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CC BY 4.0 · Journal of Child Science 2022; 12(01): e172-e181
DOI: 10.1055/s-0042-1757914
Review Article

Measles-Associated CNS Complications: A Review

Reena Jain
1   Department of Pediatrics, Government Medical College and Hospital, Chandigarh, India
,
Roosy Aulakh 
1   Department of Pediatrics, Government Medical College and Hospital, Chandigarh, India
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Abstract

Measles virus infection is a common infectious disease of childhood, incidence of which is still high in developing countries. Other than the morbidity associated with the acute systemic infection, the measles virus can cause serious fatal neural complications. It can either enter the brain leading to acute encephalitis like primary measles encephalitis and acute post infectious measles encephalomyelitis or it may persist in brain cells (as mutated virus) leading to long-term neurodegenerative diseases like measles inclusion body encephalitis and subacute sclerosing pan encephalitis. The patho-clinical features, treatment, and the outcomes of these complications are different and should be identified in time for early diagnosis and management.

Keywords

measles virus - primary measles encephalitis - acute post infectious measles encephalomyelitis - measles inclusion body encephalitis - subacute sclerosing pan encephalitis


Publication History

Received: 02 July 2021

Accepted: 09 September 2022

Article published online:
06 November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Ferreira CSA, Frenzke M, Leonard VHJ, Welstead GG, Richardson CD, Cattaneo R. Measles virus infection of alveolar macrophages and dendritic cells precedes spread to lymphatic organs in transgenic mice expressing human signaling lymphocytic activation molecule (SLAM, CD150). J Virol 2010; 84 (06) 3033-3042
    CrossrefPubMedGoogle Scholar
  • 2 Frenzke M, Sawatsky B, Wong XX. et al. Nectin-4-dependent measles virus spread to the cynomolgus monkey tracheal epithelium: role of infected immune cells infiltrating the lamina propria. J Virol 2013; 87 (05) 2526-2534
    CrossrefPubMedGoogle Scholar
  • 3 Sindhu TG, Geeta MG, Krishnakumar P, Sabitha S, Ajina KK. Clinical profile of measles in children with special reference to infants. Trop Doct 2019; 49 (01) 20-23
    CrossrefPubMedGoogle Scholar
  • 4 Ben-Chetrit E, Oster Y, Jarjou'i A. et al. Measles-related hospitalizations and associated complications in Jerusalem, 2018-2019. Clin Microbiol Infect 2020; 26 (05) 637-642
    CrossrefPubMedGoogle Scholar
  • 5 Marie JC, Saltel F, Escola JM, Jurdic P, Wild TF, Horvat B. Cell surface delivery of the measles virus nucleoprotein: a viral strategy to induce immunosuppression. J Virol 2004; 78 (21) 11952-11961
    CrossrefPubMedGoogle Scholar
  • 6 Moss WJ, Griffin DE. Measles. Lancet 2012; 379 (9811): 153-164
    CrossrefPubMedGoogle Scholar
  • 7 Wolfson LJ, Grais RF, Luquero FJ, Birmingham ME, Strebel PM. Estimates of measles case fatality ratios: a comprehensive review of community-based studies. Int J Epidemiol 2009; 38 (01) 192-205
    CrossrefPubMedGoogle Scholar
  • 8 World Health Organization. Progress towards regional measles elimination worldwide, 2000–2017. Wkly Epidemiol Rec 2018; 9: 649-660
    PubMedGoogle Scholar
  • 9 Strebel PM, Orenstein WA. Measles. N Engl J Med 2019; 381 (04) 349-357
    CrossrefPubMedGoogle Scholar
  • 10 World Health Organization. Immunization, vaccines and biologicals: new measles surveillance data for. 2019
    PubMedGoogle Scholar
  • 11 World Health Organization. Ten threats to global health in 2019.
    PubMedGoogle Scholar
