Submitted to the 54th Annual Meeting of the American Academy of Neurology
November 15, 2001
Active Human Herpesvirus Six Infections And Multiple Sclerosis: Clinical
And Treatment Relationships.
K.K. Knox¹, L.J. Lobeck², E.F. Maas² And D.R. Carrigan¹.
Institute for Viral Pathogenesis¹, Milwaukee
Wisconsin and Department of Neurology, Medical College of Wisconsin².
Objective: The goal of these studies was to assess multiple sclerosis
(MS) patients for evidence of active human herpesvirus six (HHV-6) infections
and to correlate those findings with the clinical and therapy status of the
Background: Several laboratories have presented data linking the pathogenesis
of MS to active HHV-6 infections. Different diagnostic technologies have been
used in these studies including immunohistochemical staining of tissues, polymerase
chain reaction analysis of serum samples and isolation of the virus from blood
samples. The majority of the work from our laboratory has involved staining
of MS patient derived CNS and lymphoid tissues for HHV-6 antigens and isolation
of the virus from peripheral blood leukocytes of MS patients by a rapid culture
procedure (Knox et al.; Clin Infect Dis 2000; 31:894-903). In the studies described
here we have used an alternate methodology, i.e. serum PCR, to address this
issue. Methods: Blood samples were obtained at the time of new clinical relapse
in patients with relapsing-remitting MS and assessed for active HHV-6 infection
by serum PCR. Then, several weeks later (mean interval:68 days), a second blood
sample was obtained from the same patients and assessed for active HHV-6 infection.
Patients' changes of Expanded Disability Status Scale (EDSS) from the relapse
and treatments at the time samples were obtained were noted. Results: 5 of 39
(13%) patients had at least one sample positive for active HHV-6 infection with
viral loads varying from 9 X 103 to 5 X 105 viral genomes per ml of serum. Variant
typing of the positive samples was possible with 3 of the 5 positives, and 2
were HHV-6 variant A. Four of the five (80%) positive samples were obtained
at the time of relapse whereas only one (20%) positive was observed in a patient
after relapse. The HHV-6 positive patients suffered a larger change in their
EDSS (mean EDSS change of 1.4) than the HHV-6 negative patients (mean EDSS change
of 0.7). It was also found that the patients receiving either beta interferon
or glatirimar acetate (copaxone) were less likely to be HHV-6 positive (2/30;
7%) than the patients receiving no treatment 3/9; 33%). Since the majority (>75%)
of the patients on therapy were receiving beta interferon, the decreased positivity
for active HHV-6 may reflect the known antiviral properties of beta interferon.
Conclusions: The findings presented here demonstrate that active HHV-6
infections can frequently be detected at the time of clinical relapse in patients
with relapsing- remitting MS and confirm the work of other laboratories that
have used serum PCR to detect such infections. Also, we observed that patients
with active HHV-6 infections at the time of relapse show a greater degree of
residual disability than HHV-6 negative patients and that patients who are receiving
beta interferon or glatirimar acetate therapies are at reduced risk for the
occurrence of detectable active HHV-6 infections.