Predictors of Function, Activity, and Participation of Stroke Patients Undergoing Intensive Rehabilitation: A Multicenter Prospective Observational Study Protocol.

Background: The complex nature of stroke sequelae, the heterogeneity in rehabilitation pathways, and the lack of validated prediction models of rehabilitation outcomes challenge stroke rehabilitation quality assessment and clinical research. An integrated care pathway (ICP), defining a reproducible rehabilitation assessment and process, may provide a structured frame within investigated outcomes and individual predictors of response to treatment, including neurophysiological and neurogenetic biomarkers. Predictors may differ for different interventions, suggesting clues to personalize and optimize rehabilitation. To date, a large representative Italian cohort study focusing on individual variability of response to an evidence-based ICP is lacking, and predictors of individual response to rehabilitation are largely unexplored. This paper describes a multicenter study protocol to prospectively investigate outcomes and predictors of response to an evidence-based ICP in a large Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation. Methods: All patients with diagnosis of ischemic or hemorrhagic stroke confirmed both by clinical and brain imaging evaluation, admitted to four intensive rehabilitation units (adopting the same stroke rehabilitation ICP) within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled (expected sample: 270 patients). Measures will be taken at admission (T0), at discharge (T1), and at follow-up 6 months after a stroke (T2), including clinical data, nutritional, functional, neurological, and neuropsychological measures, electroencephalography and motor evoked potentials, and analysis of neurogenetic biomarkers. Statistics: In addition to classical multivariate logistic regression analysis, advanced machine learning algorithms will be cross-validated to achieve data-driven prognosis prediction models. Discussion: By identifying data-driven prognosis prediction models in stroke rehabilitation, this study might contribute to the development of patient-oriented therapy and to optimize rehabilitation outcomes. Clinical Trial Registration: ClinicalTrials.gov, NCT03968627. https://www.clinicaltrials.gov/ct2/show/NCT03968627?term=Cecchi&cond=Stroke&draw=2&rank=2.

The Visual Scanning Test: a newly developed neuropsychological tool to assess and target rehabilitation of extrapersonal visual unilateral spatial neglect.

PURPOSE: Visual unilateral spatial neglect (VUSN) is a neuropsychological condition commonly experienced after stroke whereby patients are unable to attend to stimuli on the controlesional side of their space. VUSN can occur in the personal, peripersonal, and/or extrapersonal portion of patient's space. Traditional paper-and-pencil neuropsychological tests are widely used to evaluate VUSN, but they assess peripersonal VUSN. Instead, personal and extrapersonal neglect are less easily evaluated. The aim of this study was to present normative values for the Visual Scanning Test (VST), a new neuropsychological tool to quantitatively assess the extrapersonal VUSN. METHODS: Eighty-six healthy subjects took part in the study (61 female), with a mean age of 52.8 years (SD = 17.0) and a mean of 14.0 years of education (SD = 5.2). The VST involved a visual search for a target between similar visual distractors, projected in the far space. The test was administered twice to each participant, with an interval of 2 weeks. From the recorded data, it was possible to obtain indexes related to the reaction times and to the accuracy of the performance on the VST. RESULTS: Multiple linear regression analysis revealed that age and education significantly influenced VST-derived indexes. From the regression analysis, a correction grid for raw scores was built. Adjusted scores were then ranked, and by means of a non-parametric procedure, tolerance limits (both outer and inner one-sided) were defined. CONCLUSIONS: The present study provided normative data for the VST in an Italian population useful for both clinical and research purposes. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03931798.

Long-term services for the care and rehabilitation of people with severe acquired brain injury: a multicentre, cross-sectional study of 536 Italian families.

BACKGROUND: People with severe acquired brain injuries (ABIs) require complex, long-term multidisciplinary healthcare, and social welfare programmes, and their families experience social and emotional consequences that profoundly condition their quality of life. OBJECTIVE: To investigate whether the possibility of gaining access to local rehabilitation and other services positively influences not only the quality of life of the patients but also the quality of life of their families. METHODS: The sample consisted of 536 families of patients with severe ABIs. They were administered a specific 50-item questionnaire with a mix of multiple choice answers, dichotomous (yes/no) answers, or answers based on a Likert-type scale. RESULTS: The results suggest that the long-term services provided to patients are substantially satisfactory but the data concerning the patients' social and working reintegration are discomforting. Furthermore, the families experience profound social discomfort related to their economic, emotional and caregiving burden regardless of the number and quality of the rehabilitation services activated, or the amount of welfare support received. CONCLUSIONS: Post-severe ABI services provided at a local level should include not only long-term rehabilitative and social support for the patients, but also long-term social and psychological support for their families.

ERK pathway activation bidirectionally affects visual recognition memory and synaptic plasticity in the perirhinal cortex.

ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala, or striatum. The perirhinal cortex (PRHC) plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity. We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the object recognition task (ORT). We have then tested performance in the ORT in Ras-GRF1 knock-out (KO) mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72 h retention interval, suggesting a longer lasting recognition memory. In parallel with behavioral data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.

Divided attention during retrieval suppresses false recognition in confabulation.

The present research tested the hypothesis that false recognition in confabulating patients results, at least in part, from sustained processing of irrelevant information about test items. Thus, we predicted that false recognition would be reduced if cognitive resources available for such a processing are experimentally reduced. Two experiments provided evidence consistent with this proposal. In Experiment 1, confabulating patients exhibited lower false recognition in a divided attention (DA) compared to a full attention (FA) retrieval condition. The opposite trend was observed in non-confabulating patients with comparable memory and executive deficits and normal controls. In Experiment 2, in a Deese-Roediger-McDermott paradigm, confabulating patients exhibited lower false recognition to lures that were unrelated to the studied words in the DA compared to the FA retrieval condition, but unvaried levels of false recognition to critical lures. In contrast, false recognition to both unrelated and critical lures increased in non-confabulating patients and normal controls in the DA compared to the FA condition. These results are consistent with the hypothesis that an excessive processing of task-irrelevant memories at retrieval may contribute to false recognition in confabulating patients.