Herpes encephalitis during natalizumab treatment in multiple sclerosis

Abstract

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

“…Although there are a number of case reports suggesting overrepresentation of symptomatic HSV and VZV infections in natalizumab-treated MS patients, [15][16][17][18][19][20][21] valid data on the incidence of symptomatic HSV or VZV reactivation in MS patients with and without natalizumab treatment are not available; therefore, it is presently not possible to link the increased incidence of significant rises of anti-VZV IgG levels with an increased risk of symptomatic VZV reactivation or reinfection. At least for four of the six patients, the rise of anti-VZV IgG levels was not accompanied by herpes zoster nor other clinical symptoms of VZV disease, indicating subclinical reactivation or reinfection in these cases.…”

“…13 Furthermore, a growing number of case reports are suggestive of an increase in the risk of HSV and VZV infections in MS patients undergoing treatment with fingolimod 14 and natalizumab. [15][16][17][18][19][20][21] A study on functional T-cell analyses in patients treated with fingolimod also shows a slightly reduced antiviral T-cell response with respect to herpes viruses, occasionally accompanied by subclinical reactivation of VZV or Epstein-Barr virus (EBV) in the saliva. 22 Nevertheless, larger studies defining susceptibility to neurotropic herpesvirus infections in differently treated MS patients, in comparison to healthy people, are missing.…”

Infection Risk in Patients on Multiple Sclerosis Therapeutics

“…A review of some 20 cases of such herpes and/or varicella cases associated with natalizumab use was published in 2013 [84]. The authors searched the US FDA Adverse Event Reporting System (FAERS) and MEDLINE to identify infections that were laboratory confirmed by PCR of the CSF for herpes simplex virus or varicella zoster virus, noting reports of varicella zoster virus myelitis [85][86][87], herpes simplex encephalitis [88], herpes simplex virus meningitis [89], and zoster [90]. Of the 20 patients, seven received prior immunosuppressives, seven did not receive immunosuppressives, and data were missing for the remaining six patients.…”

Comorbid autoimmune pathology in patients treated with disease modifying drugs

“…Рассматриваемые в этой части обзора препараты не сами вызывают аутоиммунных реакций, но на фоне их применения возможны тяжелые осложне-ния другого рода -развитие оппортунистических инфекций, ярким примером которых являются про-грессирующая лейкоэнцефалопатия и онкопатоло-гия [56][57][58].…”