disease name].
 
OR
 
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
OR


Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
* There are no established measures for the secondary prevention of [[COVID-19|COVID-19-]]<nowiki/>associated [[encephalopathy]].
* 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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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Adnan Haider, M.B.B.S.[2], Wajeeha Aiman, M.D.[3], Fahimeh Shojaei, M.D.

Synonyms and keywords:Encephalopathy in COVID-19, COVID-19 encephalopathy

Overview

Encephalopathy is an alteration of the level or contents of consciousness due to brain dysfunction and can result from global or focal brain lesions. SARS-CoV-2 which is the member of coronavirus family has caused many neurological complications including encephalopathy. Acute toxic encephalopathy is caused by toxemia, hypoxia and metabolic disorders due the systemic viral infection (viral sepsis).

Historical Perspective

  • COVID-19, a disease caused by SARS-CoV-2 first emerged in Wuhan, China in December 2019.
  • It then spread so rapidly that it was declared as pandemic in Feb, 2020.
  • It mostly presents with respiratory symptoms like flue, dry cough, fever, fatigue, dyspnea.
  • Although rare but neurological manifestations have been reported throughout the spectrum of COVID-19 pandemic.
  • These neurological symptoms range from headache, anosmia, meningitis, encephalitis, Guillain Berre Syndrome,and stroke. Encephalopathy is rare and few case has been reported with acute encephalopathy during the severe systemic SARS-CoV-2 infection.

Classification

Pathophysiology

  • Severe COVID-19 infection can lead to dysfunction of multiple organs of the body that can lead to hypoxic or metabolic insults to brain and cause encephalopathy.
  • Encephalitis/meningitis are caused by neurotropism of SARS-CoV-2 to brain and meninges through ACE2 receptors.[1]
  • Encephalopathy is caused by hyper inflammation of brain by following three mechanisms;
  • cytokine storm
  • Hypoxic brain injury
  • molecular mimicry

Cytokine storm

  • SARS-CoV-2 causes several neurological complications through production of inflammatory cytokines (mainly IL-6) from glial cells called cytokine storm syndrome.[2]
  • SARS-CoV-2 activates CD4 cells of the immune system and CD4 cells activate macrophages by producing granulocyte-macrophage colony stimulating factors. Actiavted macrophages now produce IL-6.
  • IL-6 is a major cytokine of cytokine storm syndrome and leads to multiple organ failure. This severe organ damage leads to metabolic and toxic changes in the body which causes brain dysfunction and leads to SARS-CoV-2 related encephalopathy.[3]
  • This fact can be supported by the evidence that tocilizumab which is IL-6 antagonist is used in severe COVID-19 infections.[4]

Hypoxic Brain Injury

  • The hall mark of severe COVID-19 infection is dyspnea and hypoxemia due Acute Respiratory distress syndrome (ARDS).
  • This hypoxia and hypoxemia is sometimes enough to cause diffuse brain injury and cause encephalopathy.[5]

Molecular Mimicry

  • Post-infectious encephalomyelitis, an autoimmune demyelinating disease of the brain, can be triggered by the SARS‐CoV‐2 virus.[6]
  • SARS-CoV-2 is considered to have similar antigenic determinants as that of some antigens present on human neuronal cells.
  • Immunological response to the SARS‐CoV‐2 virus cross-react with the myelin autoantigens, resulting in post-infectious encephalomyelitis.
  • Neuropathological findings confirmed vascular and demyelinating pathology in a patient who died from COVID-19.[7]

Causes

  • COVID-19-associated encephalopathy may be caused by SARS-CoV-2.
  • To read more about this virus, click here.

Differentiating COVID-19-associated encephalopathy 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

Screening

Natural History, Complications, and Prognosis

Complications


 
 
 
 
 
 
 
 
Encephalopathy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memory loss
 
Epilepsy
 
Personality changes
 
Hearing/vision loss
 
Coma/Death

Diagnosis

Diagnostic Study of Choice

Signs and symptoms

Common Symptoms

Less Common Symptoms

13 cases of COVID-19-associated encephalopathy cases have been analyzed in the table below:

Patient No. Early symptoms Later presentation Lab. Findings Specific Tests Imaging studies
CSF bacterial panel viral panel (VZV, CMV, HSV1, HSV2) SARS-CoV-2 MRI/CT scan
on nasopharyngeal sawab on CSF
1. Poyiadji et.al reported a case report of a female in her late fifties who presented with COVID-19 associated acute hemorrhagic necrotizing encephalopathy[8] fever

cough

altered mentation Not possible due to traumatic rupture Negative Negative RT-PCR for SARS-CoV-2 positive on nasopharyngeal swab Negative
  • Noncontrast head CT images demonstrated symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram
  • Brain MRI demonstrated hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions
2. A 74 year male who had traveled from Europe to USA was presented to emergency with COVID-19 related encephalopathy[9] Fever

cough

headache

altered mentationn

  • WBCs =4
  • RBCs = 0
  • Glucose 75
  • Proteins 68
Negative Negative positive Negative CT scan normal
3. 59 year female with history of aplastic anemia presented with COVID-19 related acute necrotizing encephalopathy involving brain stem. She returned from trip to Afghanistan[10] fever

cough

headache

  • seizure
  • reduced consciousness
  • flexion of upper limbs
  • speech arrest


  • CSF opening pressure = 28 cm water
  • Protein 2.3
  • WBCs= 4 cells
Negative Negative RT-PCR positive Negative MRI showed diffuse swelling and hemorrhage in the brain stem and both amygdalae
4. Benameur et. al reported a 31 year old african american presented with COVID-19 related encephalopathy.[11] fever

dyspnea

  • ARDS and was intubated
  • Comatosed post intubation
  • absent brain reflexes
  • CSF opening pressure= 30 cm water
  • proteins >200mg/dl
  • WBCs 115 nucleated cells
  • Glucose normal
Negative Negative RT-PCR positive for SARS-CoV-2 Negative MRI howed nonenhancing cerebral edema and diffusion weighted imaging abnormalities predominantly involving the right cerebral hemisphere, as well as brain herniation
5.Benameur et. al reported a 34 year old african american with hypertension presented with COVID-19 related encephalopathy.[11] fever

cough

dyspnea

  • multiple myoclonus
  • absent corneal and gag reflexes
  • comatosed
  • CSF opening pressure= 48 cm of water
  • no pleocytosis
  • normal glucose
  • mildly elevated proteins
Negative Negative positive RT-PCR for SARS-CoV-2 Negative Brain MRI on day 15 showed a nonenhancing hyperintense lesion within the splenium of the corpus callosum
6. Benameur et. al reported a 64 year old african american with hypertension presented with COVID-19 related encephalopathy.[11] Fever

Cough

Dyspnea

  • profound encephalopathy
  • absent with withdrawl to pain stimuli
  • myoclonus
  • absent deep tendon reflexes
Normal Negative Negative RT-PCR positive for SARS-CoV-2 Negative MRI showed an equivocal nonenhancing area of fluid-attenuated inversion recovery abnormality in the right temporal lobe.
7. Espinosa et. al presented a case report of COVID-19 related encephalopathy[12] Fever

Dry cough

  • ARDS
  • comatosed after he was off ventilator
  • no response to painful stimuli
  • decreased activity of brain on EEG
WBCs =2 cells

proteins = 27

glucose = 68

Negative Negative Positive PCR for SARS-CoV-2 Negative on MRI diffusion-weighted imaging shows an area of restricted diffusion in the left parietocoritcal region
8. Byrness et. al reported a case of 36 years old male who was suspected to have drug overdose but later was diagnosed with COVID-19 related encephalopathy [13] Presented with suspected drug overdose. urine screen positive for cocaine, opiates and benzodiazepenes
  • Fever 39.8 (2nd day)
  • agitation
  • choreiform movements of upper extremities
CSF findings negative for bacterial or viral meningitis/encephalitis Negative Negative RT-PCR positive for SARS-CoV-2 Negative (MRI) was obtained which demonstrated multiple focal enhancing lesions primarily affecting the bilateral medial putamen and left cerebellum
9. A 64 year old female presented with posterior reversible encephalopathy syndrome (PRES) and was reported by reported by Cariddi et. al[14] fever

dyspnea

On 25th day of admission when she was weaned off sedation she had:
  • blurred vision
  • altered mentation
  • left nasolabial fold was reduced
  • reduced reflexes
CSF negative for bacterial or viral findings Negative negative RT-PCR positive for SARS-CoV-2 negative
  • Brain CT and CTA were consistent with hemorrhagic Posterior Reversible Encephalopathy Syndrome
  • On day 56 a brain MRI showed a reduction of the bilateral edema with bilateral occipital foci of subacute hemorrhage
10. A 48 year old male, ail pilot presented with hemorrhagic posterior reversible encephalopathy syndrome[15] fever

dyspnea

  • High grade fever (2nd day)
  • altered mentation
  • ARDS
NA Negative negative RT-PCR positive for SARS-CoV-2 negative MRI showed vasogenic edema in the posterior parieto-occipital regions with subacute blood products suggestive of hemorrhagic posterior reversible encephalopathy syndrome (PRES)
11. Hayashi et.al reported the first case of COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion in 75-year-old male[16]
  • Left dominant kinetic tremors
  • walking instability
  • urinary incontinence
  • fever day 2
  • Hypoxemia
NA negative negative RT-PCR on throat swab positive for SARS-CoV-2 Negative (MRI) of the brain revealed an abnormal hyperintensity in the splenium of corpus callosum (SCC), suspicious for clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS)
12. Cani et. al reported Frontal encephalopathy related to hyperinflammation in 77-year-old female with COVID-19[17] fever

respiratory symptoms

  • Altered consciousness
  • no goal directed activity
  • myoclonus
  • positive primitive reflexes
normal negative negative SARS-CoV-2 positive on RT-PCR Negative MRI displayed diffuse white-matter lesions consistent with chronic small vessel disease without contrast enhancement
13. Encephalopathy and seizure activity in a 41-year-old COVID-19 well-controlled HIV patient was reported by Haddad S et.al[18] Fever

fatigue

chills

cough

  • confusion
  • agitation
  • seizure
  • EEG showed evidence of diffuse slowing but no epileptiform activity.
WBCs = 0

RBCs = 5 cells

Proteins = 102

Glucose = 81

Negative negative SARS-CoV-2 positive on RT-PCR neagtive NA

Physical Examination

  • Physical examination of COVID-19 associated encephalopathy is usually difficult to perform as patients are confused and non cooperative.
  • So, clinicians usually do focused examinations in encephalopathic patients.

Appearance of the patient

  • Generally, the patients with COVID-19 associated encephalopathy are not oriented to time, place and persons.
  • Patients are usually agitated and sedated medically sometimes.
  • Patients have dusky appearance usually due to concurrent pulmonary disease in most cases of COVID-19 associated encephalopathy.

Vital signs

Neurological examination

Common findings in COVID-19 associated neurological examinations are:

  • Inattention
  • Altered mentation
  • speech arrest
  • Multifocal myoclonus
  • Postural action tremors
  • flapping motions of an outstretched, dorsiflexed hand (asterixis)
  • reduced reflexes

Laboratory Findings

Electrocardiogram

X-ray

  • A Chest x-ray may be helpful in the diagnosis of COVID-19-associated respiratory disease.

Echocardiography or Ultrasound

CT scan

  • Head CT scan may be helpful in the diagnosis of COVID-19-associated encephalopathy.
  • Findings on head CT scan suggestive of COVID-19-associated encephalopathy include:
    • Noncontrast head CT images demonstrated symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram,
    • Hemorrhagic Posterior Reversible Encephalopathy Syndrome.

MRI

  • Brain MRI is helpful in the diagnosis of COVID-19-associated encephalopathy.
  • Findings on brain MRI suggestive of COVID-19-associated encephalopathy include:
    • Hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions,
    • Diffuse swelling and hemorrhage in the brain stem and both amygdalae,
    • Nonenhancing cerebral edema and diffusion weighted imaging abnormalities,
    • Brain herniation
    • Nonenhancing hyperintense lesion.

Other Imaging Findings

Other imaging studies may be helpful in the diagnosis of COVID-19-associated encephalopathy include:

Other Diagnostic Studies

Other diagnostic studies for COVID-19-associated encephalopathy include:

Treatment

Medical Therapy

The mainstay of medical therapy for viral encephalitis are:

Symptomatic Treatment

Surgery

Primary Prevention

Secondary Prevention

References

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  11. 11.0 11.1 11.2 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).
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