104 research outputs found
Patterns of motor signs in spinocerebellar ataxia type 3 at the start of follow-up in a reference unit
Background: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder that affects the cerebellar system
and other subcortical regions of the brain. As for other cerebellar diseases, the severity of this type of ataxia can be
assessed with the Scale for Assessment and Rating of Ataxia (SARA) which gives a total score that reflects functional
impairment out of 8 cerebellar function tests. SCA3 patients score profile is heterogeneous on at the start of follow
up. This study investigates possible patterns in those profiles and analyses the impact of other usually concurrent
signs of impairment of extracerebellar motor systems in that profile variability by means of multivariate statistical
approaches.
Methods: Seventeen patients with SCA3 underwent systematic anamnesis, neurological and SARA assessment,
visual evaluation of 123I-Ioflupane (DaTSCAN) single-photon emission computed tomography (SPECT) imaging and
electrophysiological studies (nerve conduction and electromyography). Patterns in the profiles of SARA item scores
were investigated by hierarchical clustering after multivariate correspondence analysis. A network analysis was used
to represent relationships between SARA item scores, clinical, genetic and neurological examination parameters as
well as abnormalities of DaTSCAN SPECT imaging and electrophysiological studies.
Results: The most frequently altered SARA items in all patients are gait and stance, and three profiles of SCA3
patients can be distinguished depending mainly on their degree of impairment in those two items. Other SARA
items like the score on heel-shin slide contribute less to the classification. Network analysis shows that SARA item
scores configure a single domain that is independent of the size of the mutated expanded allele and age of onset,
which are, in turn closely and inversely correlated. The severity of cerebellar dysfunction is correlated with longer
disease duration, altered visual evaluation of DaTSCAN SPECT imaging and decreased patellar reflexes. Neither the
presence of pyramidal or extrapyramidal signs nor the intensity of polyneuropathy is correlated with the SARA
items scores.
Conclusions: Pattern recognition approaches are useful tools to describe clinical phenotypes of ataxias and to
identify particular configurations of cerebellar signsDr. Arpa has received grant funding from TRA-052 (MSPSI) and EFACTS 242.19
Gait analysis under the lens of statistical physics
Human gait; Irreversibility; Multi-fractal analysisMarcha humana; Irreversibilidad; Análisis multifractalMarxa humana; Irreversibilitat; Anàlisi multifractalHuman gait is a fundamental activity, essential for the survival of the individual, and an emergent property of the interactions between complex physical and cognitive processes. Gait is altered in many situations, due both to external constraints, as e.g. paced walk, and to physical and neurological pathologies. Its study is therefore important as a way of improving the quality of life of patients, but also as a door to understanding the inner working of the human nervous system. In this review we explore how four statistical physics concepts have been used to characterise normal and pathological gait: entropy, maximum Lyapunov exponent, multi-fractal analysis and irreversibility. Beyond some basic definitions, we present the main results that have been obtained in this field, as well as a discussion of the main limitations researchers have dealt and will have to deal with. We finally conclude with some biomedical considerations and avenues for further development.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 851255). M.Z. and F.O. acknowledges the Spanish State Research Agency through Grant MDM-2017–0711 funded by MCIN/AEI/10.13039/501100011033. Authors acknowledge support from the Escuela Universitaria de Fisioterapia de la ONCE
Gait phenotypes in paediatric hereditary spastic paraplegia revealed by dynamic time warping analysis and random forests
