Gait Profile Score in multiple sclerosis patients with low disability

BackgroundGait abnormalities are subtle in multiple sclerosis (MS) patients with low disability and need to be better determined. As a biomechanical approach, the Gait Profile Score (GPS) is used to assess gait quality by combining nine gait kinematic variables in one single value. This study aims i) to establish if the GPS can detect gait impairments and ii) to compare GPS with discrete spatiotemporal and kinematic parameters in low-disabled MS patients.MethodThirty-four relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score ≤2 (mean age 36.32 ± 8.72 years; 12 men, 22 women; mean EDSS 1.19 ± 0.8) and twenty-two healthy controls (mean age 36.85 ± 7.87 years; 6 men, 16 women) matched for age, weight, height, body mass index and gender underwent an instrumented gait analysis.ResultsNo significant difference in GPS values and in spatiotemporal parameters was found between patients and controls. However patients showed a significant alteration at the ankle and pelvis level.ConclusionGPS fails to identify gait abnormalities in low-disabled MS patients, although kinematic analysis revealed subtle gait alterations. Future studies should investigate other methods to assess gait impairments with a gait score in low-disabled MS patients.     

Gait tests in multiple sclerosis: Reliability and cut-off values

BackgroundGait limitation is one of the most common disabilities in people with multiple sclerosis (MS). Several studies have used gait parameters to determine the effects of different therapies. However, few studies have determined their reproducibility, also the therapeutic effects could be overestimated.Research questionTo examine the reproducibility in gait measurements during short and long distances.MethodsIn this cross-sectional study we recruited a group of MS patients and compare it to a control group. The participants performed the following tests in a fixed order: a 25-foot walk at a comfortable speed, at a fast speed and during a dual task, a timed up-and-go test (TUG) and a six- minute walk test (6MWT). Two measurements were conducted a week apart. Systematic error was evaluated by the Student t-test, reliability by the intra-class correlation coefficients (ICC) and agreement by the minimum detectable change (MDC₉₅).ResultsA total of 58 people with MS and 19 healthy people were included. The absence of systematic error was only found for the fast speed condition. The reliability of the gait parameters had moderate to high ICC values (ICC > 0.7) except for the dual task cost (DTC) which was 0.45. The MDC₉₅ was higher in people with MS compared to healthy people, and it was higher in people with MS for gait speeds in all conditions (> 34%). For the TUG and 6MWT, the MDC₉₅ were 51.5% and 31.7% respectively. For people with MS the smallest MDC₉₅ was found for the stance time for all conditions (6.8%), whereas the highest was found for the dual task cost (158.7%).SignificanceThe MDC₉₅ values were higher than the cut-off point based on the minimally important clinical difference (MICD) proposed in previous studies. Thus, the MDC₉₅ should be used as a cut-off rather than MICD values.     

多发硬化病人的丘脑损伤和长期残障进展

目的评估磁化转移(MT)MR成像所显示初期丘脑萎缩和异常及其后12个月的变化,以预测一组相对大样本的间断发作型多发硬化(MS)病人在8年时间里残障的进展     

Gait deficits in people with multiple sclerosis: A systematic review and meta-analysis

BackgroundMultiple Sclerosis (MS) results in postural instability and gait abnormalities which are associated with accidental falls.ObjectiveThis systematic review and meta-analysis aims to quantify the effect of MS on gait to inform the development of falls prevention interventions.MethodsA systematic literature search identified case-control studies investigating differences in gait variables between people with MS and healthy controls. Meta-analysis examined the effect of MS on gait under normal and fast paced conditions.ResultsForty-one studies of people with Expanded Disability Status Scale (EDSS) 1.8 to 4.5 were included, of which 32 contributed to meta-analysis. A large effect of MS was found on stride length (Standardised Mean Difference, SMD = 1.27, 95% CI{0.93, 1.61}), velocity (SMD = 1.12, 95% CI{0.85, 1.39}), double support duration (SMD = 0.85, 95% CI{0.51, 1.2}), step length (SMD = 1.15, 95% CI{0.75, 1.5})and swing phase duration (SMD = 1.23, 95% CI{0.06, 2.41}). A moderate effect was found on step width and stride time with the smallest effect found on cadence (SMD = 0.43, 95% CI{0.14, 0.72}). All effect sizes increased for variables investigated under a fast walking pace condition (for example the effect on cadence increased to SMD = 1.15, 95% CI{0.42, 1.88}).ConclusionsMS has a significant effect on gait even for those with relatively low EDSS. This effect is amplified when walking at faster speeds suggesting this condition may be more beneficial for assessment and treatment. No studies investigated the association between these deficits and falls. Further investigation relating to the predictive or protective nature of these deficits in relation to falls is warranted.     

Quantifying gait abnormalities in persons with multiple sclerosis with minimal disability

Abnormalities in gait kinematics in persons with multiple sclerosis (PwMS) who have mild disability have been noted using motion capture systems. However, it is not clear if these abnormalities can be detected with clinically feasible technology. This investigation examined if the spatiotemporal markers of gait including variability metrics can distinguish between PwMS with minimal disability and controls with clinically feasible technology. 43 PwMS with minimal disability and 43 healthy controls completed four walking trials along a 26 foot long pressure sensitive pathway (GAITRite). Spatiotemporal markers of gait including variability metrics were determined. Statistical analysis revealed that PwMS walked slower, with fewer, shorter, wider steps and spent a greater percentage of a gait cycle in double support than controls. Additionally, PwMS had greater variability in the time between steps, single support percent and step width than controls. Collectively, the results highlight that PwMS, in the absence of clinical gait impairment, have subtle but detectable differences in gait and that these alterations can be detected with clinically feasible technology. The current results raise the possibility of targeting walking deviations earlier in disability progression in PwMS.     

Gait stability at early stages of multiple sclerosis using different data sources

BackgroundPeople at early stages of multiple sclerosis have subtle balance problems that may affect gait stability. However, differences in methods of determining stability such as sensor type and placements, may lead to different results and affect their interpretation when comparing to controls and other studies.QuestionsDo people with multiple sclerosis (PwMS) exhibit lower gait stability? Do location and type of data used to calculate stability metrics affect comparisons?Methods30 PwMS with no walking impairments as clinically measured and 15 healthy controls walked on a treadmill at 1.2 ms⁻¹ while 3D acceleration data was obtained from sacrum, shoulder and cervical markers and from an accelerometer placed at the sacrum. The local divergence exponent was calculated for the four data sources. An ANOVA with group (multiple sclerosis and control) and data source as main factors was used to determine the effect of disease, data source and their interaction on stability metrics.ResultsPwMS walked with significantly less stability according to all sensors (no interaction). A significant effect of data source on stability was also found, indicating that the local divergence exponent derived from sacrum accelerometer was lower than that derived from the other 3 sensor locations.SignificancePwMS with no evident gait impairments are less stable than healthy controls when walking on a treadmill. Although different data sources can be used to determine MS-related stability deterioration, a consensus about location and data source is needed. The local divergence exponent can be a useful measure of progression of gait instability at early stages of MS.     

Serial contrast-enhanced MR in patients with multiple sclerosis and varying levels of disability.

PURPOSETo compare the rates of enhancement and changes in lesion burden in patients with multiple sclerosis (MS) and varying levels of disability.METHODSMonthly enhanced MR images of the brain were obtained for 6 months from seven patients with mildly disabling relapsing-remitting MS and from seven patients with secondary progressive MS and severe disability. At entry and 1 year later, two unenhanced T2-weighted images of the brain were also obtained.RESULTSDespite the fact that both groups had clinically active disease and had similar increases in unenhanced MR lesion load, the total number of enhancing lesions was 239 in patients with relapsing-remitting MS (42 on the baseline images, 151 new and 46 persistent during follow-up) (average number of lesions per patient per year was 68) and 21 in those with secondary progressive MS (five on the baseline images, 13 new, and three persistent during follow-up) (average number of lesions per patients per year was seven).CONCLUSIONOur data indicate that the rate of enhancement significantly decreases in the more advanced phases of MS. This is important when planning clinical trials, and suggests that mechanisms underlying lesion formation might be dissimilar in different MS patient groups.     

