In patients with suspected dementia with Lewy bodies the detection of the disease-associated α-synuclein in easily accessible tissues amenable to be collected using minimally invasive procedures, remains a major diagnostic challenge. This approach has the potential to take advantage of modern molecular assays for the diagnosis of α–synucleinopathy and, in turn, to optimize the recruitment and selection of patients in clinical trials, using drugs directed at counteracting α-synuclein aggregation. In this study, we explored the diagnostic accuracy of α-synuclein real-time quaking-induced conversion assay by testing olfactory mucosa and CSF in patients with a clinical diagnosis of probable (n = 32) or prodromal (n = 5) dementia with Lewy bodies or mixed degenerative dementia (dementia with Lewy bodies/Alzheimer’s disease) (n = 6). Thirty-eight patients with non-α-synuclein-related neurodegenerative and non-neurodegenerative disorders, including Alzheimer’s disease (n = 10), sporadic Creutzfeldt-Jakob disease (n = 10), progressive supranuclear palsy (n = 8), corticobasal syndrome (n = 1), fronto-temporal dementia (n = 3) and other neurological conditions (n = 6) were also included, as controls. All 81 patients underwent olfactory swabbing while CSF was obtained in 48 participants. At the initial blinded screening of olfactory mucosa samples, 38 out of 81 resulted positive while CSF was positive in 19 samples out of 48 analyzed. After unblinding of the results, 27 positive olfactory mucosa were assigned to patients with probable dementia with Lewy bodies, five with prodromal dementia with Lewy bodies and three to patients with mixed dementia, as opposed to three out 38 controls. Corresponding results of CSF testing disclosed 10 out 10 positive samples in patients with probable dementia with Lewy bodies and six out of six with mixed dementia, in addition to three out of 32 for controls. The accuracy among results of real-time quaking-induced conversion assays and clinical diagnoses was 86.4% in the case of olfactory mucosa and 93.8% for CSF. For the first time, we showed that α-synuclein real-time quaking induced conversion assay detects α-synuclein aggregates in olfactory mucosa of patients with dementia with Lewy bodies and with mixed dementia. Additionally, we provided preliminary evidence that the combined testing of olfactory mucosa and CSF raised the concordance with clinical diagnosis potentially to 100%. Our results suggest that nasal swabbing might be considered as a first line screening procedure in patients with a diagnosis of suspected dementia with Lewy bodies followed by CSF analysis, as a confirmatory test, when the result in the olfactory mucosa is incongruent with the initial clinical diagnosis.
BackgroundRecently there has been a progressive loss of specialty related skills for nephrologists. Among the skills we find the kidney biopsy that has a central role in diagnosis of renal parenchymal disease. One of the causes might be the belief that the kidney biopsy should be performed only in larger Centers which can rely on the presence of a renal pathologist and on nephrologists with a large experience. This trend may increase in the short term procedural safety but may limit the chance of in training nephrologists to become confident with the technique.MethodsWe evaluated renal biopsies performed from May 2002 to October 2016 in our Hospital, a mid-sized facility to determine whether the occurrence of complications would be comparable to those reported in literature and whether the increase in the number of biopsy performing physicians including nephrology fellows which took place since January 2012, after our Nephrology Unit became academic, would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies. Three hundred thirty seven biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24 h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the biopsy.ResultsComplications occurred in 18.7% of patients, of these only 1,2% were major complications. Complications were more common in female (28%) compared to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis, kidney function and complication rates; hypertension was not associated to a higher risk in complications. The increase of biopsy performing personnel was not associated to an increase in complication rates (18,7% both pre and post 2012) or with an increase of major complications (1.2% vs 1,2%).ConclusionsKidney biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are guaranteed even if the procedure is performed by a larger number of less experienced nephrologists as long as under tutor supervision, thus kidney biopsy should become an integral part of a nephrology fellow training allowing more widespread diffusion of this technique.
This study draws attention on the importance of nonlinear approach in EEG analysis and the potential role of cognitive task in highlighting EEG alterations at very early stages of cognitive impairment; EEG could therefore have a practical impact on dementia diagnosis.
Speech apraxia is a disorder of speech motor planning/programming leading to slow rate, articulatory distortion, and distorted sound substitutions. We describe the clinical profile evolution of a patient presenting with slowly progressive isolated speech apraxia that eventually led to the diagnosis of corticobasal syndrome (CBS), supporting the evidence that this rare speech disorder can be the first presentation of CBS. Moreover, we found a novel variant in MAPT gene, which is hypothesized to be disease-causing mutation. These results underscore the importance of genetic analysis - particularly in selected atypical cases - for in vivo understanding of possible pathophysiological disease process.
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