  • 12 Miller DL. Frequency of complications of measles, 1963. Report on a national inquiry by the public health laboratory service in collaboration with the society of medical officers of health. BMJ 1964; 2 (5401): 75-78
    PubMedGoogle Scholar
  • 13 Reuter D, Schneider-Schaulies J. Measles virus infection of the CNS: human disease, animal models, and approaches to therapy. Med Microbiol Immunol (Berl) 2010; 199 (03) 261-271
    CrossrefPubMedGoogle Scholar
  • 14 Pratakpiriya W, Ping Teh AP, Radtanakatikanon A. et al. Expression of canine distemper virus receptor nectin-4 in the central nervous system of dogs. Sci Rep 2017; 7 (01) 349
    CrossrefPubMedGoogle Scholar
  • 15 Pratakpiriya W, Seki F, Otsuki N. et al. Nectin4 is an epithelial cell receptor for canine distemper virus and involved in neurovirulence. J Virol 2012; 86 (18) 10207-10210
    CrossrefPubMedGoogle Scholar
  • 16 Generous AR, Harrison OJ, Troyanovsky RB. et al. Trans-endocytosis elicited by nectins transfers cytoplasmic cargo, including infectious material, between cells. J Cell Sci 2019; 132 (16) jcs235507
    CrossrefPubMedGoogle Scholar
  • 17 Ferren M, Horvat B, Mathieu C. Measles encephalitis: towards new therapeutics. Viruses 2019; 11 (11) 1017
    CrossrefPubMedGoogle Scholar
  • 18 Watanabe S, Shirogane Y, Sato Y, Hashiguchi T, Yanagi Y. New insights into measles virus brain infections. Trends Microbiol 2019; 27 (02) 164-175
    CrossrefPubMedGoogle Scholar
  • 19 Laksono BM, de Vries RD, McQuaid S, Duprex WP, de Swart RL. Measles virus host invasion and pathogenesis. Viruses 2016; 8 (08) 210
    CrossrefPubMedGoogle Scholar
  • 20 Bechmann I, Galea I, Perry VH. What is the blood-brain barrier (not)?. Trends Immunol 2007; 28 (01) 5-11
    CrossrefPubMedGoogle Scholar
  • 21 Buchanan R, Bonthius DJ. Measles virus and associated central nervous system sequelae. Semin Pediatr Neurol 2012; 19 (03) 107-114
    CrossrefPubMedGoogle Scholar
  • 22 Cherry JD, Harrison GJ, Kaplan SL, Hotez PJ, Steinbach WJ. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 2014
    Google Scholar
  • 23 Gendelman HE, Wolinsky JS, Johnson RT, Pressman NJ, Pezeshkpour GH, Boisset GF. Measles encephalomyelitis: lack of evidence of viral invasion of the central nervous system and quantitative study of the nature of demyelination. Ann Neurol 1984; 15 (04) 353-360
    CrossrefPubMedGoogle Scholar
  • 24 ter Meulen V, Müller D, Käckell Y, Katz M, Meyermann R. Isolation of infectious measles virus in measles encephalitis. Lancet 1972; 2 (7788): 1172-1175
    CrossrefPubMedGoogle Scholar
  • 25 Esolen LM, Takahashi K, Johnson RT. et al. Brain endothelial cell infection in children with acute fatal measles. J Clin Invest 1995; 96 (05) 2478-2481
    CrossrefPubMedGoogle Scholar
  • 26 Hosoya M. Measles encephalitis: direct viral invasion or autoimmune-mediated inflammation?. Intern Med 2006; 45 (14) 841-842
    CrossrefPubMedGoogle Scholar
  • 27 Johnson RT, Griffin DE, Hirsch RL. et al. Measles encephalomyelitis–clinical and immunologic studies. N Engl J Med 1984; 310 (03) 137-141
    CrossrefPubMedGoogle Scholar
  • 28 Mustafa MM, Weitman SD, Winick NJ, Bellini WJ, Timmons CF, Siegel JD. Subacute measles encephalitis in the young immunocompromised host: report of two cases diagnosed by polymerase chain reaction and treated with ribavirin and review of the literature. Clin Infect Dis 1993; 16 (05) 654-660
    CrossrefPubMedGoogle Scholar
  • 29 Forni AL, Schluger NW, Roberts RB. Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous ribavirin. Clin Infect Dis 1994; 19 (03) 454-462
    CrossrefPubMedGoogle Scholar
  • 30 Pickering LK, Baker CJ, Long SS, McMillan JA. Measles: American Academy of Pediatrics, Red Book. Report of the Committee on Infectious Diseases. 2006; 27: 441-452
