Communication and cognitive impairments and healthcare decision-making in MND: A narrative review

Rationale: Motor neurone disease (MND) is a neurodegenerative disease presenting with progressive weakness of voluntary muscles. For any condition, person-centred healthcare relies on the sharing of information and a mutual understanding of the person’s needs and preferences. Decision-making in MND becomes more complex as there is no cure and a high prevalence of co-morbid communication and/or cognitive difficulties. Objective: To identify the reported impact of communication and/or cognitive impairment on patient and carer involvement in healthcare decision-making in MND. Methods: A review and synthesis of studies addressing issues of communication impairment and/or cognitive impairment in relation to decision-making focussed on MND was conducted. Articles were excluded if they were reviews, case studies, conference papers or commentaries. To be included studies needed to address issues of communication impairment or cognitive impairment specifically in relation to decision-making. Relevant data was extracted verbatim and subjected to content analysis to support the narrative summary. Results: Seventy-six articles were identified and 35 articles screened. Six articles met inclusion criteria each describing examples of decision-making in MND. There was limited data related to communication and/or cognitive impairment and the impact these impairments may have on decision-making despite recognition that many people with MND may lose verbal communication or develop subtle cognitive impairments. The literature is primarily from the perspective of others. Conclusion: This review highlights that the current body of literature exploring decision-making within the MND population presents us with extremely limited insights into the impact of communication and/or cognitive impairments on healthcare decision-making. Extant literature focuses on interventions (namely ventilation and gastrostomy), the broad process of decision-making, or cognitive assessment of decision-making ability. Whilst most studies acknowledge that deficits in communication or cognition impact the decision-making process, this issue is not the focus of any study

Humour processing in frontotemporal lobar degeneration: A behavioural and neuroanatomical analysis.

Humour is a complex cognitive and emotional construct that is vulnerable in neurodegenerative diseases, notably the frontotemporal lobar degenerations. However, humour processing in these diseases has been little studied. Here we assessed humour processing in patients with behavioural variant frontotemporal dementia (n = 22, mean age 67 years, four female) and semantic dementia (n = 11, mean age 67 years, five female) relative to healthy individuals (n = 21, mean age 66 years, 11 female), using a joint cognitive and neuroanatomical approach. We created a novel neuropsychological test requiring a decision about the humorous intent of nonverbal cartoons, in which we manipulated orthogonally humour content and familiarity of depicted scenarios. Structural neuroanatomical correlates of humour detection were assessed using voxel-based morphometry. Assessing performance in a signal detection framework and after adjusting for standard measures of cognitive function, both patient groups showed impaired accuracy of humour detection in familiar and novel scenarios relative to healthy older controls (p < .001). Patient groups showed similar overall performance profiles; however the behavioural variant frontotemporal dementia group alone showed a significant advantage for detection of humour in familiar relative to novel scenarios (p = .045), suggesting that the behavioural variant syndrome may lead to particular difficulty decoding novel situations for humour, while semantic dementia produces a more general deficit of humour detection that extends to stock comedic situations. Humour detection accuracy was associated with grey matter volume in a distributed network including temporo-parietal junctional and anterior superior temporal cortices, with predominantly left-sided correlates of processing humour in familiar scenarios and right-sided correlates of processing novel humour. The findings quantify deficits of core cognitive operations underpinning humour processing in frontotemporal lobar degenerations and suggest a candidate brain substrate in cortical hub regions processing incongruity and semantic associations. Humour is a promising candidate tool with which to assess complex social signal processing in neurodegenerative disease

How predictive are temporal lobe changes of underlying TDP-43 pathology in the ALS-FTD continuum?

Detection of underling proteinopathies is becoming increasingly important across neurodegenerative conditions due to upcoming disease intervention trials. In this review, we explored how temporal lobe changes in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can potentially predict underlying TDP-43 pathology subtypes in FTD. To date, emphasis has been given to frontal lobe changes in the study of the cognitive and behavioural impairments in both syndromes but an increasing number of pathological, imaging and neuropsychological studies suggest how temporal lobe changes could critically affect the cognition and behaviour of these conditions. In this current article, we reviewed pathological, imaging as well as clinical/neuropsychological findings of temporal involvement in the ALS-FTD continuum, how they relate to temporal lobe changes and the underlying TDP-43 pathology in FTD. Findings across studies show that TDP-43 pathology occurs and coincides in many structures in ALS and FTD, but especially in the temporal lobes. In particular, anterior and medial temporal lobes atrophy is consistently found in ALS and FTD. In addition, memory and language impairment as well as emotional and Theory of Mind (ToM) processing deficits that are characteristics of the two diseases are highly correlated to temporal lobe dysfunction. We conclude by showing that temporal lobe changes due to TDP-43 type B might be particular predictive of TDP-43 type B pathology in behavioural variant FTD (bvFTD), which clearly needs to be investigated further in the future

Effect of Varenicline vs. Placebo on Reactivity to Tobacco and Alcohol Cues in Smokers who are Light Drinkers

Varenicline is used to treat tobacco dependence. While varenicline decreases craving during a quit attempt, no studies have investigated its effect on cue-induced craving. Varenicline has also been shown to decrease alcohol consumption in animal and humans. This double-blind, randomized, placebo-controlled trial investigated the effect of varenicline on tobacco and alcohol cue-induced craving and alcohol consumption in dependent smokers/light drinkers. Tobacco and alcohol craving were assessed at baseline and after 2-weeks of drug administration using the QSU and ACQ. Significant decreases in cigarette and alcohol craving were observed between the pre- and post-drug session in the varenicline group on QSU Factor 1(87.5811.66 vs.70.5820.79, p=0.008) and ACQ Total (3.371.16 vs. 2.661.15, p=0.004) scores. This effect remained significant after correction for craving during neutral cues in the alcohol but not tobacco condition. No significant decreases in alcohol consumption were seen. These results suggest varenicline decreases overall craving, but not cue-induced craving specifically.MAS

Expression of P53 and P63 in the urinary bladder neoplasms and correlation with other prognostic factors

The motive to perform this study was to assess the expression of p53 and p63 in bladder neoplasia of patients undergoing radical cystectomy (because of invasive bladder cancer and T1G3 tumours resistant to BCG treatment) and to correlate the expression with prognostic factors such the stage of disease, the grade of the disease and the survival and the significance of these in the prognosis of patients.We studied 100 cases of patients who underwent radical cystectomy in 2nd Urological Department,University of Athens at Sismanoglio Hospital due to invasive carcinoma of the bladder and superficial carcinoma (T1G3) resistant to intravesical BCG therapy. Pieces from paraffin blocks from the histological preparation of cystectomy stained in Pathology120Department of the upper Hospital, by immunohistochemical method using anti p53 monoclonal antibody DO-7 (Biocare Medical, Concord, CA, USA) To study the expression of the protein p53, and the anti p63 monoclonal antibody BC4A4 (Biocare Medical Concord, CA, USA) to study the expression of the protein p63. The measurement of the expression of proteins p53 and p63 was semiquantitative method in categories from 0 to 3 depending on the response. The above results and the ratio of the expression of a protein relative to the other associated with other prognostic factors such as the final stage of the disease, the degree of malignancy of the tumor, the existence or not lymphatic infiltration in histological preparation of radical cystectomy and the existence infiltrated the pelvic lymph nodes. The patient follow-up was at least three years after radical cystectomy and became either a telephone interview or examination in the outpatient clinic. The prognostic significance of the change of expression of these proteins and their correlation will be studied by calculating the contribution to relapse free survival and overall survival in patients. The statistical analysis of the results was performed with the statistical program SPSS 19.00. The analysis of the study showed that it presented significant relationship of p53 and p63 with prognostic factors mentioned above. A multivariate analysis of the variables used did not result in a statistically significant result and forth and detailed tables for each category comparison of these results.The expression of p54 and p63 biomarkers studied (individually and / or in combination) in patients who underwent radical cystectomy due to invasive bladder CA and T1G3 resistant BCG therapy found to have no statistically significant prognostic value. Although, it was found a statistically significant difference with the stage of disease and the expression of p53.