A Kinect-based perceptive assessment battery for motor dysfunction in multiple sclerosis and other neuroinflammatory disorders

Background: Objective tools for prognosis and disease progression monitoring in multiple sclerosis (MS) are lacking. The visuomotor system could be used to track motor dysfunction at the micron scale through the monitoring of fixational microsaccades. Aims: The aim of this study was to evaluate whether microsaccades are correlated with standard MS disability metrics and to assess whether these methods play a predictive role in MS disability. Method: We used a custom-built retinal eye tracker, the tracking scanning laser ophthalmoscope (TSLO), to record fixation in 111 participants with MS and 100 unaffected controls. Results: In MS participants, a greater number of microsaccades showed significant association with higher Expanded Disability Status Scale score (EDSS, p < 0.001), nine-hole peg test (non-dominant: p = 0.006), Symbol Digit Modalities Test (SMDT, p = 0.014), and Functional Systems Scores (FSS) including brainstem ( p = 0.005), cerebellar ( p = 0.011), and pyramidal ( p = 0.009). Both brainstem FSS and patient-reported fatigue showed significant associations with microsaccade number, amplitude, and peak acceleration. Participants with MS showed a statistically different average number ( p = 0.020), peak vertical acceleration ( p = 0.003), and vertical amplitude ( p < 0.001) versus controls. Logistic regression models for MS disability were created using TSLO microsaccade metrics and paraclinical tests with ⩾80% accuracy. Conclusion: Microsaccades provide objective measurements of MS disability level and disease worsening.

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Diffusion Tensor and Magnetization Transfer Imaging Correlates of Motor Dysfunction in the Spinal Cord in Multiple Sclerosis (S21.002)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.s21.002 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. S21.002-S21.002 ◽

Cited By ~ 1

Author(s):

J. Oh ◽

K. Zackowski ◽

M. Chen ◽

S. Newsome ◽

S. Smith ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Diffusion Tensor ◽

Magnetization Transfer ◽

Motor Dysfunction ◽

Magnetization Transfer Imaging

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PADI2-mediated citrullination is required for efficient oligodendrocyte differentiation and myelination

10.1101/425348 ◽

2018 ◽

Cited By ~ 1

Author(s):

Ana Mendanha Falcão ◽

Mandy Meijer ◽

Antonella Scaglione ◽

Puneet Rinwa ◽

Eneritz Agirre ◽

...

Keyword(s):

Multiple Sclerosis ◽

Corpus Callosum ◽

Therapeutic Strategy ◽

Chromatin Accessibility ◽

Motor Dysfunction ◽

Peptidylarginine Deiminase ◽

Oligodendrocyte Differentiation ◽

Associated Proteins ◽

Arginine Residues ◽

Related Proteins

Citrullination, the deimination of arginine residues into citrulline, has been implicated in the aetiology of several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver of pathology, through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutic strategy for MS. Here, in contrast, we show citrullination by peptidylarginine deiminase 2 (PADI2) is required for normal oligodendrocyte differentiation, myelination and motor function. We identify several targets for PADI2, including myelin-related proteins and chromatin-associated proteins, implicating PADI2 in epigenetic regulation. Accordingly, we observe that PADI2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of oligodendrocyte differentiation genes. Moreover, mice lacking PADI2, display motor dysfunction and decreased number of myelinated axons in the corpus callosum. We conclude that citrullination is required for oligodendrocyte lineage progression and myelination and suggest its targeted activation in the oligodendrocyte lineage might be beneficial in the context of remyelination.

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Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

Neural Plasticity ◽

10.1155/2015/307175 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 29

Author(s):

Dominika Justyna Ksiazek-Winiarek ◽

Piotr Szpakowski ◽

Andrzej Glabinski

Keyword(s):

Multiple Sclerosis ◽

Neural Plasticity ◽

Neuronal Plasticity ◽

Developmental Stages ◽

Neurodegenerative Disorder ◽

Neuronal Damage ◽

Brain Plasticity ◽

Motor Dysfunction ◽

Functional Studies ◽

Repair Mechanisms

Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets.

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Predictors of effectiveness of multidisciplinary rehabilitation treatment on motor dysfunction in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513508834 ◽

2013 ◽

Vol 20 (7) ◽

pp. 862-870 ◽

Cited By ~ 6

Author(s):

G Liberatore ◽

F Clarelli ◽

A Nuara ◽

D Ungaro ◽

R Gatti ◽

...

Keyword(s):

Multiple Sclerosis ◽

Outcome Measures ◽

Inpatient Rehabilitation ◽

Functional Independence ◽

Rehabilitation Program ◽

Activity Limitation ◽

Motor Dysfunction ◽

Short Term ◽

Rehabilitation Treatment ◽

Edss Score

Objectives: To identify clinical predictors of effectiveness of a motor rehabilitation treatment in a cohort of multiple sclerosis (MS) patients. Materials and methods: We analysed 212 consecutive patients who underwent a short-term (3–7 weeks) intensive (two hours per day, five days per week), individualised, goal-oriented inpatient rehabilitation program. Activity limitation and impairment were measured on admission and discharge of the rehabilitation trial using the motor sub-items of the Functional Independence Measure (mFIM) and the Expanded Disability Status Scale (EDSS) score. Multivariate logistic regression models have been tested to evaluate the role of clinical baseline features on rehabilitation effectiveness. Results: According to pre-defined outcome measures, 75.1% of MS patients improved in either activity limitation (≥5 points delta mFIM) or impairment (≥1.0 delta EDSS score if baseline EDSS was ≤5.5, or ≥0.5 if baseline EDSS was >5.5), and 35.4% of MS patients improved in both outcomes. A relapsing-remitting course of disease, a more severe baseline impairment and activity limitation level, a shorter disease duration and a less severe balance dysfunction were predictive of the effectiveness of rehabilitation. Discussion: These data confirm that an intensive inpatient rehabilitation program is able to produce a short-term relevant improvement on clinical and functional outcome measures and suggest some clinical features which can be considered as potential predictors of the outcome of rehabilitative intervention.

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Toward a Consensus on Rehabilitation Outcomes in MS: Gait and Fatigue

International Journal of MS Care ◽

10.7224/1537-2073-11.2.67 ◽

2009 ◽

Vol 11 (2) ◽

pp. 67-78 ◽

Cited By ~ 14

Author(s):

Brian Hutchinson ◽

Susan J. Forwell ◽

Susan Bennett ◽

Theodore Brown ◽

Herb Karpatkin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Outcome Measures ◽

Consensus Conference ◽

Timed Up And Go ◽

Assessment Battery ◽

Rehabilitation Professionals ◽

Rehabilitation Outcomes ◽

Dynamic Gait Index ◽

Dynamic Gait

A multidisciplinary consensus conference was held on November 28–29, 2007, by the Consortium of Multiple Sclerosis Centers (CMSC) to determine the most appropriate outcome measures for gait and fatigue in people with multiple sclerosis (MS). The goals of this conference were to 1) improve understanding of gait and fatigue outcome measures being used by rehabilitation professionals treating people with MS; 2) establish consensus on outcome measures; and 3) establish consensus on required follow-up for transfer of this knowledge to rehabilitation professionals. The consensus conference and this document are the initial steps toward achieving the stated goals. Although many measures of fatigue exist, it was recommended that a global outcome measure for fatigue be developed that would 1) include a screen for the functional ramifications of fatigue for activities and participation; 2) be quick and easy to administer; 3) demonstrate psychometric integrity for MS; and 4) examine fatigue over a continuum of the MS disease course. In addition, it was recommended that an assessment battery for fatigue be developed. With respect to gait outcome measures, it was agreed that the following tools should be included in a preliminary chart for use in a clinical setting: the Timed 25-Foot Walk, Timed Up and Go test, Dynamic Gait Index, 6-Minute Walk, and self-reported 12-item Multiple Sclerosis Walking Scale. The global outcome fatigue measure and assessment battery are currently being developed, and work on a detailed gait outcome measures chart and additional research on commonly used gait outcome measures are in progress.

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Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis

Neurotherapeutics ◽

10.1007/s13311-020-00958-8 ◽

2020 ◽

Author(s):

Vittoria Borgonetti ◽

Maria Domenica Sanna ◽

Laura Lucarini ◽

Nicoletta Galeotti

Keyword(s):

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Rna Binding ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Rna Binding Protein ◽

Motor Dysfunction ◽

Autoimmune Encephalomyelitis ◽

Activated Microglia ◽

Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood–brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.