    PubMedGoogle Scholar
  • 31 Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis 2004; 189 (suppl 1): S4-S16
    CrossrefPubMedGoogle Scholar
  • 32 Ota MO, Moss WJ, Griffin DE. Emerging diseases: measles. J Neurovirol 2005; 11 (05) 447-454
    CrossrefPubMedGoogle Scholar
  • 33 Fisher DL, Defres S, Solomon T. Measles-induced encephalitis. QJM 2015; 108 (03) 177-182
    CrossrefPubMedGoogle Scholar
  • 34 Mayer MC, Meinl E. Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more. Ther Adv Neurol Disord 2012; 5 (03) 147-159
    CrossrefPubMedGoogle Scholar
  • 35 O'Connor KC, McLaughlin KA, De Jager PL. et al. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med 2007; 13 (02) 211-217
    CrossrefPubMedGoogle Scholar
  • 36 't Hart BA, Hintzen RQ, Laman JD. Preclinical assessment of therapeutic antibodies against human CD40 and human interleukin-12/23p40 in a nonhuman primate model of multiple sclerosis. Neurodegener Dis 2008; 5 (01) 38-52
    CrossrefPubMedGoogle Scholar
  • 37 't Hart BA, Hintzen RQ, Laman JD. Multiple sclerosis - a response-to-damage model. Trends Mol Med 2009; 15 (06) 235-244
    CrossrefPubMedGoogle Scholar
  • 38 Liebert UG, Hashim GA, ter Meulen V. Characterization of measles virus-induced cellular autoimmune reactions against myelin basic protein in Lewis rats. J Neuroimmunol 1990; 29 (1-3): 139-147
    CrossrefPubMedGoogle Scholar
  • 39 Banwell BL. Acquired demyelination of the central nervous system. In: Maria B. ed. Current Management in Child Neurology. 2005. 03 486-493
    Google Scholar
  • 40 Menge T, Kieseier BC, Nessler S, Hemmer B, Hartung HP, Stüve O. Acute disseminated encephalomyelitis: an acute hit against the brain. Curr Opin Neurol 2007; 20 (03) 247-254
    CrossrefPubMedGoogle Scholar
  • 41 Tenembaum S, Chitnis T, Ness J, Hahn JS, Group IPMS. International Pediatric MS Study Group. Acute disseminated encephalomyelitis. Neurology 2007; 68 (16, suppl 2): S23-S36
    CrossrefPubMedGoogle Scholar
  • 42 Bennetto L, Scolding N. Inflammatory/post-infectious encephalomyelitis. J Neurol Neurosurg Psychiatry 2004; 75 (Suppl. 01) i22-i28
    CrossrefPubMedGoogle Scholar
  • 43 Chowdhary J, Ashraf SM, Khajuria K. Measles with acute disseminated encephalomyelitis (ADEM). Indian Pediatr 2009; 46 (01) 72-74
    PubMedGoogle Scholar
  • 44 Fox A, Hung TM, Wertheim H. et al. Acute measles encephalitis in partially vaccinated adults. PLoS One 2013; 8 (08) e71671
    CrossrefPubMedGoogle Scholar
  • 45 Albertyn C, van der Plas H, Hardie D. et al. Silent casualties from the measles outbreak in South Africa. S Afr Med J 2011; 101 (05) 313-314 , 316–317
    CrossrefPubMedGoogle Scholar
  • 46 Hughes I, Jenney ME, Newton RW, Morris DJ, Klapper PE. Measles encephalitis during immunosuppressive treatment for acute lymphoblastic leukaemia. Arch Dis Child 1993; 68 (06) 775-778
    CrossrefPubMedGoogle Scholar
  • 47 Freeman AF, Jacobsohn DA, Shulman ST. et al. A new complication of stem cell transplantation: measles inclusion body encephalitis. Pediatrics 2004; 114 (05) e657-e660
    CrossrefPubMedGoogle Scholar
  • 48 Bitnun A, Shannon P, Durward A. et al. Measles inclusion-body encephalitis caused by the vaccine strain of measles virus. Clin Infect Dis 1999; 29 (04) 855-861
    CrossrefPubMedGoogle Scholar
  • 49 Hardie DR, Albertyn C, Heckmann JM, Smuts HEM. Molecular characterisation of virus in the brains of patients with measles inclusion body encephalitis (MIBE). Virol J 2013; 10: 283
    CrossrefPubMedGoogle Scholar
  • 50 Ha MN, Delpeut S, Noyce RS. et al. Mutations in the fusion protein of measles virus that confer resistance to the membrane fusion inhibitors carbobenzoxy-D-Phe-L-Phe-Gly and 4-nitro-2- phenylacetyl amino-benzamide. J Virol 2017; 91 (23) e01026-e17
