JAMA neurology
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Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined. ⋯ Longitudinal CSF biomarker patterns consistent with AD are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline. Such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline.
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Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and therapeutic trials in MS. ⋯ This study provides in vivo evidence that CLs are associated with cognitive and physical disability in MS and that leukocortical and subpial lesion subtypes have differing clinical relevance. Quantitative assessments of CL burden on high-field MRI may further our understanding of the development of disability and progression in MS and lead to more effective treatments.
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Necrotizing autoimmune myopathy (NAM) is characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Data are limited concerning differences among etiologic subgroups and treatment outcomes in NAM. ⋯ Necrotizing autoimmune myopathy was idiopathic in half of this cohort with clinical and histopathologically defined disease. In the remainder, NAM was associated with statin medication, cancer, or connective tissue disease. One in 4 patients was SRP-IgG positive, and 1 in 3 was HMGCR-IgG positive. The disease was usually not controlled by corticosteroid monotherapy. Presentation, course, and outcomes did not differ significantly in seropositive, seronegative, and statin-associated cases. Early aggressive immunosuppressant therapy improved outcomes, and risk of relapse was high during medication dose reduction or withdrawal.