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}}  
{{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==
Line 23: Line 28:


* 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.
* 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.
*Encephalitis/meningitis are caused by neurotropism of SARS-CoV-2 to brain and meninges through ACE2 receptors.<ref name="pmid15165741">{{cite journal| author=Turner AJ, Hiscox JA, Hooper NM| title=ACE2: from vasopeptidase to SARS virus receptor. | journal=Trends Pharmacol Sci | year= 2004 | volume= 25 | issue= 6 | pages= 291-4 | pmid=15165741 | doi=10.1016/j.tips.2004.04.001 | pmc=7119032 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15165741  }}</ref>
*Encephalopathy is caused by hyper inflammation of brain by following three mechanisms;
*Encephalopathy is caused by hyper inflammation of brain by following three mechanisms;


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=== Cytokine storm ===
=== Cytokine storm ===


* SARS-CoV-2 causes several neurological complications through production of inflammatory cytokines (mainly IL-6) from glial cells called '''cytokine storm syndrome'''.<ref name="pmid32227123">{{cite journal| author=Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L | display-authors=etal| title=Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia. | journal=J Infect Dis | year= 2020 | volume= 221 | issue= 11 | pages= 1762-1769 | pmid=32227123 | doi=10.1093/infdis/jiaa150 | pmc=7184346 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32227123  }}</ref>
* SARS-CoV-2 causes several neurological complications through production of inflammatory cytokines (mainly IL-6) from glial cells called '''cytokine storm syndrome'''.<ref name="pmid32114747">Chen C, Zhang XR, Ju ZY, He WF (2020) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=32114747 [Advances in the research of mechanism and related immunotherapy on the cytokine storm induced by coronavirus disease 2019].] ''Zhonghua Shao Shang Za Zhi'' 36 (6):471-475. [http://dx.doi.org/10.3760/cma.j.cn501120-20200224-00088 DOI:10.3760/cma.j.cn501120-20200224-00088] PMID: [https://pubmed.gov/32114747 32114747]</ref>
*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.
*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.<ref name="pmid32114747">{{cite journal| author=Chen C, Zhang XR, Ju ZY, He WF| title=[Advances in the research of mechanism and related immunotherapy on the cytokine storm induced by coronavirus disease 2019]. | journal=Zhonghua Shao Shang Za Zhi | year= 2020 | volume= 36 | issue= 6 | pages= 471-475 | pmid=32114747 | doi=10.3760/cma.j.cn501120-20200224-00088 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32114747 }}</ref>
*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.<ref name="pmid30416428">{{cite journal| author=Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM| title=Neurologic Alterations Due to Respiratory Virus Infections. | journal=Front Cell Neurosci | year= 2018 | volume= 12 | issue= | pages= 386 | pmid=30416428 | doi=10.3389/fncel.2018.00386 | pmc=6212673 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30416428 }}</ref>
*This fact can be supported by the evidence that '''tocilizumab which is IL-6 antagonist''' is used in severe COVID-19 infections.<ref name="pmid32234467">{{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>
*This fact can be supported by the evidence that '''tocilizumab which is IL-6 antagonist''' is used in severe COVID-19 infections.<ref name="pmid32234467">{{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>


=== Hypoxic Brain Injury ===
=== Hypoxic Brain Injury ===


* The hall mark of severe COVID-19 infection is dyspnea and hypoxemia due Acute Respiratory distress syndrome (ARDS).<ref name="pmid32444880">{{cite journal| author=Buckner FS, McCulloch DJ, Atluri V, Blain M, McGuffin SA, Nalla AK | display-authors=etal| title=Clinical Features and Outcomes of 105 Hospitalized patients with COVID-19 in Seattle, Washington. | journal=Clin Infect Dis | year= 2020 | volume=  | issue=  | pages=  | pmid=32444880 | doi=10.1093/cid/ciaa632 | pmc=7314181 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32444880  }}</ref>
* 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. <ref name="pmid32409443">{{cite journal| author=Vashisht R, Duggal A| title=Respiratory failure in patients infected with SARS-CoV-2. | journal=Cleve Clin J Med | year= 2020 | volume=  | issue=  | pages=  | pmid=32409443 | doi=10.3949/ccjm.87a.ccc025 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32409443  }}</ref>
* This hypoxia and hypoxemia is sometimes enough to cause diffuse brain injury and cause encephalopathy.<ref name="pmid32409443">{{cite journal| author=Vashisht R, Duggal A| title=Respiratory failure in patients infected with SARS-CoV-2. | journal=Cleve Clin J Med | year= 2020 | volume=  | issue=  | pages=  | pmid=32409443 | doi=10.3949/ccjm.87a.ccc025 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32409443  }}</ref>


=== Molecular Mimicry ===
=== Molecular Mimicry ===
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* SARS-CoV-2 is considered to have similar antigenic determinants as that of some antigens present on human neuronal cells.
* 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.<ref name="pmid32561222">{{cite journal| author=Nalleballe K, Reddy Onteddu S, Sharma R, Dandu V, Brown A, Jasti M | display-authors=etal| title=Spectrum of neuropsychiatric manifestations in COVID-19. | journal=Brain Behav Immun | year= 2020 | volume=  | issue=  | pages=  | pmid=32561222 | doi=10.1016/j.bbi.2020.06.020 | pmc=7297688 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32561222  }}</ref>
* 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.<ref name="pmid32449057">{{cite journal| author=Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF| title=Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. | journal=Acta Neuropathol | year= 2020 | volume= 140 | issue= 1 | pages= 1-6 | pmid=32449057 | doi=10.1007/s00401-020-02166-2 | pmc=7245994 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32449057  }}</ref>
*Neuropathological findings confirmed vascular and demyelinating pathology in a patient who died from COVID-19.<ref name="pmid32449057">{{cite journal| author=Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF| title=Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. | journal=Acta Neuropathol | year= 2020 | volume= 140 | issue= 1 | pages= 1-6 | pmid=32449057 | doi=10.1007/s00401-020-02166-2 | pmc=7245994 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32449057  }}</ref>


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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" | +
|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 [[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:<nowiki/><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
|-
|'''Hepatic encephalopathy'''
| ++
| ++
| ++
|<nowiki>++</nowiki>
|<nowiki>++</nowiki>
|<nowiki>++</nowiki>
|<nowiki>++</nowiki>
|<nowiki>++</nowiki>
|<nowiki>++</nowiki>
|<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==


* There is insufficient evidence to recommend routine screening for [[COVID-19]]-associated [[encephalopathy]].
*To view screening for COVID-19, [[COVID-19 screening|click here]].


==Natural History, Complications, and Prognosis==


Patients of all age groups may develop [disease name].
*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]].


OR
==== Complications ====


The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
*Long term [[neurological]] [[Complication (medicine)|complications]] can develop according to the involved [[brain]] [[parenchymal]] area.


OR
<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}}


[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
==Diagnosis==
===Diagnostic Study of Choice===


OR
* 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]].


[Chronic disease name] is usually first diagnosed among [age group].
===Signs and symptoms===


OR
==== Common Symptoms ====


[Acute disease name] commonly affects [age group].
* These are the common presenting features:
** [[Fever]],
** [[Shortness of breath]]
** [[Headache]],
** Impaired [[consciousness]]
** [[Cough]]
** [[Fatigue]]


==== Less Common Symptoms ====


* There are few [[symptoms]] which are not present in all patients with [[COVID-19]]-associated [[encephalopathy]]:
** Transient [[generalized seizure]],
** Absent [[brain]] [[reflexes]],
** [[Myoclonus]],
** [[Speech difficulties|Speech difficul]]<nowiki/>ty,
** [[Chorea|Choreiform]] movements,
** [[Paralysis]],
** [[Dizziness]],
** [[Sedation]],
** [[Comatose|Coma]].


There is no racial predilection to [disease name].
13 cases of [[COVID-19]]-associated [[encephalopathy]] cases have been analyzed in the table below:
{| class="wikitable"
|-
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Patient No.</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>
! 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>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>Imaging studies</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>viral panel (VZV, CMV, HSV1, HSV2)</small>
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>SARS-CoV-2</small>
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>MRI/CT scan</small>
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>on nasopharyngeal sawab</small>
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |<small>on CSF</small>
|-
| 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<ref name="pmid32228363">{{cite journal| author=Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B| title=COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. | journal=Radiology | year= 2020 | volume=  | issue=  | pages= 201187 | pmid=32228363 | doi=10.1148/radiol.2020201187 | pmc=7233386 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32228363  }}</ref>


OR
|fever


[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
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<ref name="pmid32328364">{{cite journal| author=Filatov A, Sharma P, Hindi F, Espinosa PS| title=Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. | journal=Cureus | year= 2020 | volume= 12 | issue= 3 | pages= e7352 | pmid=32328364 | doi=10.7759/cureus.7352 | pmc=7170017 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32328364  }}</ref>
|Fever


[Disease name] affects men and women equally.
cough
|headache


OR
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<ref name="pmid32457227">{{cite journal| author=Dixon L, Varley J, Gontsarova A, Mallon D, Tona F, Muir D | display-authors=etal| title=COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia. | journal=Neurol Neuroimmunol Neuroinflamm | year= 2020 | volume= 7 | issue= 5 | pages=  | pmid=32457227 | doi=10.1212/NXI.0000000000000789 | pmc=7286661 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32457227  }}</ref>
|fever


[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.
cough


headache
|
* seizure
* reduced consciousness
* flexion of upper limbs
* speech arrest


<br />
|
* 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.<ref name="pmid32487282">{{cite journal| author=Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T | display-authors=etal| title=Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020. | journal=Emerg Infect Dis | year= 2020 | volume= 26 | issue= 9 | pages=  | pmid=32487282 | doi=10.3201/eid2609.202122 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32487282  }}</ref>
|fever


The majority of [disease name] cases are reported in [geographical region].
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.<ref name="pmid32487282" />
|fever


OR
cough


[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
dyspnea
|
* multiple myoclonus
* absent corneal and gag reflexes
* comatosed
|
* CSF opening pressure= 48 cm of water


==Risk Factors==
* no pleocytosis
There are no established risk factors for COVID-19-associated encephalopathy.
* 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.<ref name="pmid32487282" />
|Fever


==Screening==
Cough
There is insufficient evidence to recommend routine screening for COVID-19-associated encephalopathy.


==Natural History, Complications, and Prognosis==
Dyspnea
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
|
* 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<ref name="pmid32499974">{{cite journal| author=Espinosa PS, Rizvi Z, Sharma P, Hindi F, Filatov A| title=Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy, MRI Brain and Cerebrospinal Fluid Findings: Case 2. | journal=Cureus | year= 2020 | volume= 12 | issue= 5 | pages= e7930 | pmid=32499974 | doi=10.7759/cureus.7930 | pmc=7266087 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32499974  }}</ref>
|[[Fever]]


OR
[[Dry cough]]
|
* ARDS
* comatosed after he was off ventilator
* no response to painful stimuli
* decreased activity of brain on EEG
|WBCs =2 cells


Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
proteins = 27


OR
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 <ref name="pmid32458578">{{cite journal| author=Byrnes S, Bisen M, Syed B, Huda S, Siddique Z, Sampat P | display-authors=etal| title=COVID-19 encephalopathy masquerading as substance withdrawal. | journal=J Med Virol | year= 2020 | volume=  | issue=  | pages=  | pmid=32458578 | doi=10.1002/jmv.26065 | pmc=7283690 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32458578  }}</ref>
|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<ref name="pmid32583053">{{cite journal| author=Princiotta Cariddi L, Tabaee Damavandi P, Carimati F, Banfi P, Clemenzi A, Marelli M | display-authors=etal| title=Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient. | journal=J Neurol | year= 2020 | volume=  | issue=  | pages=  | pmid=32583053 | doi=10.1007/s00415-020-10001-7 | pmc=7312113 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32583053  }}</ref>
|fever


Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
dyspnea
|On 25th day of admission when she was weaned off sedation she had:


==Diagnosis==
* blurred vision
===Diagnostic Study of Choice===
* altered mentation
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
* 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<ref name="pmid32439646">{{cite journal| author=Franceschi AM, Ahmed O, Giliberto L, Castillo M| title=Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection. | journal=AJNR Am J Neuroradiol | year= 2020 | volume= 41 | issue= 7 | pages= 1173-1176 | pmid=32439646 | doi=10.3174/ajnr.A6595 | pmc=7357664 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32439646  }}</ref>
|fever


OR
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<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
* 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<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


The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
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<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


OR
chills


The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
cough
|
* confusion
* agitation
* seizure
* EEG showed evidence of diffuse slowing but no epileptiform activity.
|WBCs = 0
RBCs = 5 cells


OR
Proteins = 102


There are no established criteria for the diagnosis of [disease name].
Glucose = 81
|Negative
|negative
|SARS-CoV-2 positive on RT-PCR
|neagtive
|NA
|}


===History and Symptoms===
===Physical Examination===
The majority of patients with [disease name] are asymptomatic.
 
OR
 
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].


===Physical Examination===
* Physical examination of COVID-19 associated encephalopathy is usually difficult to perform as patients are confused and non cooperative.
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
* So, clinicians usually do focused examinations in encephalopathic patients.


OR
==== Appearance of the patient ====


Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
* 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.


OR
==== Vital signs ====


The presence of [finding(s)] on physical examination is diagnostic of [disease name].
* Usually, patients with COVID-19 associated encephalopathy have high grade fever.
* Autonomic instability with [[tachycarida]]/[[bradycardia]], [[hypotnesion]]/hypertension


OR
==== Neurological examination ====
Common findings in COVID-19 associated neurological examinations are:


The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
* Inattention
* Altered mentation
* [[speech]] arrest
* Multifocal [[myoclonus]]
* Postural action tremors
* flapping motions of an outstretched, dorsiflexed hand ([[asterixis]])
* reduced reflexes


===Laboratory Findings===
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR


There are no diagnostic laboratory findings associated with [disease name].
* Laboratory findings consistent with the diagnosis of [[COVID-19]]-associated [[encephalopathy]] include [[CSF]] [[analysis]], [[RT-PCR]] for [[SARS-CoV-2]] on [[nasopharyngeal]] swab and on [[CSF]].
* [[RT-PCR]] for [[SARS-CoV-2]] on [[CSF]] is usually normal among patients with [[COVID-19]]-associated [[encephalopathy]].
* Some patients with [[COVID-19]]-associated [[encephalopathy]] may have reduced activity of [[brain]] on [[EEG]], whih is usually suggestive of progression.


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].


OR
* There are no [[ECG]] findings associated with [[COVID-19]]-associated [[encephalopathy]].
 
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].


OR
* There are no [[x-ray]] findings associated with [[COVID-19]]-associated [[encephalopathy]].


An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
* A Chest [[x-ray]] may be helpful in the diagnosis of [[COVID-19]]-associated respiratory disease.
 
OR
 
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


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


There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
* There are no [[echocardiography]] findings associated with [[COVID-19]]-associated [[encephalopathy]].
* [[Echocardiography]] may be helpful in the diagnosis of [[COVID-19]]-associated [[cardiac]] disease.


===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
*[[Brain]] [[MRI]] is helpful in the [[diagnosis]] of [[COVID-19]]-associated [[encephalopathy]].
 
* Findings on [[brain]] [[MRI]]  suggestive of [[COVID-19]]-associated [[encephalopathy]] include:
[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].
**[[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,
OR
** Nonenhancing cerebral edema and diffusion weighted imaging abnormalities,
 
** Brain herniation
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].
** 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
* MR [[spectroscopy]],
 
*[[CT angiography|CT angiogram]] and
[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].
*[[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
==== Symptomatic Treatment ====


Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
* 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.
OR
* [[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]].
The majority of cases of [disease name] are self-limited and require only supportive care.
*[[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.
OR
*[[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]]
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
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
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.
* 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.
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 available vaccines against [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]].
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}}
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Latest revision as of 23:47, 12 December 2020

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For COVID-19 frequently asked outpatient questions, click here.
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For COVID-19 patient information, click here.

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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