MRI abnormalities in Creutzfeldt-Jakob disease and other rapidly progressive dementia

Objective: To investigate brain MRI abnormalities in a cohort of patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt-Jakob disease (CJD). Methods: One hundred and seven patients with diagnosis of prion disease (60 with definite sCJD, 33 with probable sCJD and 14 with genetic prion disease) and 40 non-prion related RPD patients (npRPD) underwent brain MRI including DWI and FLAIR. MRIs were evaluated with a semiquantitative rating score, which separately considered abnormal signal extent and intensity in 22 brain regions. Clinical findings at onset, disease duration, cerebrospinal-fluid 14-3-3 and t-tau protein levels, and EEG data were recorded. Results: Among patients with definite/probable diagnosis of CJD or genetic prion disease, 2/107 had normal DWI-MRI: in one patient a 2-months follow-up DWI-MRI showed CJD-related changes while the other had autopsy-proven CJD despite no DWI abnormalities 282 days after clinical onset. CJD-related cortical changes were detected in all lobes and involvement of thalamus was common. In the npRPD groups, 6/40 patients showed DWI alterations that clustered in three different patterns: (1) minimal/doubtful signal alterations (limbic encephalitis, dementia with Lewy bodies); (2) clearly suggestive of alternative diagnoses (status epilepticus, Wernicke or metabolic encephalopathy); (3) highly suggestive of CJD (mitochondrial disease), though cortical swelling let exclude CJD. Conclusions: In the diagnostic work-up of RPD, negative/doubtful DWI makes CJD diagnosis rather unlikely, while specific DWI patterns help differentiating CJD from alternative diagnoses. The pulvinar sign is not exclusive of the variant form

Cerebrospinal Fluid Markers in Sporadic Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated181 tau, and amyloid beta (Aβ) peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most sensitive indicators of sCJD, the highest sensitivity, specificity and positive predictive value were obtained when all the above markers were combined. The latter approach also allowed a reliable differential diagnosis with other neurodegenerative dementias

Opinion, knowledge, and clinical experience with functional neurological disorders among Italian neurologists: results from an online survey

Background: Functional neurological disorders (FND) are disabling medical conditions commonly seen in neurological practice. Neurologists play an essential role in managing FND, from establishing a diagnosis to coordination of multidisciplinary team-based treatment for patients. With this study, we investigated the knowledge and the clinical experience of Italian neurologists in managing patients with FND. Methods: Members of the Italian Society of Neurology were invited via e-mail to participate in this ad hoc online survey; 492 questionnaires were returned completed. Results: The term "Functional neurological disorders" in reference to FND was used more frequently than other psychological (e.g., psychogenic or conversion), or descriptive terms (e.g., non-organic or stress-related). When speaking with patients, the respondents stated that they preferred explaining symptoms based on abnormal functioning of the nervous system than discussing mental illness and that they would refer their patient to a psychologist rather than to a psychiatrist. Few considered that physiotherapy and psychiatric interventions are useful approaches to treating FND. Some believed that patients simulate their symptoms. Conclusions: Overall, the responses suggest that knowledge about scientific advances in FND is somewhat sparse. A psychiatric-centered view of FND opens the way to an approach in which neurobiological and psychological aspects constitute essential factors of the condition. In this context, professional education could improve understanding of FND and optimize patient management

Patients with Alzheimer’s disease dementia show partially preserved parietal ‘hubs’ modeled from resting-state alpha electroencephalographic rhythms

Introduction: Graph theory models a network by its nodes (the fundamental unit by which graphs are formed) and connections. ‘Degree’ hubs reflect node centrality (the connection rate), while ‘connector’ hubs are those linked to several clusters of nodes (mainly long-range connections). Methods: Here, we compared hubs modeled from measures of interdependencies of between-electrode resting-state eyes-closed electroencephalography (rsEEG) rhythms in normal elderly (Nold) and Alzheimer’s disease dementia (ADD) participants. At least 5 min of rsEEG was recorded and analyzed. As ADD is considered a ‘network disease’ and is typically associated with abnormal rsEEG delta (<4 Hz) and alpha rhythms (8–12 Hz) over associative posterior areas, we tested the hypothesis of abnormal posterior hubs from measures of interdependencies of rsEEG rhythms from delta to gamma bands (2–40 Hz) using eLORETA bivariate and multivariate-directional techniques in ADD participants versus Nold participants. Three different definitions of ‘connector’ hub were used. Results: Convergent results showed that in both the Nold and ADD groups there were significant parietal ‘degree’ and ‘connector’ hubs derived from alpha rhythms. These hubs had a prominent outward ‘directionality’ in the two groups, but that ‘directionality’ was lower in ADD participants than in Nold participants. Discussion: In conclusion, independent methodologies and hub definitions suggest that ADD patients may be characterized by low outward ‘directionality’ of partially preserved parietal ‘degree’ and ‘connector’ hubs derived from rsEEG alpha rhythms

Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia

Introduction: We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis. Methods: The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants. Results: TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P&nbsp;&lt;&nbsp;0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected. Discussion: TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients

&quot;Delirium Day&quot;: A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys