Top

Published in:

01-08-2021 | Herpes Virus | Neurological Update

An overview of viral infections of the nervous system in the immunosuppressed

Author: Peter G. E. Kennedy

Published in: Journal of Neurology | Issue 8/2021

Abstract

Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.

Kennedy PGE, Mogensen TH (2020) J Determinants of neurological syndromes caused by varicella zoster virus (VZV). J Neurovirol. https://doi.org/10.1007/s13365-020-00857-w ((Online ahead of print))CrossRefPubMedPubMedCentral

Wijdicks EFM (1999) Neurologic complications in transplant recipients: a bird’s eye view. In: Wijdicks EFM (ed) Neurologic complications in organ transplant recipients. Butterworth and Co (Publishers) Ltd, Great Britain, pp 57–62

Tolkoff-Rubin NE, Kees Hovingh G, Rubin RH (1999) Central nervous system Infections. In: Wijdicks EFM (ed) Neurologic complications in organ transplant recipients. Butterworth and Co (Publishers) Ltd, Great Britain, pp 141–168

Kennedy PGE, Rovnak J, Badani H, Cohrs RJ (2015) A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation. J Gen Virol 96(Pt7):1581–1602. https://doi.org/10.1099/vir.0.000128CrossRefPubMedPubMedCentral

Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, Grose C, Hambleton S, Kennedy PGE, Oxman MN, Seward JF, Yamanishi K (2015) Varicella-Zoster virus infection. Nat Rev Dis Primers 1:15016. https://doi.org/10.1038/nrdp.2015.16CrossRefPubMedPubMedCentral

Kennedy PGE, Gershon AA (2018) Clinical Features of Varicella-Zoster Virus. Infec Virus 10(11):609. https://doi.org/10.3390/v10110609CrossRef

Brainin M, Barnes M, Baron JC, Gilhus NE, Hughes R, Selmaj K, Waldemar G (2004) Guidance for the preparation of neurological management guidelines by EFNS scientific task forces–revised recommendations. Eur J Neurol 9:577–581. https://doi.org/10.1111/j.1468-1331.2004.00867.xCrossRef

Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O, Kennedy PGE (2010) Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol 12(5):331–343. https://doi.org/10.1111/j.1468-1331.2005.01126.xCrossRef

Steiner I, Schmutzhard E, Sellner J, Chaudhuri A, Kennedy PG (2012) EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system. Eur J Neurol 19(10):1278–1291. https://doi.org/10.1111/j.1468-1331.2012.03808.xCrossRefPubMed

10.

Steiner I, Kennedy PGE, Pachner AR (2007) The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 6:1015–1028CrossRefPubMed

11.

Kennedy PGE (2004) Viral encephalitis: causes, differential diagnosis, and management. J Neurol Neurosurg Psychiat 75:i10–i15. https://doi.org/10.1136/jnnp.2003.034280 ((suppl))CrossRefPubMedPubMedCentral

12.

Jouanguy E, Béziat V, Mogensen TH, Casanova JL, Tangye SG, Zhang SY (2020) Human inborn errors of immunity to herpes viruses. Curr Opin Immunol 62:106–122. https://doi.org/10.1016/j.coi.2020.01.004 (Epub 2020 Jan)CrossRefPubMedPubMedCentral

13.

Lim HK, Seppänen M, Hautala T, Ciancanelli MJ, Itan Y, Lafaille FG, e al, (2014) TLR3 deficiency in herpes simplex encephalitis: high allelic heterogeneity and recurrence risk. Neurology 83(21):1888–1897. https://doi.org/10.1212/WNL.0000000000000999 (Epub 2014 Oct 22)CrossRefPubMedPubMedCentral

14.

Gilden DH and Tyler KL (2005) Herpesvirus infection and peripheral neuropathy. In peripheral neuropathy 4th edition. Editors PJ Dyck and PK Thomas, Elsevier Saunders, USA Chapter 93 2117–2128

15.

Fodor PA, Levin MJ, Weinberg A, Sandberg E, Sylman J, Tyler KL (1998) Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology 51(2):554–559. https://doi.org/10.1212/wnl.51.2.554CrossRefPubMed

16.

Gilden DH, Wright RR, Schneck SA, Gwaltney JM Jr, Mahalingam R (1994) Zoster sine herpete, a clinical variant. Ann Neurol 35:530–533CrossRefPubMed

17.

Kennedy PGE (2011) Zoster sine herpete: it would be rash to ignore it. Neurology 76:416–417CrossRefPubMed

18.

Nagel MA, Gilden D (2013) Complications of varicella zoster virus reactivation. Curr Treat Options Neurol 15:439–445CrossRefPubMedPubMedCentral

19.

Forman SJ, Openshaw H (1999) Bone marrow (Hematopoietic cell) transplantation. In: Wijdicks EFM (ed) Neurologic complications in organ transplant recipients. Butterworth and Co (Publishers) Ltd, Great Britain, pp 45–54

20.

Kennedy PGE (2016) Issues in the treatment of neurological conditions caused by reactivation of varicella zoster virus (VZV). Neurotherapeutics 13(3):509–513CrossRefPubMedPubMedCentral

21.

Nagel MA, Forghani B, Mahalingam R, WellishMC CRJ, Russman AN, Katzan I, Lin R, Gardner CJ, Gilden DH (2007) The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 68:1069–1073CrossRefPubMed

22.

