The role of sensory systems in the association between balance and walking in people with multiple sclerosis.

BACKGROUND: In Multiple Sclerosis, it has been demonstrated that balance is related to performances in walking tasks at different levels of complexity. However, it is unknown how the different sensory systems involved in balance control contribute to walking. This observational study investigates the associations between somatosensory, vestibular, and visual systems and measures of self-reported walking and walking capacity at different complexity levels (i.e. low, medium, and high). METHODS: People with MS with EDSS<6 were assessed through the Sensory Organization Test (SOT), 12-Item MS Walking Scale (MSWS-12), Timed 25-Foot Walk (T25FW), Timed Up-and-Go Test (TUG), and Six-Spot-Step-Test (SSST). T25FW, TUG and SSST are measures of low, medium and high walking capacity, respectively. RESULTS: Forty-five PwMS were enrolled (EDSS: 3.4 ± 1.3). Capacity/ability walking measures were moderate-to-highly significantly associated (p < 0.01). Balance measures from SOT showed significant correlation (p < 0.05) between vestibular system and all the walking measures; between visual system and T25FW, SSST and MSWS-12; between the degree to which the patient relies on the visual system to maintain balance with conflicting visual surroundings information (VIS PREF) and T25FW and TUG. In the multivariate analyses, only VIS PREF significantly correlated (p < 0.05) with T25FW (std. Beta=0.42) and TUG (std. Beta=0.38). CONCLUSIONS: Vestibular and visual systems are associated with walking capacity. However, tasks with higher complexity levels require more visual attention towards ground obstacles, as often seen in real-life activities, whereas simpler walking tasks seem to require visual attention towards the surroundings.

Italian adaptation and psychometric validation of the Fatigue Impact Scale (FIS) and its modified versions in adults with multiple sclerosis: a Rasch analysis study.

Purpose: Several outcome measures are available to assess the severity of fatigue in people with multiple sclerosis (MS). The aim of this study was to adapt the Italian version of the Fatigue Impact Scale (FIS-40) and its modified versions: a 21-item Modified scale (MFIS-21), its 5-item short version (MFIS-5), and an 8-item version for daily use (DFIS-8) and investigate their measurement properties through classical theory-test (CTT) and Rasch analysis (RA).Methods: 229 Italian-speaking adults with MS were included. Questionnaires were cross-culturally translated and subjected to CTT (i.e. internal consistency through Cronbach's alpha and unidimensionality through confirmatory factor analysis [CFA]) and RA. (i.e. internal construct validity, reliability, and targeting).Results: Internal consistency was high for all scales (>0.850). Final CFAs reported issues in the unidimensionality for all scales except for FIS-40. Baseline RA revealed a misfit for all scales. After adjusting for local dependency, FIS-40, MFIS-21, and MFIS-5 fitted the Rasch model (RM). MFIS-21 and D-FIS-8 required a structural modification, i.e. item deletions to satisfy the RM.Conclusion: The FIS-40, MFIS-21, MFIS-5, and DFIS-8 achieved the fit to the RM after statistical and structural modifications. The fit to the RM allowed for providing ordinal-to-interval measurement conversion tables for all the questionnaires.

The Fatigue Impact Scale (FIS-40), the 21-item Modified scale (MFIS-21), its 5-item short version (MFIS-5) and the 8-item version for daily use (DFIS-8) have been successfully cross-culturally validated in Italian.The FIS-40 and its versions fit the Rasch Model with minimal changes, determining that the studied outcomes represent a unidimensional construct, i.e. fatigue in multiple sclerosis.The final Rasch Model enables the transformation of scores into interval-level measurements, allowing clinicians to gauge the distance between individuals' scores on the scale continuum.Interval-level transformation allows rehabilitation professionals to better interpret clinical changes and researchers to apply parametric statistics.

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 × 1.0 cm) or large (1.5 × 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.

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 α 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 α = 0.84; MW-D: Cronbach's α = 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.

Focus on neglected features of cognitive rehabilitation in MS: Setting and mode of the treatment.

