Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data.

Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data. Methods: A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review. Results: The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature. Conclusion: We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years.

A wearable system for visual cueing gait rehabilitation in Parkinson's disease: a randomized non-inferiority trial.

BACKGROUND: Gait disturbances represent one of the most disabling features of Parkinson's disease (PD). AIM: The aim of this study was to evaluate the non-inferiority of a new wearable visual cueing system (Q-Walk) for gait rehabilitation in PD subjects, compared to traditional visual cues (stripes on the floor). DESIGN: Open-label, monocentric, randomized controlled non-inferiority trial. SETTING: Outpatients. POPULATION: Patients affected by idiopathic PD without cognitive impairment, Hoehn and Yahr stage II-IV, Unified Parkinson's Disease Rating Scale motor section III ≥2, stable drug usage since at least 3 weeks. METHODS: At the enrollment (T0), all subjects underwent a clinical/functional evaluation and the instrumental gait and postural analysis; then they were randomly assigned to the Study Group (SG) or Control Group (CG). Rehabilitation program consisted in 10 consecutive individual sessions (5 sessions/week for 2 consecutive weeks). Each session included 60 minutes of conventional physiotherapy plus 30 minutes of gait training by Q-Walk (SG) or by traditional visual cues (CG). Follow-up visits were scheduled at the end of the treatment (T1) and after 3 months (T2). RESULTS: Fifty-two subjects were enrolled in the study, 26 in each group. The within-groups analysis showed a significant improvement in clinical scales and instrumental data at T1 and at T2, compared to baseline, in both groups. According to the between-group analysis, Q-Walk cueing system was not-inferior to the traditional cues for gait rehabilitation. The satisfaction questionnaire revealed that most subjects described the Q-Walk cueing system as simple, motivating and easily usable, possibly suitable for home use. CONCLUSIONS: Data showed that motor rehabilitation of PD subjects performed by means of the new wearable Q-Walk cueing system was feasible and as effective as traditional cues in improving gait parameters and balance. CLINICAL REHABILITATION IMPACT: Wearable devices can act as an additional rehabilitation strategy for long-term and continuous care, allowing patients to train intensively and extensively in household settings, favoring a tailor-made and personalized approach as well as remote monitoring.

Neurorehabilitation in brain tumours: evidences and suggestions for spreading of knowledge and research implementation.

PURPOSE OF REVIEW: The last few decades have seen an increase in life expectancy in brain tumour patients; however, many patients report sensory-motor and cognitive disabilities due to the tumour itself, but also to the effect of anticancer treatments (surgery, radiotherapy, chemotherapy), supportive treatments, as well as individual patient factors. This review outlines the principles on which to base neurorehabilitation treatments, with the aim of stimulating an early rehabilitative management, in order to reduce disability and functional limitation and improve the quality of life of the persons affected by brain tumour. RECENT FINDINGS: Although not definitive, evidences suggest that an early neurorehabilitative evaluation, performed with a multidisciplinary approach, may identify the different functional impairments that can affect people with brain tumour. Furthermore, identifying and classifying the person's level of functioning is useful for designing achievable recovery goals, through the implementation of tailored multidisciplinary rehabilitation programs. The involvement of different professional figures allows to treat all the components (physical, cognitive, psychological and participation) of the person, and to redesign one's life project, lastly improving the quality of life. SUMMARY: Overall, the evidences suggest a critical need for the development of this clinical area by spreading the concept of rehabilitation among neuro-oncologists and producing high quality research.

Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson's disease: current evidence and future perspectives.

INTRODUCTION: Non-motor symptoms (NMS) affect patients with Parkinson's disease (PD) from the prodromal to the advanced stages. NMS phenotypes greatly vary and have a huge impact on patients' and caregivers' quality of life (QoL). The management of cognitive and neuropsychiatric NMS remains an unmet need. AREAS COVERED: The authors, herein, review the dopaminergic and non-dopaminergic pathogenesis, clinical features, assessment, and pharmacological and non-pharmacological treatments of cognitive and neuropsychiatric NMS in PD. They discuss the current evidence and report the findings of an overview of ongoing trials on pharmacological and selected non-pharmacological strategies. EXPERT OPINION: The treatment of cognitive and neuropsychiatric NMS in PD is poorly explored, and therapeutic options are unsatisfactory. Pharmacological treatment of cognitive NMS is based on symptomatic active principles used in Alzheimer's disease. Dopamine agonists, selective serotonin, and serotonin-norepinephrine reuptake inhibitors have some evidence on PD-related depression. Clozapine, quetiapine, and pimavanserin may be considered for psychosis in PD. Evidence on the treatment of other neuropsychiatric NMS is limited or lacking. Addressing pathophysiological and clinical issues, which hamper solid evidence on the treatment of cognitive and neuropsychiatric NMS, may reduce the impact on QoL for PD patients and their caregivers.

Impact of healthcare-associated infections on functional outcome of severe acquired brain injury during inpatient rehabilitation.

To describe healthcare-associated infections in inpatient neuro-rehabilitation and their impact on functional outcome, a multicenter observational study with severe acquired brain injury (sABI) patients was performed. Patients were divided into infected (INF-group) or not infected (noINF-group) and assessed at admission and discharge, by means of the Glasgow Coma Scale (GCS), the Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), the Disability Rating Scale (DRS), and the modified Barthel Index (mBI). One hundred-nineteen patients were included in the INF-group, and 109 in the noINF-group. Culture specimens were found positive for bloodstream (43.8%), respiratory tract (25.7%), urinary tract (16.2%), gastro-intestinal system (8.6%) and skin (2.4%) infections. Multiple microorganisms were the most frequent (58.1%) and 55.5% of patients needed functional isolation due to multidrug resistant germs. The functional status of both groups improved after rehabilitation, but multivariable analyses showed that the INF-group showed a significantly lower gain to GCS (p = 0.008), DRS (p = 0.020) and mBI (p = 0.021) compared to the noINF-group. Length of stay (LOS) and number of skipped rehabilitative sessions were not statistically different between the groups; mortality rate was significantly higher in the INF-group (p = 0.04). Infected sABI patients showed longer LOS, significant increased mortality, and a lower functional outcome than not infected patients.

The Effect of Robotic Assisted Gait Training With Lokomat® on Balance Control After Stroke: Systematic Review and Meta-Analysis.

Introduction: Disturbances of balance control are common after stroke, affecting the quality of gait and increasing the risk of falls. Because balance and gait disorders may persist also in the chronic stage, reducing individual independence and participation, they represent primary goals of neurorehabilitation programs. For this purpose, in recent years, numerous technological devices have been developed, among which one of the most widespread is the Lokomat®, an actuated exoskeleton that guide the patient's limbs, simulating a symmetrical bilateral gait. Preliminary evidence suggests that beyond gait parameters, robotic assisted gait training may also improve balance. Therefore, the aim of this systematic review was to summarize evidence about the effectiveness of Lokomat® in improving balance in stroke patients. Methods: Randomized controlled trials published between January 1989 and August 2020, comparing Lokomat® training to conventional therapy for stroke patients, were retrieved from seven electronic databases. Balance, assessed by means of validated clinical scales, was considered as outcome measure. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the methodological quality of the studies. The study protocol was registered on PROSPERO (no. CRD42020197531). Results: After the removal of the duplicates, according to the inclusion criteria, 13 studies were selected, involving 445 subacute or chronic stroke patients. Eleven papers contributed to three meta-analyses. Favorable results for recovery of balance in stroke survivors treated with Lokomat® were shown using Timed Up and Go (pooled mean difference = -3.40, 95% CI -4.35 to -2.44; p < 0.00001) and Rivermead Mobility Index as outcome measures (pooled mean difference = 0.40, 95% CI 0.26-0.55; p < 0.00001). Inconclusive results were found when balance was measured by means of the Berg Balance Scale (pooled mean difference = 0.17, 95% CI -0.26 to 0.60; p = 0.44). Conclusions: Overall, most studies have shown beneficial effects of Lokomat® on balance recovery for stroke survivors, at least comparable to conventional physical therapy. However, due to the limited number of studies and their high heterogeneity, further research is needed to draw more solid and definitive conclusions.

The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Background: Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease. Methods: Ninety-one subjects (mean age = 70.29 ± 7.70 years)-healthy older adults (HCs, n = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, n = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, n = 20), and patients with mild Alzheimer's disease (mild AD, n = 25)-were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups. Results: The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p < 0.001), time (p < 0.001), distance (p < 0.001), and total Smart Aging score (p < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used. Conclusion: These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.

Factors influencing cognitive performance after 1-year treatment with direct oral anticoagulant in patients with atrial fibrillation and previous ischemic stroke: a pilot study.

Anticoagulant treatment as stroke prevention, particularly direct oral anticoagulant (DOAC), may reduce the risk of dementia in patients with atrial fibrillation (AF). We aimed to assess factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. We recruited 33 ischemic stroke patients who were discharged from Verona Stroke Unit with diagnosis of AF and prescription of treatment with DOAC. For each cognitive test, we estimated the effect of T0 (first session) variables on T1 (1-year session) cognitive performance using ordinal logistic regression fitted to a 1 point-shift from 4 to 0 on ESs. The effect of T0 clinical variables was presented as odds ratio (OR) with 95% confidence interval (CI) after adjustment for T0 total score of the corresponding cognitive test. Sustained AF (OR: 4.259, 95% CI 1.071-16.942) and ischemic heart disease (OR: 6.654, 95% CI 1.329-33.300) showed a significant effect on T1 MoCA Test; congestive heart failure on T1 RAVLT Immediate recall (OR: 9.128, 95% CI 1.055-78.995), T1 RAVLT Delayed recall (OR: 7.134, 95% CI 1.214-52.760), and T1 Trail Making Test (Part A) (OR: 16.989, 95% CI 1.765-163.565); sustained AF (OR: 5.055, 95% CI 1.224-20.878) and hyperlipidemia (OR: 4.764, 95% CI 1.175-19.310) on T1 Digit span forward Test; ischemic heart disease (aOR: 8.460, 95% CI 1.364-52.471) on T1 Stroop Color and Word Test (time); Dabigatran use (aOR: 0.084, 95% CI 0.013-0.544) on FAB; age ≥ 75 years (aOR: 0.058, 95% CI 0.006-0.563) and hyperlipidemia (aOR: 5.809, 95% CI 1.059-31.870) on T1 Phonemic word fluency Test; female sex (aOR: 6.105, 95% CI 1.146-32.519), hyperlipidemia (aOR: 21.099, 95% CI 2.773-160.564), total Modified Fazekas Scale score > 1 (aOR: 78.530, 95% CI 3.131-1969.512) on Semantic word fluency Test. Sustained AF, ischemic heart disease, congestive heart failure, hyperlipidemia, and female sex were the factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. Modified Fazekas Scale score in the first session was the only radiological variable that had a significant effect on cognitive performance.

Non-invasive Brain and Spinal Stimulation for Pain and Related Symptoms in Multiple Sclerosis: A Systematic Review.

Background: Neuropathic and nociceptive pain frequently affect patients with multiple sclerosis (MS), with a prevalence close to 90% and significant impact on general health and quality of life. Pharmacological strategies are widely used to treat pain in MS, but their effectiveness and side-effects are controversial. Among non-pharmacological treatments for pain, non-invasive brain and spinal stimulation (NIBSS) has shown promising preliminary results in MS. Objective: Systematic review to investigate the effect of NIBSS for the management of pain in MS. Methods: A literature search using Pubmed, Science Direct and Web of Science was conducted from databases inception to February 21, 2020 for studies assessing the analgesic effect of NIBSS on pain in MS. Results: A total of 279 records were title- and abstract-screened, nine were assessed for full text and included. The NIBSS techniques explored were transcranial direct current stimulation (N = 5), transcranial magnetic stimulation (N = 2), transcranial random noise stimulation (N =1), transcutaneous spinal direct current stimulation (N = 1). The targets were the primary motor cortex (M1; N = 4), the left dorsolateral pre-frontal cortex (DLPFC; N = 3), the spinal cord (N = 1), unspecified brain target (N = 1). The study designs were randomized (N = 7), open label (N = 1), single case report (N = 1). Despite the differences in study design, target and NIBSS technique that impeded a meta-analysis, all the studies converge in showing a significant improvement of pain after active NIBSS with less consistent effects on other symptoms of the pain-related cluster (depression, fatigue, cognition) and quality of life. Conclusions: Excitatory NIBSS over M1, left DLPFC and spinal cord appear to be the most effective protocols for pain in MS. Open questions include the use of neurophysiological or neuroimaging surrogate outcome measures, the stratification of patients according to the clinical profiles and underlying pathogenetic mechanisms and the combination of NIBSS to pharmacological treatment, neurorehabilitation, or psychotherapy to improve the clinical effect. The duration of the effect to NIBSS and the feasibility and efficacy of telemedicine NIBSS protocols are other open key questions.

