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==Differentiating COVID-19-associated encephalitis from other Diseases==
==Differentiating COVID-19-associated encephalitis from other Diseases==
[[COVID-19]]-associated [[encephalitis]] must be differentiated from other [[diseases]] that cause [[fever]], [[headache]], and [[altered mental status]] with or without [[cough]], such as:<ref name="pmid32251791" /><ref name="pmid32479911">{{cite journal| author=Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K| title=COVID-19-Associated Encephalitis Mimicking Glial Tumor. | journal=World Neurosurg | year= 2020 | volume= 140 | issue=  | pages= 46-48 | pmid=32479911 | doi=10.1016/j.wneu.2020.05.194 | pmc=7256557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32479911  }}</ref>  
[[COVID-19]]-associated [[encephalitis]] must be differentiated from other [[diseases]] that cause [[fever]], [[headache]], and [[altered mental status]] with or without [[cough]], such as:<ref name="pmid32251791" /><ref name="pmid32479911">{{cite journal| author=Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K| title=COVID-19-Associated Encephalitis Mimicking Glial Tumor. | journal=World Neurosurg | year= 2020 | volume= 140 | issue=  | pages= 46-48 | pmid=32479911 | doi=10.1016/j.wneu.2020.05.194 | pmc=7256557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32479911  }}</ref>  
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 50px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Similarities}}
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Differentials}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | Classic triad of [[fever]], [[nuchal rigidity]], and [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Photophobia]], [[phonophobia]], [[rash]] associated with [[meningococcemia]], concomitant [[sinusitis]] or [[otitis]], swelling of the [[fontanelle]] in infants (0-6 months)
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fever]], [[headache]], [[hemiparesis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on the location of the abscess; clinically, [[visual disturbance]] including [[papilledema]], decreased [[sensation]]; on imaging, a [[lesion]] demonstrates both ring enhancement and central restricted diffusion
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Demyelinating disease]]s'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ataxia]], [[lethargy]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Multiple sclerosis]]: clinically, [[nystagmus]], [[internuclear ophthalmoplegia]], [[Lhermitte's sign]]; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”)
[[Acute disseminated encephalomyelitis]]: clinically, [[somnolence]], [[myoclonic]] movements, and [[hemiparesis]]; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Substance abuse]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Tremor]], [[headache]], [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, [[paranoia]], sudden [[panic]], [[anxiety]], [[hallucination]]s
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Electrolyte disturbance]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fatigue]], [[headache]], [[nausea]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on deficient ions; clinically, [[edema]], [[constipation]], [[hallucination]]s; on [[EKG]], abnormalities in [[T wave]], [[P wave]], [[QRS complex]]; possible presentations include [[arrhythmia]], [[dehydration]], [[renal failure]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Stroke]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ataxia]], [[aphasia]], [[dizziness]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on classification of stroke; presents with positional [[vertigo]], high [[blood pressure]], [[extremities|extremity]] weakness
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Intracranial hemorrhage]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Headache]], [[coma]], [[dizziness]]
| style="padding: 5px 5px; background: #F5F5F5;" | Lobar [[hemorrhage]], [[numbness]], [[tingling]], [[hypertension]], [[hemorrhagic diathesis]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Trauma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Headache]], [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Amnesia]], [[loss of consciousness]], [[dizziness]], [[concussion]], [[contusion]]
|-
|}


* [[Meningitis]]
* [[Meningitis]]

Revision as of 22:31, 13 July 2020

COVID-19 Microchapters

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Pathophysiology

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Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

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Surgery

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Case #1

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Wajeeha Aiman, M.D.[2]

Synonyms and keywords: Encephalitis covid-19

Overview

Encephalitis is inflammation of the brain parenchyma and it is commonly caused by viruses. COVID-19 is a virus related to the severe acute respiratory syndrome coronavirus (SARS-CoV) group and named as SARS-CoV-2. Covid-19 associated encephalitis was first discovered by Moriguchi T. et al. a Japanese critical care physician in late February 2020 during the pandemic of SARS-Coronavirus-2: SARS-CoV-2. The association between COVID-19 and encephalitis was made during this pandemic started in December in Wuhan, China and named as Wuhan coronavirus. There is no established system for the classification of COVID-19 associated encephalitis. The exact pathogenesis of COVID-19 encephalitis is not fully understood. COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough.