Cognitive rehabilitation in multiple sclerosis (MS) aims at reducing patients' cognitive impairments, improving their awareness and ability to take cognitive difficulties into account in their daily living. However, at this moment, more high-quality randomized trials are needed to draw conclusion about the effectiveness of cognitive interventions in MS. Although existing studies provide clear descriptions of intervention key ingredients (e.g. targeted cognitive domain as well as treatment frequency and duration) and the practical details needed to manage these key elements (e.g. restorative approaches, compensatory strategies, or environmental modifications), other crucial aspects received less attention in rehabilitation research. The aim of this topical review is to try to elucidate some critical issues that were only partly addressed and analyzed by the scientific literature: setting (center-based vs home-based) and mode (individual vs group) of the cognitive rehabilitation treatment.

Predominant cognitive phenotypes in multiple sclerosis: Insights from patient-centered outcomes.

BACKGROUND: Since combining information from different domains could be useful to increase prediction accuracy over and above what can be achieved at the level of single category of markers, this study aimed to identify distinct and predominant subtypes, i.e., cognitive phenotypes, in people with multiple sclerosis (PwMS) considering both cognitive impairment and mood disorders. METHODS: A latent class analysis (LCA) was applied on data from 872 PwMS who were tested with Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT) and Hospital Anxiety and Depression Scale (HADS). Furthermore, the distribution of demographic (i.e., age, gender, years of education) and clinical characteristics (i.e., disease duration, disease course, disability level) was examined amongst the identified phenotypes. RESULTS: Based on model fit and parsimony criteria, LCA identified four cognitive phenotypes: 1) only memory difficulties (n = 247; 28.3%); 2) minor memory and language deficits with mood disorders (n = 185; 21.2%); 3) moderate memory, language and attention impairments (n = 164; 18.8%); 4) severe memory, language, attention, information processing and executive functions difficulties (n = 276; 31.7%). CONCLUSIONS: Since less is known about the progressive deterioration of cognition in PwMS, a taxonomy of distinct subtypes that consider information from different clustered domains (i.e., cognition and mood) represents both a challenge and opportunity for an advanced understanding of cognitive impairments and development of tailored cognitive treatments in MS.

MAM-36 and ABILHAND as outcome measures of multiple sclerosis hand disability: an observational study.

BACKGROUND: Impaired upper limb functionality and dexterity are common in people with multiple sclerosis (PwMS) and lead to increased dependency and reduced quality of life. AIM: The aim of this study was to compare the ability of the Manual Abilites Measure 36 (MAM-36) and the ABILHAND questionnaire to recognize an involvement of the upper limbs in PwMS, and to compare their results with those of other patient reported outcomes (PRO) evaluating disability, functional independence, symptoms of anxiety and depression, fatigue and quality of life. DESIGN: The study design was observational. SETTING: The setting of the study was outpatient. POPULATION: The study population included fifty-one PwMS (mean age of 56.31 years, age range of 33-82 years, 72.5% of patients were females). METHODS: For each patient were collected MAM-36, ABILHAND questionnaire, expanded disability status scale (EDSS), Functional Independence measure (FIM), Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS) and Life Satisfaction Index (LSI). RESULTS: A strong correlation between MAM-36 and the ABILHAND questionnaire (Spearman r: 0.79; P<0.0001) were found. We obtained a significant correlation between MAM-36 and EDSS (Spearman r: -0.5; P=0.0002), FIM (Spearman r: 0.55; P<0.0001); we did not observe a correlation with MFIS (Spearman r: -0.33; P=0.02); moreover we found a similar trend between ABILHAND and EDSS (Spearman r: -0.47; P=0.0005), FIM (Spearman r: 0.61; P<0.0001), MFIS (Spearman r: -0.41; P=0.002). CONCLUSIONS: In PwMS the assessment of upper limbs is fundamental since it closely related to the level of disability of the person. Both MAM-36 and ABILHAND Questionnaire are equally able to detect upper limb dysfunctions in PwMS. CLINICAL REHABILITATION IMPACT: Both MAM-36 and ABILHAND can be used for upper limbs evaluation, within a multidimensional approach that seems to be the best way to evaluate PwMS.

Spatial constraints and cognitive fatigue affect motor imagery of walking in people with multiple sclerosis.

Motor imagery (MI) is the mental simulation of an action without any overt motor execution. Interestingly, a temporal coupling between durations of real and imagined movements, i.e., the so-called isochrony principle, has been demonstrated in healthy adults. On the contrary, anisochrony has frequently been reported in elderly subjects or those with neurological disease such as Parkinson disease or multiple sclerosis (MS). Here, we tested whether people with MS (PwMS) may have impaired MI when they imagined themselves walking on paths with different widths. When required to mentally simulate a walking movement along a constrained pathway, PwMS tended to overestimate mental movement duration with respect to actual movement duration. Interestingly, in line with previous evidence, cognitive fatigue was found to play a role in the MI of PwMS. These results suggest that investigating the relationship between cognitive fatigue and MI performances could be key to shedding new light on the motor representation of PwMS and providing critical insights into effective and tailored rehabilitative treatments.

Predictors of clinically significant anxiety in people with multiple sclerosis: A one-year follow-up study.

BACKGROUND: Mood disorders, such as depression and anxiety, are frequent in people with Multiple Sclerosis (PwMS). Although anxiety has a well-recognized negative influence on family, work and social life, it has received less attention than depression. Thus, it is still under debate which risk factors can predict anxiety, its evolution over time and the extent of its effect on disability progression. OBJECTIVE: The aim of this retrospective study was to identify potential demographic, clinical and self-reported predictors that contribute to clinically significant anxiety at one-year follow up, measured by the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS). METHODS: Data was acquired from a cohort of 608 subjects with MS, and included domains potentially meaningful for clinically significant anxiety. Associations between each variable and clinically significant anxiety at one-year follow-up were assessed with univariate and multivariate logistic regression analyses. RESULTS: Lower educational level, relapsing-remitting disease course, presence of clinically significant anxiety at baseline, higher depression and fatigue perception were significant predictors for clinically significant anxiety at one-year follow up. CONCLUSION: Findings confirm the importance of identifying risk factors for clinically significant anxiety in predicting prognosis and planning early intervention.

Lower urinary tract dysfunction in patients with multiple sclerosis: A post-void residual analysis of 501 cases.

INTRODUCTION: Lower urinary tract symptoms (LUTS) are common in individuals with multiple sclerosis (MS), and can have a significant impact on quality of life (QoL). Prevalence of LUTS in MS ranges from 32% to 96.8%, including storage or voiding symptoms or a combination of these. Post-void residual (PVR) is a very well-tolerated, non-invasive test for evaluating voiding dysfunction. The aim of the current study was to describe the distribution of PVR volumes across MS subjects with and without LUTS and to examine relationships between storage symptoms, voiding symptoms, and PVR. METHODS: A large group of subjects (N = 501) completed a questionnaire on LUTS (current bladder management, number of urinary tract infections in the last year and urological investigations). A bladder ultrasound for PVR was performed and data were collected. We used Chi-Square and the Mann-Whitney non-parametric tests respectively for categorical and continuous variables in order to assess differences between symptomatic and asymptomatic groups. The differences of PVR by LUTS status were explored using the Mann-Whitney non-parametric test for independent samples. RESULTS: Overall mean PVR was 132.4 mL (PVR>100 ml was considered an abnormal residual urine volume). Based on the LUTS questionnaire, 43 subjects (8.6%) were asymptomatic, while 458 subjects (91.4%) reported at least one LUTS. Storage-related symptoms were reported by 87.2% of subjects (437) and 65.1% (326) reported at least one voiding-related symptom. Two-third of subjects (66.5%) reported three or more LUTS. There was a statistically significant association between the presence of LUTS and the number of infections reported (p = 0.0015). The symptomatic group had significantly higher PVR than the asymptomatic group (p = 0.011). PVR significantly correlated with male gender, disability level and a progressive disease course. CONCLUSION: Results showed a high prevalence of LUTS in subjects with MS and that storage symptoms are predominant. There was an association between the presence of LUTS and a progressive disease course. The relationship between LUTS, higher PVR and the severity of disease course indicates that a comprehensive clinical evaluation should include an assessment of both neurological and micturition disorders and, importantly, PVR should be measured at every clinical assessment, despite the presence or absence of LUTS.

