Lancet neurology
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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.
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Cholinesterase inhibitors and memantine do not have regulatory approval in most of the world for treatment of vascular dementia. A systematic review and meta-analysis was undertaken to assess the evidence for efficacy and safety of cholinesterase inhibitors and memantine in vascular dementia. ⋯ Cholinesterase inhibitors and memantine produce small benefits in cognition of uncertain clinical significance in patients with mild to moderate vascular dementia. Data are insufficient to support widespread use of these drugs in vascular dementia. Individual patient analyses are needed to identify subgroups of patients with vascular dementia who might benefit.
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Multicenter Study
Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study.
The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS. ⋯ Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.
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Randomized Controlled Trial Clinical Trial
Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study.
Niemann-Pick type C disease (NPC) is an inherited neurodegenerative disorder characterised by an intracellular lipid-trafficking defect with secondary accumulation of glycosphingolipids. Miglustat, a small iminosugar, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step of glycosphingolipid synthesis. Miglustat is able to cross the blood-brain barrier, and is thus a potential therapy for neurological diseases. We aimed to establish the effect of miglustat on several markers of NPC severity. ⋯ Miglustat improves or stabilises several clinically relevant markers of NPC. This is the first agent studied in NPC for which there is both animal and clinical data supporting a disease modifying benefit.