Lancet neurology
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Semantic dementia (SD), one of the main clinical variants of frontotemporal dementia, presents a unique combination of clinical and imaging abnormalities. We describe the epidemiological, cognitive, and radiological features of SD. ⋯ Structural (MRI) and functional (fluorodeoxyglucose-PET) studies in SD emphasise the role of the temporopolar and perirhinal cortices. Unlike other frontotemporal dementia syndromes, the neuropathological findings in SD are fairly predictable: most patients have ubiquitin-positive, tau-negative neuronal inclusions.
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Atrial fibrillation (AF) is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Anticoagulant therapy reduces the risk of stroke, and the greatest benefit is seen in patients at highest absolute risk. Aspirin is a less effective alternative, and any benefit of aspirin might be due to its favourable effects on arterial thrombosis caused by vascular disease. ⋯ The underuse of anticoagulation might also be related to uncertain risk of thromboembolism in individual patients and a perceived overestimation of the benefit and underestimation of risk of bleeding with warfarin in clinical trials. In this Review, we summarise the data for and against warfarin and aspirin therapies and discuss the clinical assessments and risk stratifications that guide the use of antithrombotic therapy for stroke prevention in patients with AF. Possible barriers to the uptake of anticoagulation therapy are also discussed.
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Diagnosis and treatment of cerebral and retinal transient ischaemic attacks (TIAs) are often delayed by the lack of immediate access to a dedicated TIA clinic. We evaluated the effects of rapid assessment of patients with TIA on clinical decision making, length of hospital stay, and subsequent stroke rates. ⋯ Use of TIA clinics with 24-h access and immediate initiation of preventive treatment might greatly reduce length of hospital stay and risk of stroke compared with expected risk.
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Randomized Controlled Trial
Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial.
Friedreich's ataxia (FA) is a progressive, multisystem, degenerative disorder caused by a reduction in frataxin. Loss of frataxin results in mitochondrial dysfunction and oxidative damage in patients and model systems. Previous studies have indicated that the antioxidant idebenone (5 mg/kg daily) reduces cardiac hypertrophy, but definite improvement in neurological function has not been shown. ⋯ Treatment with higher doses of idebenone was generally well tolerated and associated with improvement in neurological function and ADL in patients with FA. The degree of improvement correlated with the dose of idebenone, suggesting that higher doses may be necessary to have a beneficial effect on neurological function.
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Clinical research into Parkinson's disease has focused increasingly on the development of interventions that slow the neurodegeneration underlying this disorder. These investigations have stimulated interest in finding objective biomarkers that show changes in the rate of disease progression with treatment. Through radiotracer-based imaging of nigrostriatal dopaminergic function, a specific class of biomarkers to monitor the progression of Parkinson's disease has been identified, and these biomarkers were used in the clinical trials of drugs with the potential to modify the course of the disease. However, in some of these studies there was discordance between the imaging outcome measures and blinded clinical ratings of disease severity. Research is underway to identify and validate alternative ways to image brain metabolism, through which the efficacy of new therapies for Parkinson's disease and related disorders can be assessed. ⋯ During recent years, spatial covariance analysis has been used with (18)F-fluorodeoxyglucose PET to detect abnormal patterns of brain metabolism in patients with neurodegenerative disorders. Rapid, automated, voxel-based algorithms have been used with metabolic imaging to quantify the activity of disease-specific networks. This approach has helped to characterise the unique metabolic patterns associated with the motor and cognitive features of Parkinson's disease. The results of several studies have shown correction of abnormal motor, but not cognitive, network activity by treatment with dopaminergic therapy and deep brain stimulation. The authors of a longitudinal imaging study of early-stage Parkinson's disease reported substantial differences in the development of these metabolic networks over a follow-up of 4 years. WHERE NEXT?: Developments in network imaging have provided the basis for several new applications of metabolic imaging in the study of Parkinson's disease. A washout study is currently underway to determine the long-duration effects of dopaminergic therapy on the network activity related to Parkinson's disease, which will be useful to plan future trials of disease-modifying drugs. Network approaches are also being applied to the study of atypical parkinsonian syndromes. The characterisation of specific patterns associated with atypical parkinsonian syndromes and classic Parkinson's disease will be the basis for a fully automated imaging-based procedure for early differential diagnosis. Efforts are underway to quantify the networks related to Parkinson's disease with less invasive imaging methods. Assessments of network activity with perfusion-weighted MRI show excellent concordance with measurements done with established radiotracer techniques. This approach will ultimately enable the assessment of abnormal network activity in people who are genetically at risk of Parkinson's disease.