Identyfikacja wirusa HSV-7 w płynie mózgowo-rdzeniowym u pacjenta z rzutowo-remisyjną postacią stwardnienia rozsianego. Opis przypadku

Pavel Dyachenko1, Anatoly Dyachenko2, Olha Smiianova2, Victoria Kurhanskaya2, Ruslan Efremin2

1Center of Infectious Disorders of the Nervous System, si “l.v. gROMASHEVSKY iNSTITUTE OF EPIDEMIOLOGY AND INFECTION DISEASES OF nams of uKRAINE”, Kyiv, Ukraine

2SUMY STATE UNIVERSITY, SUMY, UKRAINE

Abstract

Introduction: In this study, we investigated the possible involvement of Human herpesvirus 7 in multiple sclerosis.

The aim: To contribute to clarifying the controversy on the association between Human Herpesviruses 7 (HHV-7) and multiple sclerosis (MS) studying patient with relapsing-remitting MS (RRMS).

Case study: Young female admitted to adult tertiary referral, infectious diseases hospital, Kyiv, Ukraine, with signs of a focal neurological deficit. Meningeal symptoms were not detected. The preadmission illness lasted some years. Clinical diagnosis was relapsing-remitting multiple sclerosis (RRMS). On admission, general condition was of moderate severity. She has a mild fever, confusion, speech and coordination disorders, dizziness, worsening of memory, inability to walk (inferior paraparesis). Focal lesions were detected on MRI scan. The spinal fluid contained oligoclonal IgG-chains and HHV-7 DNA. After two weeks of intensive antiviral treatment, the patient’s condition improved significantly, the function of the lower limbs recovered almost completely, and she was discharged home.

Conclusion: Here we present a comprehensive clinical, radiological and virological analysis of the HHV-7-associated case of multiple sclerosis.

Wiad Lek 2018, 71, 8, -1638

Introduction

Multiple sclerosis (MS) is an important heterogeneous demyelinating disease of the central nervous system (CNS), which is based on an autoimmune conflict in genetically susceptible individuals. The viruses are thought to take play an important role in the disease pathogenesis. Several members of the Herpesviridae family to be implicated as a possible trigger for MS. By that time Epstein-Barr virus (EBV) and Human herpesvirus 6 (HHV-6) are likely candidates [1-3]. There is little evidence supporting the correlation of others herpesviruses with MS. Here we present the HHV-7-associated case of multiple sclerosis (MS).

CASE PRESENTATION AND DISCUSSION

A 33-years-old woman presented to the Center of Infectious Disorders of the Nervous System (CIDNS, Kyiv, Ukraine) in December 2017 with complaints of severe weakness, headaches, mild fever, confusion, speech and coordination disorders, dizziness, worsening of memory, difficulty in walking, decreased the ability to work. She has been ill for a long time, repeatedly turned to neurologists, including the Center of multiple sclerosis, where antibodies (Abs) to Borrelia burgdorferi (B. burg.) were detected and a suggested diagnosis of MS was made.

On admission, general condition was of moderate severity. Axillary temperature was 37.80C. The patient was normotensive with pulse beats of 70 per minute. Her physical examination showed slow mentation along with generalized slowing of her responses to verbal commands and also generalized weakness. She was emotionally labile, good contact, well oriented, and answered the questions adequately. There was tremor in her hands during a complicated Barre-probe. Stryumpel, Sharapov-Raskolnikov, Chaddok, Pussep, Barre, and Babinsky symptoms were positive on one or both sides. Inferior paraparesis was observed with more pronounced in the left leg. Muscular strength on the left leg was zero point, on the right one – 1 point (on five-point scale). Meningeal symptoms were not detected. She performed the coordination tests with intent, staggering in the Romberg pose. General blood test showed no significant changes. MR imaging brain in T2W and FLAIR mode showed mild focal hyperintense lesions in the periventricular region of the temporal lobes which had clear contours (Fig. 1). A lumbar puncture was performed just on admission. Increased level of IgG (8.84 mg/dl), and QIgG ratio (CSF/serum, 6.83) were revealed in the sample. A lot of oligoclonal IgG-chains were found by isoelectrofocusing of liquor proteins. The CSF was reported to be positive for HHV-7 DNA (2272 copies per ml). Microflora, DNA and Abs to others HVs, JC-virus, M. tuberculosis, T. gondii were not found. IgM-antibodies to B. burg. were detected in the blood by ELISA. However, specific bacterial proteins were not found with immunoblotting. So, Lyme disease wasn`t confirmed.

She was treated with Ganciclovir sodium, 500 mg intravenous per day for 2 weeks, intravenous normal human immunoglobulin 5 g per day for 5 days, and managed supportively with ademetionine, 400 mg, and citicoline, 1000 mg both intravenous daily, alpha-lipoic acid 600 mg intravenous per day for 2 weeks, shown pleocytosis of 1 cell/µl (100% lymphocytes) and, the level of protein and glucose was 0.16 g/L and 3.1 mmol/L respectively. Control CSF analysis for HHV-7 DNA made after three weeks of treatment was negative. The patients’ condition improved greatly, the legs’ strength increased significantly (right to 4, left to 3-3.5 points), and she was discharged home for further out-clinic care and rehabilitation.

There are many observations that point to a viral aetiology in MS. Several hypotheses suggest that some viruses can act as the triggers for MS [4]. Some viruses, including the herpesviruses, after primary infection, persist in the host’s body for life with periodic latency and reactivation that resemble the relapsing-remitting MS pattern [5]. Latency provides the transcription of restricted patterns of viral proteins without viral replication or chronic low-level replication. Body cells are able to control the life cycle of herpesviruses in different ways. Monocytes and bone marrow cells can suppress viral replication while in the brain and salivary gland cells chronic viral replication is observed, albeit at a low level. The Epstein-Barr virus was a first and most real candidate as a possible trigger for MS [1-3]. Recently, much attention has been given to the role of Human herpesvirus 6 (HHV-6) in MS induction and progression, but there are only a few studies regarding the significance of HHV-7 in the etiopathogenesis of MS. HHV-6 and HHV- 7 are closely related viruses having very similar biological patterns. Both viruses can infect immunocytes and thus modulate their function [6,7]. During persistency low-level expression of viral proteins (chronic infection) sometimes occurs. Viral proteins are represented in the membrane of latently infected cells, which makes these cells a target for cytotoxic T-lymphocytes (CTL). As a result, CTL begins to destroy these cells as foreign. Since the viral protein expressed on the cell membrane and myelin basic protein (MBP) have a common short-term amino acid motif, the cells expressing MBP also become a target for CTL, which ultimately leads to the development of MS [8].

Several immunological and molecular studies have supported a relationship between HHV-6 and MS [8-10]. Moreover, the associations between HHV-6 reactivation and MS disease activity have been observed, suggesting that HHV- 6 reactivation is implicated in the exacerbation of MS [10,11]. Attempts to investigate whether there be the association between HHV-7 with MS were much less. Nora-Krukle et al. [10] found HHV-7 in the blood of 10 patients with RR-MS and 14 with the SP-MS. Ben et al. studied the prevalence of all Human herpesviruses in whole blood samples collected from 51 MS patients and from 51 healthy donors. In MS patients, HHV-7 DNA was detected in 33.3% of samples, compared with 9.8% of control samples [12]. However, in most published works, the relationship between HHV-7 and MS is denied [13-16].

We, therefore, conclude that there is little evidence to make a final decision about the involvement of HHV-7 in MS, and present our case study.

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Authors’ contributions:

According to the order of the Authorship.

Conflict of interest:

The Authors declare no conflict of interest.

CORRESPONDING AUTHOR

Olha Smiianova

Sumy State University

1 Sanatorna Str., 40018, Sumy, Ukraine

tel: +380507713008

e-mail: vladlor60@ukr.net

Received: 05.08.2018

Accepted: 19.10.2018

Figure 1. Foci of the brain demyelination on MR imaging two weeks before admission.