J Clin Neurol.  2017 Jul;13(3):227-233. 10.3988/jcn.2017.13.3.227.

Neurological Complications during Treatment of Middle East Respiratory Syndrome

• Kim JE
• Heo JH
• Kim HO
• Song SH
• Park SS
• Park TH
• Ahn JY
• Kim MK
• Choi JP

• KMID: 2391665
• DOI: http://doi.org/10.3988/jcn.2017.13.3.227

Abstract

BACKGROUND AND PURPOSE
Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012.
METHODS
We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described.
RESULTS
Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2-3 weeks.
CONCLUSIONS
Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.

Keyword

Guillain-Barré syndrome; Middle East respiratory syndrome; neurological complications; peripheral neuropathy

MeSH Terms

Cohort Studies
Communicable Diseases
Coronavirus
Coronavirus Infections*
Diagnosis
Encephalitis
Guillain-Barre Syndrome
Humans
Middle East Respiratory Syndrome Coronavirus
Middle East*
Mortality
Neurologic Manifestations
Pandemics
Peripheral Nervous System Diseases
Prognosis
Republic of Korea

Figure

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  Fig. 1 Timeline of clinical events and virological results in patient 1. The onset of neurological symptoms and their course during the sedative state were uncertain, and are indicated by the dotted lines. HD: hospital day, IVIG: intravenous immunoglobulin, MV: mechanical ventilator, TA: tracheal aspirate.

Reference

1. who.int [internet]. Middle East Respiratory Syndrome Coronavirus Infections-Disease Outbreak News. cited 2016 Nov 22. Available from: http://www.who.int/emergencies/mers-cov/en.

2. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012; 367:1814–1820. PMID: 23075143.

3. mers.go.kr [internet]. Summary of MERS Statistics in the Republic of Korea. cited 2016 Nov 22. Available from: https://www.mers.go.kr/mers/html/jsp/main.jsp.

4. WHO Mers-Cov Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLoS Curr. 2013; 5:pii: ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8.

5. Desforges M, Le Coupanec A, Stodola JK, Meessen-Pinard M, Talbot PJ. Human coronaviruses: viral and cellular factors involved in neuroinvasiveness and neuropathogenesis. Virus Res. 2014; 194:145–158. PMID: 25281913.

6. Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014; 29:301–306. PMID: 25303830.

7. Arabi YM, Harthi A, Hussein J, Bouchama A, Johani S, Hajeer AH, et al. Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV). Infection. 2015; 43:495–501. PMID: 25600929.

8. Algahtani H, Subahi A, Shirah B. Neurological complications of Middle East respiratory syndrome coronavirus: a report of two cases and review of the literature. Case Rep Neurol Med. 2016; 2016:3502683. PMID: 27239356.

9. who.int [internet]. Technical Guidance on Laboratory: Middle East respiratory syndrome coronavirus (MERS-CoV). cited 2016 Nov 22. Available from: http://www.who.int/csr/disease/coronavirus_infections/technical-guidance-laboratory/en.

10. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315:801–810. PMID: 26903338.

11. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997; 336:243–250. PMID: 8995086.

12. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993; 270:2957–2963. PMID: 8254858.

13. Chong YP, Song JY, Seo YB, Choi JP, Shin HS. Rapid Response Team. Antiviral treatment guidelines for Middle East respiratory syndrome. Infect Chemother. 2015; 47:212–222. PMID: 26483999.

14. Wakerley BR, Uncini A, Yuki N. GBS Classification Group. Guillain-Barré and Miller Fisher syndromes--new diagnostic classification. Nat Rev Neurol. 2014; 10:537–544. PMID: 25072194.

15. Mori M, Kuwabara S, Fukutake T, Yuki N, Hattori T. Clinical features and prognosis of Miller Fisher syndrome. Neurology. 2001; 56:1104–1106. PMID: 11320188.

16. Shahrizaila N, Yuki N. Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome. J Neurol Neurosurg Psychiatry. 2013; 84:576–583. PMID: 22984203.

17. Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010; 17:1408–1418. PMID: 20642790.

18. Wakerley BR, Yuki N. Mimics and chameleons in Guillain-Barré and Miller Fisher syndromes. Pract Neurol. 2015; 15:90–99. PMID: 25239628.

19. Dhand UK. Clinical approach to the weak patient in the intensive care unit. Respir Care. 2006; 51:1024–1040. discussion 1040-1041. PMID: 16934166.

20. Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol. 2011; 10:931–941. PMID: 21939902.

21. van den Berg B, Fokke C, Drenthen J, van Doorn PA, Jacobs BC. Paraparetic Guillain-Barré syndrome. Neurology. 2014; 82:1984–1989. PMID: 24808021.

22. Briani C, Chemello L, Zara G, Ermani M, Bernardinello E, Ruggero S, et al. Peripheral neurotoxicity of pegylated interferon alpha: a prospective study in patients with HCV. Neurology. 2006; 67:781–785. PMID: 16966537.

23. Meriggioli MN, Rowin J. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha. Muscle Nerve. 2000; 23:433–435. PMID: 10679722.

24. Khiani V, Kelly T, Shibli A, Jensen D, Mohanty SR. Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2a therapy for chronic hepatitis C virus infection. World J Gastroenterol. 2008; 14:318–321. PMID: 18186575.

25. Ellis RJ, Marquie-Beck J, Delaney P, Alexander T, Clifford DB, McArthur JC, et al. Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy. Ann Neurol. 2008; 64:566–572. PMID: 19067367.

26. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet. 2015; 386:995–1007. PMID: 26049252.

27. Arbour N, Day R, Newcombe J, Talbot PJ. Neuroinvasion by human respiratory coronaviruses. J Virol. 2000; 74:8913–8921. PMID: 10982334.

28. Chan JF, Chan KH, Choi GK, To KK, Tse H, Cai JP, et al. Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. J Infect Dis. 2013; 207:1743–1752. PMID: 23532101.

29. Tsai LK, Hsieh ST, Chao CC, Chen YC, Lin YH, Chang SC, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol. 2004; 61:1669–1673. PMID: 15534177.

30. Umapathi T, Kor AC, Venketasubramanian N, Lim CC, Pang BC, Yeo TT, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol. 2004; 251:1227–1231. PMID: 15503102.