Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study

In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60 years, mild AD) underwent two cycles of treatments, separated by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20 min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient\u2019s global cognitive functioning lasting approximately 3 months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient.This preliminary result, although in need of further confirmation, suggests the potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Training cognitivo e demenza di Alzheimer: dati sulla plasticità cerebrale in patologie neurodegenerative

The objective of this thesis is to study the behavioural and brain changes in patients with Alzheimer’s disease (AD) following non-pharmacological treatments. The aim of the studies was to identify useful interventions to slow down the progressive cognitive decline of the disease by observing changes in cognitive functions, mood and functional abilities. In addition we analysed the changes in brain networks. Three studies were carried out with patients with mild to moderate AD, analysing different interventions and using different assessment. 1. In the first study the effectiveness of a one-year cognitive training (CT) on cognitive performance, functional abilities and emotional level has been evaluated. Results showed that repeated cycles of CT in AD patients treated with cholinesterase inhibitors were associated with autonomy in daily life and with benefits on performance tests involving mainly executive functions. These results were compared with performances of patients who did general exercise in a Day Centre. 2. In the second study changes in brain networks were also analysed, using Event- Related Potentials (ERPs), after a cycle of CT with repetition of a cognitive task. Data suggested that after repetition of a cognitive exercise there was change of strategy related to the task execution, as well as plastic re-reorganisations of cerebral networks. This functional adjustment probably arises from compensatory cognitive strategies that activated cortical networks spared by the neurodegenerative progression, especially language networks. 3. In the third study, one cycle of CT was combined with one cycle of exercise and physical activity, increasing the period of stimulation from two to four hours a day. In this case there was no evidence of a specific task strategy for implementation of the cognitive task trained every day, but there was an equally distributed pattern of activation in anterior and posterior regions, without any kind of plastic reorganisation due to the use of functional strategies for the performance of the task itself. Unlike the second study, the control task (not trained every day) showed a significant redistribution of cortical areas from the posterior (before training) to the anterior (after training) areas. This greater involvement of frontal areas was confirmed by the neuropsychological data that showed an improvement on performance tests involving mainly executive functions. Moreover, mood, perceived well-being and quality of life improves, as well as gait. The analysis of the automatic components of language showed, in both studies 2 and 3, a plastic potentiating effect indicating how learning, resulting from training conducted in an ecological context, is detectable by the technique of ERPs in AD patients. Therefore it is still possible for patients with a neurodegenerative disease to have plastic phenomena of enhancement of neural networks in linguistic areas. These studies allowed us to verify the effectiveness of CT for patients with mild to moderate AD, showing the maintenance of cognitive performance and functional activities after one year, and also cortical changes in still operating networks.L’argomento della presente attività di ricerca è stato lo studio delle modificazioni comportamentali e cerebrali in pazienti con deterioramento cognitivo di tipo Alzheimer (AD) in seguito a trattamenti non-farmacologici. Obiettivo dei diversi studi è stato quello di identificare interventi utili al rallentamento della patologia osservando le modificazioni cognitive, emotive, e funzionali. Inoltre, a livello elettrofisiologico, sono state analizzate le modificazioni dei network cerebrali. Sono stati condotti tre studi con pazienti con AD probabile di grado lieve-moderato con i quali si sono sperimentati diversi interventi aumentando e modificando progressivamente il tipo di stimolazione e le analisi effettuate. Nel primo studio si è valutata l’efficacia di cicli di training cognitivo (CT) svolti nell’arco di un anno sulla performance cognitiva e a livello emotivo e funzionale. I risultati hanno mostrato che cicli intensivi di CT, in associazione al trattamento farmacologico, permettono di migliorare la prestazione ai test che coinvolgono principalmente le funzioni esecutive di controllo, e di non perdere l’autonomia nel quotidiano. Questi risultati sono stati confrontati con pazienti che hanno svolto attività più generali e meno specifiche frequentando un Centro Diurno. Nel secondo studio sono state analizzate anche le modificazioni dei network cerebrali, utilizzando indici elettrofisiologici quali i potenziali evento-relati (ERP), dopo un ciclo di CT all’interno del quale un compito cognitivo è stato intensivamente esercitato. I dati ottenuti suggeriscono come dopo l’esercitazione di un compito cognitivo ci sia stato un apprendimento e un cambiamento delle strategie legate all’esecuzione del compito stesso, che si riflette nei cambiamenti d’attivazione corticale ottenuti al post-training, segnalando una riorganizzazione plastica dei network corticali ancora funzionanti. La maggior attivazione registrata durante il compito riproposto per tutta la durata del training a livello dei siti anteriori sinistri può essere, infatti, interpretata come un meccanismo strategico compensatorio che attiva le reti linguistiche per sopperire alla compromissione della memoria. Nel terzo studio l’intervento ha incluso CT associato a esercizi e attività fisica, aumentando la stimolazione da due a quattro ore al giorno. In questo caso non si è evidenziata una strategia compito-specifica per l’esecuzione del compito proposto, ma un pattern d’attivazione ugualmente distribuito alle regioni anteriori e posteriori, senza fenomeni di riorganizzazione plastica dovuti all’utilizzo di strategie funzionali allo svolgimento del compito stesso. A differenza del secondo studio, in questo terzo studio, il compito di controllo (non esercitato) ha mostrato la maggiore modulazione tra prima e dopo il training. In questo caso, infatti, si è osservata una significativa ridistribuzione dell’attivazione corticale dalle aree posteriori (prima del training) a quelle anteriori (dopo il training). Questo maggior coinvolgimento delle aree frontali è stato confermato ai dati neuropsicologici che hanno evidenziato un miglioramento alla performance dei test che elicitano le funzioni esecutive di controllo. Inoltre l’umore, il benessere percepito e la qualità di vita migliorano, così come anche l’andatura. Per quanto riguarda l’analisi delle componenti automatiche del linguaggio emerge chiaramente, in entrambi gli studi 2 e 3, un marcato effetto di potenziamento plastico che ha mostrato come fenomeni di apprendimento, conseguenti ad un training intensivo condotto in un contesto ecologico, siano individuabili mediante la tecnica dei potenziali evocati anche in pazienti con AD. Sono quindi ancora possibili, per questi pazienti con una patologia neurodegenerativa, fenomeni plastici di potenziamento delle reti neurali in aree fondamentali per il linguaggio. Questi studi hanno permesso di verificare l’efficacia di CT per pazienti in fase lieve-moderata evidenziando non solo un mantenimento del quadro cognitivo e funzionale a distanza di tempo, ma anche modificazioni di network cerebrali ancora funzionanti