Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Clinical presentation and course of multiple sclerosis in patients with herpesvirus infection

https://doi.org/10.14412/2074-2711-2021-1S-21-26

Full Text:

Abstract

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.

Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.

Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.

Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p<0.05). Patients in the main group had an unfavorable disease course: earlier MS onset, predominantly polysymptomatic onset, significantly higher relapse rate, faster disease progression, and higher EDSS and Functional Systems Scale (FSS) scores (p <0.05). MRI activity was also associated with EBV infection: new T1Gd+ and T2 foci were associated with an increase in VCA-IgM to EBV level. We also observed decreased DMTs effectiveness (χ2=4,6; p=0,033) and worse DMTs tolerability (χ2=5,3; p=0,022) in the main group.

Conclusion. MS patients with PHVI reactivation, have a more unfavorable course of the demyelinating process and, therefore, a greater degree of disability, compared with age-adjusted patients without a viral infection and the same disease duration.

About the Authors

M. S. Gris
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation

5, Revolutsionnaya St., Yaroslavl 150000



N. S. Baranova
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation

Natalia Sergeevna Baranova

5, Revolutsionnaya St., Yaroslavl 150000



N. N. Spirin
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation

5, Revolutsionnaya St., Yaroslavl 150000



D. S. Kasatkin
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation

5, Revolutsionnaya St., Yaroslavl 150000



D. V. Kiselev
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation

5, Revolutsionnaya St., Yaroslavl 150000



E. G. Shipova
Yaroslavl State Medical University, Ministry of Health of Russia
Russian Federation

5, Revolutsionnaya St., Yaroslavl 150000



References

1. Salazar AM, Gibbs CJ, Gajdusek DC. Viral and immune mechanisms of demyelination. Bull Soc Belge Ophtalmol. 1983 Nov;208 Pt 1:113-20.

2. Boyko AN, Bykova OV, Sivertseva SA. Rasseyannyy skleroz u detey i podrostkov: klinika, diagnostika, lecheniye [Multiple sclerosis in children and adolescents: clinical picture, diagnosis, treatment]. Moscow: Meditsinskoye informatsionnoye agentstvo; 2016. 408 p. (In Russ.).

3. McCoy L, Tsunoda I, Fujinami RS. Multiple sclerosis and virus induced immune responses: Autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity. 2006 Feb;39(1):9-19. doi: 10.1080/08916930500484799

4. Libbey JE, McCoy LL, Fujinami RS. Molecular mimicry in multiple sclerosis. Int Rev Neurobiol. 2007;79:127-47. doi: 10.1016/S0074774-2(07)79006-2

5. Zavalishin IA, Piradov MA, Boyko AN, et al. Autoimmunnyye zabolevaniya v nevrologii: Klinicheskoye rukovodstvo [Autoimmune diseases in neurology: Clinical guidelines]. Vol. 2. Moscow; 2014. 192 p. (In Russ.).

6. Alari-Pahissa E, Moreira A, Zabalza A, et al. Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the «hygiene hypothesis»? Eur J Neurol. 2018 Jul;25(7):925-33. doi: 10.1111/ene.13622. Epub 2018 Apr 15.

7. Alotaibi S. Epstein-Barr Virus in Pediatric Multiple Sclerosis. JAMA. 2004 Apr 21;291(15):1875-9. doi: 10.1001/jama.291.15.1875

8. Brettschneider J, Tumani H, Kiechle U, et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One. 2009 Nov 5;4(11):e7638. doi: 10.1371/journal.pone.0007638

9. Burgoon MP, Cohrs RJ, Bennett JL, et al. Varicella zoster virus is not a disease-relevant antigen in multiple sclerosis. Ann Neurol. 2009 Apr;65(4):474-9. doi: 10.1002/ana.21605

10. Megeryan VA. Kliniko-immunologicheskiye osobennosti bol'nykh s razlichnymi fenotipami rasseyannogo skleroza: Avtoref. dis. ... kand. med. nauk: 14.01.11 [Clinical and immunological features of patients with different phenotypes of multiple sclerosis: Author's abstract. dis. ... cand. med. sci.: 14.01.11]. Rostov-on-Don; 2018. 24 p. (In Russ.).

11. Zheleznikova GF, Skripchenko NV, Ivanova GP, et al. Gerpes viruses and multiple sclerosis. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2016;116(9):133-43. doi: 10.17116/jnevro201611691133-143 (In Russ.).

12. Lobzin SV, Golovkin VI, Semenova LA, et al. Associated multiple sclerosis. Vestnik SeveroZapadnogo gosudarstvennogo meditsinskogo universiteta im. I.I. Mechnikova. 2014;6(2):120-3 (In Russ.).

13. Popova EV, Boyko AN, Khachanova NV, Sharanova SN. Epstein-Barr virus in the pathogenesis of multiple sclerosis (a review). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2014;114(2-2):29-34 (In Russ.).

14. Kvistad S, Myhr KM, Holmoy T, et al. Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis. Mult Scler. 2014 Dec;20(14):1833-40. doi: 10.1177/1352458514533843. Epub 2014 May 19.

15. Pender MP, Csurhes PA, Lenarczyk A, et al. Decreased T cell reactivity to Epstein-Barr virus infected lymphoblastoid cell lines in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 May;80(5):498-505. doi: 10.1136/jnnp.2008.161018. Epub 2008 Nov 17.

16. Skripchenko EYu, Zheleznikova GF, Alekseeva LA, et al. Herpesviruses and biomarkers in disseminated encephalomyelitis and multiple sclerosis in children. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2021;121(3):138-45. doi: 10.17116/jnevro2021121031138 (In Russ.).

17. Najafi S, Ghane M, Poortahmasebi V, et al. Prevalence of herpes simplex virus infection in patients with relapsing-remitting multiple sclerosis: A case-control study in the North of Iran. Arch Clin Infect Dis. 2016;11(3):1-6.


Review

For citations:


Gris M.S., Baranova N.S., Spirin N.N., Kasatkin D.S., Kiselev D.V., Shipova E.G. Clinical presentation and course of multiple sclerosis in patients with herpesvirus infection. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(1S):21-26. (In Russ.) https://doi.org/10.14412/2074-2711-2021-1S-21-26

Views: 145


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)