COVID-19-associated encephalitis: Difference between revisions
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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
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COVID-19 Microchapters |
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Treatment |
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Case Studies |
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COVID-19-associated encephalitis On the Web |
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American Roentgen Ray Society Images of COVID-19-associated encephalitis |
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Risk calculators and risk factors for COVID-19-associated encephalitis |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Wajeeha Aiman, M.D.[2]
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
- 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.[1][2]
- The association between COVID-19 and encephalitis was made during this pandemic started in December in Wuhan, China and named as Wuhan coronavirus.[3]
- In March 2020, Dr. Ali A. was the first to discover the association between COVID-19 and neurological diseases e.g. encephalitis. He made a clinical diagnosis along with his team and then MRI used to diagnose the disease.[4]
- In January 2020, Chinese doctors confirmed the first case of encephalitis due to COVID-19 in a 56 year old male and they conducted gene sequencing on cerebrospinal fluid (CSF) samples and confirmed the novel virus inside brain, but it was not published.
- There have been several outbreaks of SARS and MERS.
Classification
- There is no established system for the classification of COVID-19 associated encephalitis.
- Based on the duration of symptoms, this disease is classified as acute.
Pathophysiology
- The exact pathogenesis of COVID-19 encephalitis is not fully understood.[5]
- 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 | |||||||||||||||||||||||||||||||||||||||||
- ACE2: Angiotensin converting enzyme receptor 2 is present in multiple organs e.g. lungs, brain, and kidney, etc.
- Hypercoagulability: With elevated D-dimer
- Immune injury: Cytokine activation and vascular involvement.
- Direct injury: Due to hematogenous and neuronal pathway involvement.
- Hypoxic injury: Due to anaerobic metabolism.
Causes
- Coronavirus disease 2019 (COVID-19) associated encephalitis is caused by SARS-CoV-2.
- To read more about this virus, click here.
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 |
- Meningitis
- Acute hypoglycemia
- Brain abscess
- Herpes simplex encephalitis
- Leptospirosis in humans
- Status epilepticus
- Systemic lupus erythematosus (SLE)
- Cat scratch disease
- Tuberculosis
- Sepsis
- Glial tumor
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
- Common risk factors in the development of COVID-19-associated encephalitis may be occupational, environmental, and genetic.[10]
- Risk factors for this disease are the same as for COVID-19.
- Auto-immune syndromes might be at higher risk of developing this disease due to immunosuppressive therapy.
| Autoimmune disease | Immunosuppression |
|---|---|
| Multiple sclerosis | Interferon beta |
| Myasthenia gravis | Corticosteroids |
| Neuromyelitis optica | Monoclonal antibody |
| Sarcoidosis | Corticosteroids |
| Sickle cell disease (SCD) | Crizanlizumab |
Screening
- There is insufficient evidence to recommend routine screening for COVID-19-associated encephalitis.
Natural History, Complications, and Prognosis
- If left untreated, patients with COVID-19-associated encephalitis may progress to damage the brain and cause:
| 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
- The majority of patients with COVID-19-associated encephalitis present with respiratory symptoms. e.g. cough, shortness of breath etc.
- Three cases reported till now has specific clinical manifestations:
| 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, | 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 |
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, | |
| 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
- Common physical examination findings of COVID-19-associated encephalitis include
- Generalized seizure,
- Hheadache,
- Abnormal vital signs,
- Nneck stiffness, or
- Neurological deficits can be present in this disease.
Laboratory Findings
- Positive RT-PCR in CSF or nasopharyngeal swab is diagnostic of COVID-19-associated encephalitis.
- Laboratory findings consistent with the diagnosis of COVID-19 associated encephalitis include CSF analysis, RT-PCR and MRI brain.
- D-dimer or white blood cells can be normal among patients with COVID-19-associated encephalitis.
- Some patients with COVID-19-associated encephalitis may have elevated erythrocytes in CSF which is usually suggestive of COVID-19-associated encephalitis.
Electrocardiogram
- There are no ECG findings associated with COVID-19-associated encephalitis.
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
- There are no echocardiography/ultrasound findings associated with COVID-19-associated encephalitis.
CT scan
- The findings on the CT scans associated with COVID-19-associated encephalitis are similar to MRI which is the preferred modality.
MRI
- Brain MRI may be helpful in the diagnosis of COVID-19 associated encephalitis. Findings on MRI suggestive of COVID-19 associated encephalitis include
- Hyperintensity in the right lateral ventricle's inferior horn along the wall and pan-paranasal sinusitis.
- Hyperintensity in the left temporal lobe.
- MR Spectroscopy: Decrease N-acetyl aspartate peak along with a marked elevated choline peak.
- Nonenhancing cerebral edema and restricted diffusion in the right cerebral hemisphere with brain herniation.
Other Diagnostic Studies
Other diagnostic studies for COVID-19-associated encephalitis include:
- RT-PCR of SARS-CoV-2 RNA positive in CSF and nasopharyngeal swab,
- Antibody IgM for acute infection, and
- Antibody IgG for resolved or chronic infection.
Treatment
Medical Therapy
The mainstays of medical therapy for viral encephalitis are:[6]
Symptomatic treatments:
- Anti-epileptic drugs like levetiracetam is necessary for seizure management[2].
- Anti-inflammatory like steroids are also helpful in this disease[2].
- Severe disease in these patients required intubation and mechanical ventilation[6].
- Hydorxychloroquine and some antivirals were used in these patients but they did not resolve the condition[6].
Surgery
- Focal epilepsy having focal involvement of brain parenchyma can be treated with surgery[6].
- One of these patients undergone left anterior temporal lobectomy, which improved symptoms completely without any postoperative neurologic deficit[6].
Primary Prevention
- There are no established measures for the primary prevention of COVID-19 associated encephalitis.
- Effective measure for the primary prevention of COVID-19 associated encephalitis. include social distancing and avoidance behaviors.
- There are no available vaccines against COVID-19 associated encephalitis. Multiple trial are under process for vaccinations.
Secondary Prevention
- There are no established measures for the secondary prevention of COVID-19 associated encephalitis.
References
- ↑ 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). - ↑ 2.0 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). - ↑ 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). - ↑ 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). - ↑ 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). - ↑ 6.0 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). - ↑ 7.0 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). - ↑ 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.
- ↑ Tsai LK, Hsieh ST, Chang YC (2005). "Neurological manifestations in severe acute respiratory syndrome". Acta Neurol Taiwan. 14 (3): 113–9. PMID 16252612.
- ↑ Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check
|pmid=value (help).