Clinical Measures Of Disability Research Articles

MORe PREcISE: Longitudinal patient reported outcome measures in stroke at 3 and 6 months.

Background and PurposePost-stroke morbidity is common, but little is known about the burden on patients’ lives from their own perspective. Understanding morbidity from the point of view of the patient may support targeted intervention in post-stroke recovery. This study used a stroke specific Patient Reported Outcome Measure (PROM) containing Mental health (MH) and Physical Health (PH) domains and 5 stroke specific questions. We aimed to consider trends over a 6-month period and further assess the association between the MH and PH measures and common clinical measures. MethodsA multicenter prospective cohort study was conducted at 19 hospital sites across England and Wales. Patients were enrolled from August 2018 to September 2019. Clinical measures and PROMs were assessed at three timepoints: acutely following the index stroke, at 3 and 6-months post-stroke. Clinical measures and PROMs were assessed in each of these points. ResultsPhysical health PROM domains show significant gradual improvement across the study period (χ2 42.6312, p<0.0001), whereas cognitive function domains (χ2 3.7849, p<0.875) did not echo this trend. All clinical measures (GAD-7, PHQ9, MoCA, MRS) were associated with poorer PROM MH outcomes, (aMD -4.4, CI -0.59, -0.29, p≤0.001, aMD -0.45, CI -0.59, -0.32, p=<0.001, aMD 0.75, CI 0.56, 0.95, aMD -1.91, CI -2.41, -1.47, p≤0.001). Clinical measures of disability, as per the MRS, are associated with poor PROM PH scores (aMD -0.57, 95% CI -0.94, -0.20, p=0.003). ConclusionsThis research indicates there is unmet cognitive burden in stroke survivors. PROMs may be able to measure unmet more discretely than common clinical tools that are used post-stroke. Further research and guidance on how to integrate PROMs into current clinical frameworks is essential.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus

ObjectivesTo explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. MethodsSixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. ResultsPwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26–0.39, p = 0.01–0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). ConclusionsStructural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability.

Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (St O2 ) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood. We investigated the reproducibility of fdNIRS measurements. We measured cortical hypoxia in pwMS, and the relationships between St O2 , neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of St O2 measured at 1-week intervals for 4 weeks, and at 8 weeks and ~1 year. We show that fdNIRS parameters were highly reproducible in 7 healthy control participants measured over 6 days (p > 0.05). There was low variability between and within subjects. In line with our previous findings, we show that 33% of pwMS (n = 88) have cortical microvascular hypoxia. Over 8 weeks and at ~1 year, St O2 values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and St O2 . This conclusion should be revisited as only a small proportion of the relapsing-remitting MS group (21%) was cognitively impaired. The fdNIRS parameters have high reproducibility and repeatability, and we have demonstrated that hypoxia in MS is a chronic condition, lasting at least a year. The results show a weak relationship between cognitive functioning and oxygenation, indicating future study is required. ANN NEUROL 2023;94:1067-1079.

Disability in cerebellar ataxia syndromes is linked to cortical degeneration

ObjectiveWe aimed to relate clinical measures of disability in chronic cerebellar degeneration to structural whole-brain changes using voxel-based and surface-based morphometry (vbm and sbm). We were particularly interested in remote effects of cerebellar degeneration in the cerebral cortex.MethodsWe recruited 30 patients with cerebellar degeneration of different aetiologies (downbeat nystagmus syndrome, DBN n = 14, spinocerebellar ataxia, SCA n = 9, sporadic adult late-onset ataxia, SAOA n = 7). All patients were thoroughly characterised in the motor, cognitive, vestibular and ocular–motor domains. Vbm and sbm were used to evaluate structural differences between cerebellar degeneration patients and a group of healthy age- and gender-matched volunteers. Linear regression models were used to correlate functional measures of disease progression and postural stability with whole brain volumetry.ResultsPatients with SCA and SAOA showed widespread volume loss in the cerebellar hemispheres and less prominently in the vermis. Patients with DBN showed a distinct pattern of grey matter volume (GMV) loss that was restricted to the vestibular and ocular–motor representations in lobules IX, X and V–VII. Falls were associated with brainstem white matter volume. VBM and SBM linear regression models revealed associations between severity of ataxic symptoms, cognitive performance and preferred gait velocity. This included extra-cerebellar (sub-)cortical hubs of the motor and locomotion network (putamen, caudate, thalamus, primary motor cortex, prefrontal cortex) and multisensory areas involved in spatial navigation and cognition.ConclusionFunctional disability in multiple domains was associated with structural changes in the cerebral cortex.

Regulation of the programmed cell death protein 1/programmed cell death ligand 1 axis in relapsing-remitting multiple sclerosis.

