Lancet neurology
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Parkinson's disease is characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the cause of the neuronal loss in Parkinson's disease is poorly understood. Neuroinflammatory mechanisms might contribute to the cascade of events leading to neuronal degeneration. ⋯ Overall, available data support the importance of non-cell-autonomous pathological mechanisms in Parkinson's disease, which are mostly mediated by activated glial and peripheral immune cells. This cellular response to neurodegeneration triggers deleterious events (eg, oxidative stress and cytokine-receptor-mediated apoptosis), which might eventually lead to dopaminergic cell death and hence disease progression. Finally, we highlight possible therapeutic strategies (including immunomodulatory drugs and therapeutic immunisation) aimed at downregulating these inflammatory processes that might be important to slow the progression of Parkinson's disease.
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Randomized Controlled Trial Multicenter Study
Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study.
The efficacy of natalizumab on clinical and radiological measures in the phase III Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study has prompted the investigation of whether natalizumab can increase the proportion of patients with relapsing-remitting multiple sclerosis who do not have disease activity. ⋯ Disease remission might become an increasingly attainable goal in multiple sclerosis treatment with the use of newer, more effective therapies.
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After ischaemic stroke onset, potentially viable (ie, penumbral) tissue might be salvageble for as long as 48 h. By increasing the therapeutic time window for treatment of stroke with intravenous alteplase from 3-4.5 h to 9 h, many more patients could be treated. Use of a combination of diffusion-weighted and perfusion-weighted MRI or perfusion CT might improve selection of patients with penumbral tissue. ⋯ However, the negative results of the phase III Desmoteplase In Acute ischaemic Stroke trial (DIAS-2) with desmoteplase given up to 9 h after stroke suggest that some refinements are needed. For trials of neuroprotection, the concept of freezing the penumbra (ie, preventing further deterioration of the vulnerable tissue) might be a more realistic expectation. Recent advances in penumbral imaging technology should enable a phase III alteplase trial to be done beyond 4.5 h by use of techniques to select patients with penumbral tissue.
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Progressive supranuclear palsy (PSP) is a clinical syndrome comprising supranuclear palsy, postural instability, and mild dementia. Neuropathologically, PSP is defined by the accumulation of neurofibrillary tangles. Since the first description of PSP in 1963, several distinct clinical syndromes have been described that are associated with PSP; this discovery challenges the traditional clinicopathological definition and complicates diagnosis in the absence of a reliable, disease-specific biomarker. ⋯ These new insights emphasise that the pathological events and processes that lead to the accumulation of phosphorylated tau protein in the brain are best considered as dynamic processes that can develop at different rates, leading to different clinical phenomena. Moreover, for patients for whom the diagnosis is unclear, clinicians must continue to describe accurately the clinical picture of each individual, rather than label them with inaccurate diagnostic categories, such as atypical parkinsonism or PSP mimics. In this way, the development of the clinical features can be informative in assigning less common nosological categories that give clues to the underlying pathology and an understanding of the expected clinical course.