Historical Perspective

Classification

Pathophysiology

  • It is thought that this viral encephalitis is the result of multiple pathophysiologic pathways.


 
 
 
 
 
 
 
 
SARS-CoV-2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACE2
 
Direct Injury due to Infection
 
Immune Injury
 
Hypoxic Injury
 
Hypercoagulability
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral Encephalitis
 
 
 
 
 


Causes

  • To read more about this virus, click here.
Case courtesy of Dr. Daniel J Bell, Radiopaedia.org, rID: 74536

Differentiating COVID-19-associated encephalitis from other Diseases

COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough, such as:[2][6]

Disease Similarities Differentials
Meningitis Classic triad of fever, nuchal rigidity, and altered mental status Photophobia, phonophobia, rash associated with meningococcemia, concomitant sinusitis or otitis, swelling of the fontanelle in infants (0-6 months)
Brain abscess Fever, headache, hemiparesis Varies depending on the location of the abscess; clinically, visual disturbance including papilledema, decreased sensation; on imaging, a lesion demonstrates both ring enhancement and central restricted diffusion
Demyelinating diseases Ataxia, lethargy Multiple sclerosis: clinically, nystagmus, internuclear ophthalmoplegia, Lhermitte's sign; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”)

Acute disseminated encephalomyelitis: clinically, somnolence, myoclonic movements, and hemiparesis; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders

Substance abuse Tremor, headache, altered mental status Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, paranoia, sudden panic, anxiety, hallucinations
Electrolyte disturbance Fatigue, headache, nausea Varies depending on deficient ions; clinically, edema, constipation, hallucinations; on EKG, abnormalities in T wave, P wave, QRS complex; possible presentations include arrhythmia, dehydration, renal failure
Stroke Ataxia, aphasia, dizziness Varies depending on classification of stroke; presents with positional vertigo, high blood pressure, extremity weakness
Intracranial hemorrhage Headache, coma, dizziness Lobar hemorrhage, numbness, tingling, hypertension, hemorrhagic diathesis
Trauma Headache, altered mental status Amnesia, loss of consciousness, dizziness, concussion, contusion


Epidemiology and Demographics

  • There are only 3 cases reported till now.
  • One in Japan[2], one in Turkey[6] and the recent case was reported in Atlanta, Georgia, USA[7].
  • MERS[8] and SARS-CoV[9] had neurologic manifestation like encephalitis at the time of outbreaks.

Risk Factors

Risk factors for COVID-19-associated encephalitis
Autoimmune disease Immunosuppression
Multiple sclerosis Interferon beta

Glatiramer

Corticosteroids

Myasthenia gravis Corticosteroids
Neuromyelitis optica Monoclonal antibody
Sarcoidosis Corticosteroids

Methotrexate

Azathioprine

Sickle cell disease (SCD) Crizanlizumab

Screening

Natural History, Complications, and Prognosis

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


Diagnosis

Diagnostic Study of Choice

The diagnostic study of choice for COVID-19-associated encephalitis is CSF analysis for ruling out other viral and bacterial panels with the help of RT-PCR.

History and Symptoms

Patient No. Early symptoms Later presentation GCS Lab. Findings Specific Tests Imaging studies
CBC CSF MRI/CT scan
1. 24-year-old man from Japan[2] Headache,

Fever,

Fatigue

Worsening headache, Sore throat. (Day 5)

Impaired consciousness and transient generalized seizure, (Day 9)

E4V1M1 WBCs and neutrophils
lymphocytes

CRP

Clear and colorless fluid,

Pressure=320 mmH2O,

Cell count was 12/μL–10

mononuclear and 2 polymorphonuclear cells

RT-PCR of SARS-CoV-2 RNA was positive in CSF Brain MRI:

Hyperintensity in the right lateral ventricle's inferior horn along the wall,

pan-paranasal sinusitis.

