COVID-19-associated stroke differential diagnosis

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

Overview

Disease_Name must be differentiated from Disease_A, Disease_B, and Disease_C.

Differential Diagnosis

Stroke should be differentiated from other causes of muscle weakness and paralysis such as .[1][1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]

Diseases History and Physical Diagnostic tests Other Findings
Motor Deficit Sensory deficit Cranial nerve Involvement Autonomic dysfunction Proximal/Distal/Generalized Ascending/Descending/Systemic Unilateral (UL)

or Bilateral (BL)

or

No Lateralization (NL)

Onset Lab or Imaging Findings Specific test
Acute Flaccid Myelitis + + + - Proximal > Distal Ascending UL/BL Sudden MRI (Longitudinal hyperintense lesions) MRI and CSF PCR for viral etiology Drooping eyelids

Difficulty swallowing

Respiratory failure

Adult Botulism + - + + Generalized Descending BL Sudden Toxin test Blood, Wound, or Stool culture Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis
Infant Botulism + - + + Generalized Descending BL Sudden Toxin test Blood, Wound, or Stool culture Flaccid paralysis (Floppy baby syndrome), possible respiratory paralysis
Guillian-Barre syndrome + - - - Generalized Ascending BL Insidious CSF: ↑Protein

↓Cells

Clinical & Lumbar Puncture Progressive ascending paralysis following infection, possible respiratory paralysis
Eaton Lambert syndrome + - + + Generalized Systemic BL Intermittent EMG, repetitive nerve stimulation test (RNS) Voltage gated calcium channel (VGCC) antibody Diplopia, ptosis, improves with movement (as the day progresses)
Myasthenia gravis + - + + Generalized Systemic BL Intermittent EMG, Edrophonium test Ach receptor antibody Diplopia, ptosis, worsening with movement (as the day progresses)
Electrolyte disturbance + + - - Generalized Systemic BL Insidious Electrolyte panel ↓Ca++, ↓Mg++, ↓K+ Possible arrhythmia
Organophosphate toxicity + + - + Generalized Ascending BL Sudden Clinical diagnosis: physical exam & history Clinical suspicion confirmed with RBC AchE activity History of exposure to insecticide or living in farming environment. with : Diarrhea, Urination, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Tick paralysis (Dermacentor tick) + - - - Generalized Ascending BL Insidious Clinical diagnosis: physical exam & history - History of outdoor activity in Northeastern United States. The tick is often still latched to the patient at presentation (often in head and neck area)
Tetrodotoxin poisoning + - + + Generalized Systemic BL Sudden Clinical diagnosis: physical exam & dietary history - History of consumption of puffer fish species.
Stroke +/- +/- +/- +/- Generalized Systemic UL Sudden MRI +ve for ischemia or hemorrhage MRI Sudden unilateral motor and sensory deficit in a patient with a history of atherosclerotic risk factors (diabetes, hypertension, smoking) or atrial fibrillation.
Poliomyelitis + + + +/- Proximal > Distal Systemic BL or UL Sudden PCR of CSF Asymmetric paralysis following a flu-like syndrome.
Transverse myelitis + + + + Proximal > Distal Systemic BL or UL Sudden MRI & Lumbar puncture MRI History of chronic viral or autoimmune disease (e.g. HIV)
Neurosyphilis + + - +/- Generalized Systemic BL Insidious MRI & Lumbar puncture CSF VDRL-specifc

CSF FTA-Ab -sensitive

History of unprotected sex or multiple sexual partners.

History of genital ulcer (chancre), diffuse maculopapular rash.

Muscular dystrophy + - - - Proximal > Distal Systemic BL Insidious Genetic testing Muscle biopsy Progressive proximal lower limb weakness with calf pseudohypertrophy in early childhood. Gower sign positive.
Multiple sclerosis exacerbation + + + + Generalized Systemic NL Sudden ↑CSF IgG levels

(monoclonal)

