COVID-19-associated stroke differential diagnosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
COVID-19-associated stroke should be differentiated from other causes of muscle weakness and paralysis such as botulism, guillian-Barre syndrome, Eaton Lambert syndrome, myasthenia gravis, electrolyte disturbance, organophosphate toxicity, tick paralysis (Dermacentor tick), tetrodotoxin poisoning, stroke, poliomyelitis, transverse myelitis, neurosyphilis, muscular dystrophy, multiple sclerosis exacerbation, amyotrophic lateral sclerosis, and inflammatory myopathy.
Differential Diagnosis
COVID-19-associated stroke should be differentiated from other causes of muscle weakness and paralysis such as botulism, guillian-Barre syndrome, Eaton Lambert syndrome, myasthenia gravis, electrolyte disturbance, organophosphate toxicity, tick paralysis (Dermacentor tick), tetrodotoxin poisoning, stroke, poliomyelitis, transverse myelitis, neurosyphilis, muscular dystrophy, multiple sclerosis exacerbation, amyotrophic lateral sclerosis, and inflammatory myopathy.[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 | ||
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. |
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. |
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 associated with COVID-19 should be differentiated from other diseases that can have similar presentation as stroke. These include-[17][18]
- Other COVID-19 associated neurological complications: Encephalitis, Encephalopathy, Meningitis, Seizure, Guillain-Barre syndrome, polyneuritis cranialis
- Neurologic in non-COVID patients: Transient Ischemic Attack, Brain abscess, Hemiplegic Migraine, Seizures[19], Postictal paralysis, Cerebral venous sinus thrombosis, Cerebral neoplasm[20][21], Cerebral Infections (Meningitis, Encephalitis[22], Brain Abscess, Progressive multifocal leukoencephalopathy)
- Traumatic: Epidural hematoma, Subdural hematoma, Traumatic brain Injury
- Toxic and/or Metabolic: Hypoglycemia, Hyponatremia, Drug intoxication
- Syncope
- Lyme's disease[23]
- Ear and Nose diseases[24]: Benign Paroxysmal Positional Vertigo, Vestibular Neuronitis, Meniere's Disease
- Psychiatric: Malingering, Conversion disorder
- Paraneoplastic syndromes
- Autoimmune disorders: Multiple Sclerosis[25], Acute inflammatory demyelinating polyradiculoneuropathy(Guillain-Barre syndrome)[26]
- 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
- ↑ 1.0 1.1 Kira R (February 2018). "[Acute Flaccid Myelitis]". Brain Nerve (in Japanese). 70 (2): 99–112. doi:10.11477/mf.1416200962. PMID 29433111.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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)
- ↑ 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.
- ↑ "Botulism | Botulism | CDC".
- ↑ 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.
- ↑ 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.
- ↑ Brook I (2006). "Botulism: the challenge of diagnosis and treatment". Rev Neurol Dis. 3 (4): 182–9. PMID 17224901.
- ↑ 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.
- ↑ Walling AD, Dickson G (February 2013). "Guillain-Barré syndrome". Am Fam Physician. 87 (3): 191–7. PMID 23418763.
- ↑ Gilhus NE (2011). "Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy". Autoimmune Dis. 2011: 973808. doi:10.4061/2011/973808. PMC 3182560. PMID 21969911.
- ↑ 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.
- ↑ 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.
- ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
- ↑ . doi:10.22088/cjim.8.3.213. Missing or empty
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(help) - ↑ 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.
- ↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.
- ↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.