A comparison of upper limb function in subjects with multiple sclerosis and healthy controls using an inertial measurement unit.

Upper limbs (UL) dysfunction is frequent in people with Multiple Sclerosis (PwMS). Several objective measures of UL function are proposed; however, their use is mostly confined to assess subjects with mild-to-moderate disability and requires fine motor skills, often impaired in high disability level subjects. Thus, a tool to score UL function in the advanced disease stage is lacking. The aim of the study is to analyse and compare UL unilateral and bilateral movements of healthy control (HC) and PwMS, at different disability levels, using an instrumented version (Inertial Measurement Unit, IMU) of the 15-seconds finger-to-nose test (FNT). Each movement cycle was segmented in going/adjusting/returning phases. The inter-hand interval (IHI) allowed assessing bilateral coordination (i.e. synchrony) in each phase. The larger IHI, the more severe the bilateral coordination impairment is. After stratifying PwMS for disability level (PwMSLOW, Expanded Disability Status Scale, EDSS≤5.5 and PwMSHIGH, EDSS≥6), the ANOVA on IHI showed significant differences between PwMS and HC (p<0.001) in all phases. However, only the going phase IHI showed significantly higher asynchrony in PwMSHIGH than PwMSLOW and HC (p<0.001) and no differences between PwMSLOW and HC. The going phase IHI seems to be a clinical marker specific for high disability level PwMS. These findings suggest inertial sensors during FNT could be an easy-to-use method for a more detailed quantitative characterization of UL function in PwMS also in subjects with EDSS greater than 6.

A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia.

The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.

Nine Hole Peg Test asymmetry in refining upper limb assessment in multiple sclerosis.

BACKGROUND: The Expanded Disability Status Scale (EDSS) is the most frequently used scale to measure neurologic impairment and quantify the level of disability in Multiple Sclerosis (MS) even though the scale focuses on ambulation and undervalues upper limb (UL) impairment. The 9-Hole Peg Test (9-HPT) is the gold standard for UL assessment in MS, calculating a mean score from right and left arms, even though subjects with MS often show a lateralization of neurological deficit. OBJECTIVE: The study aimed to determine whether an interaction exists between mean right-left 9-HPT scores or 9HPT score asymmetry (difference between right and left side) in predicting EDSS in MS subjects. METHODS: Demographic and disease variables and 9-HPT scores were obtained from medical records of individuals with MS collected in an ad-hoc database. Subjects with 9-HPT score ≤180 s for each arm were included. An asymmetry score was represented as the absolute value of the difference between 9-HPT scores for both arms. RESULTS: 549 subjects were included: 67.8% female, mean age 45±13.14 years, mean EDSS 3.98±2.12, 356 relapsing-remitting, 68 primary and 125 secondary progressive, mean 9-HPT scores: right arm 30.20 ± 19.99 s, left arm 31.80 ± 20.35 s. Mean asymmetry was 9.35±18.20 s. Correlation between mean right-left 9-HPT scores and EDSS was 0.58 (p<.001). Significant interaction between mean right-left 9-HPT scores and 9-HPT asymmetry in predicting EDSS scores was found. Regression slope of EDSS on mean right-left 9-HPT score decreases as asymmetry value increases (non-significance area values ≥ 40.93 s). CONCLUSIONS: Findings suggest interaction exists between mean right-left 9-HPT scores and asymmetry in predicting EDSS. A consequence of this is that, by disregarding information about asymmetry, studies exploring the association between mean right-left 9-HPT scores and global measures of disability may provide biased results. The bias tends to increase as asymmetry increases, and to be most prevalent among patients with EDSS scores > 6.

Box and block test, hand grip strength and nine-hole peg test: correlations between three upper limb objective measures in multiple sclerosis.

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.

Efficacy of levetiracetam on upper limb movement in multiple sclerosis patients with cerebellar signs: a multicenter double-blind, placebo-controlled, crossover study.

BACKGROUND AND PURPOSE: The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. METHODS: In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. RESULTS: Forty-eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0-T1) in group 1. CONCLUSIONS: Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs.

Informing MS patients on treatment options: a consensus on the process of consent taking.

In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow patient's empowerment in the decision-making process. AIMS: The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice. RESULTS: The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.

Prevalence of dysphagia in a consecutive cohort of subjects with MS using fibre-optic endoscopy.

INTRODUCTION: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems. MATHERIALS AND METHODS: Data were collected in a multicentre study from a consecutive sample of MS patients, irrespective of self-reported dysphagia. The study included 215 subjects. Possible scores for DOSS range from 7 to 1, with 7 indicating normal swallowing. RESULTS: One hundred twenty-four (57.7%) subjects demonstrated abnormal swallowing and 57 (26.5%) of these had swallowing problems that required nutrition/diet modifications when evaluated objectively with fibre-optic endoscopy. Subjects with dysphagia were more severely disabled and more often had a progressive form of MS, compared to MS subjects with normal swallowing. In subjects with EDSS, < 4, 8 (13.3%), had a DOSS < 4. Seventy-five percent of subjects older than 60 years of age had dysphagia. CONCLUSION: In this sample of MS patients, more nearly 60% showed swallowing problems.

Examining the validity of the multiple-sclerosis walking scale-12 with Rasch analysis: Results from an Italian study.

BACKGROUND: The Multiple Sclerosis Walking Scale (MSWS-12) has showed good psychometric properties in reports exploring its validity using Classical Test Theory methods. Findings from recent studies using Item Response Theory methods advance the idea that some aspects of the MSWS-12 does not fully comply with some requirements of sound measurement. RESEARCH QUESTION: The present study investigated whether the measurement properties of the Italian version of the MSWS-12 met the assumptions of the Rasch model. METHODS: Sample consisted of 199 patients with a diagnosis of MS (50% female; Mean age (SD) = 48.15 (12.33)). Analyses were performed using both unidimensional and multidimensional Rasch modeling techniques. RESULTS: Rating scale for items assessing need for support when walking, and ability to run, showed significant functioning problems. A revision of the rating scale improved the measurement properties of these items. Items assessing need for support showed signs of multidimensionality and differential item functioning when controlling for patients' disease course and EDSS score. Additionally, included items did not appear to cover the full range of impairment as observed in the sample. SIGNIFICANCE: Emerging findings are consistent with those from previous studies in highlighting the need for a revision of the current content of the MSWS-12, and the inclusion of new items assessing impairment at the lower end of the disability continuum.

A Delphi consensus statement of the Neuropathic Pain Special Interest Group of the Italian Neurological Society on pharmacoresistant neuropathic pain.

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when "the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose." Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.

Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study.

BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

Effects of Constraint-Induced Movement Therapy on upper limb activity according to a bi-dimensional kinematic analysis in progressive multiple sclerosis patients: a randomized single-blind pilot study.

Multiple sclerosis (MS) is a chronic disease of the central nervous system, characterized by demyelinization and axonal loss resulting, in 66% of cases, in upper limb motor impairment. The effects of constraint-induced movement therapy (CIMT) have recently been investigated in MS patients. The aim of this randomized single-blind pilot study was to assess the effects of CIMT on upper limb activity, specifically smoothness of movement, in patients affected by progressive MS. Patients affected by MS, and reporting reduced use primarily of one upper limb, were enrolled and randomly allocated to two different groups: a CIMT group, where treatment was performed with the less affected limb immobilized by a splint, and a control group, submitted to intensive bi-manual treatment. All evaluations were performed at baseline (T0) and after two weeks of treatment (T1) by an operator unaware of the patients' allocation. The primary outcome was the difference in movement smoothness, measured by means of a bidimensional kinematic evaluation. Secondary outcomes were: endpoint error and arm trajectory mean speed. Furthermore, patients performed the Hand Grip Strength Test (HGS) and 9-Hole Peg Test (9HPT), for both arms, at both time points. Ten patients with MS (4 males, 6 females; mean age 51.0±7.7 years) were randomly allocated to the CIMT group (n=5) and control group (n=5). There were no significant differences between groups in any of the data assessed at baseline. In the CIMT group subjects, the treatment effect, in terms of movement smoothness, was significant at the more affected limb (p=0.0376). The CIMT group displayed statistically significant improvements, versus the baseline values, in muscle strength (HGS:22.4±8.3 vs 26.0±6.0; p<0.05) and dexterity (9HPT: 31.8±6.1 vs 27.4±4.9; p<0.05) of the more affected limb. A positive, although not significant, trend in terms of muscle strength and upper limb dexterity was observed, for both limbs, in the control group after the two-week treatment. Bi-dimensional kinematic evaluation demonstrated that the CIMT group showed a significant reduction of endpoint error and higher mean speed for the more affected arm; these data are in line with the significant improvements recorded on the HGS and 9HPT. Moreover, in the CIMT group, a non-significant worsening of muscle strength was recorded for the less affected upper limb.

Direct Frequency-Comb-Driven Raman Transitions in the Terahertz Range.

We demonstrate the use of a femtosecond frequency comb to coherently drive stimulated Raman transitions between terahertz-spaced atomic energy levels. More specifically, we address the 3d ^{2}D_{3/2} and 3d ^{2}D_{5/2} fine structure levels of a single trapped ^{40}Ca^{+} ion and spectroscopically resolve the transition frequency to be ν_{D}=1,819,599,021,534±8 Hz. The achieved accuracy is nearly a factor of five better than the previous best Raman spectroscopy, and is currently limited by the stability of our atomic clock reference. Furthermore, the population dynamics of frequency-comb-driven Raman transitions can be fully predicted from the spectral properties of the frequency comb, and Rabi oscillations with a contrast of 99.3(6)% and millisecond coherence time have been achieved. Importantly, the technique can be easily generalized to transitions in the sub-kHz to tens of THz range and should be applicable for driving, e.g., spin-resolved rovibrational transitions in molecules and hyperfine transitions in highly charged ions.

Effect of organizational features on patient satisfaction with care in Italian multiple sclerosis centres.

BACKGROUND AND PURPOSE: Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients' satisfaction with healthcare. METHODS: Eighty-one centres and 707 patients (502 women, mean age 40.5 years, SD 10.2; mean education 12.2 years, SD 3.6; time since diagnosis 5.9 years, SD 1.5) were included in the analysis. The care organization and service provided by each centre were evaluated in comparison with the National Institute for Health and Care Excellence (NICE) guidelines on management of MS. Patients' satisfaction with care was measured using the patient self-assessed questionnaire 'Comunicazione medico-paziente nella Sclerosi Multipla, revised' section 2 (COSM-R section 2). RESULTS: The clinical characteristics of patients significantly affected their satisfaction. A multivariate regression model showed that higher patients' satisfaction (COSM-R score) was inversely associated with hospital size (number of patients under care) (ß = -0.21, 95% confidence interval -0.35; -0.07) and directly associated with psychological interventions (ß = 2.44, 95% confidence interval 0.29; 4.59). CONCLUSIONS: Multiple sclerosis patients from larger hospitals are less satisfied with the information received and the relationship with HPs. Building an individualized relationship between patients and HPs and tailoring the communication of information improve patients' satisfaction. Such a goal is probably less likely to be accomplished in larger centres with many incoming patients. Moreover, when the centres also provide structured psychological interventions, the patients are more satisfied.

Competition between Spin Echo and Spin Self-Rephasing in a Trapped Atom Interferometer.

We perform Ramsey interferometry on an ultracold ^{87}Rb ensemble confined in an optical dipole trap. We use a π pulse set at the middle of the interferometer to restore the coherence of the spin ensemble by canceling out phase inhomogeneities and creating a spin echo in the contrast. However, for high atomic densities, we observe the opposite behavior: the π pulse accelerates the dephasing of the spin ensemble leading to a faster contrast decay of the interferometer. We understand this phenomenon as a competition between the spin-echo technique and an exchange-interaction driven spin self-rephasing mechanism based on the identical spin rotation effect. Our experimental data are well reproduced by a numerical model.

Depressive Symptoms Correlate with Disability and Disease Course in Multiple Sclerosis Patients: An Italian Multi-Center Study Using the Beck Depression Inventory.

BACKGROUND: Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. METHODS: Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. RESULTS: 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0-8.5) and mean disease duration of 10.3 years (range 1-50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20-63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. CONCLUSIONS: Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

BACKGROUND: The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting. METHODS: We collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0-10 numerical rating scale (NRS) scale is available at baseline, after 1 month of treatment (trial period), and at 3 and 6 months. RESULTS: A total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3-2.4 p<0.001). During the 6 months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%). CONCLUSIONS: Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

Use of herbal remedies by multiple sclerosis patients: a nation-wide survey in Italy.

Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines (CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0-40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments.

New hosts for the mite Ornithonyssus bursa in Argentina.

The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations.