Contributions
Abstract: P772
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Environmental factors
Background: Multiple Sclerosis (MS) is a multi-factorial disease, probably arising from interactions between genetic predisposition and environmental exposures. Among the latter, human herpes viruses, in particular Epstein-Barr-Virus (EBV) and Human-Herpesvirus-6 (HHV-6) type-A, have been repeatedly associated with MS. However, their causative role remains unproven. HHV-6 can be integrated into the host germ-line genome (ciHHV-6). An increased frequency of integration events in MS compared to the general population would be suggestive of a causative role. Surprisingly, this possibility has never been investigated so far.
Case reports: We report five immuno-competent patients who developed a demyelinating disease suggestive of MS. Four of them presented a relapsing-remitting (r-r) course and one had a primary progressive MS. The disease started at different ages in these patients and cerebrospinal fluid (CSF) analysis at the onset revealed high copies of HHV-6 by real-Time PCR, suggesting a CNS viral infection. Brain-MRI showed multiple T2-hyperintense lesions, some of them gadolinium-enhancing. Spinal-cord was involved in four cases. Oligoclonal Bands (OB) were positive in the CSF of all patients. Isoelectrofocousing (IEF) showed pattern 3 in three subjects and pattern 2 in the others. Two of the patients were treated with iv antiviral with any improvement. High levels of HHV-6 DNA were found in whole blood, peripheral blood mononuclear cells and plasma samples. HHV-6 DNA determination in hair follicles confirmed ciHHV-6 in all patients. Acute disease was treated with iv steroids and four patients started immunomodulatory therapy with good response, to date.
Discussion: These findings reinforce the rationale for studies aimed at verifying the frequency of HHV6 chromosomal integration in MS. Studies are underway in series that include familial cases and subjects with aggressive disease
Disclosure:
- M.T. Ferrò: no disclosures
- P. Grossi:no disclosures
- A. Prelle: no disclosures
- R. Mechelli: no disclosures
- R. Renié: no disclosures
- M. Salvetti:has received research support and speaker honoraria from Biogen, Merck, Novartis, Roche, Sanofi, Teva.
Abstract: P772
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Environmental factors
Background: Multiple Sclerosis (MS) is a multi-factorial disease, probably arising from interactions between genetic predisposition and environmental exposures. Among the latter, human herpes viruses, in particular Epstein-Barr-Virus (EBV) and Human-Herpesvirus-6 (HHV-6) type-A, have been repeatedly associated with MS. However, their causative role remains unproven. HHV-6 can be integrated into the host germ-line genome (ciHHV-6). An increased frequency of integration events in MS compared to the general population would be suggestive of a causative role. Surprisingly, this possibility has never been investigated so far.
Case reports: We report five immuno-competent patients who developed a demyelinating disease suggestive of MS. Four of them presented a relapsing-remitting (r-r) course and one had a primary progressive MS. The disease started at different ages in these patients and cerebrospinal fluid (CSF) analysis at the onset revealed high copies of HHV-6 by real-Time PCR, suggesting a CNS viral infection. Brain-MRI showed multiple T2-hyperintense lesions, some of them gadolinium-enhancing. Spinal-cord was involved in four cases. Oligoclonal Bands (OB) were positive in the CSF of all patients. Isoelectrofocousing (IEF) showed pattern 3 in three subjects and pattern 2 in the others. Two of the patients were treated with iv antiviral with any improvement. High levels of HHV-6 DNA were found in whole blood, peripheral blood mononuclear cells and plasma samples. HHV-6 DNA determination in hair follicles confirmed ciHHV-6 in all patients. Acute disease was treated with iv steroids and four patients started immunomodulatory therapy with good response, to date.
Discussion: These findings reinforce the rationale for studies aimed at verifying the frequency of HHV6 chromosomal integration in MS. Studies are underway in series that include familial cases and subjects with aggressive disease
Disclosure:
- M.T. Ferrò: no disclosures
- P. Grossi:no disclosures
- A. Prelle: no disclosures
- R. Mechelli: no disclosures
- R. Renié: no disclosures
- M. Salvetti:has received research support and speaker honoraria from Biogen, Merck, Novartis, Roche, Sanofi, Teva.