    PubMedGoogle Scholar
  • 51 Mathieu C, Ferren M, Jurgens E. et al. Measles virus bearing measles inclusion body encephalitis derived fusion protein is pathogenic after infection via the respiratory route. J Virol 2019; 93 (08) e01862-e18
    CrossrefPubMedGoogle Scholar
  • 52 Rima BK, Duprex WP. Molecular mechanisms of measles virus persistence. Virus Res 2005; 111 (02) 132-147
    CrossrefPubMedGoogle Scholar
  • 53 Ohuchi M, Ohuchi R, Mifune K, Ishihara T, Ogawa T. Characterization of the measles virus isolated from the brain of a patient with immunosuppressive measles encephalitis. J Infect Dis 1987; 156 (03) 436-441
    CrossrefPubMedGoogle Scholar
  • 54 Mitus A, Holloway A, Evans AE, Enders JF. Attenuated measles vaccine in children with acute leukemia. Am J Dis Child 1962; 103: 413-418
    PubMedGoogle Scholar
  • 55 Valmari P, Lanning M, Tuokko H, Kouvalainen K. Measles virus in the cerebrospinal fluid in postvaccination immunosuppressive measles encephalopathy. Pediatr Infect Dis J 1987; 6 (01) 59-63
    CrossrefPubMedGoogle Scholar
  • 56 Baldolli A, Dargère S, Cardineau E. et al. Measles inclusion-body encephalitis (MIBE) in a immunocompromised patient. J Clin Virol 2016; 81: 43-46
    CrossrefPubMedGoogle Scholar
  • 57 Antona D, Lévy-Bruhl D, Baudon C. et al. Measles elimination efforts and 2008-2011 outbreak, France. Emerg Infect Dis 2013; 19 (03) 357-364
    CrossrefPubMedGoogle Scholar
  • 58 Mclean HQ, Fiebelkorn AP, Temte JL, Wallac GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and mortality weekly report Recommendations and reports/Centers for Disease Control 2013; 62 (RR-04): 1-34
    PubMedGoogle Scholar
  • 59 Wendorf KA, Winter K, Zipprich J. et al. Subacute sclerosing panencephalitis: the devastating measles complication that might be more common than previously estimated. Clin Infect Dis 2017; 65 (02) 226-232
    CrossrefPubMedGoogle Scholar
  • 60 World Health Organization. Weekly epidemiological record. . No. 2, 2006, 81, 13-20
    PubMedGoogle Scholar
  • 61 Simşek E, Oztürk A, Yavuz C, Kocabay K. Subacute sclerosing panencephalitis (SSPE) associated with congenital measles infection. Turk J Pediatr 2005; 47 (01) 58-62
    PubMedGoogle Scholar
  • 62 Zwiauer K, Forstenpointner E, Popow-Kraupp T, Hauser E, Jellinger KA. Rapid progressive subacute sclerosing panencephalitis after perinatally acquired measles virus infection. Lancet 1995; 345 (8957): 1124
    CrossrefPubMedGoogle Scholar
  • 63 Dasopoulou M, Covanis A. Subacute sclerosing panencephalitis after intrauterine infection. Acta Paediatr 2004; 93 (09) 1251-1253
    CrossrefPubMedGoogle Scholar
  • 64 Saurabh K, Gupta R, Khare S, Sharma S. Atypical subacute sclerosing panencephalitis with short onset latency. Indian Pediatr 2013; 50 (02) 244-245
    CrossrefPubMedGoogle Scholar
  • 65 Aulakh R, Tiwari A. Subacute sclerosing panencephalitis in a toddler: changing epidemiological trends. Case Rep Pediatr 2013; 2013: 341462
    CrossrefPubMedGoogle Scholar
  • 66 Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol 2010; 52 (10) 901-907
    CrossrefPubMedGoogle Scholar
  • 67 Babu RB, Biswas J. Bilateral macular retinitis as the presenting feature of subacute sclerosing panencephalitis. J Neuroophthalmol 2007; 27 (04) 288-291
    CrossrefPubMedGoogle Scholar
  • 68 Chiodi F, Sundqvist VA, Norrby E, Mavra M, Link H. Measles IgM antibodies in cerebrospinal fluid and serum in subacute sclerosing panencephalitis. J Med Virol 1986; 18 (02) 149-158
    CrossrefPubMedGoogle Scholar
  • 69 Kiessling WR, Hall WW, Yung LL, ter Meulen V. Measles-virus-specific immunoglobulin-M response in subacute sclerosing panencephalitis. Lancet 1977; 1 (8007): 324-327