Ogunjimi B, Zhang SY, Sørensen KB, Skipper KA, Carter-Timofte M, Kerr G et al (2017) Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections. J Clin Invest 127(9):3543–3556. https://doi.org/10.1172/JCI92280 (Epub 2017 Aug 7)CrossRefPubMedPubMedCentral

23.

Carter-Timofte ME, Paludan SR, Mogensen TH (2018) RNA polymerase III as a gatekeeper to prevent severe VZV infections. Trends Mol Med 24(10):904–915. https://doi.org/10.1016/j.molmed.2018.07.009 (Epub 2018 Aug 13)CrossRefPubMed

24.

Cinque P, Brytting M, Vago L, Castagna A, Parravicini C, Zanchetta N, D’Arminio Monforte A, Wahren B, Lazzarin A, Linde A (1993) Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1342(8868):398–401. https://doi.org/10.1016/0140-6736(93)92814-aCrossRef

25.

Said-Conti V, Amrolia PJ, Gaze MN, Stoneham S, Sebire N, Shroff R, Marks SD et al (2013) Successful treatment of central nervous system PTLD with rituximab and cranial radiotherapy. Pediatr Nephrol 28(10):2053–2056. https://doi.org/10.1007/s00467-013-2499-3 (Epub 2013 Jun 7)CrossRefPubMed

26.

Denes E, Magy L, Pradeau K, Alain S, Weinbreck P, Ranger-Rogez S (2004) Successful treatment of human herpesvirus 6 encephalomyelitis in immunocompetent patient). Emerg Infect Dis 10(4):729–731. https://doi.org/10.3201/eid1004.030587CrossRefPubMedPubMedCentral

27.

Langer-Gould A, Atlas SW, Green AJ, Bollen AW (2005) Pelletier D Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353:375–381CrossRefPubMed

28.

Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J et al (2006) Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354(9):924–933. https://doi.org/10.1056/NEJMoa054693CrossRefPubMedPubMedCentral

29.

Gheuens S, Wüthrich C, Koralnik IJ (2013) Progressive multifocal leukoencephalopathy: why gray and white matter. Annu Rev Pathol 8:189–215CrossRefPubMed

30.

Gofshteyn J, Cárdenas AM, Bearden D (2016) Treatment of chronic enterovirus encephalitis with fluoxetine in a patient with X-linked agammaglobulinemia. Pediatr Neurol 64:94–98. https://doi.org/10.1016/j.pediatrneurol.2016.06.014 (Epub 2016 Jun 25)CrossRefPubMed

31.

Fisher DL, Defres S, Solomon T (2015) QJM. Measles-induced encephalitis 108(3):177–82. https://doi.org/10.1093/qjmed/hcu113. Epub 2014 May 26

32.

Aicardi J, Goutieres F, Arsenio-Nunes ML, Lebon P (1977) Acute measles encephalitis in children with immunosuppression. Pediatrics 59(2):232–239PubMed

33.

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan China. JAMA 323(11):1061–1069. https://doi.org/10.1001/jama.2020.1585 ((Online ahead of print))CrossRefPubMedPubMedCentral

34.

Berger JR (2020) COVID-19 and the nervous system. J Neurovirol 26(2):143–148. https://doi.org/10.1007/s13365-020-00840-5 (Epub 2020 May 23)CrossRefPubMed

35.

Ahmed MU, Hanif M, Ali MJ, Haider MA, Kherani D, Memon GM, Karim AH, Sattar A (2020) Neurological manifestations of COVID-19 (SARS-CoV-2). Rev Front Neurol 11:518. https://doi.org/10.3389/fneur.2020.00518 ((eCollection 2020))CrossRef

36.

Carter-Timofte ME, Jørgensen SE, Freytag MR, Thomsen MM, Brinck Andersen NS, Al-Mousawi A, Hait AS, Mogensen TH (2020) Deciphering the role of host genetics in susceptibility to severe COVID-19. Front Immunol 11:1606. https://doi.org/10.3389/fimmu.2020.01606 ((eCollection 2020))CrossRefPubMedPubMedCentral

37.

Helleberg M, Niemann CU, Moestrup K, Kirk O, Lebech AM, Lane C, Lundgren J (2020) Persistent COVID-19 in an immunocompromised patient temporarily responsive to two courses of remdesivir therapy. J Infect Dis. https://doi.org/10.1093/infdis/jiaa446 ((jiaa446, Online ahead of print))CrossRefPubMed

Title: An overview of viral infections of the nervous system in the immunosuppressed
Author: Peter G. E. Kennedy
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keywords: Herpes Virus
Shingles
Human Alphaherpesvirus 3
Epstein-Barr Virus
Immunodeficiency
Polymerase Chain Reaction
Encephalitis
Herpes Simplex Encephalitis
Published in: Journal of Neurology / Issue 8/2021
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-10265-z

At a glance: The STEP trials

Springer Medicine

An overview of viral infections of the nervous system in the immunosuppressed

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2021

Changes of clinical, neurophysiological and nerve ultrasound characteristics in CIDP over time: a 3-year follow-up

Multifocal neutrophilic meningoencephalitis: a novel disorder responsive to anakinra

Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19

COVID-19 in cladribine-treated relapsing-remitting multiple sclerosis patients: a monocentric experience

Factors delaying intravenous thrombolytic therapy in acute ischaemic stroke: a systematic review of the literature

Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses