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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., (Copyright © 2020 Bartolo, Zucchella, Aabid, Valoriani, Mancuso and Intiso.)

One of the challenges of providing healthcare services is to enhance its value (for patients, staff and the service) by integrating the informal caregivers into the care process, both concretely managing their patient's health conditions and treatment (co-executing) and participating in the whole healthcare process (co-planning). This study aims at exploring the co-production contribution to the healthcare process, analysing whether and how it is related to higher caregivers' satisfaction with service care and reduced staff burnout, in the eyes of the staff. It also investigated two possible factors supporting caregivers in their role of co-producers, namely relationship among staff and informal caregivers related to knowledge sharing (i.e. an ability determinant supporting co-production) and related to role social conflict (i.e. a willingness determinant reducing co-production). Results of a structural equation model on a sample of 119 healthcare providers employed by neurorehabilitation centers in Italy with severe acquired brain injury confirmed that knowledge sharing positively related with caregivers' co-executing and co-planning. Also, social role conflict was negatively related with co-executing but positively with co-planning. Furthermore, co-planning resulted in being unrelated to both outcomes, whereas co-executing was associated with caregivers' satisfaction, as measured by staff perceptions. Overall, our data provided initial empirical evidence supporting the ability of the determinant's contribution in allowing informal caregivers to assume an active role in both co-production domains. Furthermore, as expected, the role of conflict willingness determinant was found to be a hindering factor for co-executing but, conversely, a trigger for co-planning. This result should be considered more carefully in future studies., (© 2020 John Wiley & Sons Ltd.)

Objective: This international multicenter, prospective, observational study aimed at identifying predictors of short-term clinical outcome in patients with prolonged disorders of consciousness (DoC) due to acquired severe brain injury., Methods: Patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS) were enrolled within 3 months from their brain injury in 12 specialized medical institutions. Demographic, anamnestic, clinical, and neurophysiologic data were collected at study entry. Patients were then followed up for assessing the primary outcome, that is, clinical diagnosis according to standardized criteria at 6 months postinjury., Results: We enrolled 147 patients (44 women; mean age 49.4 [95% confidence interval 46.1-52.6] years; VS/UWS 71, MCS 76; traumatic 55, vascular 56, anoxic 36; mean time postinjury 59.6 [55.4-63.6] days). The 6-month follow-up was complete for 143 patients (VS/UWS 70; MCS 73). With respect to study entry, the clinical diagnosis improved in 72 patients (VS/UWS 27; MCS 45). Younger age, shorter time postinjury, higher Coma Recovery Scale-Revised total score, and presence of EEG reactivity to eye opening at study entry predicted better outcome, whereas etiology, clinical diagnosis, Disability Rating Scale score, EEG background activity, acoustic reactivity, and P300 on event-related potentials were not associated with outcome., Conclusions: Multimodal assessment could identify patients with higher likelihood of clinical improvement in order to help clinicians, families, and funding sources with various aspects of decision-making. This multicenter, international study aims to stimulate further research that drives international consensus regarding standardization of prognostic procedures for patients with DoC., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

(1) Background : In addition to conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) has been investigated as a potential diagnostic and predictive tool for patients with degenerative cervical myelopathy (DCM). In this preliminary study, we evaluated the use of quantitative DTI in the clinical practice as a possible measure to correlate with upper limbs function. (2) Methods: A total of 11 patients were enrolled in this prospective observational study. Fractional anisotropy (FA) values was extracted from DTI data before and after surgery using a GE Signa 1.5 T MRI scanner. The Nine-Hole Peg Test and a digital dynamometer were used to measure dexterity and hand strength, respectively. (3) Results: We found a significant increase of FA values after surgery, in particular below the most compressed level ( p = 0.044) as well as an improvement in postoperative dexterity and hand strength. Postoperative FA values moderately correlate with hand dexterity (r = 0.4272, R₂ = 0.0735, p = 0.19 for the right hand; r = 0.2087, R₂ = 0.2265, p = 0.53 for the left hand). (4) Conclusion: FA may be used as a marker of myelopathy and could represent a promising diagnostic value in patients affected by DCM. Surgical decompression can improve the clinical outcome of these patients, especially in terms of the control of finger-hand coordination and dexterity.

Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term "high dosage" indicated ≥ 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable., Competing Interests: The authors declare no conflict of interest.

COVID-19 has rapidly become a pandemic emergency, distressing health systems in each affected country. COVID-19 determines the need for healthcare in a large number of people in an extremely short time and, like a tsunami wave, overruns emergency, infectious diseases, and pneumology departments as well as intensive care units, choking healthcare services. Rehabilitation services are also affected by this epidemic which forces radical changes both in the organization and in the operating methods. In the absence of reference literature on this issue, this report aims to provide a background documentation to support physicians and healthcare personnel involved in neurorehabilitation and rehabilitation care., (Copyright © 2020 Bartolo, Intiso, Lentino, Sandrini, Paolucci, Zampolini and the Board of the Italian Society of Neurological Rehabilitation (SIRN).)

Background: Critical illness polyneuropathy and myopathy (CIPNM) is a disabling neuropathy that occurs in intensive care unit (ICU) subjects. It was hypothesized that a low serum level or deficiency of 25(OH)D might be associated with CIPNM. The aim of the present study was to ascertain the 25(OH)D serum level in subjects with CIPNM., Method: Consecutive ICU patients admitted to neuro-rehabilitation were prospectively enrolled. At admission, vitamin D serum levels were measured and EMG examination was performed to ascertain those with CIPNM. 25(OH)D was stratified as sufficient (≥30 ng/mL) insufficient (20-29.9 ng/mL), and deficient (<20 ng/mL)., Results: Eighty-four patients (31 F, 53 M; mean age 51.7±12.6) were identified and 63 (21 F, 42 M) enrolled. CIPNM was detected in 38 (9 F, 29 M) patients. A deficient mean serum level of vitamin D was observed in the whole population: 18.1 ± 9.2 ng/mL. No difference of vitamin D serum levels was detected in subjects with and without CIPNM: 17.5 ± 8.4 and 19.0 ± 10.5 ng/mL (p=0.58), respectively., Conclusion: Almost all subjects showed Vitamin D deficiency. No difference was detected between those with and without CIPNM. The condition might represent a secondary phenomenon resulting from the inflammatory process as well as from conditions that could interfere with vitamin D metabolism., Competing Interests: The authors have no conflict of interest.

Background: The persistent trigeminal artery (PTA) is an adult carotid-basilar anastomosis with debated pathologic aspects, such as its association with brain aneurysms. True trigeminal artery aneurysms are rare vascular anomalies, reported in a few case reports., Objective: To report our experience with a ruptured trigeminal artery aneurysm and to provide a systematic review of the literature in order to analyse potential links between the anatomic configuration of the PTA and PTA aneurysm (PTAA) type, and implications of each PTAA type for the diagnostic and therapeutic approach., Methods: We reviewed the medical literature on trigeminal artery aneurysms according to the PRISMA guidelines. Population characteristics, aneurysms features, and PTA type and side were assessed., Results: 40 previously published cases of PTAAs were included in the analysis. The mean age of subjects was 55 years, with a strong female predominance (77%). Four PTAAs were accidentally discovered, while 16 caused compressive symptoms and 20 were ruptured. Successful endovascular treatment was performed in 62% of cases., Conclusions: PTAAs are rare vascular anomalies, underdiagnosed in the presence of a trigemino-cavernous fistula. Parent vessel occlusion seems to be the best therapeutic option for ruptured or symptomatic unruptured PTAAs in Saltzman type II and III PTAs. Patency of the parent vessel is the main target in Saltzman type I PTA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The ability to fabricate new materials using nanomaterials as building blocks, and with meta functionalities, is one of the most intriguing possibilities in the area of materials design and synthesis. Semiconducting quantum dots (QDs) and magnetic nanoparticles (MNPs) are co-dispersed in a liquid crystalline (LC) matrix and directed to form self-similar assemblies by leveraging the host's thermotropic phase transition. These co-assemblies, comprising 6 nm CdSe/ZnS QDs and 5-20 nm Fe 3 O 4 MNPs, bridge nano- to micron length scales, and can be modulated in situ by applied magnetic fields <250 mT, resulting in an enhancement of QD photoluminescence (PL). This effect is reversible in co-assemblies with 5 and 10 nm MNPs but demonstrates hysteresis in those with 20 nm MNPs. Transmission electron microscopy (TEM) and energy dispersive spectroscopy reveal that at the nanoscale, while the QDs are densely packed into the center of the co-assemblies, the MNPs are relatively uniformly dispersed through the cluster volume. Using Lorentz TEM, it is observed that MNPs suspended in LC rotate to align with the applied field, which is attributed to be the cause of the observed PL increase at the micro-scale. This study highlights the critical role of correlating multiscale spectroscopy and microscopy characterization in order to clarify how interactions at the nanoscale manifest in microscale functionality.

Introduction: Nowadays several plant species, such as Echinacea angustifolia L., can be considered natural important sources for therapeutic applications. Echinacea angustifolia is one of the most known medicinal plants, it shows protective and preventive effects against many chronic diseases, thanks to immunostimulant properties, mostly due to its polysaccharides and antioxidants. However, the optimisation of green extraction techniques to respect the environment is, currently, a hard challenge for the recovery of secondary metabolites., Methodology: Hydro-enzymatic extraction has been performed for the first time, it was compared with other different extraction techniques, for their efficacy in bioactive compound recovery. Phytochemical characterisation has been carried out through high-performance liquid chromatography diode array detector (HPLC-DAD) analysis and the antioxidant activity has been also measured., Results: The highest extractive yields and the strongest antioxidant activity was obtained by cellulase and xylanase enzyme extraction. The enzymatic extraction with pectinase enzyme led to a higher polysaccharide content in comparison with the literature. The hydro-enzymatic extraction method and analytical conditions allowed the identification and quantification of two compounds, to the best of our knowledge, for the first time in E. angustifolia root extract., Conclusion: The optimised extraction methods discussed in this work led to a higher polysaccharides content, in comparison to previous literature results. The enzymatic extraction seems to be the best extraction technique, in terms of antioxidant yield and efficacy in bioactive compound recovery., (© 2019 John Wiley & Sons, Ltd.)

Introduction: The progressive modular rebalancing (PMR) system is a comprehensive rehabilitation approach derived from proprioceptive neuromuscular facilitation principles. PMR training encourages focus on trunk and proximal muscle function through direct perception, strength, and stretching exercises and emphasizes bi-articular muscle function in the improvement of gait performance. Sensory cueing, such as visual cues (VC), is one of the more established techniques for gait rehabilitation in PD. In this study, we propose PMR combined with VC for improving gait performance, balance, and trunk control during gait in patients with PD. Our assumption herein was that the effect of VC may add to improved motor performance induced by the PMR treatment. The primary aim of this study was to evaluate whether the PMR system plus VC was a more effective treatment option than standard physiotherapy in improving gait function in patients with PD. The secondary aim of the study was to evaluate the effect of this treatment on motor function severity. Design: Two-center, randomized, controlled, observer-blind, crossover study with a 4-month washout period. Participants: Forty individuals with idiopathic PD in Hoehn and Yahr stages 1-4. Intervention: Eight-week rehabilitation programs consisting of PMR plus VC (treatment A) and conventional physiotherapy (treatment B). Primary outcome measures: Spatiotemporal gait parameters, joint kinematics, and trunk kinematics. Secondary outcome measures: UPDRS-III scale scores. Results: The rehabilitation program was well-tolerated by individuals with PD and most participants showed improvements in gait variables and UPDRS-III scores with both treatments. However, patients who received PMR with VC showed better results in gait function with regard to gait performance (increased step length, gait speed, and joint kinematics), gait balance (increased step width and double support duration), and trunk control (increased trunk motion) than those receiving conventional physiotherapy. While crossover results revealed some differences in primary outcomes, only 37.5% of patients crossed over between the groups. As a result, our findings should be interpreted cautiously. Conclusions: The PMR plus VC program could be used to improve gait function and severity motor of motor deficit in individuals with PD. Clinical Trial Registration : www.ClinicalTrials.gov, identifier NCT03346265.

Background: Gait disorders represent one of the most disabling features of Parkinson's disease, which may benefit from rehabilitation. No consistent evidence exists about which gait biomechanical factors can be modified by rehabilitation and which clinical characteristic can predict rehabilitation-induced improvements. Objectives: The aims of the study were as follows: (i) to recognize the gait parameters modifiable by a short-term rehabilitation program; (ii) to evaluate the gait parameters that can normalize after rehabilitation; and (iii) to identify clinical variables predicting improvements in gait function after rehabilitation. Methods: Thirty-six patients affected by idiopathic Parkinson's disease in Hoehn-Yahr stage 1-3 and 22 healthy controls were included in the study. Both clinical and instrumental (gait analysis) evaluations were performed before and after a 10-weeks rehabilitation treatment. Time-distance parameters, lower limb joint, and trunk kinematics were measured. Results: At baseline evaluation with matched speed, almost all gait parameters were significantly different between patients and healthy controls. After the 10-weeks rehabilitation, most gait parameters improved, and spatial asymmetry and trunk rotation normalized. Multiple linear regression of gender combined with Unified Parkinson's Disease Rating Scale-III predicted both ΔSpeed and ΔStep length of both sides; gender combined with Unified Parkinson's Disease Rating Scale-II predicted ΔCadence; age combined with Hoehn-Yahr score and disease duration predicted Δtrunk rotation range of motion. Conclusions: Impaired gait parameters are susceptible to improvement by rehabilitation, and younger men with Parkinson's disease who are less severely affected and at early disease stage are more susceptible to improvements in gait function after a 10-weeks rehabilitation program.

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.

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.

Background: Indocyanine green videoangiography (ICG-V) is used with increasing frequency in neurovascular surgery. ICG-V use in spinal dural arteriovenous fistulas (DAVFs) allows visualization of the hemodynamics of the fistula and to confirm its exclusion after ligation of the feeder. Here, we illustrate how ICG-V is useful for centering the surgical exposure during mini-invasive approaches to spinal DAVFs., Methods: An overweight 66-year-old woman with progressive paraparesis and sphincter disturbances underwent treatment for a spinal DAVF fed by the left T6 radicular artery. After intraoperative fluoroscopy, T6 hemilaminectomy was performed. Because of slight misplacement of the bone opening, the feeder was not visible at the dural opening. We placed a temporary clip on a perimedullary arterialized vein and performed ICG-V while removing the clip., Results: Reviewing the video clip and analyzing the direction of ICG flow inside the perimedullary venous plexus allowed us to locate the fistula with respect to the bone window and to extend the laminectomy in the correct direction., Conclusions: IGC-V can be helpful in mini-invasive approaches to spinal DAVFs to recalibrate the bone opening after misplacement of the initial hemilaminectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Background: Robot-assisted gait training (RAGT) is widely used in children with cerebral palsy (CP), but information about optimal intervention frequency and duration is still lacking and the current evidence about effect of RAGT on motor endurance and fitness is very preliminary., Objective: To investigate the effect of RAGT on motor performance and endurance in children affected by CP., Methods: Data from 14 consecutive children (6 females, age range: 4.6-15.8 years) affected by CP, who underwent a multidisciplinary rehabilitation program during a 18-24 month period, were retrospectively collected. Rehabilitation program included conventional physical therapy and RAGT (60/60 minutes, 20 daily sessions, 5 days/week). CP severity was stratified according to the Gross Motor Function Classification System. Clinical evaluation was performed by means of the six-minute walking test, the modified Ashworth scale, and RAGT measures (total distance, mean distance for session and speed)., Results: Clinical outcomes and speed did not improve after treatment, while total distance (p = 0.006) and mean distance for session (p = 0.007) significantly improved., Conclusions: Our preliminary study suggests that RAGT combined with conventional treatment may improve motor performance and endurance in children with CP. Future randomized controlled trials comparing RAGT to conventional treatment are needed.

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.

Purpose of Review: Exercise and movement are increasingly used in pain management and in palliative care, outside the traditional context of physical medicine and rehabilitation. This critical review aims to provide specialists in pain and palliative medicine with recent insights into the use of exercise and movement in the approach to musculoskeletal disorders when pain and disability are the major complaints., Recent Findings: If there is a common sense linking pain and movement in both directions, that is pain influencing movement - as a withdrawal movement or a reduction of mobility as a defense reaction - or movement evoking pain, not so clear and recognized is the link between exercise and movement in controlling pain., Summary: Conflicting results emerge between absolutely convincing basic science research confirming important effects induced by movement and exercise on pain and substantial poor low evidence level from clinical research as stated by almost all systematic reviews. The need of rigorous clinical trials is mandatory to ascertain a real clinical benefit for the use of movement and exercise for pain control.

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder caused by the deposition of abnormal proteins in neurons of the basal ganglia that limit motor ability, resulting in disability and reduced quality of life. So far, no pharmacologic therapy has been developed, and the treatment remains symptomatic. The aim of the present study is to perform a systematic investigation of the literature, and to determine the types and effects of rehabilitative interventions used for PSP. A search of all studies was conducted in MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL, and EMBASE. Twelve studies were identified, including 6 case reports, 3 case series, one case-control study, one quasi-randomized trial (i.e. not truly random) with crossover design, and one randomized controlled trial, with 88 patients investigated overall. Rehabilitative interventions varied in type, number, frequency, and duration of sessions. The most commonly used clinical measures were the Progressive Supranuclear Palsy Rating Scale (PSPRS) and Unified Parkinson's Disease Rating Scale (UPDRS). Physical exercises were the main rehabilitative strategy but were associated with other interventions and rehabilitative devices, in particular treadmill and robot-assisted gait training. All studies showed an improvement in balance and gait impairment with a reduction of falls after rehabilitation treatment. Because of poor methodological quality and the variety of rehabilitative approaches including different and variable strategies, there was insufficient evidence of the effectiveness of any specific rehabilitation intervention in PSP. Despite this finding, rehabilitation might improve balance and gait, thereby reducing falls in PSP patients., Level of Evidence: IV., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

In the last decade robotic devices have been applied in rehabilitation to overcome walking disability in neurologic diseases with promising results. Robot assisted gait training (RAGT) using the Lokomat seems not only to improve gait parameters but also the perception of well-being. Data on the psychosocial patient-robot impact are limited, in particular in the real-world of RAGT, in the rehabilitation setting. During rehabilitation training, the Lokomat can be considered an "assistive device for movement". This allowed the use of the Psychosocial Impact of Assistive Device Scale- PIADS to describe patient interaction with the Lokomat. The primary aim of this pilot study was to evaluate the psychosocial impact of the Lokomat in an in-patient rehabilitation setting using the PIADS; secondary aims were to assess whether the psychosocial impact of RAGT is different between pathological sub-groups and if the Lokomat influenced functional variables (Functional Independence Measure scale-FIM and parameters provided by the Lokomat itself). Thirty-nine consecutive patients (69% males, 54.0±18.0 years) eligible for Lokomat training, with etiologically heterogeneous walking disabilities (Parkinson's Disease, n = 10; Spinal Cord Injury, n = 21; Ictus Event, n = 8) were enrolled. Patients were assessed with the FIM before and after rehabilitation with Lokomat, and the PIADS was administered after the rehabilitative period with Lokomat. Overall the PIADS score was positive (35.8±21.6), as well as the three sub-scales, pertaining to "ability", "adaptability" and "self-esteem" (17.2±10.4, 8.9±5.5 and 10.1±6.6 respectively) with no between-group differences. All patients significantly improved in gait measure and motor FIM scale (difference after-before treatment values: 11.7±9.8 and 11.2±10.3 respectively), increased treadmill speed (0.4 ± 0.2m/s), reduced body weight support (-14.0±9.5%) and guidance force (-13.1 ± 10.7%). This pilot study indicates that Lokomat, in a real-world in-patient setting, may have a generalised approval, independent of disease, underlining the importance of the psycho-social framework for patients training with assistive robotic-devices.

Objectives: To report occurrence and identify patient's features and risk factors of heterotopic ossifications in patients with severe acquired brain injury in intensive rehabilitation centres., Design: Multicentre cross-sectional survey., Setting: A total of 48 severe acquired brain injury rehabilitation institutes., Participants: Traumatic and non-traumatic severe brain-injured patients ( N = 689) in rehabilitation centres on 28 May 2016., Main Outcome Measure: Occurrence of heterotopic ossifications diagnosed by standard radiological and/or sonographic evaluation on the basis of clinical suspicion., Results: Heterotopic ossification occurred around one or more joints in 94/689 patients (13.6%) with a significantly higher prevalence in young males. Occurrence did not significantly differ in relation to aetiology (16.3% traumatic, 19.2% anoxic, 11.7% vascular and 11.5% other). Prevalence was significantly higher in patients with diffuse (23.3%) rather than focal brain lesions (12.4%) or unspecified lesions (11.2%; chi-square = 7.81, df = 2, P = 0.020); longer duration of coma ( P = 0.0016) and ventilation support ( P = 0.0145); paroxysmal sympathetic hyperactivity (22.6% versus 11.6%; chi-square = 10.81, df = 1, P = 0.001); and spasticity (22.7% versus 10.1%; chi-square = 18.63, df = 1, P < 0.0001). A longer interval between acute brain injury and admission to rehabilitation centre was significantly associated with higher frequency of heterotopic ossifications., Conclusion: Occurrence of heterotopic ossifications is frequent in patients with severe traumatic and non-traumatic brain-injury in rehabilitation centres. Our study confirms male gender, young age, paroxysmal sympathetic hyperactivity, spasticity, longer duration of coma and ventilation and longer interval between brain injury onset and admission to rehabilitation centre as possible risk factors. Further studies are necessary to investigate the role of early appropriate rehabilitation pathways to reduce occurrence of heterotopic ossifications.

Introduction Preliminary evidences showed that telemedicine may allow a reduction of costs and an enhancement of patients' satisfaction and quality of life (QoL), with the same effectiveness of conventional methods of healthcare delivery. Literature is quite absent in relation to the use of telemedicine for patients with disorders of consciousness (DoC) whose management is delegated almost entirely to the family. In order to promote an alternative setting to manage persons affected by DoC, also supporting their families, a pilot project was designed to test the feasibility of home-care assistance based on a system of telemonitoring. Methods In total, 11 patients were supported by a telemonitoring system via a workstation installed at the patients' homes. All patients underwent a clinical and functional evaluation at enrolment, after two months, after six months and at the end of the project, after 12 months by means of clinical scales (Glasgow Coma Scale, Rancho Los Amigos Levels of Cognitive Functioning Scale, Glasgow Outcome Scale, Disability Rating Scale), while the World Health Organization (WHO) QoL, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale and a satisfaction score were completed by caregivers. Results Patients' scores at the clinical scales did not show statistically significant differences from T0 to T3. A trend toward the improvement of caregivers' QoL, anxiety and depression, as well as a high degree of satisfaction with regard to the intervention, were reported. The economic evaluation showed an average cost/day for a patient of about €70. Discussion Preliminary data suggest that the use of telemonitoring services in the management of persons affected by DoC is feasible and well accepted by caregivers, with a potential positive effect on their mood and QoL. Therefore, telemonitoring should be considered in the management of DoC patients to favour discharge from acute care and to support families in home care.

Background: Critical illness polyneuropathy and myopathy (CIPNM) frequently occur in intensive care unit (ICU) critically ill subjects; about 55-70% of subjects achieve full recovery. CIPNM can occur in ICU subjects with severe acquired brain injury (sABI), but no data have been reported regarding their outcome., Aim: The aim of the present study was to investigate the functional recovery in subjects suffering from both CIPNM and sABI and whether they had poorer outcome than those with sABI only., Design: Prospective cohort study., Setting: Dedicated rehabilitation setting., Population: Adult ICU subjects with sABI causing a disorder of consciousness graded 3-8 on the Glasgow Coma Scale admitted to a dedicated rehabilitative setting were enrolled from January 2015 to June 2016., Methods: The enrolled sample was divided in two groups: patients with CIPNM and coexistent sABI (CIPNM+sABI) and patients with sABI. Electromyography was performed in all subjects to ascertain CIPNM occurrence, at admission. Functional outcome was investigated using the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS), at admission and discharge. Mortality and length of stay (LOS) were recorded., Results: One-hundred and thirty-one patients (59 F, 72 M; mean age 54.7±15.8) were admitted to the rehabilitation setting, and 111 (47 F, 64 M; mean age: 53.6±18.4 years) were enrolled. Thirty-six (31.8%) had CIPNM+sABI, and 75 patients had isolated sABI. Significant functional outcomes in all assessment measures were observed after rehabilitation in all samples. The estimated mean scores (95% confidence interval) of LCF, DRS, GOS and mRS from a multivariate model adjusted for age, sex and time of ICU stay were: 2.85 (2.53-3.21) and 5.24 (4.81-5.71), 23.94 (22.37-25.62) and 16.04 (14.77-17.41), 2.86 (2.70-3.04) and 3.46 (3.28-3.65), and 4.91 (4.67-5.17) and 3.79 (3.58-4.02), at admission and at discharge, respectively. Despite functional improvement, CIPNM+sABI patients showed lesser improvement than those with sABI only. Furthermore, patients with both disorders had significantly higher median LOS than sABI subjects: 107 (q1-q3: 65-146), and 65 (q1-q3: 38-105) days (P=5.5x10-83), respectively. No statistically significant difference in mortality rates was found between groups., Conclusions: Subjects with CIPNM and coexistent sABI improved after rehabilitation, but had poorer recovery than those with solely sABI requiring a longer LOS., Clinical Rehabilitation Impact: The rehabilitation process in subjects suffering from CINPM is challenging and no evidence support the use of specific rehabilitative approaches to improve function and activities of daily living.

Objective: To determine whether early mobilization of patients with severe acquired brain injury, performed in the intensive/neurointensive care unit, influences functional outcome., Design: Prospective observational study., Setting: Fourteen centres in Italy., Subjects: A total of 103 consecutive patients with acquired brain injury., Methods: Clinical, neurological and functional data, including the Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale (GOS), and Functional Independence Measure (FIM) were collected at admission and every 3?5 days until discharge from the intensive/neurointensive care unit. Patients were divided into mobilization and no mobilization groups, depending on whether they received mobilization. Data were analysed by intragroup and intergroup analysis using a multilevel regression model., Results: Sixty-eight patients were included in the mobilization group. At discharge, both groups showed significant improvements in GCS, DRS, LCF and ERBI scores. The mobilization group showed significantly better improvements in FIM cognitive, GOS and ERBI. The patients in the mobilization group stayed longer in the intensive care unit (p=0.01) and were more likely to be discharged to intensive rehabilitation at a significantly higher rate (p=0.002) than patients in the no mobilization group. No adverse events were reported in either group., Conclusion: Early mobilization appears to favour the clinical and functional recovery of patients with severe acquired brain injury in the intensive care unit.

Purpose: The aim of this study was to evaluate the efficacy of a robotic-assisted gait training (RAGT), together with a conventional exercise program (CEP), to improve PD ambulation, as compared to standard gait training., Methods: Thirty-eight patients with mild PD stage (H&Y 2-2.5) were randomly assigned to an experimental group (EG) or a control group. The 19 patients in EG received 30 min RAGT (using Lokomat device), whereas the 19 controls received a conventional gait training; both groups received 30 min of CEP. Participants were evaluated before (T0), immediately after (T1), and 12 weeks after the end of treatment (T2), by using 10-MWT, Tinetti Test and the motor score of the UPDRS-III., Results: We found that Tinetti Walking (TW) (X 2 (3) = 31.75; p < 0.001), Tinetti Balance (X 2 (3) = 74.07; p < 0.001), UPDRS-III (X 2 (3) = 6.87; p < 0.001) and GDS (X 2 (3) = 28.83; p < 0.001) scores were affected by the type of the rehabilitative treatment. At T2, we found a significant difference between the two groups for TW (t = 2.62; p < 0.02, d = 0.85). Concerning all the study outcomes, a significant improvement was observed from T0 to T1 in both groups. However, the functional motor gain at T2 was maintained only in the EG., Conclusions: RAGT may significantly improve walking ability, motor function and for a maximum period of three months. Thus, our findings support the importance of a RAGT as a valid rehabilitative tool for PD.

Digital pathology is an interdisciplinary field where competency in pathology, laboratory techniques, informatics, computer science, information systems, engineering, and even biology converge. This implies that teaching students about digital pathology requires coverage, expertise, and hands-on experience in all these disciplines. With this in mind, a syllabus was developed for a digital pathology summer school aimed at professionals in the aforementioned fields, as well as trainees and doctoral students. The aim of this communication is to share the context, rationale, and syllabus for this school of digital pathology., Competing Interests: There are no conflicts of interest.

Introduction: The relationship between cognitive and functional impairment in Alzheimer Disease (AD) at the earliest stages of the disease is not well characterized. This study aimed at investigating such relationships along AD evolution by means of the Disability Assessment for Dementia (DAD)., Methods: Consecutive pairs of AD outpatients and their primary informal caregivers were enrolled. Patients were evaluated by means of the Mini Mental State Examination and neuropsychological tests. A clinician completed the Clinical Dementia Rating Scale to stage dementia severity and interviewed the caregivers to complete the Neuropsychiatric Inventory to assess behavioral disturbances and the DAD to evaluate patients' functional competence., Results: A total of 158 dyads were enrolled; the Mini Mental State Examination score was used to stratify patients into 4 groups (>24; 20 to 23.9; 10 to 19.9; <10) that were compared. The statistical analysis revealed that all the cognitive domains were positively related to functional independence, but only logical and executive functions seemed to predict autonomy. An intergroup comparison did not show significant differences in the DAD subscales measuring initiation, planning and organization, and performance. The role of education emerged, confirming the relevance of cognitive reserve., Discussion: As the field moves toward earlier intervention in preclinical AD, the detection of early functional changes may drive the definition of trials on prevention or intervention for dementia.

Purpose of Review: Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially promising effect on pain reduction. In this narrative review, we describe the available compounds for topical use in LNP syndromes and address their potential efficacy according to the literature., Recent Findings: Local anaesthetics (e.g., lidocaine, bupivacaine and mepivacaine), as well as general anaesthetic agents (e.g., ketamine), muscle relaxants (e.g., baclofen), capsaicin, anti-inflammatory drugs (e.g., diclofenac), salicylates, antidepressants (e.g., amitriptyline and doxepin), α2 adrenergic agents (e.g., clonidine), or even a combination of them have been tested in various applications for the treatment of LNP. Few of them have reached a sufficient level of evidence to support systematic use as treatment options. Relatively few systemic side effects or drug-drug interactions and satisfactory efficacy seem to be the benefits of topical treatments. More well-organized and tailored studies are necessary for the further conceptualization of topical treatments for LNP.

Background: Temporal summation of pain sensation is pivotal both in physiological and pathological nociception. In humans, it develops in parallel with temporal summation of the nociceptive withdrawal reflex (NWR) of the lower limb, an objective representation of the temporal processing of nociceptive signals into the spinal cord., Methods: To study the contribution of cortical and subcortical structures in temporal summation of pain reflex responses, we compared the fMRI signal changes related to the temporal summation threshold (TST) of the NWR with that related to the single NWR response. We studied 17 healthy subjects using a stimulation paradigm previously determined to evoke both the TST of the NWR (SUMM) and the NWR single response (SING)., Results: We found a significant activation in left (contralateral) primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), bilateral insula, anterior cingulate cortex (ACC) and bilateral thalamus during both SUMM and SING conditions. The SUMM versus SING contrast revealed a significant deactivation in the posterior cingulate cortex (PCC) and bilateral middle occipital gyrus in SUMM when compared to SING condition., Conclusions: Our data support the hypothesis that temporal summation of nociceptive reflex responses is driven through a switch between activation and deactivation of a specific set of brain areas linked to the default mode network. This behaviour could be explained in view of the relevance of the pain processing induced by temporal summation, recognized as a more significant potential damaging condition with respect to a single, isolated, painful stimulation of comparable pain intensity., Significance: The study demonstrated that TST of the NWR involves a selective deactivation of PCC., (© 2016 European Pain Federation - EFIC®.)

Pain is an important non-motor symptom in several neurological diseases, such as Parkinson's disease, cervical dystonia, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness and dementia, as well as in oncology and neuroinfectivology. To overcome the lack of evidence-based data on pain management in these diseases, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) has defined criteria for good clinical practice among Italian neurorehabilitation professionals. Here a review of the literature (PubMed, EMBASE and gray literature) on pain characteristics, treatment and impact of pain in a neurorehabilitation setting is provided. Despite the heterogeneity of data, a consensus was reached on pain management for patients with these diseases: it is an approach originating from an analysis of the available data on pain characteristics in each disease, the evolution of pain in relation to the natural course of the disease and the impact of pain on the overall process of rehabilitation. There was unanimous consensus regarding the utility of a multidisciplinary approach to pain therapy, combining the benefits of pharmacological therapy with the techniques of physiotherapy and neurorehabilitation for all the conditions considered. While some treatments could be different depending on pathology, a progressive approach to the pharmacological treatment of pain is advisable, starting with non-opioid analgesics (paracetamol) and nonsteroidal anti-inflammatory drugs as a first-line treatment, and opioid analgesics as a second-line treatment. In cases of pain secondary to spasticity, botulinum neurotoxin, and, in some cases, intrathecal baclofen infusion should be considered. Randomized controlled trials and prospective multicenter studies aimed at documenting the efficacy of pain treatment and their risk-benefit profile are recommended for these conditions.

The interplay between pain and neurorehabilitation is very complex, in that pain may be a target for treatment, but can also have negative effects on neurorehabilitation procedures. Moreover, side effects of drugs, which are currently used to treat pain, may negatively influence rehabilitation outcomes. Because of the lack of guidelines or consensus, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) was aimed to answer some open questions on the treatment of pain in this setting. To this aim, we collected evidence on the pharmacological and non-pharmacological strategies and their role in the integrated approach to pain. Despite the lack of studies in patients undergoing neurorehabilitation, current guidelines on the pharmacological treatment of nociceptive and neuropathic pain may be applied in this setting. Non-pharmacological strategies include physical therapy, invasive procedures, psychological treatments and psychotherapy, which together with pharmacological therapies play a key role in the integrated approach to pain. The ICCPN recommendations offer information to ameliorate the current treatment of pain in neurorehabilitation, and to design future studies to answer the still open questions on this topic.

Background: The growing interest in documenting the effectiveness of rehabilitation has led to a progressive increasing focus on clinical tools to measure stroke-survivors disability and recovery. In clinical practice a general agreement on the instruments to be used seems to be lacking and clinical scales are often limited to the assessment of global function., Aim: The study investigated whether the use of a selection of clinical scales/scores added to a single global measure during rehabilitation care, may lead to a better functional outcome for stroke inpatients., Design: Retrospective study., Setting: Neurorehabilitation inpatients., Population: Consecutive patients affected by first-ever stroke., Methods: Patients in the control group (CG) (N.=139) were assessed at admission and at discharge with the Functional Independence Measure (FIM), while patients in the study group (SG) (N.=127) were evaluated by means of a basic core-set of clinical scales/scores as well as with the FIM. Patients in both groups were evaluated and treated by the same multiprofessional team, following the same rehabilitative treatment approaches., Results: At discharge both groups significantly improved at the FIM total Score, compared to the admission; a significant improvement was also reported for all the clinical scales in SG. However, the CG showed longer length of stay (LOS) than the SG and between-group analysis revealed statistical significant differences in the FIM total score, in the FIM gain and in all the indices of performance (FIM efficiency, FIM absolute efficacy, FIM relative efficacy), in favor of the SG., Conclusions: The use of a selection of scales added to a global functional measure, allows a better definition of both the person's profile of disability and the rehabilitative goals, and is associated to a better functional outcome at discharge., Clinical Rehabilitation Impact: Clinical scales may be used in clinical practice to better define the person's profile of disability, allowing the design of patient tailored goals, and to favor team working.

Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting(®) (VBS), OsseoFix(®) and Spine Jack(®). VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix(®) and Spine Jack(®) are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix(®) has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting(®) and Spine Jack(®), the OsseoFix(®) has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack(®) is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors., Competing Interests: The authors have no conflicts of interest to declare.

Background: The increased survival after a severe acquired brain injury (sABI) raise the problem of making most effective the treatments in Intensive Care Unit (ICU)/Neurointensive Care Unit (NICU), also integrating rehabilitation care. Despite previous studies reported that early mobilization in ICU was effective in preventing complications and reducing hospital stay, few studies addressed the rehabilitative management of sABI patients in ICU/NICU., Aim: To collect clinical and functional data about the early rehabilitative management of sABI patients during ICU/NICU stay., Design: Prospective, observational, multicenter study., Setting: Fourteen facilities supplied by intensive neurorehabilitation units and ICU/NICUs., Population: Consecutive sABI patients admitted to ICU/NICU., Methods: Patients were evaluated at admission and then every 3-5 days. Clinical, functional and rehabilitative data, including Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), The Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome scale (GOS) and Functional Independence Measure (FIM) were collected., Results: One hundred and two patients (F/M 44/58) were enrolled. The mean duration of ICU stay was 24.7±13.9 days and the first rehabilitative evaluation occurred after 8.7±8.8 days. Regular postural changes and multijoint mobilization were prescribed in 63.7% and 64.7% cases, respectively. The mean session duration was 38±11.5 minutes. Swallowing evaluation was performed in 14.7% patients, psychological support was provided to 12.7% of patients' caregivers, while 17.6% received a psycho-educational intervention, and 28.4% were involved in interdisciplinary team meetings. The main discharge destinations were Severe Acquired Brain Injury rehabilitation units for 43.7%, intensive neurorehabilitation units for 20.7%., Conclusions: Data showed that early rehabilitation was not diffusely performed in sABI subjects in ICU/NICU and rehabilitative interventions were variable; one-third of subjects were not referred to dedicated rehabilitation unit at discharge., Clinical Rehabilitation Impact: The study stresses the need to spread and implement a rehabilitative culture also for critical ill patients due to neurological diseases.

We determined incidence and intra-hospital mortality rate of stroke in Molise, Italy, to provide information for planning regional healthcare facilities and to ameliorate stroke management in this region. This study is part of the "Rete Molisana dell'Ictus Cerebrale (REMOLIC)" study, a population-based Cerebrovascular Registry in Molise, from 2009 to 2013, with a cold pursuit approach. The crude annual incidence rates for total stroke per 100,000 inhabitants, notified by hospital discharge records, were 198 for 2009, 185 for 2010, 169 for 2011, and 176 for both 2012 and 2013. There was a significant decrease in risk in the years 2011-2013 [RR2011 vs. 2009: 0.85 (0.76-0.98), RR2012 vs. 2009: 0.89 (0.79-0.99), RR2013 vs. 2009: 0.89 (0.79-0.99)] as compared with 2009. For the year 2010, after adjustment to the Italian, European, and world populations, the overall incidence rates were 165, 134, and 67 per 100,000/year, respectively. Similar trends were found when men and women were analyzed separately. In the average, 20.8 % of subjects admitted for a cerebrovascular accident died during the hospitalization, among these 93.5 % in the first 28 days. The duration of hospital stay was constant in the years (2009-2012), except during 2013, where there was a significant decrease in the average (p < 0.001). Our study shows incidence rates decreasing from 2009 to 2013, while mortality rates were stable during the same years. This study underlines the need to plan better stroke management in Italy, in order to obtain outcomes more similar to those of the best performing countries.

Object: Human lactoferrin (HLF) is a natural protein with antitumor activity. The aim of this study was to investigate the effects of HLF alone and in combination with temozolomide (TMZ), a conventional chemotherapeutic, on human glioblastoma (GBM) cells., Methods: The authors cultured fresh human primary cell lines NMD and FN and the continuous cell line U87MG to evaluate proliferation in the presence of HLF alone at different doses (1, 10, and 100 mg/ml, and 1 mg/ml) and in combination with TMZ. In in vivo experiments they assessed tumor size reduction in CD1 nude mice carrying an orthotopic GBM xenograft and orally treated with HLF., Results: Lactoferrin causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line. This inhibition seemed to be modulated by the downregulation of cyclin D1 and D4. Western blot and fluorescence-activated cell sorting analysis showed inhibition of the cell cycle in G0/G1 and G2 phases. When administered in nude mice, HLF (60 mg/kg/day) decreased tumor size about 30%, as shown in both histological analyses and high-field brain MRI. Administration of HLF with TMZ enhanced the effect of chemotherapy both in vitro and in vivo., Conclusions: This study demonstrated that HLF can inhibit GBM cell growth, suggesting that this nontoxic substance may have a role in potentiating the effect of current TMZ treatment of GBM.

Hemispatial neglect due to right parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, resulting in poor functional gain. Recent research has shown that different types of neglect can impact in a different way on rehabilitation outcomes. The availability of a sensitive test, useful for distinguishing egocentric and allocentric forms of neglect, may be clinically important as all current clinical instruments fail to distinguish between these forms of disturbance, yet they differentially predict outcome. The Apples Test is a new instrument useful to evaluate both egocentric and allocentric forms of neglect. In order to establish Italian norms for this diagnostic instrument the test was administered to a sample of 412 healthy people of both genders (201 M and 211 F), aged from 20 to 80 years enrolled from 14 different rehabilitation centers in Italy. Based on the data, we established pathological performance cut-offs for the accuracy score (total omission errors), the asymmetry score for egocentric neglect (omission error difference), the asymmetry score for allocentric neglect (commission error difference) and execution time. The usefulness of the Apples Test for diagnostic purposes is illustrated by presenting three patients with different forms of neglect (egocentric, allocentric and mixed neglect).