Clinical assessment and MRI Blurry vision, urinary incontinence, fatigue
Amyotrophic lateral sclerosis + - - - Generalized Systemic BL Insidious Normal LP (to rule out DDx) MRI & LP Patient initially presents with upper motor neuron deficit (spasticity) followed by lower motor neuron deficit (flaccidity).
Inflammatory myopathy + - - - Proximal > Distal Systemic UL or BL Insidious Elevated CK & Aldolase Muscle biopsy Progressive proximal muscle weakness in 3rd to 5th decade of life. With or without skin manifestations.
  • Stroke in COVID-19 positive patients vs. Stroke in non-COVID-19 patients: A retrospective cohort study (15th March,2020 to 19th April,2020) conducted by Yaghi et. al. in hospitalized patients in New York Healthcare systems compared stroke characteristics in patients with and without COVID-19[27]. This study included 3,556 COVID-19 positive patients, out of which 32 patients were diagnosed with ischemic stroke based on imaging. These COVID-19 positive stroke patients were then compared with 46 hospitalized stroke patients without COVID-19. Based on findings of this study-
    • Younger patient population (average age-63 years) as compared to relatively older patient population (average age-70 years) in non-COVID-19 patients.
    • Severe stroke (National Institutes of Health Stroke Scale- average score 19) as compared to non-COVID patients with lesser average score (8) seen on National Institutes of Health Stroke Scale
    • Higher D-dimer levels which point towards severe blood clotting (10,000 in this study). Relatively lower D-dimer levels (525 in this study) were seen in non-COVID patients.
    • Mostly Cryptogenic stroke seen in COVID-19 patients.
    • Increased mortality seen in COVID-19 patients.
    • Most of COVID-19 patients did not have any history of prior stroke (only 3.1% reported stroke history) as opposed to non-COVID patient group in which prior history of stroke was reported in 13%.
    • Non-COVID patients were more likely to have higher blood pressure levels.
  • Further studies are going on to understand the clinical characteristics specific to stroke in COVID-19 patients. It has been observed that the findings vary in different countries possibly due to racial/ethnicity variations. Since strokes have been reported in critically ill COVID-19 patients, hence, it is difficult to diagnose stroke in intubated and sedated COVID-19 patients.
  • Stroke in COVID-19 positive patients vs. Stroke in Influenza patients: Out of 1916 COVID-19 patients (Emergency Department visits or were hospitalized with COVID-19) in retrospective cohort study which included patients from two academic hospitals in New York, 31 patients (1.6%) with median age 69 years, experienced acute ischemic stroke. The majority of these patients were men (58%). 8 patients (26%] had initial presentation as stroke while 23 had stroke over the course of the disease after testing positive for COVID-19.
  • Based on this study, the COVID-19 patients have much higher incidence of stroke when compared to influenza patients.[28]

