Lancet neurology
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Intracellular accumulation of altered and misfolded proteins is the basis of most neurodegenerative disorders. Altered proteins are usually organised in the form of toxic multimeric complexes that eventually promote neuronal death. ⋯ What then goes wrong in these pathologies? Recent studies have shown that a primary failure in autophagy, a mechanism for clearance of intracellular components in lysosomes, could be responsible for the accumulation of these altered proteins inside the affected neurons. In this Review we summarise our current knowledge on the contribution of autophagy to the maintenance of normal cellular homoeostasis, its changes in neurodegenerative disorders, and the role of aggravating factors such as oxidative stress and ageing on autophagic failure in these pathologies.
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Non-convulsive status epilepticus (NCSE) is one of the great diagnostic and therapeutic challenges of modern neurology. Because the clinical features of this disorder may be very discrete and sometimes hard to differentiate from normal behaviour, NCSE is usually overlooked and consequently not treated properly. ⋯ In order to improve overall care of patients with NCSE, strict diagnostic criteria are needed that should be based on clinical alterations and ictal electroencephalographic changes. NCSE should be terminated rapidly to prevent patients from serious injuries, particularly if consciousness is impaired.
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Multicenter Study
Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study.
Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. ⋯ A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.