Aim: To evaluate the effects of the combination of d-chiro-inositol (DCI) and alpha lipoic acid on menses and metabolic disorders in women with polycystic ovary syndrome (PCOS)., Methods: Forty-six women (26 study group subjects and 20 controls) of reproductive age with PCOS according to Rotterdam criteria were enrolled in this prospective study. Fasting serum samples were collected from each woman. Homeostasis model of insulin resistance, insulin levels, lipid profile, frequency of menstrual cycles, number of ovarian peripheral cysts and BMI of both groups were investigated at baseline and after 180 days. Clinical and metabolic aspects of women on DCI and lipoic acid treatment underwent improvement (p < 0.5) with respect to the control group. Regarding lipid profile, no statistically difference was observed in total cholesterol and triglycerides levels in both groups at follow-up with respect the baseline values (p = NS)., Conclusion: DCI and alpha lipoic acid treatment has been thought because it plays an essential role in mitochondrial specific pathways that generate energy from glucose and its potent effect as antioxidant. The association might have a strong impact on metabolic profile even with a short-term treatment. Further investigations are needed to evaluate other effects on reproductive physiology of women with PCOS.

Introduction: Selegiline (l-deprenyl) is a selective monoamine oxidase type B inhibitor that has been shown to have neurotrophic and anti-apoptotic properties and to protect neurons in different experimental models of cerebral ischaemia. The aim of this explorative study was to investigate whether selegiline could enhance cognitive and functional recovery in stroke survivors., Methods: This was a randomized controlled study in which patients enrolled within two weeks of stroke underwent a clinical and functional evaluation and a neuropsychological assessment. The patients were given selegiline (10mg/day) or matched placebo once a day for six weeks in addition to standard rehabilitation care., Results: Of 137 stroke survivors, 47 patients met the inclusion criteria and were randomly assigned to the Study Group (n=23) or the Control Group (n=24). The statistical analysis showed a significant improvement in most neuropsychological tests after two and six weeks in the study group; these improvements were not replicated in the control group. The between-group analysis revealed that the domains of attention and executive functions benefited most from the drug treatment. With regard to functional status, comparison of clinical scores at admission and discharge showed a statistically significant enhancement in both groups without statistically significant differences between the groups., Conclusions: These preliminary results suggest that selegiline administered in the subacute phase can promote cognitive functioning in stroke patients. Further studies will elucidate whether and how this enhancement can impact on functional recovery in the short and in the long term., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.

Endovascular treatment of wide-neck bifurcation aneurysms is challenging and often requires adjunctive techniques and devices. We report our experience with the hybrid Y stenting with the waffle-cone technique, combining Y stent-assisted coiling and waffle-cone stenting techniques. This approach has been described only in a single case report using a combination of open and closed cell stents. We describe four cases treated by hybrid Y stenting with the waffle-cone procedure with a variation from the originally reported technique, consisting in deploying two closed cell stents. All patients were successfully treated without complications. We propose hybrid Y stenting with the waffle-cone for the treatment of wide-neck bifurcation aneurysms as a bailout technique after failure of Y stent-assisted coiling.

Introduction: Pisa syndrome (PS) is a tonic lateral flexion of trunk that represents a disabling complication of advanced Parkinson disease (PD). Conventional rehabilitation treatment (CT) ameliorates axial posture and trunk mobility in PD patients, but the improvement tends to wane in 4-6 months. Botulin toxin (BT) may reduce muscle hyperactivity, therefore improving CT effectiveness. We evaluated whether the injection of incabotulinum toxin type A (iBTA) into the hyperactive trunk muscles might improve the effectiveness of rehabilitation in a group of PD patients with PS., Methods: Twenty-six PD patients were enrolled in a randomized placebo-controlled trial. Group A was treated with iBTA before undergoing CT (a 4-week intensive programme), while Group B received saline before the 4-week CT treatment. Patients were evaluated at baseline, at the end of the rehabilitative period, 3 and 6 months with kinematic analysis of movement, UPDRS, Functional Independence Measure and Visual Analog Scale for pain., Results: At the end of the rehabilitation period, both groups improved significantly in terms of static postural alignment and of range of motion. Group A showed a significantly more marked reduction in pain score as compared with Group B and a more prolonged efficacy on several clinical and kinematic variables., Conclusions: Our preliminary data suggest that BT may be considered an important addition to the rehabilitation programme for PD subjects with PS for improving axial posture and trunk mobility, as well as for a better control of pain., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cognitive impairment is a frequent complication of stroke. The aim of this study was to evaluate the effectiveness of cognitive training performed early after stroke. Ninety-two patients were randomly assigned to either the study group (SG) or the control group (CG). Cognitive rehabilitation consisted of 16 individual one-hour sessions in which patients performed therapist- guided computer exercises. The patients in the CG performed a sham intervention. After four weeks all the patients were re-evaluated. In the SG, significant improvements (p<0.05) were detected in all neuropsychological measures at the post-training evaluation, while the CG showed mild (not statistically significant) improvements on cognitive tests. Between-group analysis revealed statistically significant differences in the domains of memory and visual attention. Cognitive training performed early after stroke seems to be a viable option for improving cognitive outcome in stroke survivors. Further studies should assess whether this may favor their reintegration into everyday life.

Background: Acute ischemic stroke (AIS) is influenced by gender, age, and the brain site affected. Better characterization of AIS is necessary for improving guidelines, prevention, and destination of resources., Methods: Demographics, prestroke conditions, etiology, subtypes, specific hospital outcome, clinical and laboratory parameters, and mortality rates were prospectively registered in 105 southern Italian patients., Results: AIS became more frequent in women than in men after age 65 years. Cryptogenic AIS decreased with age independently of sex and lesion site. Cerebellum-brainstem stroke was more prevalent in men, whereas anterior AIS was more frequent in women. There were no overall differences in 6- and 12-month survival rates based on site or sex; however, mortality rates were high after age 80 years. Chronic kidney disease was more frequent in patients with cerebellum-brainstem stroke, and its prevalence increased significantly with age independently of sex. Association of AIS with arterial hypertension, diabetes, and previous myocardial infarction increased with age, whereas that with active smoking decreased with age, independently of sex and site., Conclusion: Specific AIS etiology and blood characteristics associated independently to the youngest and oldest AIS patients, respectively. Chronic kidney disease was a specific predictor of cerebellum-brainstem AIS. AIS mortality showed peculiar association with the oldest patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)