Temporal prediction of multiple sclerosis evolution from patient-centered outcomes

Multiple Sclerosis is a degenerative condition of the central nervous system that affects nearly 2.5 million of individuals in terms of their physical, cognitive, psychological and social capabilities. Despite the high variability of its clinical presentation, relapsing and progressive multiple sclerosis are considered the two main disease types, with the former possibly evolving into the latter. Recently, the attention of the medical community toward the use of patient-centered outcomes in multiple sclerosis has significantly increased. Such patient-friendly measures are devoted to the assessment of the impact of the disease on several domains of the patient life. In this work, we investigate on use of patient-centered outcomes to predict the evolution of the disease and to assess its impact on patients\u201a\uc4\uf4 lives. To this aim, we build a novel temporal model based on gradient boosting classification and multiple-output elastic-net regression. The model provides clinically interpretable results along with accurate predictions of the disease course evolution

Development and psychometric properties of a self-assessed knowledge questionnaire for caregivers of people with multiple sclerosis (CareKoMS): a cross-sectional study

ObjectivesKnowledge about multiple sclerosis (MS) is crucial for those who provide care and support as caregivers. However, despite the key benefits of acquiring relevant information to properly assume the caregiving role, caregivers' knowledge of MS is poorly investigated. The aim of this study was to develop and validate the Caregivers' Knowledge of Multiple Sclerosis (CareKoMS), a self-assessed questionnaire, to test MS knowledge in caregivers of people with MS. DesignCross-sectional study. SettingItaly. ParticipantsTwo-hundred caregivers (female: 49%) were asked to self-administer the 32-item CareKoMS questionnaire; they had a median age of 60 years (IQR: 51-68 years) and a medium-high educational level (36.5% primary school and 63.5% high school/university). Item analysis using item difficulty index, item discrimination index, Kuder-Richardson-20 coefficient and item-total correlation were assessed. Once excluding less useful items, reliability, floor and ceiling effects and construct validity were calculated on the 21-item CareKoMS final version. ResultsPsychometric evaluation indicates that the 21-item CareKoMS was a good questionnaire with no ceiling or floor effects registered. Internal consistency was satisfactory and acceptable as indicated by the mean value of 0.74 of Kuder-Richardson-20. No ceiling or floor effects have been observed. Interestingly, educational level and disease duration correlated with MS knowledge. ConclusionCareKoMS is a valid self-assessed questionnaire on MS knowledge for caregivers that may be used in clinical practice and research. Assessing knowledge of MS among caregivers is essential to facilitate their caregiving role and thus decrease the burden of disease management

Profile and burden of the family caregiver: the caring experience in multiple sclerosis. An observational study

Background The broad implications of caring for a family member with a chronic medical condition, such as MS, can lead caregivers to experience a high burden of care. The aim of the study was to describe profile of MS caregivers and their burden and to explore potential factors influencing this burden. Methods 200 family caregivers of a person with MS completed survey questionnaires across a cross-sectional study. Many information were collected: caregiver socio-demographic and health-related data, caregiving activities, knowledge of MS, coping strategies, mood, social support received and care recipient information. Caregiving burden was measured by the ZBI (Zarit Burden Interview). The extent to which the variables explained caregiver burden was analyzed using a hierarchical approach. Results 68% of the caregivers reported a perceived burden of care (ZBI score > 20). Our results show that physical and mental related-health variables are important predictive factors of the care burden, explaining much of the observed variance (40.9%). Conclusion Family caregivers in MS continue to make up the shortfall produce by national health and welfare systems. We highlighted the importance of good physical and mental health in decreasing perceived burden. Working to alleviate psychological distress through mechanisms focus on reducing worries and perceived burden may be a valid approach

Effects of Social Conditions in a Virtual Exergame for Cognitive Rehabilitation in Multiple Sclerosis

Rehabilitation is essential for individuals with multiple sclerosis (MS) to improve their quality of life and mitigate the progression of the disease. Cognitive deficits, which commonly affect MS patients, significantly impact daily functioning and well-being. This paper focuses on the development of a digital version of the Tangram puzzle using virtual reality (VR) to promote logical reasoning, attention, and social interactions to enhance engagement in cognitive rehabilitation for MS patients. The developed simulation integrates social presence in the form of a non-playable character (NPC) intending to improve player performance and motivation to ultimately promote engagement and adherence to treatment. A user study involving different game modes with the NPC in either a supporting or interfering role, was conducted to evaluate the effectiveness and usability of the Tangram VR exergame. After collecting and analyzing questionnaire scores and performance data, our results suggest that the application was well-received by users, and the introduction of an NPC had an impact in terms of execution times and sense of frustration, depending on its behaviour. Nonetheless, only a limited set of significant differences between modes was found, suggesting that further study is necessary to validate the results fully

Mind wandering in people with Multiple Sclerosis: A psychometric study

Background: Although mind wandering (MW) is associated with various psychological aspects frequently affected in people with Multiple Sclerosis (PwMS), there is lack of validated tools to assess MW in this clinical population.Objective: This psychometric study aimed to assess structural and construct validity and reliability of a brief Italian version of Mind Wandering (MW) Scale that measures two different dimensions of MW, i.e., spontaneous (MW-S) and deliberate (MW-D).Methods: Structural validity of the MW Scale was assessed by explorative factor analysis (EFA). To investigate construct validity, mood (Hospital Anxiety Depression Scale) and personality (10-items Big Five Inventory Test) were correlated with MW constructs. Reliability was assessed by Cronbach's alpha for internal consistency and intraclass correlation coefficients.Results: EFA confirmed two distinct constructs of MW, i.e., MW-S and MW-D, also in PwMS. This tool appropriately fits the graded response model, supporting validity (about 79% of hypotheses for convergent and discriminant constructs confirmed) and internal consistency (MW-S: Cronbach's alpha = 0.84; MW-D: Cronbach's alpha = 0.88).Conclusion: MW Scale could be a useful tool to measure MW also in PwMS. As MW seems to be connected to clinical manifestations of MS, a detailed assessment of MW should be encouraged in clinical practice

Motor imagery has a priming effect on motor execution in people with multiple sclerosis

Priming is a learning process that refers to behavioral changes caused by previous exposure to a similar stimulus. Motor imagery (MI), which involves the mental rehearsal of action representations in working memory without engaging in actual execution, could be a strategy for priming the motor system. This study investigates whether MI primes action execution in Multiple Sclerosis (MS). Here, 17 people with MS (PwMS) and 19 healthy subjects (HS), all right-handed and good imaginers, performed as accurately and quickly as possible, with a pencil, actual or mental pointing movements between targets of small (1.0 x 1.0 cm) or large (1.5 x 1.5 cm) size. In actual trials, they completed five pointing cycles between the left and right targets, whereas in mental trials, the first 4 cycles were imagined while the fifth was actually executed. The fifth cycle was introduced to assess the MI priming effect on actual execution. All conditions, presented randomly, were performed with both dominant (i.e., right) and non-dominant arms. Analysis of the duration of the first 4 cycles in both actual and mental trials confirmed previous findings, showing isochrony in HS with both arms and significantly faster mental than actual movements (anisochrony) in PwMS (p < 0.01) [time (s); HS right: actual: 4.23 +/- 0.15, mental: 4.36 +/- 0.16; left: actual: 4.32 +/- 0.15, mental: 4.43 +/- 0.18; PwMS right: actual: 5.85 +/- 0.16, mental: 5.99 +/- 0.21; left: actual: 6.68 +/- 0.20, mental: 5.94 +/- 0.23]; anisochrony in PwMS was present when the task was performed with the non-dominant arm. Of note, temporal analysis of the fifth actual cycle showed no differences between actual and mental trials for HS with both arms, whereas in PwMS the fifth actual cycle was significantly faster after the four actual cycles for the non-dominant arm (p < 0.05) [time (s); HS right: actual: 1.03 +/- 0.04, mental: 1.03 +/- 0.03; left: actual: 1.08 +/- 0.04, mental: 1.05 +/- 0.03; PwMS right: actual: 1.48 +/- 0.04, mental: 1.48 +/- 0.06; left: actual: 1.66 +/- 0.05, mental: 1.48 +/- 0.06]. These results seem to suggest that a few mental repetitions of an action might be sufficient to exert a priming effect on the actual execution of the same action in PwMS. This would indicate further investigation of the potential use of MI as a new motor-cognitive tool for MS neurorehabilitation

Motor imagery as a function of disease severity in multiple sclerosis: An fMRI study

Motor imagery (MI) is defined as mental execution without any actual movement. While healthy adults usually show temporal equivalence, i.e., isochrony, between the mental simulation of an action and its actual performance, neurological disorders are associated with anisochrony. Unlike in patients with stroke and Parkinson disease, only a few studies have investigated differences of MI ability in multiple sclerosis (MS). However, the relationship among disease severity, anisochrony and brain activation patterns during MI has not been investigated yet. Here, we propose to investigate MI in MS patients using fMRI during a behavioral task executed with dominant/non-dominant hand and to evaluate whether anisochrony is associated with disease severity. Thirty-seven right-handed MS patients, 17 with clinically isolated syndrome (CIS) suggestive of MS and 20 with relapsing-remitting MS (RR-MS) and 20 right-handed healthy controls (HC) underwent fMRI during a motor task consisting in the actual or imaged movement of squeezing a foam ball with the dominant and non-dominant hand. The same tasks were performed outside the MRI room to record the number of actual and imagined ball squeezes, and calculate an Index of performance (IP) based on the ratio between actual and imagined movements. IP showed that a progressive loss of ability in simulating actions (i.e., anisochrony) more pronounced for non-dominant hand, was found as function of the disease course. Moreover, anisochrony was associated with activation of occipito-parieto-frontal areas that were more extensive at the early stages of the disease, probably in order to counteract the changes due to MS. However, the neural engagement of compensatory brain areas becomes more difficult with more challenging tasks, i.e., dominant vs. non-dominant hand, with a consequent deficit in behavioral performance. These results show a strict association between MI performance and disease severity, suggesting that, at early stages of the disease, anisochrony in MI could be considered as surrogate behavioral marker of MS severity

Upper limb motor rehabilitation impacts white matter microstructure in multiple sclerosis

Upper limb impairments can occur in patients with multiple sclerosis, affecting daily living activities; however there is at present no definite agreement on the best rehabilitation treatment strategy to pursue. Moreover, motor training has been shown to induce changes in white matter architecture in healthy subjects.This study aimed at evaluating the motor behavioral and white matter microstructural changes following a 2-month upper limb motor rehabilitation treatment based on task-oriented exercises in patients with multiple sclerosis.Thirty patients (18 females and 12 males; age. = 43.3. ±. 8.7. years) in a stable phase of the disease presenting with mild or moderate upper limb sensorimotor deficits were randomized into two groups of 15 patients each. Both groups underwent twenty 1-hour treatment sessions, three times a week. The "treatment group" received an active motor rehabilitation treatment, based on voluntary exercises including task-oriented exercises, while the "control group" underwent passive mobilization of the shoulder, elbow, wrist and fingers.Before and after the rehabilitation protocols, motor performance was evaluated in all patients with standard tests. Additionally, finger motor performance accuracy was assessed by an engineered glove.In the same sessions, every patient underwent diffusion tensor imaging to obtain parametric maps of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The mean value of each parameter was separately calculated within regions of interest including the fiber bundles connecting brain areas involved in voluntary movement control: the corpus callosum, the corticospinal tracts and the superior longitudinal fasciculi.The two rehabilitation protocols induced similar effects on unimanual motor performance, but the bimanual coordination task revealed that the residual coordination abilities were maintained in the treated patients while they significantly worsened in the control group (p. = 0.002). Further, in the treatment group white matter integrity in the corpus callosum and corticospinal tracts was preserved while a microstructural integrity worsening was found in the control group (fractional anisotropy of the corpus callosum and corticospinal tracts: p. = 0.033 and p. = 0.022; radial diffusivity of the corpus callosum and corticospinal tracts: p. = 0.004 and p. = 0.008). Conversely, a significant increase of radial diffusivity was observed in the superior longitudinal fasciculi in both groups (p. = 0.02), indicating lack of treatment effects on this structure, showing damage progression likely due to a demyelination process.All these findings indicate the importance of administering, when possible, a rehabilitation treatment consisting of voluntary movements. We also demonstrated that the beneficial effects of a rehabilitation treatment are task-dependent and selective in their target; this becomes crucial towards the implementation of tailored rehabilitative approaches. © 2013 The Authors

Brain activity pattern changes after adaptative working memory training in multiple sclerosis

Cognitive impairment and related abnormal brain activity are common in people with multiple sclerosis (PwMS). Adaptive training based on working memory (WM) has been shown to ameliorate cognitive symptoms, although the effects at a neural level are unclear. The aim of this study was to expand the existing research on the effects of an adaptive WM rehabilitative intervention on brain functional activity in PwMS. A sample of eighteen PwMS performed an 8-week home-based cognitive rehabilitation treatment based on adaptive WM training. PwMS were assessed before and after treatment using a validated neuropsychological battery and undergoing an fMRI session while carrying out a cognitive task (i.e., Paced Visual Serial Addition Test - PVSAT). fMRI activations were compared to the activation pattern elicited by eighteen matched healthy subjects performing the same task. At baseline, we found abnormal brain activity during PVSAT in PwMS when compared to healthy subjects, with a pattern including several bilateral activation clusters. Following rehabilitation, PwMS improved cognitive performance, as evaluated by the neuropsychological battery, and showed a different activation map with clusters mainly located in the right cerebellum and in the left hemisphere. The only significant cluster in the right hemisphere was located in the inferior parietal lobule, and the BOLD signal extracted in this area significantly correlated with cognitive performance both before and after the treatment. We suggest that WM training can improve the cognitive performance and reduce the abnormal activation of PwMS by partially maintaining or even restoring brain cognitive function