Varicella zoster virus in progressive forms of multiple sclerosis

Objective

The apparent association between varicella zoster virus (VZV) and multiple sclerosis (MS) has been described. In patients with relapse/remission (R/R) MS we have found high loads of VZV DNA in lymphocytes and in cerebrospinal fluid (CSF), as well as abundant viral particles in CSF visualized by electron microscopy at the time of relapse. Both, the molecular and the ultrastructural evidence of VZV became negative in the same patients at the time of remission.

Methods

In the present study we analyzed the presence of VZV in patients with progressive forms of MS; DNA from VZV was searched by real-time PCR in blood lymphocytes and in CSF of 20 patients with progressive MS. Ultrastructural study searching for viral particles in CSF was made with transmission electron microscopy.

Results

VZV DNA was found in the CSF from 65% of cases with progressive MS- and VZV-like viral particles were found in 30% of these patients. Nonetheless, the amount of DNA and the number of viral particles were lower than those that have been found in MS patients with R/R at the time of relapse, but higher than those found during remission.

Conclusion

Similar to findings in patients with R/R MS, VZV might be associated to progressive MS, but in minor quantity. In these cases, the virus may produce a chronic, relentless infection or trigger a process of immune-mediated demyelination.     

Anti‐EBNA‐1 IgG is not a reliable marker of multiple sclerosis clinical disease activity

Background: Sero‐epidemiological studies have demonstrated the association between multiple sclerosis (MS) and prior Epstein–Barr virus (EBV) infection. It has been hypothesized that intermittent peripheral EBV reactivation may drive continuing central inflammation. Recent investigation has shown significant differences in median serum levels of anti‐EBV nuclear antigen‐1 (EBNA‐1) IgG between disease subgroups and positive correlation with disease activity reflected by number of Gd‐enhancing lesions and T2 lesion volume. These important data have led to hopes that anti‐EBNA‐1 IgG may be useful as an easily accessible and effective biomarker of disease activity. Methods: We examined the applicability of these findings in routine clinical practice, assessing a well‐characterized cohort of 100 subjects (25 primary progressive, 25 stable relapsing remitting, 25 active relapsing remitting seen in acute relapse and 25 controls) for serum anti‐EBNA‐1 IgG using both the Liaison quantitative chemiluminescent assay and Biotest ELISA. Results: We were unable to show a difference in quantitative analysis of serum anti‐EBNA‐1 IgG levels between disease subgroups and no correlation with phenotypic characteristics including age at onset (r = ?0.17, P = 0.16), disease duration (r = 0.03, P = 0.78), EDSS (r = 0.03, P = 0.78) or MSSS (r = 0.02, P = 0.9). In addition, there was only moderate correlation between the two test methods used (intraclass correlation coefficient 0.67; 0.56–0.78) suggesting potential problems with test interpretation. Conclusions: We have been unable to determine a clinical value for serum anti‐EBNA‐1 IgG levels in MS or to confirm reported association with disease course and clinical disease activity.     

Varicella zoster virus infection in neurological patients in Bulgaria

Journal of NeuroVirology - The clinical manifestations of neurological complications associated with varicella zoster virus (VZV) are non-specific and indistinguishable from those of other viral...     

Cortical atrophy is relevant in multiple sclerosis at clinical onset

Introduction Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated. Methods 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed. Results We found a significant global cortical thinning in p-MS (2.22 ± 0.09 mm), RR-MS (2.16 ± 0.10 mm) and SP-MS (1.98 ± 0.11 mm) compared to CIS (2.51 ± 0.11 mm) and HV (2.48 ± 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = −0.393, p = 0.03) and absent in p-MS (r = −0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas. Discussion Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. Received in revised from: 8 August 2006     

Epstein–Barr virus neutralizing and early antigen antibodies in multiple sclerosis

Background: Our objective was to determine whether antibodies against the Epstein–Barr virus (EBV) nuclear antigen‐1 (EBNA‐1), early antigen (EA), and EBV neutralizing antibodies (NeutAb) are altered in multiple sclerosis (MS). Methods: We measured EBNA‐1 IgG, EA IgG, and EA IgA using quantitative ELISA. We measured NeutAb using a quantitative competitive ELISA. We studied 80 patients with MS, 80 matched controls, and 19 patients with MS with samples collected both whilst stable and in relapse. Results: Epstein–Barr virus nuclear antigen‐1 IgG and EA IgA were increased in MS compared to controls. The EBNA‐1 index value was 23.3 ± 18.3 in the patients with MS (mean ± SD) and 16.3 ± 17.4 in the controls (P = 0.007, paired t‐test). EA IgA had a median value of 1.964 in the patients with MS and 1.248 in the controls (P = 0.029, Wilcoxon signed rank test). EA IgG and NeutAb were not significantly different. None of the antibody levels were altered in relapse. The correlation between concentrations of different antibodies was minimal. Conclusions: IgG antibodies to EBNA‐1 are significantly increased in MS. IgA antibodies against EBV EA are also increased. The EBV neutralizing antibody response is similar in MS and controls.     

Varicella zoster virus encephalitis in a patient with a solid carcinoma: a case report

Journal of Neurology -     

Varicella zoster virus (VZV) oculomeningoencephalomyeloradiculitis: a previously undescribed constellation

Journal of NeuroVirology - A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO,...     

Fatigue in multiple sclerosis is not due to sleep apnoea

Fatigue is a frequent and disabling phenomenon among patients with multiple sclerosis (MS). Daytime sleepiness is a typical symptom of the sleep apnoea/hypopnoea syndrome due to nocturnal hypoxia and recurrent arousals causing sleep fragmentation. Since MS plaques are often found in the midbrain, brain stem and upper cervical cord on magnetic resonance imaging (MRI) we hypothesized that fatigue in MS patients might be caused by a central respiratory dysfunction. We investigated 10 patients with definite MS by oligography, two questionnaires assessing fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth Sleepiness Scale, ESS), MRI and pulmonary function tests. A total of six patients had either an elevated FSS and/or an elevated ESS. None of the six patients with an elevated FSS and/or ESS has an apnoea index > 5/hour. CT₉₀ was normal in nine patients. We conclude that fatigue and daytime sleepiness in MS cannot be explained by nocturnal apnoeas or oxygen desaturations. The Fatigue Severity Scale should be integrated to the extended Barthel index, which is a new instrument for disability assessment in MS patients.     

Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis

Cannabinoids may exhibit symptom control in multiple sclerosis (MS). We show here that cannabinoid receptor (CBR) agonists can also be immunosuppressive and neuroprotective in models of MS. Immunosuppression was associated with reduced: myelin-specific T cell responses; central nervous system infiltration and reduced clinical disease. This was found to be largely CB(1)R-dependent and only occurred at doses that induced significant cannabimimetic effects that would not be achieved clinically. Lower, non-immunosuppressive doses of cannabinoids however, slowed the accumulation of nerve loss and disability, despite failing to inhibit relapses. This further highlights the neuroprotective potential of cannabinoids to slow the progression of MS.