Healthcare-Associated Infections in Subjects With Severe Acquired Brain Injury: The Effect of Microbial Colonization on the Functional Outcome. Data From a Multicenter Observational Study.

Background: Hospital-acquired infections (HAIs) and microbial colonization are a worldwide serious threat for human health. Neurological patients with infections who undergo rehabilitation have a significantly poor recovery. The effect of microbial colonization on the functional outcome in severe acquired brain injury (sABI) subjects is still unclear. Aim: The aim of this multicenter observational study was to describe the clinical impact of HAIs and colonization on the functional outcome of sABI subjects admitted to inpatient neurorehabilitation. Methods: Patients were assigned to three groups: infected (INF), not infected (noINF), and colonized (COL). The Glasgow Coma Scale (GCS), the Rancho Los Amigos Levels of Cognitive Functioning Scale, Disability Rating Scale, and modified Barthel Index (mBI) assessments were performed both at admission and discharge. Results: Two hundred sixty-five (92 female/173 male) patients were enrolled: 134 were assigned to INF, 63 to COL, and 68 to noINF. In the INF group, 231 culture specimens were found positive for bloodstream (44.2%), respiratory tract (25.5%), urinary tract (18.6%), gastrointestinal tract (8.3%), skin (3%), and cerebrospinal fluid (0.4%) infections. After rehabilitation, all groups showed a significant improvement in all assessment tests, except for the noINF group that did not show any improvement in GCS. Both noINF and COL groups showed a significantly higher gain in mBI than the INF group (p = 0.000). The COL group showed a significantly higher gain than the noINF group in GCS (p = 0.001). A significantly lower improvement was detected in the INF group than the COL and noINF groups. The rate of patients who needed functional isolation was higher in the INF group than the COL group. Length of stay (LOS) (in days) was 56 ± 50.7, 88.3 ± 55, and 101.3 ± 73.6 for noINF, INF, and COL groups, respectively. The number of deaths in the INF group was significantly higher (24.6%) than the noINF group (7.4%) (p = 0.005) and comparable to the COL group (19%). Conclusion: Colonized sABI patients obtained a similar functional outcome to that of subjects who had no infections, even if they needed a significantly higher LOS.

Non-invasive Brain Stimulation for Gambling Disorder: A Systematic Review.

Background: Gambling disorder (GD) is the most common behavioral addiction and shares pathophysiological and clinical features with substance use disorders (SUDs). Effective therapeutic interventions for GD are lacking. Non-invasive brain stimulation (NIBS) may represent a promising treatment option for GD. Objective: This systematic review aimed to provide a comprehensive and structured overview of studies applying NIBS techniques to GD and problem gambling. Methods: A literature search using Pubmed, Web of Science, and Science Direct was conducted from databases inception to December 19, 2019, for studies assessing the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (t-DCS) on subjects with GD or problem gambling. Studies using NIBS techniques on healthy subjects and those without therapeutic goals but only aiming to assess basic neurophysiology measures were excluded. Results: A total of 269 articles were title and abstract screened, 13 full texts were assessed, and 11 were included, of which six were controlled and five were uncontrolled. Most studies showed a reduction of gambling behavior, craving for gambling, and gambling-related symptoms. NIBS effects on psychiatric symptoms were less consistent. A decrease of the behavioral activation related to gambling was also reported. Some studies reported modulation of behavioral measures (i.e., impulsivity, cognitive and attentional control, decision making, cognitive flexibility). Studies were not consistent in terms of NIBS protocol, site of stimulation, clinical and surrogate outcome measures, and duration of treatment and follow-up. Sample size was small in most studies. Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the efficacy of NIBS interventions for GD. Further methodologically sound, robust, and well-powered studies are needed.

