COVID-19-associated encephalopathy differential diagnosis

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


Overview

COVID-19-associated encephalopathy must be differentiated from other causes of headache, seizure and loss of consciousness such as encephalitis, meningitis, stroke, tumor, brain hemorrhage, neurosyphilis, migraine, hypertensive encephalopathy, wernicke’s encephalopathy, abscess, drug toxicity, and seizure.

Differential Diagnosis

COVID-19-associated encephalopathy must be differentiated from other causes of headache, seizure and loss of consciousness such as encephalitis, meningitis, stroke, tumor, brain hemorrhage, neurosyphilis, migraine, hypertensive encephalopathy, wernicke’s encephalopathy, abscess, drug toxicity, and seizure.

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
Meningitis + - - - - + + - - History of fever and malaise - ↑ Leukocytes,

↑ Protein

↓ Glucose

CSF analysis[1] Fever, neck

rigidity

Encephalitis + + +/- +/- - - + +/- + History of fever and malaise + ↑ Leukocytes, ↓ Glucose CSF PCR Fever, seizures, focal neurologic abnormalities
Brain tumor[2] + - - - + + + - + Weight loss, fatigue + Cancer cells[3] MRI Cachexia, gradual progression of symptoms
Hemorrhagic stroke + + + + + + + + - Hypertension + - CT scan without contrast[4][5] Neck stiffness
Subdural hemorrhage + + + + + - - - + Trauma, fall + Xanthochromia[6] CT scan without contrast[4][5] Confusion, dizziness, nausea, vomiting
Neurosyphilis[7][8] + - + + + + - + - STIs + ↑ Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[9]

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 ↑ protien 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 [10] Blurry vision, urinary incontinence, fatigue
Seizure + + - - + + - - + Previous history of seizures - Mass lesion Clinical assesment and EEG [11] Confusion, apathy, irritability,

Other differentials

COVID-19-associated 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:[12][13][14][15][16][17][18][19][20][21][22]

Diseases History and Symptoms Physical Examination Laboratory Findings
Personality changes Altered level of consciousness Hand tremors (asterixis) Slurred speech Writing disturbances Voice monotonous Impaired memory Elevated blood ammonia Hyponatremia hypokalemia
Hepatic encephalopathy ++ ++ ++ ++ ++ ++ ++ ++ ++ ++
Alcohol intoxication + + -/+ ++ + - + - -/+ -/+
Alcohol withdrawal + + - ++ + - + - -/+ -/+
Uremia ++ ++ + -/+ -/+ -/+ - ++ Hyperkalemia
Wernicke encephalopathy + + -/+ + + + ++ - - -
Toxic encephalopathy from drugs + + -/+ -/+ + -/+ + + -/+ -/+
Altered intracranial pressure + -/+ - -/+ -/+ - -/+ - - -
Intoxication by chemical agents -/+ -/+ -/+ -/+ -/+ - - - -/+ -/+
Malnutrition -/+ - - - -/+ - -/+ - -/+ -/+
Hypoxic brain injury - -/+ - -/+ -/+ -/+ -/+ - - -
Meningitis and encephalitis -/+ -/+ - -/+ + - - - -/+ -
Hypoglycemia -/+ -/+ - -/+ -/+ - - - -/+ -/+


References

  1. ↑ 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.
  2. ↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
  3. ↑ 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.
  4. ↑ 4.0 4.1 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  5. ↑ 5.0 5.1 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.
  6. ↑ Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  7. ↑ 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.
  8. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.
  12. ↑ Meparidze MM, Kodua TE, Lashkhi KS (2010). "[Speech impairment predisposes to cognitive deterioration in hepatic encephalopathy]". Georgian Med News (181): 43–9. PMID 20495225.
  13. ↑ Kattimani S, Bharadwaj B (2013). "Clinical management of alcohol withdrawal: A systematic review". Ind Psychiatry J. 22 (2): 100–8. doi:10.4103/0972-6748.132914. PMC 4085800. PMID 25013309.
  14. ↑ Roldán J, Frauca C, Dueñas A (2003). "[Alcohol intoxication]". An Sist Sanit Navar. 26 Suppl 1: 129–39. PMID 12813481.
  15. ↑ Seifter JL, Samuels MA (2011). "Uremic encephalopathy and other brain disorders associated with renal failure". Semin Neurol. 31 (2): 139–43. doi:10.1055/s-0031-1277984. PMID 21590619.
  16. ↑ Handler CE, Perkin GD (1983). "Wernicke's encephalopathy". J R Soc Med. 76 (5): 339–42. PMC 1439130. PMID 6864698.
  17. ↑ Kim Y, Kim JW (2012). "Toxic encephalopathy". Saf Health Work. 3 (4): 243–56. doi:10.5491/SHAW.2012.3.4.243. PMC 3521923. PMID 23251840.
  18. ↑ Hartmann A, Buttinger C, Rommel T, Czernicki Z, Trtinjiak F (1989). "Alteration of intracranial pressure, cerebral blood flow, autoregulation and carbondioxide-reactivity by hypotensive agents in baboons with intracranial hypertension". Neurochirurgia (Stuttg). 32 (2): 37–43. doi:10.1055/s-2008-1053998. PMID 2497395.
  19. ↑ Kumar N (2011). "Acute and subacute encephalopathies: deficiency states (nutritional)". Semin Neurol. 31 (2): 169–83. doi:10.1055/s-0031-1277986. PMID 21590622.
  20. ↑ Chiu GS, Chatterjee D, Darmody PT, Walsh JP, Meling DD, Johnson RW; et al. (2012). "Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1". J Neurosci. 32 (40): 13945–55. doi:10.1523/JNEUROSCI.0704-12.2012. PMC 3476834. PMID 23035103.
  21. ↑ Peate I (2004). "An overview of meningitis: signs, symptoms, treatment and support". Br J Nurs. 13 (13): 796–801. doi:10.12968/bjon.2004.13.13.13501. PMID 15284663.
  22. ↑ Abdelhafiz AH, Rodríguez-Mañas L, Morley JE, Sinclair AJ (2015). "Hypoglycemia in older people - a less well recognized risk factor for frailty". Aging Dis. 6 (2): 156–67. doi:10.14336/AD.2014.0330. PMC 4365959. PMID 25821643.
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