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.
•MS is an inflammatory disease that causes focal and diffuse damage to CNS.•MRI is a powerful tool to allow early diagnosis and accurate monitoring of MS.•Focal inflammation is radiologically ...detected as gadolinium-enhancing T1 lesions.•Inflammation has been demonstrated to extend beyond the focal lesions.•Advanced neuroimaging development has the aim of studying diffuse inflammation.
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.
Background and purpose
Alice in Wonderland syndrome (AIWS) is a rare neurological disorder, characterized by an erroneous perception of the body schema or surrounding space. It may be caused by a ...variety of neurological disorders, but to date, there is no agreement on which brain areas are affected. The aim of this study was to identify brain areas involved in AIWS.
Methods
We conducted a literature search for AIWS cases following brain lesions. Patients were classified according to their symptoms as type A (somesthetic), type B (visual), or type C (somesthetic and visual). Using a lesion mapping approach, lesions were mapped onto a standard brain template and sites of overlap were identified.
Results
Of 30 lesions, maximum spatial overlap was present in six cases. Local maxima were identified in the right occipital lobe, specifically in the extrastriate visual cortices and white matter tracts, including the ventral occipital fasciculus, optic tract, and inferior fronto-occipital fasciculus. Overlap was primarily due to type B patients (the most prevalent type,
n
= 22), who shared an occipital site of brain damage. Type A (
n
= 5) and C patients (
n
= 3) were rarer, with lesions disparately located in the right hemisphere (thalamus, insula, frontal lobe, hippocampal/parahippocampal cortex).
Conclusions
Lesion-associated AIWS in type B patients could be related to brain damage in visual pathways located preferentially, but not exclusively, in the right hemisphere. Conversely, the lesion location disparity in cases with somesthetic symptoms suggests underlying structural/functional disconnections requiring further evaluation.
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.
Objectives
To evaluate the accuracy of a data-driven approach, such as machine learning classification, in predicting disability progression in MS.
Methods
We analyzed structural brain images of 163 ...subjects diagnosed with MS acquired at two different sites. Participants were followed up for 2–6 years, with disability progression defined according to the expanded disability status scale (EDSS) increment at follow-up. T2-weighted lesion load (T2LL), thalamic and cerebellar gray matter (GM) volumes, fractional anisotropy of the normal appearing white matter were calculated at baseline and included in supervised machine learning classifiers. Age, sex, phenotype, EDSS at baseline, therapy and time to follow-up period were also included. Classes were labeled as stable or progressed disability. Participants were randomly chosen from both sites to build a sample including 50% patients showing disability progression and 50% patients being stable. One-thousand machine learning classifiers were applied to the resulting sample, and after testing for overfitting, classifier confusion matrix, relative metrics and feature importance were evaluated.
Results
At follow-up, 36% of participants showed disability progression. The classifier with the highest resulting metrics had accuracy of 0.79, area under the true positive versus false positive rates curve of 0.81, sensitivity of 0.90 and specificity of 0.71. T2LL, thalamic volume, disability at baseline and administered therapy were identified as important features in predicting disability progression. Classifiers built on radiological features had higher accuracy than those built on clinical features.
Conclusions
Disability progression in MS may be predicted via machine learning classifiers, mostly evaluating neuroradiological features.
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.
As atrophy represents the most relevant driver of progression in multiple sclerosis (MS), we investigated the impact of different patterns of brain and spinal cord atrophy on disability worsening in ...MS. We acquired clinical and MRI data from 90 patients with relapsing–remitting MS and 24 healthy controls (HC). Clinical progression at follow-up (mean 3.7 years) was defined according to the Expanded Disability Status Scale-Plus. Brain and spinal cord volumes were computed on MRI brain scans. After normalizing each participants’ brain and spine volume to the mean of the HC, z-score cut-offs were applied to separate pathologically atrophic from normal brain and spine volumes (accepting a 2.5% error probability). Accordingly, MS patients were classified into four groups (Group I: no brain or spinal cord atrophy
N
= 40, Group II: brain atrophy/no spinal cord atrophy
N
= 11, Group III: no brain atrophy/ spinal cord atrophy
N
= 32, Group IV: both brain and spinal cord atrophy
N
= 7). All patients’ groups showed significantly lower brain volume than HC (
p
< 0.0001). Group III and IV showed lower spine volume than HC (
p
< 0.0001 for both). Higher brain lesion load was identified in Group II (
p
= 0.049) and Group IV (
p
= 0.023) vs Group I, and in Group IV (
p
= 0.048) vs Group III. Spinal cord atrophy (OR = 3.75,
p
= 0.018) and brain + spinal cord atrophy (OR = 5.71,
p
= 0.046) were significant predictors of disability progression. The presence of concomitant brain and spinal cord atrophy is the strongest correlate of progression over time. Isolated spinal cord atrophy exerts a similar effect, confirming the leading role of spinal cord atrophy in the determination of motor disability.
Tourette syndrome (TS) and obsessive–compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD ...provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure (
n
= 16), TS + OCD (
n
= 14), OCD (
n
= 11), or controls (
n
= 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.
We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial ...distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤ 3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥ 4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients' normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10(-10) and P < 10(-7)), and mean cortical T2* in controls (P < 10(-5) and P < 10(-6)). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface.
Previous studies in cohorts of Tourette syndrome (TS) or obsessive-compulsive disorder (OCD) patients have not clarified whether these two disorders represent two clinical conditions or they are ...distinct clinical phenotypes of a common disease spectrum. The study aimed to compare functional connectivity (FC) patterns in a pediatric drug-naive cohort of 16 TS patients without any comorbidity (TS), 14 TS patients with OCD (TS + OCD), and 10 pure OCD patients as well as 11 matched controls that underwent resting state fMRI. Via independent component analysis, we examined FC in the basal ganglia (BGN), sensorimotor (SMN), cerebellum (CBN), frontoparietal (FPN), default-mode (DMN), orbitofrontal (OBFN), and salience (SAN) networks among the above cohorts and their association with clinical measures. Compared to controls, TS and TS + OCD patients showed higher FC in the BGN, SMN, CBN and DMN and lower FC in the FPN and SAN. The TS and TS + OCD groups showed comparable FC in all networks. In contrast to controls, OCD patients exhibited increased FC in the BGN, SMN, CBN, DMN, FPN, and SAN. OCD patients also showed higher FC in CBN and FPN when compared with TS and TS + OCD patients both separately and as one group. Tic severity negatively correlated with FC in CBN and FPN in the TS group, while the compulsiveness scores positively correlated with the same two networks in OCD patients. Our findings suggest common FC changes in TS and TS + OCD patients. In contrast, OCD is characterized by a distinctive pattern of FC changes prominently involving the CBN and FPN.
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