Medulla oblongata volume: a biomarker of spinal cord damage and disability in multiple sclerosis

BACKGROUND AND PURPOSE: While brain MR imaging is routinely performed, the MR imaging assessment of spinal cord pathology in multiple sclerosis (MS) is less frequent in clinical practice. The purpose of this study was to determine whether measurements of medulla oblongata volume (MOV) on routine brain MR imaging could serve as a biomarker of spinal cord damage and disability in MS.MATERIALS AND METHODS: We identified 45 patients with MS with both head and cervical spinal cord MR imaging and 29 age-matched and sex-matched healthy control subjects with head MR imaging. Disability was assessed by the expanded disability status scale (EDSS) and ambulation index (AI). MOV and upper cervical cord volume (UCCV) were manually segmented; semiautomated segmentation was used for brain parenchymal fraction (BPF). These measures were compared between groups, and linear regression models were built to predict disability.RESULTS: In the patients, MOV correlated significantly with UCCV (r = 0.67), BPF (r = 0.45), disease duration (r = −0.64), age (r = −0.47), EDSS score (r = −0.49) and AI (r = −0.52). Volume loss of the medulla oblongata was −0.008 cm³/year of age in patients with MS, but no significant linear relationship with age was found for healthy control subjects. The patients had a smaller MOV (mean ± SD, 1.02 ± 0.17 cm³) than healthy control subjects (1.15 ± 0.15 cm³), though BPF was unable to distinguish between these 2 groups. MOV was smaller in patients with progressive MS (secondary- progressive MS, 0.88 ± 0.19 cm³ and primary-progressive MS, 0.95 ± 0.30 cm³) than in patients with relapsing-remitting MS (1.08 ± 0.15 cm³). A model including both MOV and BPF better predicted AI than BPF alone (P = .04). Good reproducibility in MOV measurements was demonstrated for intrarater (intraclass correlation coefficient, 0.97), interrater (0.79), and scan rescan data (0.81).CONCLUSION: MOV is associated with disability in MS and can serve as a biomarker of spinal cord damage.

Multiple sclerosis (MS) is a multifactorial disease with a strong neurodegenerative component associated with progressive atrophy of the brain and spinal cord.¹ Previous studies have shown involvement of the spinal cord in more than 80% of the patients with clinically definite MS.^2–5 Atrophy of the spinal cord is thought to originate mainly from neurodegenerative changes, especially of the cervical segment,^4,6–10 which results in impairment of motor function.^11–16 In contrast, brain atrophy correlates well with neuropsychologic impairment.¹ The most severe and debilitating physical disability in MS seems to be of spinal origin. Therefore, it has been suggested that measurements of upper spinal cord volume provides information regarding disease progression that is complementary to the assessment of brain atrophy.Although head MR imaging is routinely performed in patients with MS, spinal cord MR imaging takes additional time and is therefore performed only on specific indications, both in the clinic and research.The medulla oblongata is the most caudal part of the brain stem and is continuous with the spinal cord. It contains nuclei that are important for autonomic control such as respiration, heart rate, blood pressure and reflexes, and white matter (WM) tracts that connect the rostral and caudal parts of the central nervous system (CNS). Ventral, dorsal, and lateral funiculi in the lower medulla oblongata are continuous with those of the spinal cord.The medulla oblongata is generally included in the field of view (FOV) of routine brain MR images of patients with MS. We set out to explore the feasibility and clinical relevance of volumetric measures of the lower medulla oblongata and hypothesized that these measures will reflect spinal cord atrophy. The relative ease to obtain such measurements from routinely performed clinical MR imaging examinations of the head makes this a potentially strong candidate for a biomarker of spinal cord damage and disability. In this work we present the results of a retrospective analysis of MR imaging-derived medulla oblongata volume (MOV) in MS to establish the relationship to spinal cord, its correlation with clinical disability and the reproducibility of this metric.     

Magnetic resonance image registration in multiple sclerosis: comparison with repositioning error and observer-based variability

PURPOSE: To study the use of image registration in the analysis of multiple sclerosis (MS) lesion volume and compare this with repositioning error and observer-based variability. MATERIALS AND METHODS: The normalized mutual information (NMI) algorithm is evaluated in an accuracy study using a phantom, followed by a validation study on magnetic resonance (MR) data of MS patients. Further, using scan-rescan MR data, the effect of registration on MS lesion volume compared with repositioning error and observer-based variability is assessed. RESULTS: The registration accuracy was near perfect in the phantom study, while the in vivo validation study demonstrated an accuracy on the order of 0.2-0.3 mm. In the scan-rescan study, quantification accounted for 15.6% of the relative variance, repositioning for 44.4%, and registration for 40.0%. CONCLUSION: NMI resulted in robust and accurate alignment of MR brain images of MS patients. Its use in the detection of changes in MS using large serial MR imaging (MRI) data warrants future evaluation.     

Smoothness of gait detects early alterations of walking in persons with multiple sclerosis without disability

In people with Multiple Sclerosis (pwMS) with little or no signs of disability, early detection of walking impairments represents a challenging issue, as simple gait metrics (e.g. speed, cadence, stride length, etc.) may not significantly differ from those of healthy individuals. In this study, we aimed to assess the existence of possible differences in spatial-temporal parameters and smoothness of gait measures (assessed through Harmonic Ratio, HR) obtained from trunk accelerations between 50 pwMS without disability (Expanded Disability Status Scale score =1) and 50 age-matched healthy controls. The results show no differences in terms of gait velocity, stride length, stance/swing and double support phases duration, while HR in the direction of motion was significantly lower in pwMS (2.92 vs. 3.67, p < 0.001), thus indicating a less smooth gait. The study of trunk accelerations through calculation of HR represents a fast, non-intrusive technique that allows early identification of anomalies in gait patterns of pwMS in absence of disability.     

Gait variability is altered in cancer survivors with self-reported neuropathy

BackgroundFalls are prevalent among cancer survivors, and neuropathy, a side effect from chemotherapy treatment, is thought to contribute to falls. While falls commonly occur during walking, there is limited information about gait function in cancer survivors with neuropathy.Research Question: What is the difference between gait speed and gait variability in cancer survivors with and without self-reported neuropathy and healthy controls?MethodsSeventeen cancer survivors and 12 healthy individuals [age: 53.5 (11.8), gender: 10 females] participated in a single testing session. Cancer survivors were grouped into neuropathy [n = 9; age: 61.9 (6.1); gender: 8 females] and no neuropathy [n = 8; age: 50.75 (14.1); gender: 7 females] based on the self-reported FACT/GOG Neurotoxicity subscale questionnaire. All participants completed two walking trials at their comfortable pace across a 6 m pressure sensitive walkway. A one-way ANOVA with Tukey’s post-hoc analysis and effect sizes were used to detect differences in gait speed, step length variability, and step width variability between groups.ResultsAlthough there were no group differences in gait speed, a significant main effect was found for step length variability (p = 0.03, η² = 0.24) between groups. Step length variability was significantly less in cancer survivors with neuropathy than healthy controls (p = 0.05, d = 1.30). There was a significant main effect for step width variability between groups (p = 0.05, η² = 0.20). Cancer survivors with neuropathy had significantly greater step width variability than healthy controls (p = 0.04, d = 1.04).SignificanceCancer survivors with neuropathy display greater step width variability and less step length variability than healthy controls. Gait variability may be a more sensitive marker than gait speed to track mobility in cancer survivors with neuropathy symptoms. Assessing and treating gait function in cancer survivors with neuropathy symptoms may improve everyday ambulation.     

