Compared with multiple sclerosis (MS) in Caucasian Americans, African American patients with MS have a greater likelihood of developing opticospinal MS and transverse myelitis and have a more aggressive disease course.

The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing.

We conclude that the BRNB and MACFIMS have comparable sensitivity among patients with MS. The sensitivity of the auditory/verbal memory tests from these batteries is similar, but the BVMTR appears to be more sensitive than the 10/36. Clinical implications are discussed.

Background: Because common viruses are encountered during childhood, pediatric multiple scle-

Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing-remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.

Recent studies using murine animal model systems indicate that clinical progression of autoimmune disease may be due to the sequential accumulation of neoautoreactivity characterized by extensive plasticity of self recognition. In the present study, we addressed the question of whether a similar paradigm of self recognition is implicated in the development of multiple sclerosis (MS), a demyelinating disease with a presumed autoimmune etiology. Our approach was to determine serial changes over a 12-18-mo period in response to an epitope-mapping series of 265 12-mer peptides of myelin proteolipid protein (PLP) by patients with isolated monosymptomatic demyelinating syndromes (IMDS), a group of distinct clinical disorders with variable rates of progression to MS. Our data showed that an extensive array of proteolipid protein peptides could elicit autoreactivity. Moreover, differential autoreactive patterns were evident within IMDS patient subpopulations. Monocentric monophasic IMDS patients with no evidence of prior subclinical disease typically showed fully sustained autoreactivity characterized by extensive plasticity, epitope focusing, shifting, and spreading of responses to new self determinants. In contrast, multicentric monophasic IMDS patients with putative evidence of prior asymptomatic lesion formation typically showed partially sustained autoreactivity characterized by abrupt abrogation of responses to an extensive array of self determinants. No sustained autoreactivity was observed in normal control subjects or in patients with other neurologic diseases. Our results indicate that self recognition associated with the development of MS is a developmental process characterized by autoreactive diversity, plasticity, and instability.

The 6-tiered MSSS grading system is a powerful tool for comparing rate of disease progression in subpopulations of interest. MSSS-based analysis demonstrates that African ancestry is a risk factor for a more rapidly disabling disease course.

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