Cognitive awareness after treatment for high-grade glioma

Objective: In patients with brain lesion, awareness of cognitive deficits is an important aspect of disease awareness. Glioblastoma (GBM) and anaplastic astrocytoma (AA) can cause cognitive deficits, but, to date, awareness of these deficits has not been documented. This study aimed to test cognitive awareness in these patients after the end of treatment. Methods: Fifty patients with GBM or AA were assessed using the Multiple Ability Self-Report Questionnaire (MASQ), State-Trait Anxiety Inventory (STAI), Self Rating Depression Scale (SRDS), and memory, attention, mental speed, abstract reasoning, and flexibility neuropsychological tests. Cognitive awareness was calculated as the concordance between the composite score of neuropsychological performance (PEC) and the total MASQ score. The controls were 48 healthy subjects. Analysis of variance and regression analysis compared subject groups and explored variables predicting perceived abilities. Results: Patients with GBM or AA showed similar attention, memory, and executive deficits compared with controls. Cognitive awareness was fair/full in 64% of patients. In the entire patients group, the worst MASQ scores were associated with neuropsychological deficits, anxiety, depression, and glioma location in the right hemisphere . In patients with fair/full awareness, MASQ scores were related to affective status and neuropsychological performance, whereas, in those with scarce/no awareness, they were related only to affective status. Conclusions: After treatment, many patients with GBM or AA are aware of their cognitive deficits. Anxiety, depression, and right hemisphere tumour exacerbate the perceived difficulties. This neurocognitive approach expands the behavioural phenotypes of high-grade gliomas and may have therapeutic implications over the course of the disease.info:eu-repo/semantics/publishedVersio

A novel missense mutation in PSEN2 gene associated with a clinical phenotype of frontotemporal dementia

Background: In Familial Alzheimer's disease defects in three genes - the amyloid precursors protein (APP) gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14 and the presenilin 2 (PSEN2) on chromosome 1- have been identified. More than 160 pathogenic missense mutations have been described in PSEN1, with wide clinic phenotypic variability. In PSEN2 only 11 missense mutations are known, in two of which (M239V and T122R) the clinical phenotype may be frontotemporal dementia-like. Methods: We present a novel PSEN2 mutation (Y231C) in an Italian patient who seven years ago, at age 55, manifested mood and behavioural disorders characterized by apathia, delusions, physical aggressive behaviour and psychomotor agitation. Language disturbances appeared one year later and mild memory loss three years later. The neuropsychological pattern suggested a main dysfunction in posterior temporal and parietal cortex. MRI showed diffuse atrophy, especially in posterior regions. Results: The genetic study showed an A-to-G mutation in exon seven of PSEN2 gene, resulting in tyrosine to cysteine substitution at residue 231. Conclusions: This new mutation confirms the variability of the phenotypes associated with PSEN2 mutations and justified the analysis of this gene in behavioural disturbances associated with degenerative dementia, at least in Italy in which PSEN2 mutations seems more frequent than in other countries

Effectiveness of valproate for the treatment of manic-like behavior in X-linked adrenoleukodystrophy

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Neuropsychological predictors of quality of life in focal epilepsy

Spontaneous complaints of outpatients with focal epilepsy often stress the relationship between cognitive deficits and Quality of Life (QOL). Consequently, the aim of the present study was to find the best neuropsychological predictors of QOL in individuals with focal epilepsy, in order to guide their ambulatory health care. A sample of 71 Portuguese patients was studied: 40 female, 47 married, with a mean age of 37.48 years (S.D. = 11.79, 16–62), mean education of 7.93 (S.D. = 4.05, 3–17), and focal epilepsy of moderate severity. A Socio-demographic and Clinical Questionnaire, the SF-36 v1, the Cognitive Functioning Scale from the ESI-55, a Seizure Control scale (items from the Liverpool Seizure Severity Scale), and several neuropsychological tests were used. Semantic Fluency was the only predictor of Physical Functioning, Role Functioning – Physical, and Mental Health; I.A. Test predicted Bodily Pain; and AttentiveMatrices predicted General Health, Vitality, and Role Functioning – Emotional. The Mental Component of the SF-36 v1 was predicted by Attentive Matrices, and the Physical Component was predicted by Semantic Fluency. Cognitive Functioning was predicted by the Token Test. Social Functioning and Seizure Control presented no statistically significant correlation with the neuropsychological indicators used. These results underscore the importance of cognitive performance to the QOL of individuals with focal epilepsy, supporting the systematic screening of cognitive performance in this population. Additionally, they suggest cognitive rehabilitation has the potential to improve these individuals’ QOL

