Shalini Bansil

Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis.

Objective ‐ To determine if sex hormones play a role in the pathogenesis of multiple sclerosis (MS) by correlating serum estradiol and progesterone levels with gadolinium (Gd) enhancing lesions on magnetic resonance imaging (MRI) in MS.

Serum soluble interleukin-2 receptor levels in chronic progressive, stable and steroid-treated multiple sclerosis

ABSTRACT Serum levels of the soluble interleukin‐2 receptor (sIL‐2R), an indicator of T cell activation, were significantly elevated in chronic progressive MS (CPMS) patients, clinically stable MS patients and in patients with other neurological diseases (OND) as compared to healthy controls. Levels of sIL‐2R in steroid treated CPMS patients were markedly lower than in untreated CPMS patients and were comparable to healthy controls. Thus, systemic T cell activation occurs in MS during clinically stable and progressive disease stages and in other neurological disorders. The ability of oral corticosteroids to depress serum sIL‐2R levels in vivo may be one mechanism by which they exert their therapeutic effect.

Serum sAPO-1/Fas levels in multiple sclerosis

Soluble APO‐1 (sAPO‐1) may prevent apoptosis of lymphocytes induced by activation of the APO‐1/Fas receptor. Objectives – To determine sAPO‐1 levels in the serum of multiple sclerosis (MS) patients and controls in order to investigate if abnormal lymphocyte apoptosis occurs in this disease. Methods – Serum samples from patients with MS, other neurological diseases, systemic lupus erythematosus and healthy controls were determined by enzyme‐linked immunosorbent assay. Results – We did not detect differences in mean serum sAPO‐1 levels between patients with multiple sclerosis and controls. Conclusions – This preliminary study suggests that resistance of peripheral blood lymphocytes to apoptosis mediated by sAPO‐1 is not likely to be a major factor in the development of autoreactive cells in MS.

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases

Decreased numbers of CD4+CD45R+ suppressor-inducer T cells have been reported in patients with a variety of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis but not in patients with other neurological diseases. We now report our findings using murine monoclonal antibodies and two-color flow cytometric analysis on CD4+CD45R+ T cells in 22 patients with chronic progressive multiple sclerosis, 23 patients with other neurological diseases and 42 normal, healthy controls. Suppressor-inducer T cells were significantly reduced (p less than 0.001) in both patients with multiple sclerosis and other neurological diseases as compared to controls. Both patient populations had elevated helper T cell subset ratios. Thus, our data suggests that decreases in suppressor-inducer T cells may represent a common immunological defect among autoimmune and presumably non-autoimmune neurological disorders.

Combination total lymphoid irradiation and low‐dose corticosteroid therapy for progressive multiple sclerosis

Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. Methods— In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double‐blind study of patients with progressive multiple sclerosis. Results— Twenty‐seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post‐therapy than those receiving TLI only or sham TLI and Kaplan Meier product‐limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow‐up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. Conclusion— These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low‐dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated.

Measles Vaccination Does Not Prevent Multiple Sclerosis

Twenty-seven young patients with multiple sclerosis (MS) were studied to determine if they had received prior measles vaccination. Fourteen patients whose immunization records were available had received measles vaccine in childhood. Eight other patients gave a history of receiving measles vaccine. These results suggest that infection by measles virus is probably not the sole cause of MS and that, unlike subacute sclerosing panencephalitis and postmeasles encephalitis, MS may not be preventable by measles vaccination given at an appropriate age.

Advances in the Pharmacological and Neurological Treatment of Patients with Multiple Sclerosis

Multiple sclerosis (MS) is an acquired inflammatory demyelinating disease of the central nervous system (CNS) believed to be of autoimmune pathogenesis. Progressive MS is a common cause of disability in young adults in the United States. Although several immunomodulating therapies have been tested in clinical and animal studies, there is no known treatment that prevents further progression and disability. Current research efforts are being focused on the development of novel, safe immunospecific treatments. Until such therapies become available, a major component of patient management should be to relieve symptoms, prevent complications, and maximize function in activities of daily living. A team approach involving health care professionals of various specialties is ideal for the management of patients with progressive MS.