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Upper limb (UL) function is often affected in people with multiple sclerosis (PwMS) and is typically assessed through objective measures, including the Nine Hole Peg Test (9-HPT), Box and Block Test (BBT), and Hand Grip Strength (HGS). It is important to include the subjective perspective of PwMS in the assessment. This study aims to evaluate associations between Manual Ability Measure-36 (MAM-36) and 9-HPT, BBT, and HGS in MS.The cross-sectional study included five Italian centers. Inclusion criteria were age ≥ 18 years, MS diagnosis, and stable disease course. Exclusion criteria were bilateral UL paralysis, and concomitant orthopedic or neurological diseases.A total of 199 PwMS were included: 128 female, mean age = 50.7 ± 13.0 years, 119 relapsing-remitting MS (RRMS), 31 primary and 49 secondary progressive MS, mean disease duration = 14.0 ± 10.4, years, mean Expanded Disability Status Scale (EDSS) = 4.6 ± 2.0. The MAM-36 showed small correlations with 9-HPT, BBT, and HGS. Correlations between MAM-36 and 9-HPT and BBT were highest among subjects with EDSS ≥ 6 and progressive MS. MAM-36 and HGS showed the highest correlations in subjects with EDSS ≤ 5 and RRMS. Combining 9-HPT and HGS provided the strongest predictive power over the MAM-36.Correlations between objective measures and MAM-36 were small to moderate, meaning that objective measures do not match subjects' perception of UL function. The combination of 9-HPT and HGS measures can help improve the assessment of UL function in activities of daily living.

The present study aims to investigate the benefits induced by physical activity/practiced sport in Charcot-Marie-Tooth 1A (CMT1A). Patients were divided into sport and no-sport groups according to their sports performance habit. Thirty-one patients were enrolled, of which 14 practiced sports and 17 did not. Clinical assessments were administered to evaluate disability, self-esteem, depression, quality of life, and pain. Statistical analysis revealed significant differences in terms of gender in the no-sport group compared to the sport group (p = 0.04). Regarding the quality of life, physical function (p = 0.001), general health (p = 0.03), social function (p = 0.04), and mental health (p = 0.006) showed better patterns in the sport group than no-sport group. Moreover, neuropathic pain was reduced in the sport group according to the Neuropathic Pain Symptom Inventory (p = 0.001) and ID-PAIN (p = 0.03). The other administered questionnaires showed no significant differences. Our study confirms that CMT1A patients, who practice sports, with a similar severity of disability, may have a better physical quality of life while suffering less neuropathic pain than their peers who do not practice sports. Results recommend the prescription of sport in CMT1A patients.

Recently, the use of robotic technology in gait and balance rehabilitation of stroke patients has been introduced, with positive results. The purpose of this study was to evaluate the effectiveness of robotic gait and trunk rehabilitation compared to robotic gait training alone on balance, activities, and participation measures in patients with subacute stroke. The study was a randomized, controlled, single blind, parallel group clinical trial. Thirty-six patients with first ischemic or hemorrhagic stroke event were enrolled, and they were randomized in two groups: Gait Group (GG), where they received only robotic treatment for gait rehabilitation through an end-effector system, and Gait/Trunk Group (GTG) where they performed end-effector gait rehabilitation and balance with a robotic platform, 3 times/week for 12 sessions/month. At the end of the study, there was an improvement in balance ability in both groups. Instead, the lower limb muscle strength and muscle tone significantly improved only in the GTG group, where we found a significant reduction in the trunk oscillations and displacement during dynamic exercises more than the GG group. The robotic platform which was added to the gait robotic treatment offers more intense and controlled training of the trunk that positively influences the tone and strength of lower limb muscles.

The SARS-CoV-2 pandemic made the use of facemasks mandatory to prevent contact with the virus. Recent studies have revealed that intensive use of facemasks significantly exacerbated pre-existing headaches and triggered de novo headaches. In our experience, some subjects also complain of symptoms of neuropathic pain in the head/facial regions. Until now, the relationship between neuropathic pain and facemasks has not been documented. The aim of the study is to investigate the occurrence of neuropathic pain related to facemask use. It is a cross-sectional survey using a questionnaire, developed following a commonly accepted outcome research methodology. Participants, both health care and non-health care workers, responded to items included in the questionnaire about the type of facemasks, time and manner of wearing them, side effects such as skin lesions, symptoms of neuropathic pain, etc.

Introduction: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice. Materials and methods: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms. Results: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group. Conclusion: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients. © 2020, Fondazione Società Italiana di Neurologia.

Multiple Sclerosis (MS) is a disease that often results in motor and/or cognitive disability. Despite the increasing availability of effective drug therapies, rehabilitation is very important means of counteracting the progression of disability and improving physical function, impacting social participation and improving quality of life. Several rehabilitation approaches can be used in the context of neuro-motor rehabilitation, but there is insufficient evidence for them in the literature.This study has the twofold purpose of: (i) investigate whether rehabilitation according to Bobath Concept can improve balance and some aspects of cognitive function in MS patients; (ii) explore whether the ability to improve postural control, an indirect index of adaptive neuroplasticity, is preserved in MS patients and whether it can be improved with rehabilitation.This is an independent wait-listed study. Forty people with MS (pwMS) were enrolled: patients in the Bobath group underwent 8 weeks of rehabilitation according to the Bobath Concept. For aim 1, pwMS were assessed at baseline (T0), at the end of the 8 weeks of treatment (T1) and after 8 weeks of observation (T2) with motor and cognitive scales. For aim 2, the same 40 pwMS were matched with healthy controls and were subjected to a postural learning task using the force platform at T0, T1 and T2.Patients in Bobath group scored better on balance and cognitive function at T1, but this improvement was not maintained at T2. All patients were less accurate than controls in the postural learning task at each assessment; however, patients also demonstrated an increase in accuracy after training, similar to that of healthy controls. The learning curve was better for patients randomized to the active group than the waitlist at T1 time, but this advantage was not maintained at the T2 assessment.In light of the results, this study supports the use of rehabilitation according to Bobath Concept to improve balance control and some executive functions in MS. Despite worse baseline performance, pwMS were able to learn a postural control task on par with healthy controls. Also, supports the hypothesis that adaptive plasticity is preserved despite MS and can be promoted by rehabilitation.

Fatigue is a disabling symptom of multiple sclerosis (MS) and impacts on daily life. The Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a new 20-item tool that investigates the aspects of fatigue in MS. It concerns motor, cognitive, social, and emotional aspects of fatigue. We aim at validating the Italian version of FSIQ-RMS in an Italian population of MS patients and demonstrate its reliability and construct validity.We included patients with diagnosis of MS, age between 18 and 70 years with ability to participate in a 90-min interview. Each patient completed the Italian version of FSIQ-RMS and Fatigue Severity Scale (FSS) at the same time. Construct validity was explored by the exploratory factor analysis; reliability was assessed with Cronbach's alpha; and test-retest stability was examined through intraclass correlation coefficient (ICC). Concurrent validity was calculated using Pearson's correlation.We enrolled 171 patients (126 female and 45 male), 83% with relapsing MS (RMS), and 17% with secondary progressive MS (SPMS). Italian FSIQ-RMS showed a Cronbach's alpha of 0.92; ICC was 0.96. Pearson's correlation coefficient between FSIQ-RMS and FSS total score was statistically significant (p 0.01); FSIQ-RMS inversely correlated also with BMI and positively with EDSS.The Italian version of FSIQ-RMS has excellent psychometric properties and can be used in research and clinical setting to evaluate physical, cognitive, and social fatigue in both RMS and SPMS.

Intensive-Care-Unit-Acquired Weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients and can have a significant impact on long-term disability. Early rehabilitation has been suggested to facilitate the natural recovery process. This is a pilot, randomized, single-blind study that aimed to evaluate the effectiveness of intensive combined technological rehabilitation treatment including focal muscle vibration and non-immersive virtual reality for patients with severe acquired brain injury (sABI) and ICU-AW. Twenty-four patients were randomized into the conventional group, which performed only conventional rehabilitation, and the experimental group, which also performed technological treatment. At baseline and after 3 weeks of treatment, assessments of motor function, autonomy, disability and quality of life were conducted. At the end of the intervention, both groups showed significant improvements. However, patients in the experimental group achieved greater improvements in disability (p = 0.001) and quality of life (p = 0.001). The results show that intensive structured rehabilitation is effective in improving the motor function, disability and quality of life of patients with severe acquired brain injury and acquired weakness. The combination of non-immersive virtual reality training and focal muscle vibration can result in a significant improvement in overall disability and quality of life compared with conventional treatment alone.

Cognitive fatigability in multiple sclerosis represents the decrease in cognitive performance over time. It is a frequent symptom that negatively affects quality of life and ability to work. There are no objective measures of cognitive fatigability. This study aimed at quantifying cognitive fatigability despite the learning effect and to clarify whether cognitive fatigability represents a free-standing phenomenon rather than an aspect of cognitive impairment. We measured information processing speed with the Symbol Digit Modalities Test, and the number of right answers was recorded every 30 s for 180 s. We approximated the number of right answers as function of time with two logarithmic models, one including a first-order term alone and the other adding also a second-order term. The coefficient of the latter (B) may quantify performance deflection and may represent cognitive fatigability. We tested 173 patients with multiple sclerosis, including 119 cognitively impaired and 54 cognitively preserved patients, and 35 healthy subjects. The performance of cognitively preserved patients showed a deflection at the end of task that was detected neither in controls nor in cognitively impaired patients and needed a second-order term to be approximated (p < .03, F = 14.02). B was explained neither by depression nor fatigue. We proposed for the first time a method to quantify cognitive fatigue via a second-order least square fit model, easily usable in the clinical practice. By using this novel approach, cognitive fatigability results to be a free-standing phenomenon that is more evident in cognitively preserved than in cognitive impaired patients.

Parkinson’s disease (PD) is a neurodegenerative pathology characterized by motor and non-motor symptoms that often lead to several impairments. Many studies show the efficacy of different rehabilitation protocols aimed to improve balance and gait functions in PD patients. However, multiple factors may influence rehabilitation outcome. Recently, it has been observed as the cognitive reserve (CR) may influence the rehabilitation outcome, helping to address the patient toward technological or conventional rehabilitation. Our study investigated how CR may affect motor rehabilitation outcomes in PD patients who undergo virtual reality (VR) rehabilitation, aimed at improving walking and balance. Thirty patients affected by idiopathic PD were enrolled. Patients underwent 12 sessions VR training, over 6 weeks (45 min). Six-Minute Walk Test (6MWT) and Berg Balance Scale (BBS) were used to assess walking and balance, respectively. CR was assessed by Cognitive Reserve Index questionnaire (CRIq). Significant correlations between CR and change from baseline in walking and balance measures were found, with a significant positive correlation between CRIq and 6MWT (r=0.50, p=0.01) and between CRIq and BBS (r=0.41, p=0.04). Our results showed that PD patients with higher CR treated with VR improved significantly more in their balance and walking distance than those with lower CR. The current study suggests that VR when aimed to improve balance and walking in PD patients is more effective in patients with higher CR.

Background Upper limb (UL) function is affected in about 50% of people with Multiple Sclerosis (PwMS). In the last decade, Patient Reported Outcome Measures (PROM) are playing an important role in clinical trial and practice. ABILIHAND-26 is a PROM that assess self-perceived manual ability defined as the capacity to manage daily activities using the upper limbs. The aim of the study is to translate the ABILHAND-26 into Italian, to explore its psychometric properties examining the associations with demographics, clinical variables, 9-Hole Peg Test (9-HPT) and Manual Ability Measures-36 (MAM-36). Materials and methods Subjects were recruited in five Italian neurological centers. They were evaluated through ABILHAND-26, 9-HPT and MAM-36. Confirmatory factor analysis and Rasch analysis were adopted to investigate the psychometric properties of the ABILHAND-26. Results Two hundred and forty-five patients were recruited. Rasch analyses showed adequate functioning and supported the unidimensionality of the scale. ABILHAND-26 showed negative correlations with age and disease duration, moderate negative correlation with EDSS and the 9-HPT scores for both arms and strong positive associations (ρ ≥ .84) with the MAM-36. Difference in ABILHAND-26 scores only emerged when comparing patients with severe disability (EDSS ≥ 6) with patients with either mild or moderate disability. t) and when comapring relapsing-remitting and secondary progressive patients. Conclusion The Italian version of the ABILHAND-26 is now available. It shows adequate reliability of the score, moderate criterion validity and strong convergent validity. ABILHAND-26 could represent a valid assessment for self-perceived ability to perform manual activity, especially for PwMS with moderate-to-high level of disability.

The Coronavirus Disease 2019 (COVID-19) pandemic is a severe ongoing global emergency. Despite high rates of asymptomatic patients, in many cases, the infection causes a rapid decline in pulmonary function due to an acute respiratory distress-like syndrome, leading to multi-organ failure and death. To date, recommendations about rehabilitation on COVID-19 are based on clinical data derived from other similar lung diseases. Rehabilitation literature lacks a standard taxonomy, limiting a proper evaluation of the most effective treatments for patients after COVID-19 infection. In this study, we assessed the clinical and rehabilitative associations and the geographical area involved in interstitial lung diseases (ILD) and in COVID-19, by a mathematical analysis based on graph theory. We performed a quantitative analysis of the literature in terms of lexical analysis and on how words are connected to each other. Despite a large difference in timeframe (throughout the last 23 years for ILD and in the last 1.5 years for COVID-19), the numbers of papers included in this study were similar. Our results show a clear discrepancy between rehabilitation proposed for COVID-19 and ILD. In ILD, the term “rehabilitation” and other related words such as “exercise” and “program” resulted in lower values of centrality and higher values of eccentricity, meaning relatively less importance of the training during the process of care in rehabilitation of patients with ILD. Conversely, “rehabilitation” was one of the most cited terms in COVID-19 literature, strongly associated with terms such as “exercise”, “physical”, and “program”, entailing a multidimensional approach of the rehabilitation for these patients. This could also be due to the widespread studies conducted on rehabilitation on COVID-19, with Chinese and Italian researchers more involved. The assessment of the terms used for the description of the rehabilitation may help to program shared rehabilitation knowledge and avoid literature misunderstandings.

BACKGROUND AND PURPOSE Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine-hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. METHODS This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right-hand dominance. All subjects underwent HGS, BBT and 9-HPT evaluation. RESULTS In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing-remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9-HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9-HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9-HPT. The BBT and 9-HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5-5.5, ≥6.0). CONCLUSION Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9-HPT were generally low.

To evaluate systematically the efficacy of exergames for balance dysfunction in neurological conditions and to identify factors of exergaming protocols that may influence their effects. We searched electronic databases for randomized clinical trials investigating the effect of commercial exergames versus alternative interventions on balance dysfunction as assessed by standard clinical scales in adults with acquired neurological disabilities. Standardized mean differences (Hedge’s g) were calculated with random-effects models. Subgroup analyses and meta-regression were run to explore potential modifiers of effect size. Out of 106 screened articles, 41 fulfilled criteria for meta-analysis, with a total of 1223 patients included. Diseases under investigation were stroke, Parkinson’s disease, multiple sclerosis, mild cognitive impairment or early Alzheimer’s disease, traumatic brain injury, and myelopathy. The pooled effect size of exergames on balance was moderate (g = 0.43, p

To evaluate systematically the efficacy of exergames for balance dysfunction in neurological conditions and to identify factors of exergaming protocols that may influence their effects.We searched electronic databases for randomized clinical trials investigating the effect of commercial exergames versus alternative interventions on balance dysfunction as assessed by standard clinical scales in adults with acquired neurological disabilities. Standardized mean differences (Hedge's g) were calculated with random-effects models. Subgroup analyses and meta-regression were run to explore potential modifiers of effect size.Out of 106 screened articles, 41 fulfilled criteria for meta-analysis, with a total of 1223 patients included. Diseases under investigation were stroke, Parkinson's disease, multiple sclerosis, mild cognitive impairment or early Alzheimer's disease, traumatic brain injury, and myelopathy. The pooled effect size of exergames on balance was moderate (g = 0.43, p 0.001), with higher frequency (number of sessions per week) associated with larger effect (β = 0.24, p = 0.01). There was no effect mediated by the overall duration of the intervention and intensity of a single session. The beneficial effect of exergames could be maintained for at least 4 weeks after discontinuation, but their retention effect was specifically explored in only 11 studies, thus requiring future investigation. Mild to moderate adverse events were reported in a minority of studies. We estimated a low risk of bias, mainly attributable to the lack of double-blindness and not reporting intention-to-treat analysis.The pooled evidence suggests that exergames improve balance dysfunction and are safe in several neurological conditions. The findings of high-frequency interventions associated with larger effect size, together with a possible sustained effect of exergaming, may guide treatment decisions and inform future research.

The effectiveness of virtual reality (VR) in the motor and cognitive rehabilitation of patients with severe acquired brain injury (sABI) is unclear. This randomized, controlled, crossover, single-blinded, pilot study investigates the cognitive and motor effects of lower limb robotic therapy with and without VR visual feedback in a group of patients with ABI. A total of 23 patients with ABI were randomized into two groups: one group (VR-NVR) underwent a 2-week rehabilitation for the lower limbs training with a robotic device (Omego®) with VR feedback, followed by 2 weeks without VR; the other group (NVR-VR) performed the protocol in the opposite order. Patients were evaluated at baseline, after two and four weeks of treatment using the Level of Cognitive Functioning scale (LCF), Disability Rating Scale (DRS), and Motricity Index for Lower Limb (MI-LL) in the most affected limb. At the end of the intervention, both groups significantly improved in all the outcomes. A significant difference was found between VR treatment versus non-VR treatment for LCF (p = 0.024) and for DRS (p = 0.043) after the second week, while no significant differences were found in the group NVR-VR at T1. Our study indicates how the combination of robotic treatment with VR is effective in enhancing the recovery of cognitive function in patients with ABI, also improving disability and muscular function. Further, VR seems to enhance the early recovery process of motor and cognitive functions.

Multiple sclerosis (MS) is a disease that heavily affects postural control, predisposing patients to accidental falls and fall-related injuries, with a relevant burden on their families, health care systems and themselves. Clinical scales aimed to assess balance are easy to administer in daily clinical setting, but suffer from several limitations including their variable execution, subjective judgment in the scoring system, poor performance in identifying patients at higher risk of falls, and statistical concerns mainly related to distribution of their scores. Today we are able to objectively and reliably assess postural control not only with laboratory-grade standard force platform, but also with low-cost systems based on commercial devices that provide acceptable comparability to gold-standard equipment. The sensitivity of measurements derived from force platforms is such that we can detect balance abnormalities even in minimally impaired patients and predict the risk of future accidental falls accurately. By manipulating sensory inputs (dynamic posturography) or by adding a concurrent cognitive task (dual-task paradigm) to the standard postural assessment, we can unmask postural control deficit even in patients at first demyelinating event or in those with a radiologic isolated syndrome. Studies on neuroanatomical correlates support the multifactorial etiology of postural control deficit in MS, with the association with balance impairment being correlated with cerebellum, spinal cord, and highly ordered processing network according to different studies. Postural control deficit can be managed by means of rehabilitation, which is the most important way to improve balance in patients with MS, but there are also suggestions of a beneficial effect of some pharmacologic interventions. On the other hand, it would be useful to pay attention to some drugs that are currently used to manage other symptoms in daily clinical setting because they can further impair postural controls of patients with MS.

Premorbid physically and intellectually enriching lifestyles have increasingly been recognized as able to mitigate the risk of disease-related disability in patients with multiple sclerosis (MS). To explore if premorbid physical activity, cognitive reserve and trait personality act as proxies for functional reserve that contributes to rehabilitation outcome. We recruited all patients previously enrolled in two pilot trials investigating the effect of home-based video game training in improving balance (Study 1) and attention (Study 2) for additional assessments with the Historical Leisure Activity Questionnaire (HLAQ; a proxy for premorbid physical activity), Cognitive Reserve Index Questionnaire (CRIQ), and Temperament and Character Inventory (TCI). Hierarchical logistic regression (HLR) analyses tested the association of HLAQ, CRIQ, and TCI with training effect on balance (static posturography) and on attention (Symbol Digit Modalities Test). We identified 94% (34/36) and 74% (26/35) of patients participating at the original Study 1 and Study 2, respectively. HLR analyses showed an exclusive “intra-modal” modulation of rehabilitation outcome by functional reserve, given that (1) larger training effect on balance was associated with higher HLAQ (OR = 2.03, p = 0.031); (2) larger training effect on attention was associated with higher CRIQ (OR = 1.27, p = 0.033). Furthermore, we found specific personality traits associated with (1) greater training effect on balance (self-directedness; OR = 1.40, p = 0.051) and lower training effect on attention (harm avoidance; OR = 0.66, p = 0.075). We hypothesize that premorbid physical and intellectual activities not only act as a buffer for limiting the MS-related damage but also as functional reserve that can be retrieved by task-oriented training to promote recovery through rehabilitation.

IntroductionDelta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation.Materials and methodsThis prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline.ResultsA total of 1845 patients were recruited from 32 MS Italian centres. At T1, 1502 (81.4%) of patients reached a Numerical Rating Scale (NRS) improvement of ≥20%, with an NRS reduction of 26.9% at T1 and of 34.4% at T5. At T5, 725 patients (48.3% of 1502) discontinued treatment with highest discontinuation rate at T2 and T3. Daily number of puffs was generally stable through the observation period. The multivariate analysis showed that higher NRS scores at baseline (OR 2.28, 95% CI 1.15 to 6.36, pDiscussionTHC:CBD effects were sustained for 18 months with a relatively stable number of puffs per day. About 50% of patients abandoned THC:CBD therapy for loss of efficacy or adverse events.

Objective: To investigate the disease-altered structure–function relationship underlying the cognitive–postural interference (CPI) phenomenon in multiple sclerosis (MS). Methods: We measured postural sway of 96 patients and 48 sex-/age-matched healthy controls by force platform in quiet standing (single-task (ST)) while performing the Stroop test (dual-task (DT)) to estimate the dual-task cost (DTC) of balance. In patient group, binary T2 and T1 lesion masks and their corresponding lesion volumes were obtained from magnetic resonance imaging (MRI) of brain. Normalized brain volume (NBV) was also estimated by SIENAX. Correlations between DTC and lesion location were determined by voxel-based lesion symptom mapping (VLSM) analyses. Results: Patients had greater DTC than controls ( p Conclusion: Our findings suggest that the CPI phenomenon in MS can be explained by disconnection along specific areas implicated in task-switching abilities and divided attention.

BackgroundNabiximols (THC/CBD Oromucosal Spray, Sativex) is used as an add-on therapy to treat moderate to severe spasticity of Multiple Sclerosis (MS).ObjectivesTo examine the impact of physiotherapy (PT) programs on effectiveness and persistence of nabiximols treatment in people with MS-related spasticity.MethodsThis is an observational multicenter study with a follow-up period of 12 weeks, conducted in routine care settings in Italy. Patients with moderate to severe MS-related spasticity who started nabiximols were included. Spasticity was evaluated by the patient-rated 0-10 numerical rating scale (NRS). Clinical data were collected at baseline (T0), 4 weeks (T1) and 12 weeks (T2) months after enrollment.ResultsA total of 297 MS patients were selected, 290 completed the 3 months follow-up period. Mean NRS scores were 7.6 ± 1.1 at T0, 5.8 ± 1.4 at T1 and 5.5 ± 1.5 at T2. At T1, 77% of patients reached ≥20% improvement (initial response, IR); 22% reached ≥30% improvement (clinically relevant response, CRR). At T1, patients undergoing PT had a higher probability to reach CRR (Odds Ratio = 2.6 95% CI 1.3-5.6, p = 0.01). Nabiximols was discontinued in 30/290 (10.3%) patients at T1 (early discontinuers) and in 71/290 (24.5%) patients at T2 (late discontinuers). The probability of being late discontinuers was reduced in patients undergoing PT (Hazard Ratio = 0.41; 95% CI 0.23-0.69, p = 0.001).ConclusionsOur real-life study confirms nabiximols' effectiveness in MS-related spasticity and suggests that the association of a PT program may improve overall response and persistence to nabiximols treatment.

To assess the distribution of nine hole peg test (9-HPT) and its clinical correlates in a large sample of patients with multiple sclerosis (MS).Data was collected in a multi-centre, cross-sectional study involving 4 Italians MS centres. We collected demographic and clinical data of 363 patients (244 women, 199 men), including year of symptom onset, disease course, Expanded Disability Status Scale (EDSS).A total of 206 (61.3%) patients scored ≥2 standard deviations (SDs) of normative values in both hands, while only 38 (11.3%) scored1 SD from normative values at 9-HPT. We found ceiling and floor effects in mildly (EDSS 3.0) and severely (EDSS 6.0) impaired patients. Patients with a primary progressive disease course and those with a more severe disability level showed the large between-hand asymmetry. In multivariate models, predictors of unimanual and bimanual impairments were primary progressive course (odds ratio [OR] = 7.27, p = 0.001) and higher EDSS score (OR = 2.13 for each step, p 0.001), respectively.We suggest that 9-HPT should be used with caution in patients with low or high disability levels. Between-hand asymmetry and stratification for age, disease course, and presence/absence of bilateral involvement should be taken into account for future study design.

We performed a dual-task experiment to explore the effect of nabiximols on postural control in 22 patients with multiple sclerosis. They were assessed with static posturography and Stroop test in single- and dual-task conditions at treatment start and after 1, 3 and 12 months. At follow-up, we found more impaired postural control in single-task ( F = 3.07, p = 0.044) and dual-task ( F = 4.90, p = 0.005) conditions in patients who continued treatment (continuers, n = 11) compared with those who discontinued (quitters, n = 11). Continuers were more impaired at Stroop test only in dual-task condition ( F = 3.17, p = 0.038). Our findings suggest that nabiximols had a detrimental effect on postural control, especially in multi-tasking conditions.

Two simultaneously performed tasks may compete for common brain network resources in patients with multiple sclerosis (MS), suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for walking and gait, data on static balance are scarce.In this cross-sectional study, 92 patients and 46 sex/age-matched healthy controls (HCs) were tested by means of static posturography under eyes opened (single-task condition) and while performing the Stroop word-colour task (dual-task condition), to estimate the dual-task cost (DTC) of standing balance. The patient group also underwent the Expanded Disability Status Scale, 25-foot walking test, 12-item MS walking scale, Modified Fatigue Impact Scale, and Symbol Digit Modalities Test.Patients had larger postural sway under both single-task and dual-task conditions (p0.001), as well as greater DTC of standing balance (p=0.021) than HCs. Although secondary progressive (SP) patients had larger sway in both conditions than relapsing-remitting (RR) patients (p0.05), these latter ones exhibited a greater DTC of postural balance (p=0.045). Deficits in sustained attention and information processing speed, as assessed by the SDMT, were also independently associated with the magnitude of DTC of standing balance (p=0.005).The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography and was associated with impaired sustained attention and information processing speed, especially in RR patients. The smaller DTC of standing balance observed in SP patients may be due to the ceiling effect of postural sway, or alternatively to the lack of postural reserve which constrained the more disabled patients to prioritize the balance over the cognitive task.

The purpose of the present study was to investigate the long-term persistence to treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting. We retrospectively collected data of patients who started BoNT-A injections and underwent regular follow-up visits. Determinants of BoNT-A discontinuation were explored in a time-to-event Cox regression analysis which included as independent variables a large set of demographic and clinical characteristics. A total of 185 patients started BoNT-A injections from 2002 to 2014 and were followed up to September 2016. Of them, data on 121 were considered in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68 (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6 months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n = 45), logistic problems or barriers to reach the structure (n = 16), and adverse events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent predictors for BoNT-A discontinuation. Our study confirms the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity.

The aim of this study was to explore the correlations between the dual-task cost (DTC) of standing balance and quality of life (QoL) in mildly disabled patients with multiple sclerosis (MS). In this cross-sectional study, patients affected by MS with an expanded disability status scale (EDSS) score of 3.0 or less and without an overt balance impairment were tested by means of static posturography under eyes-opened (single-task condition) and while performing the Stroop word-color test (dual-task condition), to estimate the DTC of standing balance. The self-reported 54-item MS quality of life questionnaire (MSQoL-54) was also administered to obtain a MS-specific assessment of health-related QoL. Among the 120 screened patients, 75 (53 women, 22 men) were tested. Although there was no impact of the DTC of standing balance on the physical and mental composite scores of MSQoL-54, patients who had a greater DTC of standing balance scored worse on role limitations due to physical problems (p = 0.007) and social function (p

Objective:To investigate which concurrent cognitive task (if any) had the most detrimental effect on balance control of patients with multiple sclerosis (MS).Methods:In a dual-task experiment, we evaluated the reciprocal effect of simultaneously performing a postural and a cognitive task on balance and cognition in 52 patients and 26 sex- and age-matched controls. Balance was assessed by static posturography, while cognition was scored as number of correct items at 3 different neuropsychological tests, i.e., the Symbol Digit Modalities Test (SDMT), word list generation (WLG), and Stroop Color-Word Test (SCWT).Results:In both single and dual-task conditions, the patients had larger postural sway and worse scores at SDMT, WLG, and SCWT than the controls (p < 0.05). Test-retest reliability was excellent for all dual-task metrics (85%–94%). By means of 2-way analyses of the variance, we found significant main effects of dual task on balance, regardless of the concurrent cognitive task (p < 0.001). There was no main effect of dual task on cognitive performance across all the 3 task conditions (p ≥ 0.1). We observed a significant condition-by-group interaction effect on balance only when the SCWT was administered as concurrent task (p = 0.01), indicating a greater dual-task cost of balance for the patients than controls (53% vs 28%, p = 0.04).Conclusions:We suggest that tasks exploring executive functions involved in discriminating conflicting stimuli may be the most suitable to unmask the cognitive-postural interference phenomenon in patients with MS. This may support the hypothesis that MS-related damage constrains brain networks to subserve both postural control and executive functions.

This study was aimed at investigating whether postural sway measures derived from a standard force platform were similar to those generated by a custom-written software (“We-Measure”) acquiring and processing data from a commercial Nintendo balance board (BB). For this purpose, 90 patients with multiple sclerosis (MS) and 50 healthy controls (HC) were tested in a single-day session with a reference standard force platform and a BB-based system. Despite its acceptable between-device agreement (tested by visual evaluation of Bland–Altman plot), the low-cost BB-based system tended to overestimate postural sway when compared to the reference standard force platform in both MS and HC groups (on average +30% and +54%, respectively). Between-device reliability was just adequate (MS: 66%, HC: 47%), while test–retest reliability was excellent (MS: 84%, HC: 88%). Concurrent validity evaluation showed similar performance between the reference standard force platform and the BB-based system in discriminating fallers and non-fallers among patients with MS. All these findings may encourage the use of this balance board-based new device in longitudinal study, rather than in cross-sectional design, thus providing a potential useful tool for multicenter settings.

Nocardiosis is a well-described infection in immunocompromised patients, and has been rarely documented in patients with AIDS. Nocardia asteroides is the most frequently isolated etiologic agent. Rare cases are due to N. brasiliensis and N. otitidiscaviarum. This work describes the first case of nocardiosis in Italy caused by N. otitidiscaviarum in an AIDS patient. A 31 year-old intravenous drug abuser with a diagnosis of full-blown AIDS, presented with high fever and lymphadenitis with a fistula draining copious purulent discharge. Broad-spectrum antibiotic therapy was initiated, but the patient did not shown any improvement. Direct examination of the pus revealed numerous gram positive rods. When cultured N. otitidiscavarium was isolated and identified by morphological and biochemical tests.