Ο σκοπός της μελέτης ήταν να προσδιοριστεί η έκφραση του p53 και του p63 στα νεοπλάσματά της ουροδόχου κύστης από ασθενείς που υποβλήθηκαν σε ριζική κυστεκτομή (λόγω διηθητικού CA ουροδόχου κύστεως και σε T1G3 ανθεκτικό σε BCG θεραπεία) και να συσχετιστεί η έκφραση τους με προγνωστικούς παράγοντες όπως το στάδιο της νόσου, ο βαθμός διαφοροποίησης της νόσου και η επιβίωση και την σημασία αυτών στην πρόγνωση των ασθενών.Μελετήθηκαν 100 περιπτώσεις ασθενών που υποβλήθηκαν σε ριζική κυστεκτομή στην Β΄ Ουρολογική Kλινική του Πανεπιστημίου Αθηνών στο Σισμανόγλειο Νοσοκομείο λόγω διηθητικού καρκινώματος της ουροδόχου κύστεως καθώς και επιφανειακού καρκινώματος (Τ1G3) ανθεκτικού σε ενδοκυστική BCG θεραπεία. Τεμάχια από μπλόκ παραφίνης από το ιστολογικό παρασκεύασμα της κυστεκτομής χρώσθηκαν στο Παθολογοανατομικό Εργαστήριο του ανωτέρου Νοσοκομείου, με ανοσοϊστοχημική μέθοδο χρησιμοποιώντας το αντι p53 μονοκλωνικό αντίσωμα DO-7 (Biocare Medical, Concord, CA, USA) για την μελέτη της έκφρασης της πρωτεΐνης p53, και το αντι p63 μονοκλωνικό αντίσωμα BC4A4 (Biocare Medical Concord, CA, USA) για την μελέτη της έκφρασης της πρωτεΐνης p63. Η μέτρηση της έκφρασης των πρωτεινών p53 και p63 έγινε με ημιποσοτική μέθοδο σε κατηγορίες απο 0 έως 3 ανάλογα με την ανταπόκριση. Τα ανωτέρω αποτελέσματα καθώς και ο λόγος της έκφρασης της μιας πρωτεΐνης σε σχέση με την άλλη συσχετίστηκαν με άλλους προγνωστικούς παράγοντες όπως το τελικό στάδιο της νόσου, τον βαθμό κακοήθειας του όγκου, την ύπαρξη ή όχι λεμφαγγειακής διήθησης στο ιστολογικό παρασκεύασμα της ριζικής118κυστεκτομής και την ύπαρξη διηθημένων πυελικών λεμφαδένων. Η παρακολούθηση των ασθενών ήταν τουλάχιστον έως τρία χρόνια μετά την ριζική κυστεκτομή και έγινε είτε με τηλεφωνική συνέντευξη είτε με εξέταση στα εξωτερικά ιατρεία. Η προγνωστική σημασία της αλλαγής έκφρασης των ανωτέρω πρωτεϊνών και της μεταξύ τους συσχέτισης θα μελετηθεί υπολογίζοντας την συμβολή τους στην ελεύθερη υποτροπής επιβίωση καθώς και στην ολική επιβίωση των ασθενών. Η στατιστική ανάλυση των αποτελεσμάτων πραγματοποιήθηκε με το στατιστικό πρόγραμμα SPSS 19.00. Η ανάλυση της μελέτης κατέδειξε ότι δε παρουσιάζεται στατιστικά σημαντική σχέση του p53 και του p63 με τους προγνωστικούς παράγοντες που προαναφέρθηκαν. Η πολυπαραγοντική ανάλυση των μεταβλητών που χρησιμοποιήθηκαν δεν κατέληξε σε κάποιο στατιστικά σημαντικό αποτέλεσμα ενώ παρατέθηκαν και οι αναλυτικοί πίνακες για κάθε κατηγορία σύγκρισης των παραπάνω αποτελεσμάτων.Η έκφραση των βιοδεικτών p54 και p63 που μελετήθηκαν (μεμονωμένα ή/και σε συνδυασμό) σε ασθενείς που υποβλήθηκαν σε ριζική κυστεκτομή λόγω διηθητικού CA ουροδόχου κύστεως και σε T1G3 ανθεκτικό σε BCG θεραπεία, δεν διαπιστώθηκε να παρέχoυν καμία στατιστικά σημαντική προγνωστική αξία στην εκτίμηση των ασθενών αυτών. Διαπιστώθηκε όμως στατιστικά σημαντική διαφορά με το στάδιο της νόσου και την έκφραση του p5

Bladder perivascular epithelioid cell tumor: A novel rare neoplasm

Perivascular epithelioid cell tumors (PEComas) have recently been defined as a group of neoplasms that have in common the co-expression of melanocytic and smooth muscle markers. We report a novel case of a rare bladder PEComa and we review the relevant literature. Copyright © 2011 S. Karger AG