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

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.

Keywords

• multiple sclerosis
• herpesvirus infection
• virus-associated relapse
• immunomodulatory therapy
• disability