2. 35-year-old woman from Turkey[6] Flu like symptoms Headache, nausea, dizziness, and

drug-refractory seizures.

E4V5M6 NA NA RT-PCR and antibody tests positive Brain MRI: Hyperintensity in the left temporal lobe.

MR Spectroscopy: Decrease N-acetyl aspartate peak along with a marked elevated choline peak.

3. 31-year-old African American woman[7] SCD patient with dyspnea Paralysis and sedation (Day 13)

Comatose (Day 15) and death (Day 16)

E0V0M0 NA Pressure=30cmH2O

115 nucleated cell /ml

7374 erythrocytes

/ml

Protein> 200mg/dl

RT=PCR for SARS-CoV-2 was positive in nasopharyngeal swab Brain MRI: Nonenhancing cerebral edema and restricted diffusion in the right cerebral hemisphere with brain herniation.

Physical Examination

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of COVID-19 associated encephalitis include CSF analysis, RT-PCR and MRI brain.

Electrocardiogram

X-ray

  • There are no x-ray findings associated with COVID-19-associated encephalitis. However, an x-ray may be helpful in the diagnosis of COVID-19 respiratory disease.

Echocardiography or Ultrasound

CT scan

  • The findings on the CT scans associated with COVID-19-associated encephalitis are similar to MRI which is the preferred modality.

MRI

Other Diagnostic Studies

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

Treatment

Medical Therapy

The mainstays of medical therapy for viral encephalitis are:[6]

Symptomatic treatments:

Surgery

Primary Prevention

Secondary Prevention

References

  1. Velavan TP, Meyer CG (2020). "The COVID-19 epidemic". Trop Med Int Health. 25 (3): 278–280. doi:10.1111/tmi.13383. PMC 7169770 Check |pmc= value (help). PMID 32052514 Check |pmid= value (help).
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).
  3. Riou J, Althaus CL (2020). "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020". Euro Surveill. 25 (4). doi:10.2807/1560-7917.ES.2020.25.4.2000058. PMC 7001239 Check |pmc= value (help). PMID 32019669 Check |pmid= value (help).
  4. Asadi-Pooya AA, Simani L (2020). "Central nervous system manifestations of COVID-19: A systematic review". J Neurol Sci. 413: 116832. doi:10.1016/j.jns.2020.116832. PMC 7151535 Check |pmc= value (help). PMID 32299017 Check |pmid= value (help).
  5. Baig AM (2020). "Neurological manifestations in COVID-19 caused by SARS-CoV-2". CNS Neurosci Ther. 26 (5): 499–501. doi:10.1111/cns.13372. PMC 7163592 Check |pmc= value (help). PMID 32266761 Check |pmid= value (help).
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K (2020). "COVID-19-Associated Encephalitis Mimicking Glial Tumor". World Neurosurg. 140: 46–48. doi:10.1016/j.wneu.2020.05.194. PMC 7256557 Check |pmc= value (help). PMID 32479911 Check |pmid= value (help).
  7. 7.0 7.1 Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T; et al. (2020). "Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020". Emerg Infect Dis. 26 (9). doi:10.3201/eid2609.202122. PMID 32487282 Check |pmid= value (help).
  8. Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK; et al. (2017). "Middle East Respiratory Syndrome". N Engl J Med. 376 (6): 584–594. doi:10.1056/NEJMsr1408795. PMC 5362064. PMID 28177862.
  9. Tsai LK, Hsieh ST, Chang YC (2005). "Neurological manifestations in severe acute respiratory syndrome". Acta Neurol Taiwan. 14 (3): 113–9. PMID 16252612.
  10. Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check |pmid= value (help).


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