MR imaging quantitation of gray matter involvement in multiple sclerosis and its correlation with disability measures and neurocognitive testing.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system and manifests both physical and neurocognitive disabilities. Although predominantly a disease of the white matter, MS is also characterized by lesions in the gray matter. Previous pathologic studies have found that cortical and deep gray matter lesions comprised 5% and 4%, respectively, of total lesions. Using software for lesion detection and quantitation, our study was designed to determine MS involvement in the cortical and deep gray matter and to correlate gray matter lesion load with neurocognitive function and the Kurtzke Expanded Disability Status Scale. METHODS: Using a semiautomated segmentation algorithm that detected and delineated all possible brain MS lesions on MR images, we investigated gray matter lesion volume in 18 patients with untreated relapsing-remitting MS. Cortical and deep gray matter lesions then were correlated with the neurocognitive and physical disability measurements. RESULTS: We found that cortical gray matter lesions comprised approximately 5.7% of the total lesion volume, whereas deep gray matter lesions comprised another 4.6% in this patient cohort. No strong correlations were found between gray matter lesions and disability status or neurocognitive function. CONCLUSION: These results are similar to those found in previous pathologic studies. The cortical lesion load in cases of relapsing-remitting MS, as measured by MR imaging, represents less than 6% of the total lesion volume and does not correlate with disability measures or neurocognitive tests.     

Intraobserver and interobserver variability in measuring changes in lesion volume on serial brain MR images in multiple sclerosis.

PURPOSEWe evaluated the intraobserver and interobserver variability in measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick MR sections in patients with multiple sclerosis.METHODSEighteen 18 patients were scanned on two separate occasions with a mean interval of 16.4 months between the two examinations. In each session, a scan with 24 contiguous 5-mm-thick axial sections and another with 40 contiguous 3-mm-thick axial sections was acquired consecutively without moving the patient. We assessed MR lesion load by using a semiautomated local thresholding technique.RESULTSLesion volume was significantly higher on images with 3-mm-thick sections than on those with 5-mm-thick sections both at baseline and at follow up. Significant increases in total lesion volume were observed during the follow-up period on images obtained with both 5- and 3-mm-thick sections. The intra- and interobserver variability in measurements of changes in lesion volume was significantly higher on images with 5-mm-thick sections than on those with 3-mm-thick sections.CONCLUSIONOur data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis.     

Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis

PURPOSE: To determine annual rates of volumetric changes in the whole-brain parenchyma of patients with relapsing-remitting and secondary progressive multiple sclerosis (MS) and test the hypothesis that these changes correlate with clinical disability. MATERIALS AND METHODS: A computer-assisted segmentation technique with thin-section magnetic resonance (MR) imaging was used in 36 patients with MS (27 relapsing-remitting, nine secondary progressive) and in 20 control subjects to quantify brain and cerebrospinal fluid volumes. To determine the degree of brain atrophy, the percentage brain parenchyma volume (PBV) relative to that of intracranial contents was calculated. RESULTS: At the beginning of the study, the PBV was smaller in the MS group than in the control group (P = .007); brain parenchyma volumes were similar. The median rate of brain volume loss was 17.3 mL per year in patients with relapsing-remitting MS and 23.6 mL per year in those with secondary progressive MS. There was a negative correlation between brain atrophy and Expanded Disability Status Scale (EDSS) score in patients with secondary progressive MS (r = -0.69, P = .004) and no correlation in patients with relapsing-remitting MS. T2 lesion volume did not correlate with brain atrophy in either group. CONCLUSION: The correlation between brain atrophy and EDSS score was better in patients with secondary progressive MS than in those with relapsing-remitting MS.