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Pediatric Multiple Sclerosis in Tunisia: A Retrospective Study over 11 Years

BioMed Research International ◽

10.1155/2017/4354826 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Nedia Ben Achour ◽

Ibtihel Rebai ◽

Sarra Raddadi ◽

Hanene Benrhouma ◽

Hedia Klaa ◽

...

Keyword(s):

Multiple Sclerosis ◽

Type 1 Diabetes ◽

Retrospective Study ◽

Tertiary Care ◽

Age At Onset ◽

Management Strategies ◽

Motor Dysfunction ◽

Female Ratio ◽

Pediatric Multiple Sclerosis

Introduction. Pediatric multiple sclerosis (pMS) is a rare demyelinating disorder with an onset before the age of 18 years. In this study, we aimed to investigate the characteristics of pMS in Tunisian children. Patients and Methods. We conducted a retrospective study over 11 years (2005–2016) including all patients diagnosed with pMS according to the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria of 2012 and followed up in a tertiary care research center. Epidemiological, clinical, neuroimaging, laboratory, and therapeutic data were collected and analyzed. Results. There were 21 patients. The male-female ratio was 1 : 3. Mean age at onset was 11 years (range: 3–17 years). Three patients had type 1 diabetes. Polyfocal presentation was preponderant (81%) with motor dysfunction in 57% of patients. Paroxysmal dystonia was noticed in 24%. All patients were diagnosed with relapsing-remitting form. Interferon beta was prescribed in 80% with a reduction of annual relapse rate. Conclusion. The annual incidence of pMS in Tunisian children aged below 18 years could be estimated as 0.05 per 100,000. Singular features in our cohort were the frequent association with type 1 diabetes and the increased occurrence of dystonia. Greater awareness of pMS may be helpful to improve management strategies of children and their families.

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Mobile Brain/Body Imaging of cognitive-motor impairment in multiple sclerosis: deriving EEG-based neuro-markers during a dual-task walking study

10.1101/743328 ◽

2019 ◽

Author(s):

Pierfilippo De Sanctis ◽

Brenda R. Malcolm ◽

Peter C. Mabie ◽

Ana A. Francisco ◽

Wenzhu B. Mowrey ◽

...

Keyword(s):

Multiple Sclerosis ◽

Task Performance ◽

Dual Task ◽

Cognitive Task ◽

Motor Impairment ◽

Event Related Potentials ◽

Motor Dysfunction ◽

Task Load ◽

Dual Task Performance ◽

Related Potentials

ABSTRACTIndividuals with a diagnosis of multiple sclerosis (MS) often present with deficits in the cognitive as well as the motor domain. The ability to perform tasks that rely on both domains may therefore be particularly impaired. Yet, behavioral studies designed to measure costs associated with performing two tasks at the same time such as dual-task walking have yielded mixed results. Patients may mobilize additional brain resources to sustain good levels of performance. To test this hypothesis, we acquired event-related potentials (ERP) in thirteen individuals with MS and fifteen healthy control (HC) participants performing a Go/NoGo response inhibition task while sitting (i.e., single task) or walking on a treadmill (i.e., dual-task). In previous work, we showed that the nogo-N2 elicited by the cognitive task was reduced when healthy adults are also asked to walk, and that nogo-N2 reduction was accompanied by sustained dual-task performance. We predicted that some MS patients, similar to their healthy peers, may mobilize N2-indexed brain resources and thereby reduce costs. Somewhat to our surprise, the HC group performed the Go/NoGo task more accurately while walking, thus showing a dual-task benefit, whereas, in line with expectation, the MS group showed a trend towards dual-task costs. The expected nogo-N2 reduction during dual-task walking was found in the HC group, but was not present at the group level in the MS group, suggesting that this group did not modulate the nogo-N2 process in response to higher task load. Regression analysis for the pooled sample revealed a robust link between nogo-N2 reduction and better dual-task performance. We conclude that impaired nogo-N2 adaptation reflects a neurophysiological marker of cognitive-motor dysfunction in MS.

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