The Hereditary Spastic Paraplegias (HSP) are a group of heterogeneous disorders with a wide spectrum of underlying neural pathology, and hence HSP patients express a variety of gait abnormalities. Classification of these phenotypes May help in monitoring disease progression and personalizing therapies. This is currently managed by measuring values of some kinematic and spatio-temporal parameters at certain moments during the gait cycle, either in the doctor´s surgery room or after very precise measurements produced by instrumental gait analysis (IGA). These methods, however, do not provide information about the whole structure of the gait cycle. Classification of the similarities among time series of IGA measured values of sagittal joint positions throughout the whole gait cycle can be achieved by hierarchical clustering analysis based on multivariate dynamic time warping (DTW). Random forests can estimate which are the most important isolated parameters to predict the classification revealed by DTW, since clinicians need to refer to them in their daily practice. We acquired time series of pelvic, hip, knee, ankle and forefoot sagittal angular positions from 26 HSP and 33 healthy children with an optokinetic IGA system. DTW revealed six gait patterns with different degrees of impairment of walking speed, cadence and gait cycle distribution and related with patient’s age, sex, GMFCS stage, concurrence of polyneuropathy and abnormal visual evoked potentials or corpus callosum. The most important parameters to differentiate patterns were mean pelvic tilt and hip flexion at initial contact. Longer time of support, decreased values of hip extension and increased knee flexion at initial contact can differentiate the mildest, near to normal HSP gait phenotype and the normal healthy one. Increased values of knee flexion at initial contact and delayed peak of knee flexion are important factors to distinguish GMFCS stages I from II- III and concurrence of polyneuropathyDGA was in receipt of a grant from Sociedad Española de Neurología Pediátrica
(SENEP). Publication fee was supported by EUF-ONCE-UAM and Asociación Española de
Paraparesia Espástica Familiar (AEPEF)
Permutation entropy and irreversibility in gait kinematic time series from patients with mild cognitive decline and early Alzheimer’s dementia
Permutation entropy; Irreversibility; Mild cognitive impairmentEntropía de permutación; Irreversibilidad; Defecto cognitivo leveEntropia de permutació; Irreversibilitat; Deteriorament cognitiu lleuGait is a basic cognitive purposeful action that has been shown to be altered in late stages of neurodegenerative dementias. Nevertheless, alterations are less clear in mild forms of dementia, and the potential use of gait analysis as a biomarker of initial cognitive decline has hitherto mostly been neglected. Herein, we report the results of a study of gait kinematic time series for two groups of patients (mild cognitive impairment and mild Alzheimer’s disease) and a group of matched control subjects. Two metrics based on permutation patterns are considered, respectively measuring the complexity and irreversibility of the time series. Results indicate that kinematic disorganisation is present in early phases of cognitive impairment; in addition, they depict a rich scenario, in which some joint movements display an increased complexity and irreversibility, while others a marked decrease. Beyond their potential use as biomarkers, complexity and irreversibility metrics can open a new door to the understanding of the role of the nervous system in gait, as well as its adaptation and compensatory mechanisms.This research was funded through the Premio del Ilustre Colegio Profesional de Fisioterapeutas de la Comunidad De Madrid, prize number ICPFM-IX-2013
Toward an Automatic Assessment of Cognitive Dysfunction in Relapsing–Remitting Multiple Sclerosis Patients Using Eye Movement Analysis
Multiple sclerosis; Ocular markers; Prediction methodsEsclerosis múltiple; Marcadores oculares; Métodos de predicciónEsclerosi múltiple; Marcadors oculars; Mètodes de prediccióDespite the importance of cognitive function in multiple sclerosis, it is poorly represented in the Expanded Disability Status Scale (EDSS), the commonly used clinical measure to assess disability, suggesting that an analysis of eye movement, which is generated by an extensive and well-coordinated functional network that is engaged in cognitive function, could have the potential to extend and complement this more conventional measure. We aimed to measure the eye movement of a case series of MS patients with relapsing–remitting MS to assess their cognitive status using a conventional gaze tracker. A total of 41 relapsing–remitting MS patients and 43 age-matched healthy controls were recruited for this study. Overall, we could not find a clear common pattern in the eye motor abnormalities. Vertical eye movement was more impaired in MS patients than horizontal movement. Increased latencies were found in the prosaccades and reflexive saccades of antisaccade tests. The smooth pursuit was impaired with more corrections (backup and catchup movements, p<0.01). No correlation was found between eye movement variables and EDSS or disease duration. Despite significant alterations in the behavior of the eye movements in MS patients, which are compatible with altered cognitive status, there is no common pattern of these alterations. We interpret this as a consequence of the patchy, heterogeneous distribution