Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis.

BACKGROUND AND PURPOSE: Infections with human herpesvirus 6A (HHV-6A) and Epstein-Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS. METHODS: In this nested case-control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20-29 and 30-39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6-2.7). CONCLUSIONS: This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.

Multiple sclerosis and cognitive decline: is ApoE-4 a surrogate marker?

BACKGROUND - The role of the apolipoprotein E (ApoE) polymorphism has been well demonstrated in neurodegenerative disorders such as Alzheimer. However, its role in multiple sclerosis (MS) remains unclear. AIMS - The aims of our study were as follows: (i) to assess whether ApoE-4 might be a surrogate marker of cognitive decline in MS; (ii) to confirm the presence of cognitive impairment in mildly disabled patients treated with interferon-beta; and (iii) to analyse the correlation between cognitive disturbances and clinical variables. MATERIAL AND METHODS - Fifty relapsing-remitting MS patients underwent a battery of neuropsychological tests and were genotyped for ApoE. Their scores were compared with those of 35 controls. RESULTS - No association was found between ApoE-4 and cognitive impairment. Significant differences in most domains were observed between MS and the control group. Cognitive decline was not related to disability progression. CONCLUSION - No association between cognitive impairment and ApoE-4 or clinical markers was detected in our MS patients.

Anticipation of age at onset in multiple sclerosis: methodologic pitfalls.

BACKGROUND/AIM: There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time. METHODS: The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method. RESULTS: Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found. CONCLUSION: Anticipation of age at onset is undetectable when adjusted for follow-up time.

Interferón-beta y hepatitis autoinmune en la esclerosis múltiple: ¿causa-efecto o asociación? / No disponible

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Effect of glatiramer acetate (Copaxone) on the immunophenotypic and cytokine profile and BDNF production in multiple sclerosis: a longitudinal study.

We assessed the effect of glatiramer acetate (GA) on the immunophenotypic and cytokine profile and the BDNF production by peripheral blood mononuclear cells, and their association with the clinical response in 19 naïve-treated MS patients prospectively followed-up after GA therapy. Two patients withdrew the therapy. After a median follow-up of 21 months, twelve were considered responders and five as non-responders. Non-responder patients had significant longer disease duration and a higher EDSS score at baseline. In the responder group, a significant decrease in the percentage of INF-gamma producing total lymphocytes, CD4+ and CD8+ T cells, and reduced percentage of IL-2 producing CD4+ and CD8+ T cells were observed at 12, 18 and 24 months. These changes were associated with a significant increase in the percentage of CD3+, CD4+ and CD4(+) CD45RA(+) T cells, and BDNF production from month 6 that remained significant throughout the study. We did not observe significant changes in the nonresponder group for any of the parameters studied. Our data suggest that GA treatment induces a downmodulation of proinflammatory cytokines associated with the regulation of the peripheral T cell compartment and with increased production of BDNF that might be related to the clinical response.

[Opsoclonus-myoclonus syndrome in patient with ovarian cancer]. / Síndrome opsosclonus -mioclonus en paciente con cáncer de ovario.

The opsoclonus-myoclonus syndrome is a rare entity as a paraneoplastic disorder usually associated to neuroblastoma in children and breast cancer or oat-cell lung carcinoma in adults. The association of opsoclonus-myoclonus syndrome and ovarian carcinoma is very unusual, to our knowledge there is only two cases reported in the literature. In both of them the opsoclonus-myoclonus syndrome preceded the neoplasy, improving with its treatment. In our patient opsoclonus began after ovarian cancer diagnosis, after chemotherapy and radiotherapy, improving with corticoid and clonazepan therapy.

Síndrome opsoclonus-mioclonus en paciente con cáncer de ovario / Opsoclonus-myoclonus syndrome in patient with ovarian cancer

El síndrome opsoclonus-mioclonus (SOM) es un trastorno poco frecuente que ha sido descrito como manifestación paraneoplásica, fundamentalmente asociado al neuroblastoma en niños y a tumores de mama y pulmón en adultos. La asociación con cáncer de ovario es excepcional habiéndose descrito sólo dos casos en la literatura; en ambos el patrón clínico fue similar precediendo el SOM a la neoplasia y mejorando con el tratamiento de la misma. A diferencia de estos en el caso que presentamos, el SOM se manifestó posteriormente al diagnóstico de cáncer de ovario, después del tratamiento de quimioterapia y radioterapia, mejorando con corticoides y clonazepan (AU)

Posterior alien hand syndrome after a right thalamic infarct.

The alien hand syndrome, as originally defined, should be reserved for cases in which the hand feels foreign "together with" observable involuntary motor activity. These involuntary movements are unusual during or after acute stroke. Three varieties of alien hand syndrome have been reported, involving lesions of the corpus callosum alone, the corpus callosum plus dominant medial frontal cortex, and posterior cortical and subcortical areas. A patient with posterior alien hand syndrome of vascular aetiology is reported. Imaging studies disclosed an isolated infarction of the right thalamus sparing other cerebral regions.