MS Disease Research Articles

Multiple sclerosis progression in a natural history study: predictive value of cerebrospinal fluid free kappa light chains.

To determine the relationship between baseline CSF immunologic abnormalities and MS disease progression; To determine progression rates in an untreated, recently-diagnosed MS sample using several validated clinical measures. CSF immune abnormalities are common in MS but have not been linked to disease progression. Thirty-six patients with definite (n = 28), probable (n = 2), or possible (n = 6) MS were studied prospectively. Baseline CSF was analyzed for free kappa and lambda light chains, myelin basic protein, IgG synthesis rate, and IgG index. MS patients were entered into the study within 5 years of symptom onset and examined semiannually for as long as 53.4 months (median length of follow up 38.9 months). MS progression was defined as sustained worsening on the following clinical measurement instruments: the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI), the 9 Hole Peg Test (9HT) and the Box and Blocks test (BBT). Kaplan-Meier estimates of disease progression were calculated and the relationship between baseline CSF values and disease progression was determined using Cox proportional hazards regression models. By 36 months, 33% (95% CI = 10.3, 55.7) of patients had progressed on EDSS and 49.7% (95% CI = 27.7, 71.7) had progressed on at least one of the outcome measures. Patients with CSF free kappa chain levels in the upper quartile had a significantly higher risk of progression on EDSS (Hazard Ratio 3.78; p = 0.04) and 9HT (Hazard Ratio 10.77, p = 0.04). In this study, CSF free kappa light chains predicted subsequent physical deterioration in prospectively evaluated MS patients. If this is confirmed by larger studies, then CSF free kappa light chains could serve as a target for intervention in therapeutic trials.

Immunoregulatory cells: Potential role in MS and other autoimmune disease

Immunoregulatory cells: Potential role in MS and other autoimmune disease

Immunoregulatory cells: Potential role in MS and other autoimmune disease

Immunoregulatory cells: Potential role in MS and other autoimmune disease

Multiple Sclerosis etiology — an Epstein-Barr virus hypothesis

The opinion has been expressed frequently in the literature that MS is caused by a combination of an environmental agent and genetic factors, possibly with an autoimmune component. However, the specific environmental agent has not as yet been identified. This paper describes cumulative circumstantial evidence which strongly points to a post-pubertal primary Epstein-Barr virus infection as this unidentified etiological event in the induction of MS disease.

Pediatric Cardiology for Practitioners

<h3>Background and Objectives:</h3> The timing of neurodegeneration in MS remains unclear. It is critical to understand the dynamics of neuroaxonal loss if we hope to prevent or forestall permanent disability in MS. We therefore used a deeply phenotyped longitudinal cohort to assess and compare rates of neurodegeneration in retina and brain throughout the MS disease course. <h3>Methods:</h3> We analyzed 597 MS patients who underwent longitudinal OCT imaging annually for 4.5±2.4 years and 432 patients who underwent longitudinal MRI scans for 10±3.4 yrs, quantifying macular ganglion-cell–inner plexiform layer (GCIPL) volume and cortical gray matter (CGM) volume. To evaluate the rate of loss, linear mixed-effects modeling with subject-specific intercepts and slopes were fitted using restricted maximum likelihood estimation. The association between the slope of decline in the anatomical structure and the age of entry in the cohort (categorized by the MRI cohort’s age quartiles) was assessed by linear regression models. <h3>Results:</h3> The rate of CGM volume loss declined with increasing age of study entry (1.3%/year atrophy for the age of entry in the cohort &lt;35 years; 1.1% for age &gt;35 years and &lt;41; 0.97% for age &gt;41 years and &lt;49; 0.9% for age &gt;49 years) while the rate of GCIPL thinning was highest in patients in the youngest quartile, fell by more than 50% in the following age quartile, and then stabilized (0.7%/year thinning for the age of entry in the cohort &lt;35 years; 0.29% for age &gt;35 years and &lt;41; 0.34% for age &gt;41 years and &lt;49; 0.33% for age &gt;49 years). <h3>Conclusions:</h3> An age-dependent reduction in retinal and cortical volume loss rates during RRMS suggests deceleration in neurodegeneration in the earlier period of disease and further indicates that the period of greatest adaptive-immune-mediated inflammatory activity is also the period with the greatest neuroaxonal loss.

SERUM ASSAY FOR CYTOPLASMIC CANDIDA ANTIGEN (CA) IN CHILDREN WITH SYSTEMIC (SC) OR MUCOSAL SURFACE (MS) CANDIDAL INFECTION

38 sera of 10 pts with Candida sp infection proven by culture of MS, body fluid/cavity, or IV catheter were tested for CA by quantitative immunofluorescence assay. SC was suspected in all pts. Each had ≥ 1 elevated CA level, (nl = 15 ± 10 ng/ml). 6 pts (Gp A) had SC (See Table). MS disease only occurred in 4 pts (Gp B); 3 had no SC at autopsy and 1 recovered without antifungal rx.In Gp A, Candida sp was not isolated from MS in 3 pts. All Gp B patients had MS colonized. The mean peak CA for each group was higher (p < .05) than nl. No difference was noted between mean peak CA Gp A (127 ± 76) and Gp B (131 ± 96). The data show MS colonization does not predict SC and that elevated CA occurs with both SC and MS disease.

Cellular immune response to measles, mumps, and vaccinia viruses in multiple sclerosis

The cell-mediated immune response to measles, mumps, and vaccinia viruses was studied in MS patients, normal controls, and neurological disease controls using a lymphocyte proliferation assay. A small but significant difference was found in the response to measles between the MS and normal control groups but not between the MS and neurological disease control groups. In each of the groups, the response of both peripheral blood leukocytes and purified T-cells to measles was significantly less than the response to mumps or vaccinia. The lower response to measles was not due to the presence of blocking factors or to lack of antigenicity of the measles virus preparation used in the assay. These findings suggest that differences exist in the normal immune response between these viruses. Precise quantitation of the immunological response to viruses in MS and other disease states will depend on identification of the various functionally reactive cell populations.