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Reply:
  
    	
Michael F. Goldberg, Morton F. Goldberg, R. Cerejo and A.H. Tayal

  
    	
American Journal of Neuroradiology August 2020,  41 (8) E64; DOI: https://doi.org/10.3174/ajnr.A6686 

  
  
  



  


  
  



			

		

	
	
 	
	  
  

		
		

			

			  

  
      
  
  

    
  


  
  



  
      
  
  

    

  

    

  
      
  
  

    
We thank Morelli et al for their interest in our article and their feedback.
We think it is important to remember that coronavirus disease 2019 (COVID-19) was first recognized in December 2019, only 6 months ago.1 Therefore, there will be inherent limitations to the size, scope, and implications of any research that can occur in such a truncated period.
In addition, as we acknowledge in our article, the patient described in our case report died on hospital day 3, before the completion of a complete laboratory work-up; furthermore, no postmortem examination was performed.2 So, we agree with Morelli et al that it will require larger studies of more prolonged duration to draw definitive causal relationships between COVID-19 and various disease states, including acute cerebrovascular disease.
Until such studies occur, we would refer Morelli et al to the early-but-substantial medical literature that indicates a strong association between COVID-19 and cerebrovascular disease. This includes a retrospective study of 214 patients with COVID-19 in China, which revealed a 5.7% incidence of stroke in severely affected patients.3 In a case series of 64 patients with severe COVID-19, three of 13 patients who underwent brain MRIs demonstrated evidence of ischemic stroke.4 Researchers in New York City recently published a case series of 5 young patients (less than 50 years-old) with COVID-19 who presented with large-vessel stroke during a 2-week period; this represented an almost 7-fold increase in the frequency of large-vessel stroke seen in patients in this age group.5 Because severely affected patients with COVID-19 are often intubated and sedated, the presence of stroke can be overlooked, and the current estimates of the incidence of stroke may, therefore, be spuriously low.6 Additionally, Umapathi et al7 reported an association between large-vessel stroke and the somewhat similar 2004 Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) outbreak. Combined with the growing literature on coagulopathy in severely affected patients with COVID-19, we think that dismissing this information as anecdotal belies reasonable evidence for a causative association between COVID-19 and cerebrovascular disease.8-10
Like Morelli et al, we also subscribe to the principle of Occam’s razor. The patient described in our case report had tested positive for SARS-CoV-2 sixteen days before admission. Initially, he had a relatively benign course with mild respiratory symptoms and myalgia, and he had no preceding neurologic deficits. Several hours before admission, however, he developed, nearly simultaneously, stroke symptoms and respiratory distress, which ultimately led to CT-confirmed acute respiratory distress syndrome (ARDS) and hemodynamic instability. We do not think the synchronous timing of these disparate symptoms is coincidental. Rather, the delayed onset of both respiratory and neurologic symptoms in COVID-19 is suggestive of a maladaptive immune response, including cytokine storm syndrome, resulting in not only ARDS but also abnormalities in the clotting cascade and endothelial inflammation.11,12 Therefore, ascribing this patient’s stroke to COVID-19 is entirely consistent with Occam’s razor—to do otherwise risks invoking the Hickam dictum, which is the assignment of multiple different and independent diagnoses to explain a variety of signs and symptoms.13
Indicates open access to non-subscribers at www.ajnr.org
References
  1. 1.↵
    1. Phelan  AL, 
    2. Katz  R, 
    3. Gostin  LO
    . The novel coronavirus originating in Wuhan, China: challenges for global health governance. JAMA 2020 Jan 30. [Epub ahead of print] doi:10.1001/jama.2020.1097 pmid:31999307
    CrossRefPubMed
  2. 2.↵
    1. Goldberg  MF, 
    2. Goldberg  MF, 
    3. Cerejo  R, et al
    . Cerebrovascular disease in COVID-19. AJNR Am J Neuroradiol 2020;41:1170–72 doi:10.3174/ajnr.A6588 pmid:32409316
    Abstract/FREE Full Text
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    1. Mao  L, 
    2. Jin  H, 
    3. Wang  M, et al
    . Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:1–9 doi:10.1001/jamaneurol.2020.1127 pmid:32275288
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    1. Helms  J, 
    2. Kremer  S, 
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    . Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020;382:2268–70 doi:10.1056/NEJMc2008597 pmid:32294339
    CrossRefPubMed
  5. 5.↵
    1. Oxley  TJ, 
    2. Mocco  J, 
    3. Majidi  S, et al
    . Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020;382:e60 doi:10.1056/NEJMc2009787 pmid:32343504
    CrossRefPubMed
  6. 6.↵
    1. Yaghi  S, 
    2. Ishida  K, 
    3. Torres  J, et al
    . SARS2-CoV-2 and stroke in a New York health care system. Stroke 2020 May 20. [Epub ahead of print] doi:10.1161/STROKEAHA.120.030335] pmid:32432996
    CrossRefPubMed
  7. 7.↵
    1. Umapathi  T, 
    2. Kor  AC, 
    3. Venketasubramanian  N, et al
    . Large-artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol 2004;251:1227–31 doi:10.1007/s00415-004-0519-8 pmid:15503102
    CrossRefPubMed
  8. 8.↵
    1. Wan  S, 
    2. Xiang  Y, 
    3. Fang  W, et al
    . Clinical features and treatment of COVID-19 patients in Northeast Chongqing. J Med Virol 2020;92:797–806 doi:10.1002/jmv.25783 pmid:32198776
    CrossRefPubMed
  9. 9.
    1. Helms  J, 
    2. Tacquard  C, 
    3. Severac  F, et al
    . High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020;46:1089–98 doi:10.1007/s00134-020-06062-x pmid:32367170
    CrossRefPubMed
  10. 10.↵
    1. Arachchillage  DR, 
    2. Laffan  M
    . Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844–47 doi:10.1111/jth.14768 pmid:32291954
    CrossRefPubMed
  11. 11.↵
    1. Mehta  P, 
    2. McAuley  DF, 
    3. Brown  M, et al
    . COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–34 doi:10.1016/S0140-6736(20)30628-0 pmid:32192578
    CrossRefPubMed
  12. 12.↵
    1. Berlin  DA, 
    2. Gulick  RM, 
    3. Martinez  FJ
    . Severe Covid-19. N Engl J Med 2020 May 15. [Epub ahead of print] doi:10.1056/NEJMcp2009575 pmid:32412710
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  13. 13.↵
    1. Miller  WT
    . Letter from the editor: Occam versus Hickam. Semin Roentgenol 1998;33:213 doi:10.1016/S0037-198X(98)80001-1
    CrossRef
  


  
  



  
      
  
  

    
  


  
  



  




  


  
  



  
      
  
  

    
  


  
  



  
      
  
  

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 American Journal of Neuroradiology Aug 2020, 41 (8) E64; DOI: 10.3174/ajnr.A6686 

  
  
  



  


  
  



  
      
  
  

    

  
    
  
  
    
  
  
    
  


  


  
  



  
      
  
  

    
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