Costanza Giannì

Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.

Objective. To evaluate the effectiveness of a home-based rehabilitation of balance using the Nintendo Wii Balance Board System (WBBS) in patients affected by multiple sclerosis (MS). Methods. In this 24-week, randomized, 2-period crossover pilot study, 36 patients having an objective balance disorder were randomly assigned in a 1:1 ratio to 2 counterbalanced arms. Group A started a 12-week period of home-based WBBS training followed by a 12-week period without any intervention; group B received the treatment in reverse order. As endpoints, we considered the mean difference (compared with baseline) in force platform measures (ie, the displacement of body center of pressure in 30 seconds), 4-step square test (FSST), 25-foot timed walking test (25-FWT), and 29-item MS Impact Scale (MSIS-29), as evaluated after 12 weeks and at the end of the 24-week study period. Results. The 2 groups did not differ in baseline characteristics. Repeated-measures analyses of variance showed significant time × treatment effects, indicating that WBBS was effective in ameliorating force platform measures (F = 4.608, P = .016), FSST (F = 3.745, P = .034), 25-FWT (F = 3.339, P = .048), and MSIS-29 (F = 4.282, P = .023). Five adverse events attributable to the WBSS training (knee or low back pain) were recorded, but only 1 patient had to retire from the study. Conclusion. A home-based WBBS training might potentially provide an effective, engaging, balance rehabilitation solution for people with MS. However, the risk of WBBS training-related injuries should be carefully balanced with benefits. Further studies, including cost-effectiveness analyses, are warranted to establish whether WBBS may be useful in the home setting.

The diagnostic accuracy of static posturography in predicting accidental falls in people with multiple sclerosis.

Background. Quantitative posturography has been reported as a reliable tool to measure balance in people with multiple sclerosis (MS). However, data on its diagnostic accuracy in predicting the occurrence of falls are lacking. Objective. To determine sensitivity, specificity, predictive values, and accuracy of posturography in detecting falls in MS subjects over a 3-month follow-up period. Methods. One hundred consecutive patients with MS were tested by the Berg Balance Scale (BBS) and by static posturography on a monoaxial platform. Participants recorded the occurrence of accidental falls for the next 3 months. Abnormal cutoff values for static standing balance measures were set at 2 standard deviations above the mean values obtained from 50 healthy controls (HC). The diagnostic accuracy of the BBS and static posturography was analyzed with respect to the prospectively collected data on the occurrence of falls. Results. Posturometric measures in participants with MS were significantly worse than in HC (all P values <.0001); however, only the center of pressure (COP) path with open eyes condition had substantial test–retest reliability. Static posturography was more sensitive (88% vs 37%) and accurate (75% vs 63%), but slightly less specific (67% vs 81%), than the BBS in predicting accidental falls. A logistic regression analysis revealed that the worse the COP path, the greater the risk for accidental falls (odds ratio = 1.08; P < .0001), even after adjusting for sex, age, disease duration, body mass index, MS subtype, Expanded Disability Status Scale, and BBS score. Conclusion. The COP path measurement in static position is a sensitive and accurate tool to identify people with MS who are at risk of accidental falls.

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis

Objective: To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing–remitting multiple sclerosis (RRMS) patients. Methods: In this post-marketing, prospective, observational study in two Italian multiple sclerosis (MS) centres, a total of 285 RRMS patients who failed a first-line treatment with interferon beta (IFNβ) or glatiramer acetate (GA) were considered. Patients were subdivided according to the strategy adopted after the failure (defined as the occurrence of ≥2 relapses or 1 relapse with residual disability): the switching (SWI) group, i.e. those switched among different IFNβ formulations, or from IFNβ to GA and vice versa; and the escalating (ESC) group, i.e. those escalated to natalizumab. Proportions of patients free from different types of disease activity (relapses, sustained disability progression, new active lesions on MRI, or a combination of them) were calculated at 12 and 24 months. Since patients were not randomized to treatment group, propensity score (PS)-adjusted Cox regression models were built to control for several potential confounders. Results: At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. After 24 months we observed greater proportions of patients in the ESC than SWI group free from relapse (p < 0.0001), disability progression (p = 0.0045), MRI activity (p = 0.0003), and combined activity (p < 0.0001). PS-adjusted models confirmed these findings, with hazard ratios ranging from 0.38 to 0.56 favours the ESC group. Conclusion: We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.

Pulse monthly steroids during an elective interruption of natalizumab: A post-marketing study

Background and purpose:  Temporary discontinuation of natalizumab is sometimes considered as the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). However, interruption of natalizumab may result in a re‐start of disease activity.

A systematic review of factors associated with accidental falls in people with multiple sclerosis: a meta-analytic approach:

Objective: To determine whether there are demographic, clinical, and instrumental variables useful to detect fall status of patients with multiple sclerosis. Data sources: PubMed and the Cochrane Library. Review methods: Eligible studies were identified by two independent investigators. Only studies having a clear distinction between fallers and non-fallers were included and meta-analysed. Odds ratios (ORs) and standard mean differences (SMDs) were calculated and pooled using fixed effect models. Results: Among 115 screened articles, 15 fulfilled criteria for meta-analyses, with a total of 2425 patients included. Proportion of fallers may vary from 30% to 63% in a time frame from 1 to 12 months. No significant publication bias was found, even though 12/15 studies relied on retrospective reports of falls, thus introducing recall biases. Risk factors for falls varied across studies, owing to heterogeneity of populations included and clinical instruments used. The meta-analytic approach found that, compared with non-fallers, fallers had longer disease duration (SMD = 0.14, p = 0.02), progressive course of disease (OR = 2.02, p < 0.0001), assistive device for walking (OR = 3.16, p < 0.0001), greater overall disability level (SMD = 0.74, p < 0.0001), slower walking speed (SMD = 0.45, p = 0.0005), and worse performances in balance tests (Berg Balance Scale: SMD = −0.48, p = 0.002; Timed up-and-go test, SMD = 0.31, p = 0.04), and force-platform measures (postural sway) with eyes opened (SMD = 0.71, p = 0.006) and closed (SMD = 0.83, p = 0.01), respectively. Conclusion: Elucidations regarding risk factors for accidental falls in patients with multiple sclerosis (PwMs) are provided here, with worse disability score, progressive course, use of walking aid, and poorer performances in static and dynamic balance tests strongly associated with fall status.

Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis

Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS). In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI). In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations.

Neuroimaging techniques to assess inflammation in Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic neurological disease that represents a leading cause of disability in young adults and is characterized by inflammation and degeneration of both white matter (WM) and gray matter (GM). Defining the presence or absence of inflammation on individual basis is a key point in choosing the therapy and monitoring the treatment response. Magnetic resonance imaging (MRI) represents the most sensitive non-invasive tool to monitor inflammation in the clinical practice. Indeed, in the early phase of inflammation MRI detects new lesions as extrusion of gadolinium contrast agents across the altered blood-brain-barrier (BBB). The occurrence of MRI lesions is used to confirm diagnosis and has been validated as surrogate marker of relapse to monitor response to treatments. However, focal gadolinium-enhancing lesions represent only an aspect of neuroinflammation. Recent studies have suggested the presence of a widespread inflammation of the central nervous system (CNS), which is mainly related to microglial cells activation occurring both at the edge of chronic focal lesions and throughout the normal-appearing brain tissue. New imaging techniques have been developed to study diffuse inflammation taking place outside the focal plaques. The scope of this review is to examine the various neuroimaging techniques and those biophysical quantities that can be non-invasively detected to enlighten the different aspects of neuroinflammation. Some techniques are commonly used in the clinical practice, while others are used in the research field to better understand the pathophysiological mechanisms of the disease and the role of inflammation.