References

  1. ↑ 1.0 1.1 Kira R (February 2018). "[Acute Flaccid Myelitis]". Brain Nerve (in Japanese). 70 (2): 99–112. doi:10.11477/mf.1416200962. PMID 29433111.
  2. ↑ Hopkins SE (November 2017). "Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations". Curr Treat Options Neurol. 19 (12): 48. doi:10.1007/s11940-017-0480-3. PMID 29181601.
  3. ↑ Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR (September 2016). "Acute flaccid myelitis: A clinical review of US cases 2012-2015". Ann. Neurol. 80 (3): 326–38. doi:10.1002/ana.24730. PMC 5098271. PMID 27422805.
  4. ↑ Chong PF, Kira R, Mori H, Okumura A, Torisu H, Yasumoto S, Shimizu H, Fujimoto T, Hanaoka N, Kusunoki S, Takahashi T, Oishi K, Tanaka-Taya K (February 2018). "Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015". Clin. Infect. Dis. 66 (5): 653–664. doi:10.1093/cid/cix860. PMC 5850449. PMID 29028962.
  5. ↑ Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters H, Tyler KL, Abzug MJ, Dominguez SR (August 2018). "Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality". Lancet Infect Dis. 18 (8): e239–e247. doi:10.1016/S1473-3099(18)30094-X. PMID 29482893. Vancouver style error: initials (help)
  6. ↑ Chen IJ, Hu SC, Hung KL, Lo CW (September 2018). "Acute flaccid myelitis associated with enterovirus D68 infection: A case report". Medicine (Baltimore). 97 (36): e11831. doi:10.1097/MD.0000000000011831. PMC 6133480. PMID 30200066.
  7. ↑ "Botulism | Botulism | CDC".
  8. ↑ McCroskey LM, Hatheway CL (May 1988). "Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract". J. Clin. Microbiol. 26 (5): 1052–4. PMC 266519. PMID 3290234.
  9. ↑ Lindström M, Korkeala H (April 2006). "Laboratory diagnostics of botulism". Clin. Microbiol. Rev. 19 (2): 298–314. doi:10.1128/CMR.19.2.298-314.2006. PMC 1471988. PMID 16614251.
  10. ↑ Brook I (2006). "Botulism: the challenge of diagnosis and treatment". Rev Neurol Dis. 3 (4): 182–9. PMID 17224901.
  11. ↑ Dimachkie MM, Barohn RJ (May 2013). "Guillain-Barré syndrome and variants". Neurol Clin. 31 (2): 491–510. doi:10.1016/j.ncl.2013.01.005. PMC 3939842. PMID 23642721.
  12. ↑ Walling AD, Dickson G (February 2013). "Guillain-Barré syndrome". Am Fam Physician. 87 (3): 191–7. PMID 23418763.
  13. ↑ Gilhus NE (2011). "Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy". Autoimmune Dis. 2011: 973808. doi:10.4061/2011/973808. PMC 3182560. PMID 21969911.
  14. ↑ Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA (May 2004). "Transverse Myelitis: pathogenesis, diagnosis and treatment". Front. Biosci. 9: 1483–99. PMID 14977560.
  15. ↑ Amato AA, Greenberg SA (December 2013). "Inflammatory myopathies". Continuum (Minneap Minn). 19 (6 Muscle Disease): 1615–33. doi:10.1212/01.CON.0000440662.26427.bd. PMID 24305450.
  16. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  17. ↑ . doi:10.22088/cjim.8.3.213. Missing or empty |title= (help)
  18. ↑ Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J (2016). "Stroke mimic diagnoses presenting to a hyperacute stroke unit". Clinical Medicine. 16 (5): 423–426. doi:10.7861/clinmedicine.16-5-423. ISSN 1470-2118.
  19. ↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.
  20. ↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ Almoussa, Mohamad; Goertzen, Angelika; Fauser, Barbara; Zimmermann, Christoph W. (2015). "Stroke as an Unusual First Presentation of Lyme Disease". Case Reports in Neurological Medicine. 2015: 1–4. doi:10.1155/2015/389081. ISSN 2090-6668.
  24. ↑ Kerber, Kevin A.; Brown, Devin L.; Lisabeth, Lynda D.; Smith, Melinda A.; Morgenstern, Lewis B. (2006). "Stroke Among Patients With Dizziness, Vertigo, and Imbalance in the Emergency Department". Stroke. 37 (10): 2484–2487. doi:10.1161/01.STR.0000240329.48263.0d. ISSN 0039-2499.
  25. ↑ 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.
  26. ↑ de Montaudouin, M.; Fleury, O.; Rouanet, M.; Renou, P.; Rouanet, F.; Sibon, Igor (2014). "Hyperacute Guillain-Barré syndrome mimicking stroke: report of 3 cases". The American Journal of Emergency Medicine. 32 (9): 1152.e3–1152.e5. doi:10.1016/j.ajem.2014.02.019. ISSN 0735-6757.
  27. ↑ Yaghi, Shadi; Ishida, Koto; Torres, Jose; Mac Grory, Brian; Raz, Eytan; Humbert, Kelley; Henninger, Nils; Trivedi, Tushar; Lillemoe, Kaitlyn; Alam, Shazia; Sanger, Matthew; Kim, Sun; Scher, Erica; Dehkharghani, Seena; Wachs, Michael; Tanweer, Omar; Volpicelli, Frank; Bosworth, Brian; Lord, Aaron; Frontera, Jennifer (2020). "SARS-CoV-2 and Stroke in a New York Healthcare System". Stroke. 51 (7): 2002–2011. doi:10.1161/STROKEAHA.120.030335. ISSN 0039-2499.
  28. ↑ Merkler, Alexander E.; Parikh, Neal S.; Mir, Saad; Gupta, Ajay; Kamel, Hooman; Lin, Eaton; Lantos, Joshua; Schenck, Edward J.; Goyal, Parag; Bruce, Samuel S.; Kahan, Joshua; Lansdale, Kelsey N.; LeMoss, Natalie M.; Murthy, Santosh B.; Stieg, Philip E.; Fink, Matthew E.; Iadecola, Costantino; Segal, Alan Z.; Cusick, Marika; Campion, Thomas R.; Diaz, Ivan; Zhang, Cenai; Navi, Babak B. (2020). "Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza". JAMA Neurology. doi:10.1001/jamaneurol.2020.2730. ISSN 2168-6149.
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