Brain : a journal of neurology
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Despite the significant impact of postoperative delirium on surgical outcomes and the long-term prognosis of older patients, its neural basis has not yet been clarified. In this study we investigated the impact of premorbid brain microstructural integrity, as measured by diffusion tensor imaging before surgery, on postoperative delirium incidence and severity, as well as the relationship among presurgical cognitive performance, diffusion tensor imaging abnormalities and postoperative delirium. Presurgical diffusion tensor imaging scans of 136 older (≥70 years), dementia-free subjects from the prospective Successful Aging after Elective Surgery study were analysed blind to the clinical data and delirium status. ⋯ After further controlling for general cognitive performance, diffusion tensor imaging abnormalities of the cerebellum, hippocampus, thalamus and basal forebrain still remained associated with delirium incidence and severity. This study raises the intriguing possibility that structural dysconnectivity involving interhemispheric and fronto-thalamo-cerebellar networks, as well as microstructural changes of structures involved in limbic and memory functions predispose to delirium under the stress of surgery. While the diffusion tensor imaging abnormalities observed in the corpus callosum, cingulum, and temporal lobe likely constitute the neural substrate for the association between premorbid cognition, as measured by general cognitive performance, and postoperative delirium, the microstructural changes observed in the cerebellum, hippocampus, thalamus and basal forebrain seem to constitute a separate phenomenon that predisposes to postsurgical delirium independent of presurgical cognitive status.
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Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. ⋯ A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process.
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Inherited erythromelalgia, the first human pain syndrome linked to voltage-gated sodium channels, is widely regarded as a genetic model of human pain. Because inherited erythromelalgia was linked to gain-of-function changes of sodium channel Na(v)1.7 only a decade ago, the literature has mainly consisted of reports of genetic and/or clinical characterization of individual patients. This paper describes the pattern of pain, natural history, somatosensory profile, psychosocial status and olfactory testing of 13 subjects with primary inherited erythromelalgia with mutations of SCN9A, the gene encoding Na(v)1.7. ⋯ By contrast, significantly decreased cold and heat pain thresholds were found at unaffected sites. Sensory profiles varied considerably between affected and unaffected sites, suggesting the existence of small fibre neuropathy in symptomatic sites. This in-depth clinical characterization of a well-defined inherited erythromelalgia population indicates the importance of characterizing the pain phenotype in individuals before undertaking clinical trials, given the inherent variability of pain both between and within inherited erythromelalgia subjects, even those within a family who carry the same mutation.
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Cerebral accumulation of amyloid-β is thought to be the starting mechanism in Alzheimer's disease. Amyloid-β can be detected by analysis of cerebrospinal fluid amyloid-β42 or amyloid positron emission tomography, but it is unknown if any of the methods can identify an abnormal amyloid accumulation prior to the other. Our aim was to determine whether cerebrospinal fluid amyloid-β42 change before amyloid PET during preclinical stages of Alzheimer's disease. ⋯ The results were replicated after adjustments of different factors and when using different cut-offs for amyloid-β abnormality including a positron emission tomography classification based on the florbetapir uptake in regions where the initial amyloid-β accumulation occurs in Alzheimer's disease. This is the first study to show that individuals who have abnormal cerebrospinal amyloid-β42 but normal amyloid-β positron emission tomography have an increased cortical amyloid-β accumulation rate similar to those with both abnormal cerebrospinal fluid and positron emission tomography and higher rate than subjects where both modalities are normal. The results indicate that cerebrospinal fluid amyloid-β42 becomes abnormal in the earliest stages of Alzheimer's disease, before amyloid positron emission tomography and before neurodegeneration starts.
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Multicenter Study
MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases.
Accurately distinguishing between different degenerative dementias during life is challenging but increasingly important with the prospect of disease-modifying therapies. Molecular biomarkers of dementia pathology are becoming available, but are not widely used in clinical practice. Conversely, structural neuroimaging is recommended in the evaluation of cognitive impairment. ⋯ Using automated classification based on all six rating scales, the accuracy (estimated using the area under the receiver-operator curves) for distinguishing each pathological group from controls ranged from 0.86-0.97; and from one another, 0.75-0.92. These results were substantially better than the accuracy of any single scale, at least as good as expert reads, and comparable to previous studies using molecular biomarkers. Visual rating scores from magnetic resonance images routinely acquired as part of the investigation of dementias, offer a practical, inexpensive means of improving diagnostic accuracy.