Oral Dalfampridine Improves Standing Balance Detected at Static Posturography in Multiple Sclerosis

We report a 14-week post-marketing experience on 20 patients with multiple sclerosis (MS) who started prolonged-release (PR) oral dalfampridine 10 mg twice daily according to European Medicine Agency criteria. They underwent serial static posturography assessments and the dizziness handicap inventory (DHI) to investigate whether PR dalfampridine could impact standing balance and self-reported perception of balance. The incidence of accidental falls per person per month was also recorded throughout the study. Eight (40%) patients, who had a relevant improvement in walking speed, were defined as treatment responders. They showed a significant improvement of standing balance (with respect to pretreatment assessment) when contrasted with 12 (60%) nonresponders (F [4,15] = 3.959, P = 0.027). No significant changes in DHI score, as well as in its functional, physical, and emotional subscales, were found in both responders and nonresponders at the end of study (all P values are ≥0.2). Treatment response did not affect the incidence of accidental falls. Future studies based on larger sample sizes, and with longer followup, are required to confirm the beneficial effect of PR dalfampridine on standing balance.

identifying responders and nonresponders to interferon therapy in multiple sclerosis

Abstract Interferon beta is a well established disease-modifying agent used for relapsing-remitting multiple sclerosis. Despite treatment, a relevant proportion of patients continue to experience clinical (ie, relapses, worsening of disability) and magnetic resonance imaging (MRI) activity. Early identification of responders and nonresponders to interferon beta is strongly recommended to select patients who need a prompt switch to another disease-modifying agent and to ultimately avoid accumulation of fixed disability over time. Detecting responders and nonresponders to interferon beta can be challenging, mainly because of the lack of a clear and shared clinical definition of response to treatment. Clinical features at the start of treatment should be considered as prognostic factors, but MRI parameters assessed during treatment, such as contrast-enhancing lesions or new T2-hyperintense lesions, may be sensitive markers of response to interferon beta. Quantitative scoring systems derived from a combination of relapses and MRI activity have recently been proposed as practical tools for use in the everyday clinical setting. Blood biomarkers, such as neutralizing antibodies to interferon beta and Myxovirus resistance protein A, provide further useful information for detecting responders and nonresponders to interferon beta. However, since the presence of neutralizing antibodies can only partially explain the nonresponse to interferon beta, biomarkers of interferon beta activity possibly related to the pathogenesis of the disease could represent a future step toward a tailored, long-lasting effective treatment against multiple sclerosis.

Freezing of gait in Parkinson’s disease: gray and white matter abnormalities

Freezing of gait (FOG) is a disabling disorder that often affects Parkinson’s disease (PD) patients in advanced stages of the disease. To study structural gray matter (GM) and white matter (WM) changes in PD patients with and without FOG, twenty-one PD patients with FOG (PD-FOG), 16 PD patients without FOG (PD-nFOG) and 19 healthy subjects (HS) underwent a standardized MRI protocol. For the gray matter evaluation, cortical volume (CV), cortical thickness (CTh), and surface area (SA) were analyzed using the FreeSurfer pipeline. For the white matter evaluation, DTI images were analyzed using tracts constrained by underlying anatomy (TRACULA) toolbox in FreeSurfer. PD-FOG patients exhibited lower CTh than HS in the mesial surface of both cerebral hemispheres, including the superior frontal gyrus, paracentral lobule, posterior cingulate cortex, precuneus and pericalcarine cortex, and in the right dorsolateral prefrontal cortex. Moreover, significant WM changes were observed in PD-FOG patients in comparison with HS in the superior longitudinal fasciculus, uncinate fasciculus, cingulum cingulate gyrus and inferior longitudinal fasciculus (prevalently in the right hemisphere) and in the frontal radiations of the corpus callosum. DTI abnormalities in specific WM bundles correlated significantly with cognitive measures. The damage of multiple cortical areas involved in high-level gait control together with WM disruption between motor, cognitive and limbic structures may represent the anatomical correlate of FOG.