The hidden information in patient-reported outcomes and clinician-assessed outcomes: multiple sclerosis as a proof of concept of a machine learning approach.

Machine learning (ML) applied to patient-reported (PROs) and clinical-assessed outcomes (CAOs) could favour a more predictive and personalized medicine. Our aim was to confirm the important role of applying ML to PROs and CAOs of people with relapsing-remitting (RR) and secondary progressive (SP) form of multiple sclerosis (MS), to promptly identifying information useful to predict disease progression. For our analysis, a dataset of 3398 evaluations from 810 persons with MS (PwMS) was adopted. Three steps were provided: course classification; extraction of the most relevant predictors at the next time point; prediction if the patient will experience the transition from RR to SP at the next time point. The Current Course Assignment (CCA) step correctly assigned the current MS course with an accuracy of about 86.0%. The MS course at the next time point can be predicted using the predictors selected in CCA. PROs/CAOs Evolution Prediction (PEP) followed by Future Course Assignment (FCA) was able to foresee the course at the next time point with an accuracy of 82.6%. Our results suggest that PROs and CAOs could help the clinician decision-making in their practice.

Innovative quantitative testing of hand function in Charcot-Marie-Tooth neuropathy.

To describe a new test to quantitatively evaluate hand function in patients affected by Charcot-Marie-Tooth neuropathy (CMT). The sensor-engineered glove test (SEGT) was applied to CMT patients (N: 26) and compared with a cohort of healthy controls (HC, N: 26). CMT patients were further divided into subjects with clinically normal (group 1) or impaired hand (group 2) function. The SEGT parameters evaluated were touch duration, inter-tapping interval, and movement rate parameters of two different sequences: finger tapping (FT) and index-medium-ring-little (IMRL) performed at self-paced mode (SPM) and maximum velocity (MV). Hand function and strength were assessed by the 9-hole peg test (9HPT) and dynamometry. Disability of patients was measured by the CMT neuropathy score. CMT patients had significantly worst performances at SEGT than controls regarding the rate of execution of both FT (at MV) and IMRL sequences (at SPM and MV). The rate parameter at MV in IMRL sequence showed a significant trend of decreasing in its average between HC (n: 26, rate = 3.08 ± 0.52 Hz), group 1 (n: 9, rate = 2.64 ± 0.66 Hz) and group 2 (n: 17, rate = 2.19 ± 0.45 Hz) (p for trend <0.001). No correlations were found with either 9HPT, dynamometry, electrophysiology, and the CMT neuropathy score. The SEGT test is sensitive to show hand dysfunction in CMT patients, with and without clinically impaired hands.

Brown-Vialetto-Van Laere syndrome: clinical and neuroradiological findings of a genetically proven patient.

The Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disorder characterized by progressive pontobulbar palsy, sensorineural deafness and mixed spinal and upper motor neuropathy. Mutations in the C20orf54 gene have been linked to the disease and recently we reported the first Italian case of a BVVLS family with an intriguing C20orf54 genotype. However, the pathomechanisms underlying BVVLS are still unknown. Here we present the particular disease course with partial response to immunosuppressive therapy of our BVVLS patient for whom we hypothesize that dysimmune factors may have played a role in disease physiopathology.

Outcome measures and rehabilitation treatment in patients affected by Charcot-Marie-Tooth neuropathy: a pilot study.

OBJECTIVE: : We evaluated the sensitivity of various rehabilitation and lung function scales to detect differences between people with Charcot-Marie-Tooth (CMT) disease and healthy controls. We also studied whether these measurements are sensitive to disclose changes in patients with CMT disease after rehabilitative treatment. DESIGN: : Eight patients with different types of CMT participated in the study. Data were gathered at baseline; at the end of the treadmill training, stretching, respiratory, and proprioceptive exercise (TreSPE) treatment period; and after a washout period of 6 mos. The following instruments were used for data collection: Medical Research Council scale for lower limb strength; Tinetti Balance Scale; Physical Performance Battery; ankle angle, oxygen consumption, and lung function tests; peak treadmill velocity and slope; time to walk 6 m; and CMT Neuropathy Score. The participants underwent TreSPE treatment twice every week for 8 wks. RESULTS: : All rehabilitative measures were significantly worse in subjects with CMT disease than in healthy controls. Lung function was always normal except for the maximum expiratory pressure and maximum inspiratory pressure. No dropouts or worsening in any of the different outcome measures were observed after TreSPE. The ankle angle and the time to walk 6 m were the only measures that significantly improved after treatment. CONCLUSIONS: : The rehabilitative outcome measures used in this protocol are useful in detecting clinical impairment in people with CMT disease. Lung function tests were confirmed to be minimally abnormal in patients with CMT disease. The TreSPE treatment, besides being safe and well tolerated, induced some training effects in CMT neuropathy, in the absence of lung function amelioration and effort tolerance. Follow-up showed that CMT patients should be treated at least twice every year because a regression of all outcome measures to the baseline state was found after a 6-mo washout period.

Inherited neuropathies.

OPINION STATEMENT: Inherited peripheral neuropathies are among the most common hereditary diseases of the nervous system. Charcot-Marie-Tooth (CMT) disease, also known from previous classifications as hereditary motor and sensory neuropathy (HMSN), is certainly the most common inherited neuropathy. In the past several years, various treatments for CMT have been proposed, although specific therapies are not yet available. In clinical practice, rehabilitative strategies remain the most helpful therapeutic approach to these patients. There is still a lack of consensus on the best way to rehabilitate patients affected by CMT. Based on our personal experience and on a review of the literature, we first recommend the prescription of ankle-foot orthoses (AFO) for patients affected by CMT; the choice of which patient, which AFO, and when to apply it depends on the individual condition of each patient and on the experience of the physician/therapist. Second, adaptive equipment (eg, button hook, long-handled shoehorn, elastic shoe laces) is available to compensate for hand deformities, sensory loss, and weakness. Third, moderate to intense strength training and aerobic exercise are well tolerated by patients affected by CMT; further studies are needed to establish whether these approaches are effective in improving their motor function and strength. There is not enough evidence to recommend muscle stretching exercises or proprioceptive kinesiotherapy, although in our experience both approaches may be helpful in selected CMT patients to prevent tendon retractions, muscle tightening, and loss of strength, and to improve balance. There is growing knowledge of the underlying genetic defects and molecular pathophysiology in CMT. To date, only a few clinical trials in CMT patients have been performed. A neurotrophic factor, neurotrophin 3, was used in a small sample of CMT1A patients with promising results, but it has not been tested in a larger cohort and there is currently no reason to suggest this therapy for CMT1A neuropathy. Based on positive results in an animal model of CMT1A, three trials with ascorbic acid (AA) were completed in a large number of patients with this neuropathy, with results that were negative overall. Therefore, it is not possible to recommend the use of AA in CMT1A patients at this time, but the results of a larger Italian-UK study and an American trial with higher doses of AA are still awaited. It is important to remember that a superimposed inflammatory/disimmune process may complicate the course of the neuropathy; in this case, severe worsening (especially motor) in a matter of weeks or months is a "red flag" that should suggest immunosuppressive or immunomodulatory treatment such as steroids, intravenous immunoglobulin, or plasma exchange. In fact, steroid-sensitive cases of HMSN were described many years ago, well before the genetic diagnosis was available. Symptomatic treatment to reduce neuropathic and nociceptive pain, both of which have been reported in patients affected by CMT, should be prescribed according to recently published guidelines for the therapy of pain. No evidence suggests any specific surgical intervention or change in diet or lifestyle for patients affected by various types of CMT.