COVID-19-associated encephalitis differential diagnosis

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


Overview

COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough, such as meningitis, stroke, tumor, brain hemorrhage, neurosyphilis, migraine, hypertensive encephalopathy, wernicke’s encephalopathy, abscess, drug toxicity, and seizure.

Differential Diagnosis


Diseases Symptoms Physical Examination Past medical history Diagnostic tests Other Findings
Headache ↓LOC Motor weakness Abnormal sensory Motor Deficit Sensory deficit Speech difficulty Gait abnormality Cranial nerves CT /MRI CSF Findings Gold standard test
Encephalitis + + +/- +/- - - + +/- + History of fever and malaise + ↑ Leukocytes, ↓ Glucose CSF PCR Fever, seizures, focal neurologic abnormalities
Meningitis + - - - - + + - - History of fever and malaise - ↑ Leukocytes,

↑ Protein

↓ Glucose

CSF analysis[2] Fever, neck

rigidity

Brain tumor[3] + - - - + + + - + Weight loss, fatigue + Cancer cells [4] MRI Cachexia, gradual progression of symptoms
Hemorrhagic stroke + + + + + + + + - Hypertension + - CT scan without contrast[5][6] Neck stiffness
Subdural hemorrhage + + + + + - - - + Trauma, fall + Xanthochromia [7] CT scan without contrast[5][6] Confusion, dizziness, nausea, vomiting
Neurosyphilis[8][9] + - + + + + - + - STIs + ↑ Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[10]

Blindness, confusion, depression,

Abnormal gait

Complex or atypical migraine + - + + - - + - - Family history of migraine - - Clinical assesment Presence of aura, nausea, vomiting
Hypertensive encephalopathy + + - - - - + + - Hypertension + - Clinical assesment Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy - + - - - + + + + History of alcohal abuse - - Clinical assesment and lab findings Ophthalmoplegia, confusion
CNS abscess + + - - + + + - - History of drug abuse, endocarditis, immunosupression + ↑ leukocytes, ↓ glucose and ↑ protein MRI is more sensitive and specific High grade fever, fatigue,nausea, vomiting
Drug toxicity - + - + + + - + - - - - Drug screen test Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder + + + + + + + + History of emotional stress - - Diagnosis of exclusion Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia) - + + + + + - - + - - Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia Depends on the cause Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation - - + + - + + + + History of relapses and remissions + ↑ CSF IgG levels

(monoclonal bands)

Clinical assesment and MRI [11] Blurry vision, urinary incontinence, fatigue
Seizure + + - - + + - - + Previous history of seizures - Mass lesion Clinical assesment and EEG [12] Confusion, apathy, irritability,


References

  1. ↑ 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).
  2. ↑ Carbonnelle E (2009). "[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]". Med Mal Infect. 39 (7–8): 581–605. doi:10.1016/j.medmal.2009.02.017. PMID 19398286.
  3. ↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
  4. ↑ Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions". Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.
  5. ↑ 5.0 5.1 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  6. ↑ 6.0 6.1 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
  7. ↑ Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  8. ↑ Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
  9. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  10. ↑ Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.
  11. ↑ Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). "Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group". Arch Neurol. 51 (1): 61–6. PMID 8274111.
  12. ↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.
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