RESUMO
The "total distance walked" obtained during a standardized walking test is an integral component of physical fitness and health status tracking in a range of consumer and clinical applications. Wearable inertial sensors offer the advantages of providing accurate, objective, and reliable measures of gait while streamlining walk test administration. The aim of this study was to develop an inertial sensor-based algorithm to estimate the total distance walked using older subjects with impaired fasting glucose (Study I), and to test the generalizability of the proposed algorithm in patients with Multiple Sclerosis (Study II). All subjects wore two inertial sensors (Opals by Clario-APDM Wearable Technologies) on their feet. The walking distance algorithm was developed based on 108 older adults in Study I performing a 400 m walk test along a 20 m straight walkway. The validity of the algorithm was tested using a 6-minute walk test (6MWT) in two sub-studies of Study II with different lengths of a walkway, 15 m (Study II-A, n = 24) and 20 m (Study II-B, n = 22), respectively. The start and turn around points were marked with lines on the floor while smaller horizontal lines placed every 1 m served to calculate the manual distance walked (ground truth). The proposed algorithm calculates the forward distance traveled during each step as the change in the horizontal position from each foot-flat period to the subsequent foot-flat period. The total distance walked is then computed as the sum of walk distances for each stride, including turns. The proposed algorithm achieved an average absolute error rate of 1.92% with respect to a fixed 400 m distance for Study I. The same algorithm achieved an absolute error rate of 4.17% and 3.21% with respect to an averaged manual distance for 6MWT in Study II-A and Study II-B, respectively. These results demonstrate the potential of an inertial sensor-based algorithm to estimate a total distance walked with good accuracy with respect to the manual, clinical standard. Further work is needed to test the generalizability of the proposed algorithm with different administrators and populations, as well as larger diverse cohorts.
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Marcha , Caminhada , Idoso , Algoritmos , Pé , Humanos , Teste de CaminhadaRESUMO
This study investigates the potential of passive monitoring of gait and turning in daily life in people with multiple sclerosis (PwMS) to identify those at future risk of falls. Seven days of passive monitoring of gait and turning were carried out in a pilot study of 26 PwMS in home settings using wearable inertial sensors. The retrospective fall history was collected at the baseline. After gait and turning data collection in daily life, PwMS were followed biweekly for a year and were classified as fallers if they experienced >1 fall. The ability of short-term passive monitoring of gait and turning, as well as retrospective fall history to predict future falls were compared using receiver operator curves and regression analysis. The history of retrospective falls was not identified as a significant predictor of future falls in this cohort (AUC = 0.62, p = 0.32). Among quantitative monitoring measures of gait and turning, the pitch at toe-off was the best predictor of falls (AUC = 0.86, p < 0.01). Fallers had a smaller pitch of their feet at toe-off, reflecting less plantarflexion during the push-off phase of walking, which can impact forward propulsion and swing initiation and can result in poor foot clearance and an increased metabolic cost of walking. In conclusion, our cohort of PwMS showed that objective monitoring of gait and turning in daily life can identify those at future risk of falls, and the pitch at toe-off was the single most influential predictor of future falls. Therefore, interventions aimed at improving the strength of plantarflexion muscles, range of motion, and increased proprioceptive input may benefit PwMS at future fall risk.
Assuntos
Esclerose Múltipla , Marcha/fisiologia , Humanos , Projetos Piloto , Equilíbrio Postural , Estudos Retrospectivos , Caminhada/fisiologiaRESUMO
Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in the MR proton transverse relaxation time (T2). Therefore, the examination of T2 changes in individual muscles may be useful for the monitoring of disease progression in DMD. In this study, we used the mean T2, percentage of elevated pixels and T2 heterogeneity to assess changes in the composition of dystrophic muscles. In addition, we used fat saturation to distinguish T2 changes caused by edema and inflammation from fat infiltration in muscles. Thirty subjects with DMD and 15 age-matched controls underwent T2 -weighted imaging of their lower leg using a 3-T MR system. T2 maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). The mean T2 of the traced regions of interest, width of the T2 histograms and percentage of elevated pixels were calculated. We found that, even in young children with DMD, lower leg muscles showed elevated mean T2, were more heterogeneous and had a greater percentage of elevated pixels than in controls. T2 measures decreased with fat saturation, but were still higher (P < 0.05) in dystrophic muscles than in controls. Further, T2 measures showed positive correlations with timed functional tests (r = 0.23-0.79). The elevated T2 measures with and without fat saturation at all ages of DMD examined (5-15 years) compared with unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema and fat infiltration. This study shows that T2 mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T2 mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic interventions in DMD.
Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/diagnóstico , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Humanos , Perna (Membro)/patologia , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND OBJECTIVES: Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder with a well-characterized disease phenotype but considerable interindividual heterogeneity that is not well understood. The aim of this study was to evaluate the effects of dystrophin variations and genetic modifiers of DMD on rate and age of muscle replacement by fat. METHODS: One hundred seventy-five corticosteroid treated participants from the ImagingDMD natural history study underwent repeated magnetic resonance spectroscopy (MRS) of the vastus lateralis (VL) and soleus (SOL) to determine muscle fat fraction (FF). MRS was performed annually in most instances; however, some individuals had additional visits at 3 or 6 monthss intervals. FF changes over time were modeled using nonlinear mixed effects to estimate disease trajectories based on the age that the VL or SOL reached half-maximum change in FF (mu) and the time required for FF change (sigma). Computed mu and sigma values were evaluated for dystrophin variations that have demonstrated the ability to lead to a mild phenotype as well as compared between different genetic polymorphism groups. RESULTS: Participants with dystrophin gene deletions amenable to exon 8 skipping (n = 4) had minimal increases in SOL FF and had an increase in VL mu value by 4.4 years compared with a reference cohort (p = 0.039). Participants with nonsense variations within exons that may produce milder phenotypes (n = 11) also had minimal increases in SOL and VL FFs. No differences in estimated FF trajectories were seen for individuals amenable to exon 44 skipping (n = 10). Modeling of the SPP1, LTBP4, and thrombospondin-1 (THBS1) genetic modifiers did not result in significant differences in muscle FF trajectories between genotype groups (p > 0.05); however, trends were noted for the polymorphisms associated with long-range regulation of LTBP4 and THBS1 that deserve further follow-up. DISCUSSION: The results of this study link the historically mild phenotypes seen in individuals amenable to exon 8 skipping and with certain nonsense variations with alterations in trajectories of lower extremity muscle replacement by fat.
Assuntos
Distrofina , Distrofia Muscular de Duchenne , Humanos , Distrofina/genética , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Éxons , Imageamento por Ressonância Magnética/métodos , Progressão da DoençaRESUMO
BACKGROUND: Secondary progressive multiple sclerosis (SPMS) is characterized by worsening of postural control and brain atrophy. However, little is known about postural deficits and their neuroanatomical correlates in this population. We aimed to determine the neuroanatomical correlates of postural deficits in people with SPMS and whether posture control deteriorates concomitantly with the brain and spinal cord atrophy in 2 years in SPMS. METHODS: This study is a post hoc analysis of data from 27 people with SPMS (mean ± SE age, 58.6 ± 1.1 years). Participants had magnetic resonance imaging (MRI) of the brain and cervical spinal cord followed by sway testing using inertial sensors during standing with eyes open (EO) and eyes closed without (EC) and with (ECC) a cognitive task. Partial correlations investigated relationships between postural control and MRI measures at baseline and 2 years. RESULTS: At baseline, sway measures were inversely related to cortical thickness and cord cross-sectional area (CSA) during the EO task but only to cord CSA with EC (P < .05). After 2 years, the percentage change in sway amplitude and dispersion during EO tasks significantly related to the percentage decline in cord CSA (P < .01). CONCLUSIONS: Cortical and spinal cord inputs are essential for regulation of postural control during standing with EO in SPMS. Without visual input, people with SPMS preferentially rely on somatosensory inputs from the spinal cord for maintaining postural control. Postural deficits related to cord atrophy over 2 years, suggesting that postural control may be a surrogate marker of disease progression in people with SPMS.
RESUMO
OBJECTIVE: To quantify disease progression in individuals with Duchenne muscular dystrophy (DMD) using magnetic resonance biomarkers of leg muscles. METHODS: MRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired from 104 participants with DMD and 51 healthy controls using a prospective observational study design with patients with DMD followed up yearly for up to 6 years. Fat fractions (FFs) in vastus lateralis and soleus muscles were determined with 1H MRS. MRI quantitative T2 (qT2) values were measured for 3 muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach. RESULTS: MRS FF and MRI qT2 increased with DMD disease duration, with the progression time constants differing markedly between individuals and across muscles. The average age at half-maximal muscle involvement (µ) occurred 4.8 years earlier in vastus lateralis than soleus, and these measures were strongly associated with loss-of-ambulation age. Corticosteroid treatment was found to delay µ by 2.5 years on average across muscles, although there were marked differences between muscles with more slowly progressing muscles showing larger delay. CONCLUSIONS: MRS FF and MRI qT2 provide sensitive noninvasive measures of DMD progression. Modeling changes in these biomarkers across multiple muscles can be used to detect and monitor the therapeutic effects of corticosteroids on disease progression and to provide prognostic information on functional outcomes. This modeling approach provides a method to transform these MRI biomarkers into well-understood metrics, allowing concise summaries of DMD disease progression at individual and population levels. CLINICALTRIALSGOV IDENTIFIER: NCT01484678.
Assuntos
Biomarcadores/análise , Perna (Membro)/fisiopatologia , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Adolescente , Corticosteroides/metabolismo , Corticosteroides/farmacologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Perna (Membro)/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/tratamento farmacológico , Caminhada/fisiologiaRESUMO
Freezing of gait (FOG) is a poorly understood symptom affecting many patients with Parkinson's disease (PD). Despite growing evidence of a behavioral link between anxiety, attention and FOG in PD, no research to date has investigated the neural mechanisms that might explain this relationship. The present study therefore examined resting-state MRI functional connectivity between the amygdala, striatum and frontoparietal attentional control network in PD patients with (freezers: nâ¯=â¯19) and without FOG (non-freezers: nâ¯=â¯21) in the dopaminergic 'off' state. Functional connectivity was subsequently correlated with an objective measure of FOG severity and a subjective scale of affective disorder within each group. Connectivity between the right amygdala and right putamen was significantly increased in freezers compared to non-freezers (pâ¯<â¯0.01). Furthermore, freezers showed increased anti-coupling between the frontoparietal network and left amygdala (pâ¯=â¯0.011), but reduced anti-coupling between this network and the right putamen (pâ¯=â¯0.027) as compared to non-freezers. Key functional connections between the amygdala, putamen and frontoparietal network were significantly associated with FOG severity and a fear of falling. This study provides the first evidence that dysfunctional fronto-striato-limbic processes may underpin the link between anxiety and FOG in PD. It is proposed that freezers have heightened striato-limbic load and reduced top-down attentional control at rest, which when further challenged by the parallel processing demands of walking may precipitate FOG.
Assuntos
Transtornos Neurológicos da Marcha/fisiopatologia , Sistema Límbico/fisiopatologia , Doença de Parkinson/fisiopatologia , Afeto , Idoso , Antiparkinsonianos/uso terapêutico , Mapeamento Encefálico , Circulação Cerebrovascular , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Humanos , Sistema Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Oxigênio/sangue , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , DescansoRESUMO
OBJECTIVE: The main objective of this study was to examine the effect of disease on strength in two functionally important lower limb muscles for a period of 2 yrs in children with Duchene muscular dystrophy. DESIGN: Seventy-seven Duchene muscular dystrophy children participated in this study. Plantar flexors, knee extensors, strength, and performance on timed tests (6-min walk, 4-stairs, 10-m walk, supine-up) were assessed yearly for 2 yrs. Multivariate normal regression was used to assess changes in strength over time in the Duchene muscular dystrophy group. Spearman correlations were computed to examine relationship between strength and function. RESULTS: Normalized plantar flexor and knee extensor strength showed a significant decrease (P < 0.05) over 2 yrs, with larger declines in knee extensor. At baseline, knee extensor strongly correlated with performance on timed tests. However, plantar flexor strength was found to be a stronger predictor of loss in ambulatory function. Modest correlations (r = 0.19-0.34) were found between the decline in strength and functional performance over 2 yrs. CONCLUSIONS: This study describes the loss of lower limb strength in a large cohort of Duchene muscular dystrophy children for 2 yrs. The findings support that lower limb strength alone cannot account for the decline in performance on functional tests, and the role of other contributing factors, such as compensatory strategies, should be considered.
Assuntos
Extremidade Inferior/fisiopatologia , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/fisiopatologia , Desempenho Físico Funcional , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Joelho/fisiopatologia , Estudos Longitudinais , Masculino , Fatores de Tempo , Teste de CaminhadaRESUMO
BACKGROUND: Duchenne muscular dystrophy (DMD), an inherited recessive X chromosome-linked disease, is the most severe childhood form of muscular dystrophy. Boys with DMD experience muscle loss, with infiltration of intramuscular fat into muscles. OBJECTIVES: This case series describes the progression of DMD in boys using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Magnetic resonance results are then compared with an established functional timed test. METHODS: Four boys with DMD and 4 healthy age-matched controls were chosen from a larger cohort. Boys with DMD were assessed at 4 time points over 2 years, with controls assessed at baseline only. Progression of the disease was documented by assessing the plantar flexors using MRI and MRS techniques and by assessing ambulation using the 30-Foot Fast Walk Test. RESULTS: Transverse relaxation time (T2) values were elevated in all boys with DMD at baseline. The lipid ratio increased rapidly as the disease progressed in 2 boys. Discrete changes in T2 in the other 2 boys with DMD indicated a slower disease progression. Magnetic resonance imaging and MRS allowed monitoring of the disease over all time periods regardless of ambulation status. LIMITATIONS: The magnetic resonance data were collected with 2 different magnets at 2 different field strengths (1.5 and 3.0 T). Although we corrected for this difference, care must be taken in interpreting data when different image collection systems are used. This was a case series of 4 boys with DMD taken from a larger cohort study. CONCLUSIONS: Magnetic resonance imaging and MRS are objective, noninvasive techniques for measuring muscle pathology and can be used to detect discrete changes in both people who are ambulatory and those who are nonambulatory. These techniques should be considered when monitoring DMD progression and assessing efficacy of therapeutic interventions.
Assuntos
Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Adolescente , Estudos de Casos e Controles , Criança , Teste de Esforço , Humanos , Estudos Longitudinais , Masculino , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/fisiopatologia , Caminhada/fisiologiaRESUMO
OBJECTIVE: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS). METHODS: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. RESULTS: Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation. CONCLUSIONS: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD.
Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Perna (Membro) , Músculo Esquelético/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Criança , Pré-Escolar , Estudos Transversais , Humanos , Perna (Membro)/crescimento & desenvolvimento , Perna (Membro)/patologia , Perna (Membro)/fisiopatologia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Força Muscular/efeitos dos fármacos , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Resultado do TratamentoRESUMO
The purpose of this study was to assess the contractile and non-contractile content in thigh muscles of patients with Duchenne muscular dystrophy (DMD) and determine the relationship with functional abilities. Magnetic resonance images of the thigh were acquired in 28 boys with DMD and 10 unaffected boys. Muscle strength, timed functional tests, and the Brookes Lower Extremity scale were also assessed. Non-contractile content in the DMD group was significantly greater than in the control group for six muscles, including rectus femoris, biceps femoris-long head and adductor magnus. Non-contractile content in the total thigh musculature assessed by MRI correlated with the Brookes scale (r(s)=0.75) and supine-up test (r(s)=0.68), as well as other functional measures. An age-related specific torque increase was observed in the control group (r(s)=0.96), but not the DMD (r(s)=0.06). These findings demonstrate that MRI measures of contractile and non-contractile content can provide important information about disease progression in DMD.
Assuntos
Contração Muscular/fisiologia , Força Muscular/fisiologia , Distrofia Muscular de Duchenne/fisiopatologia , Coxa da Perna/fisiopatologia , Adolescente , Fatores Etários , Criança , Progressão da Doença , Humanos , Extremidade Inferior/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/diagnóstico , TorqueRESUMO
BACKGROUND CONTEXT: Findings on imaging of noncontractile anatomic abnormalities and the intensity of low back pain have weak associations because of false-positive rates among asymptomatic individuals. This association might be stronger for contractile tissues. PURPOSE: The purpose of this study was to examine the relationship between location and reports of pain intensity in the low back and exercise-induced muscle damage to the lumbar paraspinal muscles. STUDY DESIGN: Nondiagnostic observational study in a laboratory setting. METHODS: Delayed onset muscle soreness was induced in the low back of healthy pain-free volunteers. Measures of pain intensity (100-mm visual analog scale [VAS]) and location (area on the pain diagram) were taken before and 48 hours after exercise. Muscle damage was quantified using mechanical pain thresholds, motor performance deficits, and transverse relaxation time (T2)-weighted magnetic resonance imaging (MRI). Changes pre- to postexercise in signal intensity on T2-weighted imaging within the erector spinae, pain intensity, pain area, mechanical pain threshold, and isometric torque were assessed using paired t tests. Bivariate correlations were conducted to assess associations among muscle damage, pain intensity, and pain drawing area. RESULTS: Twenty participants volunteered (11 women; average age, 22.3 years; average body mass index, 23.5) for study participation. Reports of pain intensity at 48 hours ranged from 0 to 59 mm on the VAS. Muscle damage was confirmed by reductions in mechanical threshold (p=.011) and motor performance (p<.001) and by changes in T2-weighted MRI (p=.007). This study was powered to find an association of at least r=0.5 to be statistically significant. Correlations of continuous variables revealed no significant correlations between pain intensity and measures of muscle damage (ranging between -0.075 and 0.151). There was a significant association between the remaining torque deficit at 48 hours and pain area. CONCLUSIONS: The results of this study indicate that there was no association between the magnitude of muscle damage in the lumbar erector spinae and reported pain intensity in the low back. In future studies, larger cohorts may report statistically significant associations, but our data suggest that there will be low magnitude potentially indicating limited clinical relevance.