Telemedicine and Virtual Reality for Cognitive Rehabilitation: A Roadmap for the COVID-19 Pandemic.

The current COVID-19 pandemic presents unprecedented new challenges to public health and medical care delivery. To control viral transmission, social distancing measures have been implemented all over the world, interrupting the access to routine medical care for many individuals with neurological diseases. Cognitive disorders are common in many neurological conditions, e.g., stroke, traumatic brain injury, Alzheimer's disease, and other types of dementia, Parkinson's disease and parkinsonian syndromes, and multiple sclerosis, and should be addressed by cognitive rehabilitation interventions. To be effective, cognitive rehabilitation programs must be intensive and prolonged over time; however, the current virus containment measures are hampering their implementation. Moreover, the reduced access to cognitive rehabilitation might worsen the relationship between the patient and the healthcare professional. Urgent measures to address issues connected to COVID-19 pandemic are, therefore, needed. Remote communication technologies are increasingly regarded as potential effective options to support health care interventions, including neurorehabilitation and cognitive rehabilitation. Among them, telemedicine, virtual reality, augmented reality, and serious games could be in the forefront of these efforts. We will briefly review current evidence-based recommendations on the efficacy of cognitive rehabilitation and offer a perspective on the role of tele- and virtual rehabilitation to achieve adequate cognitive stimulation in the era of social distancing related to COVID-19 pandemic. In particular, we will discuss issues related to their diffusion and propose a roadmap to address them. Methodological and technological improvements might lead to a paradigm shift to promote the delivery of cognitive rehabilitation to people with reduced mobility and in remote regions.

Towards a Redefinition of Cognitive Frailty.

BACKGROUND: The progressive aging of the population will dramatically increase the burden of dementia related to Alzheimer's disease (AD) and other neurodegenerative disorders in the future. Because of the absence of drugs that can modify the neuropathological substrate of AD, research is focusing on the application of preemptive and disease-modifying strategies in the pre-symptomatic period of the disease. In this perspective, the identification of people with cognitive frailty (CF), i.e., those individuals with higher risk of developing dementia, on solid pathophysiological bases and with clear operational clinical criteria is of paramount importance. OBJECTIVE/METHODS: This hypothesis paper reviews the current definitions of CF, presents and discusses some of their limitations, and proposes a framework for updating and improving the conceptual and operational definition of the CF construct. RESULTS: The potential for reversibility of CF should be supported by the assessment of amyloid, tau, and neuronal damage biomarkers, especially in younger patients. Physical and cognitive components of frailty should be considered as separate entities, instead of part of a single macro-phenotype. CF should not be limited to the geriatric population, because trajectories of amyloid accumulation are supposed to start earlier than 65 years in AD. Operational criteria are needed to standardize assessment of CF. CONCLUSION: Based on the limitations of current CF definitions, we propose a revised one according to a multidimensional subtyping. This new definition might help stratifying CF patients for future trials to explore new lifestyle interventions or disease-modifying pharmacological strategies for AD and dementia.

QTc Prolongation in Patients with Dementia and Mild Cognitive Impairment: Neuropsychological and Brain Imaging Correlations.

The QTc interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. This marker is often prolonged in acute and chronic neurological conditions. The cause of the cerebrogenic QT prolongation remains unclear. The aim of the study was to analyze the relation between QTc interval and the degree of cognitive impairment and structural brain imaging changes in patients with dementia and mild cognitive impairment (MCI). To this aim, 269 patients were screened, of whom 61 met one or more exclusion criteria. The remaining 208 patients (56 control subjects, 44 patients with MCI, and 108 with dementia) were recruited. Eighty-five patients using drugs causing prolongation of QT interval were further excluded. The QT interval was measured manually in all 12 leads by a single blinded observer, assuming the longest QT value adjusted for heart rate by using the Bazett's formula. All patients underwent a structural brain imaging and the following measures were obtained: the bicaudate ratio and the periventricular hyperintensity and deep white matter hyperintensity using the modified Fazekas scale. Prolonged QTc interval was prevalent in 1) patients with dementia, especially in those with moderate-severe degree; 2) subjects with impairment of praxis and attention, low functional status, and behavioral symptoms; 3) patients with global and temporal atrophy and with higher scores on the Fazekas or leukoaraiosis scales. Degenerative and vascular processes might play a main role in QTc interval prolongation because of the damage to brain areas involved in the control of the autonomic cardiac nervous system.

Comorbidities in elderly patients with glioblastoma: a field-practice study.

AIM: This single-center study evaluated the effect of comorbidities on progression-free and overall survival in elderly patients with glioblastoma multiforme (GBM). PATIENTS & METHODS: Comorbid conditions were identified in each patient with the modified version of the cumulative illness rating scale (CIRS). RESULTS:  Total of 118 patients with GBM were enrolled. An age of >75 years at diagnosis, high CIRS, comorbidity index and performance status play a predictive role on survival. CONCLUSION: Comorbidities play an important prognostic role in elderly patients with GBM, a factor too often neglected in clinical practice. If the prognostic role of comorbidity measured by CIRS on outcome will be confirmed, it would be interesting to add it in the algorithm for treatment choice in elderly GBM patients.

Rehabilitation in oldest-old stroke patients: a comparison within over 65 population.

BACKGROUND: Considering the demographic trend, characterized by a marked aging due to the increase in life expectancy and the improvement in medical care, in the next future elderly patients will represent the majority of stroke victims with a strong impact on rehabilitative services. AIM: To investigate and characterize differences in functional outcome in elderly patients after stroke. DESIGN: Observational study. SETTING: Post-acute inpatient rehabilitation. POPULATION: Subjects aged ≥65 years with acute (i.e. within 30 days from onset) ischemic or hemorrhagic stroke. METHODS: At admission, all patients underwent neurological and clinical examination, functional evaluation and laboratory assessment. Comorbidities and clinical complications during hospital stay were recorded. Functional status was evaluated by means of the Functional Independence Measure (FIM) administered at admission and discharge. All patients underwent neuromotor rehabilitation, and speech therapy in case of aphasia, once a day, six days per week. RESULTS: The study enrolled 402 patients, who were stratified in three groups according to age: 145 patients in Group 1, the young-old (65-74.9 years, G1), 206 in Group 2, the middle-old (75-84.9 years, G2) and 51 in Group 3, the oldest-old (≥85 years, G3). At discharge, FIM total scores increased significantly for all the groups (P<0.001); however FIM gains, as well as the efficiency parameters derived from FIM were significantly lower in G3 when compared with G1 and G2. G3 showed a significantly higher rate of comorbidities and a higher presence of pressure sores; infections occurred mainly in G2 and G3. Hospitalization was significantly longer for G1 and G2 with respect to G3, while mortality rates were significantly higher in G2 and G3 with respect to G1. The variables that predicted functional outcome were age, previous stroke, stroke severity and functional status at admission. CONCLUSIONS: Despite advancing age seems to be associated with a reduced effectiveness of the rehabilitation process and a greater number of complications, intensive rehabilitation can produce significant functional gains for all stroke survivors, regardless of age. CLINICAL REHABILITATION IMPACT: Understanding the specificity of this population will offer older subjects targeted interventions and, for health systems, better allocation of resources and the development of more effective approaches.

Identifying clinical complexity in patients affected by severe acquired brain injury in neurorehabilitation: a cross sectional survey.

