Lancet neurology
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Multiple system atrophy is an adult-onset, sporadic, and progressive neurodegenerative disease. People with this disorder report a wide range of motor and non-motor symptoms. Overlap in the clinical presentation of multiple system atrophy with other movement disorders (eg, Parkinson's disease and progressive supranuclear palsy) is a concern for accurate and timely diagnosis. ⋯ Diagnostic criteria were revised in 2022 with the intention to improve the accuracy of a diagnosis of multiple system atrophy, particularly for early disease stages. Early signals of efficacy in clinical trials have indicated the potential for disease-modifying therapies for multiple system atrophy, although no trial has yet provided unequivocal evidence of neuroprotection in this rare disease. The advances in pathophysiology could play a part in biomarker discovery for early diagnosis as well as in the development of disease-modifying therapies.
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The ability to mount an interferon-mediated innate immune response is essential in protection against neurotropic viruses, but antiviral type I interferons also have neurotoxic potential. The production of type I interferons can be triggered by self-derived nucleic acids, and the brain can be susceptible to inappropriate upregulation of type I interferon signalling. ⋯ Recent developments include new insights into the pathogenesis of these disorders that involve dysregulated type I interferon signalling, as well as advances in their diagnosis and management. The role of type I interferons in brain cellular health suggests the future therapeutic potential of approaches that target these interferons and their signalling.
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The concept of frailty, now being adopted in most medical disciplines, is attracting growing interest in neurology. Every day, most neurologists care for patients with varying degrees of frailty, from very mild to very severe. Frailty exacerbates patients' health needs, complicates clinical decision making, and negatively affects their health outcomes. ⋯ Doing so can provide information that is crucial for diagnosis, prognostication, and care planning. Consideration of frailty can help to elucidate the pathophysiological underpinnings of age-related neurological disorders, clarify the clinical validity and utility of candidate biomarkers, and identify novel therapeutic targets. Randomised controlled trials investigating late-life neurological diseases that address frailty have the potential to provide insight into these complex disorders.
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Progressive cerebral volume loss on MRI is a hallmark of Alzheimer's disease and has been widely used as an outcome measure in clinical trials, with the prediction that disease-modifying treatments would slow loss. However, in trials of anti-amyloid immunotherapy, the participants who received treatment had excess volume loss. Explanations for this observation range from reduction of amyloid β plaque burden and related inflammatory changes through to treatment-induced toxicity. ⋯ Better understanding of the causes and consequences of these changes is important to enable informed decisions about treatments. Patient-level analyses of data from the trials are urgently needed, along with longitudinal follow-up and neuroimaging data, to determine the long-term trajectory of these volume changes and their clinical correlates. Post-mortem examination of cerebral tissue from treated patients and evaluation of potential correlation with antemortem neuroimaging findings are key priorities.
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The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. ⋯ Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe.