Optical coherence tomography in patients with a history of juvenile multiple sclerosis reveals early retinal damage.

BACKGROUND AND PURPOSE: Some 3%-10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years ('early' onset MS, EOMS). Optical coherence tomography is a non-invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age- or disease-duration-matched later onset MS (LOMS) and healthy controls (HCs). METHODS: In this observational cross-sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral-domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients. RESULTS: In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease-duration-matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients. CONCLUSIONS: These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS.

Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions.

T cells with a CD4(+) CD8(+) double-positive (DP) phenotype are present in small numbers in the peripheral blood of healthy humans and may have anti-viral capacities. Here we investigate numbers and function of DP T cells in patients with relapsing-remitting multiple sclerosis (MS), either treatment-naive or under therapy with natalizumab. Flow cytometry analysis revealed that frequencies of circulating DP T cells in treatment-naive and natalizumab-treated MS patients are comparable to healthy controls. These cells have a memory phenotype with cytotoxic potential, express high levels of CD49d and are similarly functional in treatment-naive as well as natalizumab-treated MS patients. DP T cells were enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS lesions. In conclusion, DP T cells are functional in MS and may play a role in the immune surveillance of the central nervous system, but do not display functional impairment under natalizumab therapy.

Aquaporin-4 antibody negative recurrent isolated optic neuritis: clinical evidence for disease heterogeneity.

Recurrent optic neuritis is frequently observed in multiple sclerosis (MS) and is a typical finding in neuromyelitis optica (NMO). Patients that lack further evidence of demyelinating disease are diagnosed with RION (recurrent isolated optic neuritis) or CRION (chronic relapsing inflammatory neuropathy) if they require immunosuppressive therapy to prevent further relapses. The etiology and disease course of this rare condition are not well defined. We studied a series of 10 patients who presented with recurrent episodes of isolated optic neuritis (ON, n=57) and were followed over a median of 3.5 years. Visual acuity was severely reduced at the nadir of the disease (20/200 to 20/800). All patients had MRI non-diagnostic for MS/NMO and were aquaporin-4 antibody negative. Six patients fulfilled the CRION criteria. In two of these a single ON followed by a long disease-free interval preceded development of CRION for years, suggesting the conversion of an initially "benign" isolated ON into the chronic relapsing course. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis in 5 patients, identical oligoclonal bands in serum and CSF were observed in 2 patients, while the others remained negative. In conclusion, recurrent ON is a disease entity that requires aggressive glucocorticoid and eventually long-term immunosuppressive therapy to prevent substantial visual impairment.

Physical activity in multiple sclerosis: a comparative study of vitamin D, brain-derived neurotrophic factor and regulatory T cell populations.

BACKGROUND: Previous studies suggest beneficial effects of exercise in multiple sclerosis (MS). However, knowledge on the effects of physical activity on the immune system is limited. OBJECTIVE: To assess potential relationships between cardiorespiratory fitness, cognitive function, and immune parameters in physically active and inactive MS patients. METHODS: We identified 83 patients with relapsing-remitting disease, an unrestricted walking range, and stable interferon-ß treatment from our data base. Based on the subjective report of physical activity, the lower/inactive (n = 21) and upper/active quartiles (n = 21) of patients were selected. We assessed the frequency of T cells, B cells, NK cells, monocytes and regulatory T cell populations by flow cytometry, measured brain-derived neurotrophic factor and vitamin D serum levels by ELISA, and conducted spiroergometry and transcranial sonography. RESULTS: Physical activity and cardiorespiratory fitness were not associated with brain-derived neurotrophic factor, frequency of T regulatory cells or any other immune cell subpopulation. However, we found a positive correlation of vitamin D serum levels with cardiorespiratory fitness. CONCLUSION: Overall, we found no negative effect of physical activity on the immune system. The association between vitamin D and cardiorespiratory fitness most likely reflects longer hours of sunlight exposure in active patients, suggesting a desirable 'side- effect' of physical activity.

Multiple sclerosis relapses are not associated with exercise.

Since multiple sclerosis (MS) often affects physically active young individuals, it is important to know if exercise can result in increased disease activity. Therefore we used a self-report questionnaire to examine the relationship of different levels of sports activity and relapses in 632 patients with MS. In order to analyse whether subjective recall might have biased the results, we performed, in a subgroup of our sample, an objective assessment of clinical data and physical fitness parameters. We were unable to find any association between sports activity and clinical relapses in either of the two analyses. The group with highest activity even shows the lowermost mean values, standard deviations and range concerning the number of relapses. Our data suggest that physical activity has no significant influence on clinical disease activity.

[Multiple sclerosis and exercise : effects of physical activity on the immune system]. / Multiple Sklerose und Sport : Auswirkungen körperlicher Aktivität auf das Immunsystem.

Multiple sclerosis is a chronic inflammatory CNS disease which accounts for functional impairment and lasting disability in young adults. Current studies demonstrate that physical activity in patients with MS counteracts depression and fatigue and may improve quality of life. Interventional studies have described a reduction of the functional impairment in MS patients. This report presents information on the effects of physical activity on the immune system and the release of neurotrophic factors, and highlights current data on a potential immunomodulatory effect of exercise in multiple sclerosis.