BACKGROUND: Literature shows that occurrence of comorbidities in people with severe acquired brain injury (sABI) is a common problem in rehabilitation stay. Consequently, patients could require an increase of interventions for diagnosis and treatment of clinical conditions, with a reduction of the rehabilitative take in charge for both clinical and organizational aspects. AIM: The first aim was to evaluate the rate of clinical conditions of sABI patients at admission in rehabilitation and the types of rehabilitative interventions performed in the first week; second objective was to explore the impact of clinical conditions on real rehabilitative take in charge. DESIGN: Cross sectional study. SETTING: Inpatient rehabilitation centers. POPULATION: The study included data from 586 sABI patients. METHODS: Collected data regarded anamnestic information, functional status assessed by means of Glasgow Outcome Scale, Levels of cognitive functioning, Early Rehabilitation Barthel Index, comorbidities at admission and type of rehabilitative interventions carried out in first week of rehabilitation stay. Spearman correlation coefficients were applied to detect possible correlations between the number of treatments in first week and clinical variables; through a multiple regression analysis the effect of patient's characteristics on rehabilitative take in charge was explored. RESULTS: Data from the sABI patients: mean age 55.1±17.1 years; etiology of sABI was vascular in 315 patients (53.8%), anoxic in 83 (14.2%), neoplastic in 17 (2.9%), infectious in 15 (2.6%), traumatic in 150 (25.6%); 6 subjects (1%) presented a mixed etiology. Need of cardiorespiratory monitoring, pressure sores, infections or presence of multi drug resistant bacteria were the most frequent comorbidities. Passive mobilization, sitting positioning, arousal/awareness stimulation, evaluation and management of dysphagia were the interventions most frequently carried out in the first week. The regression analysis showed that severe neurological and clinical conditions, acute organ failure, cardio-respiratory instability and paroxysmal sympathetic hyperactivity significantly limit access to rehabilitative sessions. CONCLUSIONS: In sABI patients clinical comorbidities requiring elevated care assistance are frequent at admission in rehabilitation from acute wards and may interfere with rehabilitative take in charge. CLINICAL REHABILITATION IMPACT: The knowledge of clinical complexity of sABI patients may improve their care pathways, promoting early and appropriate transition from acute care to rehabilitation settings.

Neuropsychological testing.

Neuropsychological testing is a key diagnostic tool for assessing people with dementia and mild cognitive impairment, but can also help in other neurological conditions such as Parkinson's disease, stroke, multiple sclerosis, traumatic brain injury and epilepsy. While cognitive screening tests offer gross information, detailed neuropsychological evaluation can provide data on different cognitive domains (visuospatial function, memory, attention, executive function, language and praxis) as well as neuropsychiatric and behavioural features. We should regard neuropsychological testing as an extension of the neurological examination applied to higher order cortical function, since each cognitive domain has an anatomical substrate. Ideally, neurologists should discuss the indications and results of neuropsychological assessment with a clinical neuropsychologist. This paper summarises the rationale, indications, main features, most common tests and pitfalls in neuropsychological evaluation.

The Multidisciplinary Approach to Alzheimer's Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment.

Background: Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia. Aim: To review, with a narrative approach, current evidence on main NPTs for AD and dementia. Methods: PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers. Results: The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden. Conclusions: Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia.

A New Standardization of the Bells Test: An Italian Multi-Center Normative Study.

Objective: The Bells Test is a cancelation task that is widely used for the diagnosis of unilateral spatial neglect (USN). With the aim of fostering more reliable use of this instrument, we set out to develop new norms adjusted for the possible influence of age, gender and education. We worked on the original version of the test. Methods: Normative data were collected from 401 healthy participants aged between 20 and 80 years. Individual factors that could affect performance (i.e., gender, age, and years of education) were considered. We computed several indices on the Bells Test including an asymmetry score, an accuracy score and execution time. Multiple regression analyses (for time measures) and generalized linear models (for accuracy measures) were used to check for the influence of individual predictors of performance on the Bells Test. Results: Data indicated a significant influence of age on the accuracy score and execution time variables and a marginally significant effect of education on the accuracy score variable. Wherever appropriate, cut-offs are provided for the three dependent scores on the Bells Test corrected for age and education. Conclusion: Based on a large normative sample, the present study provides new normative data on the Bells Test, which could lead to its reliable use in the diagnosis of USN.