PMCA-based detection of prions in the olfactory mucosa of patients with Sporadic Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder caused by the conformational conversion of the prion protein (PrPC) into an abnormally folded form, named prion (or PrPSc). The combination of the polymorphism at codon 129 of the PrP gene (coding either methionine or valine) with the biochemical feature of the proteinase-K resistant PrP (generating either PrPSc type 1 or 2) gives rise to different PrPSc strains, which cause variable phenotypes of sCJD. The definitive diagnosis of sCJD and its classification can be achieved only post-mortem after PrPSc identification and characterization in the brain. By exploiting the Real-Time Quaking-Induced Conversion (RT-QuIC) assay, traces of PrPSc were found in the olfactory mucosa (OM) of sCJD patients, thus demonstrating that PrPSc is not confined to the brain. Here, we have optimized another technique, named protein misfolding cyclic amplification (PMCA) for detecting PrPSc in OM samples of sCJD patients. OM samples were collected from 27 sCJD and 2 genetic CJD patients (E200K). Samples from 34 patients with other neurodegenerative disorders were included as controls. Brains were collected from 26 sCJD patients and 16 of them underwent OM collection. Brain and OM samples were subjected to PMCA using the brains of transgenic mice expressing human PrPC with methionine at codon 129 as reaction substrates. The amplified products were analyzed by Western blot after proteinase K digestion. Quantitative PMCA was performed to estimate PrPSc concentration in OM. PMCA enabled the detection of prions in OM samples with 79.3% sensitivity and 100% specificity. Except for a few cases, a predominant type 1 PrPSc was generated, regardless of the tissues analyzed. Notably, all amplified PrPSc were less resistant to PK compared to the original strain. In conclusion, although the optimized PMCA did not consent to recognize sCJD subtypes from the analysis of OM collected from living patients, it enabled us to estimate for the first time the amount of prions accumulating in this biological tissue. Further assay optimizations are needed to faithfully amplify peripheral prions whose recognition could lead to a better diagnosis and selection of patients for future clinical trials

Brain connectivity changes in autosomal recessive Parkinson Disease: a model for the sporadic form

Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptom

Fifty Years of Handedness Research: A Neurological and Methodological Update

Handedness, a complex human aspect that reflects the functional lateralization of the hemispheres, also interacts with the immune system. This study aimed to expand the knowledge of the lateralization of hand, foot, and eye activities in patients with immune-mediated (IM) or other (noIM) neurological diseases and to clarify the properties of the Edinburgh Handedness Inventory (EHI) in an Italian population. Three hundred thirty-four patients with IM or noIM diseases affecting the brain or spine and peripheral nervous system were interviewed about stressful events preceding the disease, subjective handedness, and familiarity for left-handedness or ambidexterity. The patients and 40 healthy subjects underwent EHI examination. In the whole group of participants, 24 items of the EHI were classified into five factors (Hand Transitive, Hand Refined, Hand Median, Foot, Eye), demonstrating good reliability and validity. Chronological age had a significant influence on hand and foot EHI factors and the laterality quotient (LQ), particularly on writing and painting. In the patient groups, EHI factors and the LQ were also predicted by age of disease onset, duration of disease, and family history of left-handedness or ambidexterity. No differences were found between patients and healthy subjects, but pencil use scored significantly lower in patients with IM diseases than in those with noIM brain diseases. These results demonstrate that the lateralization of hand and foot activities is not a fixed human aspect, but that it can change throughout life, especially for abstract and symbolic activities. Chronic neurological diseases can cause changes in handedness. This may explain why, unlike systemic immunological diseases, IM neurological diseases are not closely associated with left-handedness. In these patients, the long version of the EHI is appropriate for determining the lateralization of body activities to contextualize the neurological picture; therefore, these findings extend the Italian normative data sets

EXPERIÊNCIA DE ADULTOS COM PRÁTICAS DE (AUTO)CUIDADOS (NÃO) CONVENCIONAIS DE SAÚDE EM PORTUGAL PANDÉMICO

Introduction: Before the COVID-19 pandemic, research had shown high (and variable) prevalences of the use of Complementary and/or Alternative Medicine (CAM; eg., 70%), in adults and children, dependent, neverthless, on the type of practice. Objective: To characterize adults’ experience with conventional and non-conventional health (self-)care practices during the COVID-19 pandemic in Portugal. Method: After obtaining the necessary authorizations, between 1/10-27/11/2021, a total of 104 adults living in Portugal answered to a Google Forms questionnaire on health (self-)care practices. Results: As for the last time the participants performed any health (self-)care practice: - 47,6% evaluated the results they obtained as good and 14.3% as very good; - 59.5% were satisfied with that practice; - 27.1% considered it a non-conventional practice and 20% were not sure. In terms of health (self-)care practices: 65.2% reported using conventional and non-conventional practices. Among those who have ever used any non-conventional practice: - 50% did it using a professional and 33.9% by themselves and using a professional; - 48.4% use it rarely; - 17.9% started using it more frequently since the start of the COVID-19 pandemic; - 93.8% had never done it against the recommendation of a (conventional) health professional. Since the beginning of the pandemic: 11.2% had at least one appointment with a non-conventional health professional; and 4.1% had more appointments with non-conventional health professionals than with conventional health professionals. Regarding negative experiences with non-conventional practices, 89.7% never had any. Conclusions: Since: (a) participants were mostly satisfied with their last health (self-)care practice/its results, predominantly a conventional practice, even though the majority use both types of practices; (b) when using non-conventional practices, only a minority use it by themselves and the majority with some frequency; (c) its (generally rational) use did not increase considerably with the pandemic; and (d) few negative experiences were reported, these preliminary results are not alarming. Nevertheless, they do suggest a need to increase health care professionals’, non-conventional users’ and non-users’ knowledge about these practices to ensure patients’ safety