of white matter involvement in MS that provokes multiple combinations of impairment at different points in the different networks involved in eye motor control. Further studies are therefore required.This research was partially funding by RoboCity2030-DIH-CM Madrid Robotics Digital 366 Innovation Hub (Robotica aplicada a la mejora de la calidad de vida de los ciudadanos, Fase IV; 367 S2018/NMT-4331), funded by Comunidad de Madrid and cofunded by Structural Funds of the EU and partially funding by Universidad Politécnica de Madrid, Cooperation area. J. Benito-León is supported by the National Institutes of Health, Bethesda, MD, USA (NINDS R01 NS39422), the European Commission (grant ICT-2011-287739, NeuroTREMOR), the Ministry of Economy and Competitiveness (grant RTC-2015-3967-1, NetMD—platform for the tracking of movement disorder), and the Spanish Health Research Agency (grant FIS PI12/01602 and grant FIS PI16/00451)
Characterizing Normal and Pathological Gait through Permutation Entropy
Altres ajuts: We acknowledge the contribution of the children and their families who generously collaborated to build the gait dataset used in this study. We are also grateful to Michael R. Paul for kindly editing the English style of this manuscript. The acquisition and processing of gait data were funded by Escuela de Fisioterapia de la ONCE-UAM, through a private donation, and Agencia de Evaluación de Tecnologías Sanitarias (Instituto de Salud Carlos III), .Cerebral palsy is a physical impairment stemming from a brain lesion at perinatal time, most of the time resulting in gait abnormalities: the first cause of severe disability in childhood. Gait study, and instrumental gait analysis in particular, has been receiving increasing attention in the last few years, for being the complex result of the interactions between different brain motor areas and thus a proxy in the understanding of the underlying neural dynamics. Yet, and in spite of its importance, little is still known about how the brain adapts to cerebral palsy and to its impaired gait and, consequently, about the best strategies for mitigating the disability. In this contribution, we present the hitherto first analysis of joint kinematics data using permutation entropy, comparing cerebral palsy children with a set of matched control subjects. We find a significant increase in the permutation entropy for the former group, thus indicating a more complex and erratic neural control of joints and a non-trivial relationship between the permutation entropy and the gait speed. We further show how this information theory measure can be used to train a data mining model able to forecast the child's condition. We finally discuss the relevance of these results in clinical applications and specifically in the design of personalized medicine interventions
Permutation entropy and irreversibility in gait kinematic time series from patients with mild cognitive decline and early alzheimer’s dementia
Gait is a basic cognitive purposeful action that has been shown to be altered in late stages
of neurodegenerative dementias. Nevertheless, alterations are less clear in mild forms of dementia,
and the potential use of gait analysis as a biomarker of initial cognitive decline has hitherto mostly
been neglected. Herein, we report the results of a study of gait kinematic time series for two groups of
patients (mild cognitive impairment and mild Alzheimer’s disease) and a group of matched control
subjects. Two metrics based on permutation patterns are considered, respectively measuring the
complexity and irreversibility of the time series. Results indicate that kinematic disorganisation is
present in early phases of cognitive impairment; in addition, they depict a rich scenario, in which
some joint movements display an increased complexity and irreversibility, while others a marked
decrease. Beyond their potential use as biomarkers, complexity and irreversibility metrics can open a
new door to the understanding of the role of the nervous system in gait, as well as its adaptation and
compensatory mechanismsThis research was funded through the Premio del Ilustre Colegio Profesional de Fisioterapeutas de la
Comunidad De Madrid, prize number ICPFM-IX-201
Assessing biological and methodological aspects of brain volume loss in multiple sclerosis
Importance: Before using brain volume loss (BVL) as a marker of therapeutic response in multiple sclerosis (MS), certain biological and methodological issues must be clarified. Objectives: To assess the dynamics of BVL as MS progresses and to evaluate the repeatability and exchangeability of BVL estimates with Jacobian Integration (JI) and Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) (specifically, the Structural Image Evaluation, Using Normalisation, of Atrophy-Cross-Sectional [SIENA-X] tool or FMRIB's Integrated Registration and Segmentation Tool [FIRST]). Design, Setting, and Participants: A cohort of patients who had either clinically isolated syndrome or MS was enrolled from February 2011 through October 2015. All underwent a series of annual magnetic resonance imaging (MRI) scans. Images from 2 cohorts of healthy volunteers were used to evaluate short-term repeatability of the MRI measurements (n = 34) and annual BVL (n = 20). Data analysis occurred from January to May 2017. Main Outcomes and Measures: The goodness of fit of different models to the dynamics of BVL throughout the MS disease course was assessed. The short-term test-retest error was used as a measure of JI and FSL repeatability. The correlations (R2) of the changes quantified in the brain using JI and FSL, together with the accuracy of the annual BVL cutoffs to discriminate patients with MS from healthy volunteers, were used to measure compatibility of imaging methods. Results: A total of 140 patients with clinically isolated syndrome or MS were enrolled, including 95 women (67.9%); the group had a median (interquartile range) age of 40.7 (33.6-48.1) years. Patients underwent 4 MRI scans with a median (interquartile range) interscan period of 364 (351-379) days. The 34 healthy volunteers (of whom 18 [53%] were women; median [IQR] age, 33.5 [26.2-42.5] years) and 20 healthy volunteers (of whom 10 [50%] were women; median [IQR] age, 33.0 [28.7-39.2] years) underwent 2 MRI scans within a median (IQR) of 24.5 (0.0-74.5) days and 384.5 (366.3-407.8) days for the short-term and long-term MRI follow-up, respectively. The BVL rates were higher in the first 5 years after MS onset (R2 = 0.65 for whole-brain volume change and R2 = 0.52 for gray matter volume change) with a direct association with steroids (β = 0.280; P = .02) and an inverse association with age at MS onset, particularly in the first 5 years (β = 0.015; P = .047). The reproducibility of FSL (SIENA) and JI was similar for whole-brain volume loss, while JI gave more precise, less biased estimates for specific brain regions than FSL (SIENA-X and FIRST). The correlation between whole-brain volume loss using JI and FSL was high (R2 = 0.92), but the same correlations were poor for specific brain regions. The area under curve of the whole-brain volume change to discriminate between patients with MS and healthy volunteers was similar, although the thresholds and accuracy index were distinct for JI and FSL. Conclusions and Relevance: The proposed BVL threshold of less than 0.4% per year as a marker of therapeutic efficiency should be reconsidered because of the different dynamics of BVL as MS progresses and because of the limited reproducibility and variability of estimates using different imaging methods
Predictors of vision impairment in Multiple Sclerosis.
Visual impairment significantly alters the quality of life of people with Multiple Sclerosis (MS). The objective of this study was to identify predictors (independent variables) of visual outcomes, and to define their relationship with neurological disability and retinal atrophy when assessed by optical coherence tomography (OCT). We performed a cross-sectional analysis of 119 consecutive patients with MS, assessing vision using high contrast visual acuity (LogMar), 2.5% and 1.25% low contrast visual acuity (Sloan charts), and color vision (Hardy-Rand-Rittler plates). Quality of vision is a patient reported outcome based on an individual's unique perception of his or her vision and was assessed with the Visual Functioning Questionnaire-25 (VFQ-25) with the 10 neuro-ophthalmologic items. MS disability was assessed using the expanded disability status scale (EDSS), the MS functional composite (MSFC) and the brief repetitive battery-neuropsychology (BRB-N). Retinal atrophy was assessed using spectral domain OCT, measuring the thickness of the peripapillar retinal nerve fiber layer (pRNFL) and the volume of the ganglion cell plus inner plexiform layer (GCIPL). The vision of patients with MS was impaired, particularly in eyes with prior optic neuritis. Retinal atrophy (pRNFL and GCIPL) was closely associated with impaired low contrast vision and color vision, whereas the volume of the GCIPL showed a trend (p = 0.092) to be associated with quality of vision. Multiple regression analysis revealed that EDSS was an explanatory variable for high contrast vision after stepwise analysis, GCIPL volume for low contrast vision, and GCIPL volume and EDSS for color vision. The explanatory variables for quality of vision were high contrast vision and color vision. In summary, quality of vision in MS depends on the impairment of high contrast visual acuity and color vision due to the disease
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