    CrossrefPubMedGoogle Scholar
  • 70 Bonthius DJ, Stanek N, Grose C. Subacute sclerosing panencephalitis, a measles complication, in an internationally adopted child. Emerg Infect Dis 2000; 6 (04) 377-381
    CrossrefPubMedGoogle Scholar
  • 71 Garg RK. Subacute sclerosing panencephalitis. J Neurol 2008; 255 (12) 1861-1871
    CrossrefPubMedGoogle Scholar
  • 72 Anlar B, Aydin OF, Guven A, Sonmez FM, Kose G, Herguner O. Retrospective evaluation of interferon-beta treatment in subacute sclerosing panencephalitis. Clin Ther 2004; 26 (11) 1890-1894
    CrossrefPubMedGoogle Scholar
  • 73 Saini AG, Sankhyan N, Padmanabh H, Sahu JK, Vyas S, Singhi P. Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities. Eur J Paediatr Neurol 2016; 20 (03) 435-438
    CrossrefPubMedGoogle Scholar
  • 74 Kumar N, Ranjan A, Kumar A, Kumar B. Teaching NeuroImages: isolated pontine involvement in subacute sclerosing panencephalitis. Neurology 2018; 91 (03) e293-e294
    CrossrefPubMedGoogle Scholar
  • 75 Singhi P, Saini AG, Sankhyan N, Gupta P, Vyas S. Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis. J Child Neurol 2015; 30 (01) 87-90
    CrossrefPubMedGoogle Scholar
  • 76 Garg RK, Mahadevan A, Malhotra HS, Rizvi I, Kumar N, Uniyal R. Subacute sclerosing panencephalitis. Rev Med Virol 2019; 29 (05) e2058
    CrossrefPubMedGoogle Scholar
  • 77 Mahadevan A, Vaidya SR, Wairagkar NS. et al. Case of fulminant-SSPE associated with measles genotype D7 from India: an autopsy study. Neuropathology 2008; 28 (06) 621-626
    CrossrefPubMedGoogle Scholar
  • 78 Cattaneo R, Schmid A, Eschle D, Baczko K, ter Meulen V, Billeter MA. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell 1988; 55 (02) 255-265
    CrossrefPubMedGoogle Scholar
  • 79 Patterson JB, Cornu TI, Redwine J. et al. Evidence that the hypermutated M protein of a subacute sclerosing panencephalitis measles virus actively contributes to the chronic progressive CNS disease. Virology 2001; 291 (02) 215-225
    CrossrefPubMedGoogle Scholar
  • 80 Kweder H, Ainouze M, Cosby SL. et al. Mutations in the H, F, or M proteins can facilitate resistance of measles virus to neutralizing human anti-MV sera. Adv Virol 2014; 2014: 205617
    CrossrefPubMedGoogle Scholar
  • 81 Campbell H, Andrews N, Brown KE, Miller E. Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol 2007; 36 (06) 1334-1348
    CrossrefPubMedGoogle Scholar
  • 82 Bellini WJ, Rota JS, Lowe LE. et al. Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005; 192 (10) 1686-1693
    CrossrefPubMedGoogle Scholar
  • 83 Landrigan PJ, Witte JJ. Neurologic disorders following live measles-virus vaccination. JAMA 1973; 223 (13) 1459-1462
    CrossrefPubMedGoogle Scholar
  • 84 Weibel RE, Caserta V, Benor DE, Evans G. Acute encephalopathy followed by permanent brain injury or death associated with further attenuated measles vaccines: a review of claims submitted to the National Vaccine Injury Compensation Program. Pediatrics 1998; 101 (3 Pt 1): 383-387
    CrossrefPubMedGoogle Scholar
  • 85 Encephalitis Surveillance, 1965 Annual Summary. Atlanta: National Communicable Disease Center; 1966: 15
    Google Scholar
  • 86 Belgamwar RB, Prasad S, Appaya P. Measles, mumps, rubella vaccine induced subacute sclerosing panencephalitis. J Indian Med Assoc 1997; 95 (11) 594
    PubMedGoogle Scholar
  • 87 Weekly Epidemiological Record. 2006 , vol. 81, 02
    PubMedGoogle Scholar
  • 88 Saha V, John TJ, Mukundan P. et al. High incidence of subacute sclerosing panencephalitis in south India. Epidemiol Infect 1990; 104 (01) 151-156
    CrossrefPubMedGoogle Scholar
  • 89 John T. Measles vaccination and risk of SSPE – reply. Indian Pediatr 1999; 36 (03) 318
    PubMedGoogle Scholar