The programmed cell death protein 1/programmed cell death ligand 1 axis plays an important role in the adaptive immune system and has influence on neoplastic and inflammatory diseases, while its role in multiple sclerosis is unclear. Here, we aimed to analyse expression patterns of programmed cell death protein 1 and programmed cell death ligand 1 on peripheral blood mononuclear cells and their soluble variants in multiple sclerosis patients and controls, to determine their correlation with clinical disability and disease activity. In a cross-sectional study, we performed in-depth flow cytometric immunophenotyping of peripheral blood mononuclear cells and analysed soluble programmed cell death protein 1 and programmed cell death ligand 1 serum levels in patients with relapsing-remitting multiple sclerosis and controls. In comparison to control subjects, relapsing-remitting multiple sclerosis patients displayed distinct cellular programmed cell death protein 1/programmed cell death ligand 1 expression patterns in immune cell subsets and increased soluble programmed cell death ligand 1 levels, which correlated with clinical measures of disability and MRI activity over time. This study extends our knowledge of how programmed cell death protein 1 and programmed cell death ligand 1 are expressed in the membranes of patients with relapsing-remitting multiple sclerosis and describes for the first time the elevation of soluble programmed cell death ligand 1 in the blood of multiple sclerosis patients. The distinct expression pattern of membrane-bound programmed cell death protein 1 and programmed cell death ligand 1 and the correlation between soluble programmed cell death ligand 1, membrane-bound programmed cell death ligand 1, disease and clinical factors may offer therapeutic potential in the setting of multiple sclerosis and might improve future diagnosis and clinical decision-making.

Occurrence and Severity of Coronavirus Disease 2019 Are Associated With Clinical Disability Worsening in Patients With Multiple Sclerosis.

Large-scale observational studies have shown that, in patients with multiple sclerosis (MS), the risk of becoming more severely ill from coronavirus disease 2019 (COVID-19) is determined by older age, male sex, cardiovascular comorbidities, African American ethnicity, progressive disease, recent use of corticosteroids, and B cell-depleting disease-modifying treatment. In contrast, the effect of COVID-19 on the disease course of MS has been studied much less extensively. Our main goal was to explore whether COVID-19 is associated with accelerated clinical disability worsening in patients with MS. Since March 2020, demographics and infectious outcome (categorized as ambulatory, hospitalized, and/or death) of patients with MS who developed COVID-19 have been collected at the Belgian National MS Center in Melsbroek. On February 28, 2022, this database was locked and complemented with clinical disability measures-Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk Test (T25FWT), 9-Hole Peg Test (9HPT), and Symbol Digit Modalities Test (SDMT)-that were available from a larger local database, obtained during routine medical follow-up. For each parameter, the first 2 assessments before COVID-19 diagnosis (T0 and T1; T1 is the closest to COVID-19 diagnosis), and the first thereafter (T2), were retrieved. We identified 234 unique cases of COVID-19. Thirty-one patients were hospitalized (13.2%), and 5 died (2.1%) as a result of their infection. Among survivors with complete EDSS results (N = 138), mean annualized T1-to-T2 EDSS worsening was more pronounced, compared with the respective change between T0 and T1 (0.3 ± 0.9 vs 0.1 ± 0.9, p = 0.012). No such differences were found for the T25FWT, 9HPT, and SDMT scores. Severe COVID-19 (hospitalization) was associated with clinically relevant T1-to-T2 EDSS worsening (OR 2.65, p = 0.042). Vaccination coverage in the total cohort was 53.8%. Being unprotected by vaccination at the time of infection was associated with a worse COVID-19 outcome (hospitalization and/or death; OR 3.52, p = 0.002) but not with clinically relevant T1-to-T2 EDSS worsening. The occurrence and severity of COVID-19 are both associated with clinical disability worsening in patients with MS. Vaccination protects against a more severe course of COVID-19 in this specific population. The study has been registered at ClinicalTrials.gov (study registration number: NCT05403463).

Longitudinal changes of deep gray matter shape in multiple sclerosis

ObjectiveThis study aimed to investigate longitudinal deep gray matter (DGM) shape changes and their relationship with measures of clinical disability and white matter lesion-load in a large multiple sclerosis (MS) cohort. Materials and MethodsA total of 230 MS patients (179 relapsing-remitting, 51 secondary progressive; baseline age 44.5 ± 11.3 years; baseline disease duration 12.99 ± 9.18) underwent annual clinical and MRI examinations over a maximum of 6 years (mean 4.32 ± 2.07 years). The DGM structures were segmented on the T1-weighted images using the “Multiple Automatically Generated Templates” brain algorithm. White matter lesion-load was measured on T2-weighted MRI. Clinical examination included the expanded disability status scale, 9-hole peg test, timed 25-foot walk test, symbol digit modalities test and paced auditory serial addition test. Vertex‐wise longitudinal analysis of DGM shapes was performed using linear mixed effect models and evaluated the association between average/temporal changes of DGM shapes with average/temporal changes of clinical measurements, respectively. ResultsA significant shrinkage over time of the bilateral ventrolateral pallidal and the left posterolateral striatal surface was observed, whereas no significant shape changes over time were observed at the bilateral thalamic and right striatal surfaces. Higher average lesion-load was associated with an average inwards displacement of the global thalamic surface with relative sparing on the posterior side (slight left-side predominance), the antero-dorso-lateral striatal surfaces bilaterally (symmetric on both sides) and the antero-lateral pallidal surface (left-side predominance). There was also an association between shrinkage of large lateral DGM surfaces with higher clinical motor and cognitive disease severity. However, there was no correlation between any DGM shape changes over time and measurements of clinical progression or lesion-load changes over time. ConclusionsThis study showed specific shape change of DGM structures occurring over time in relapse-onset MS. Although these shape changes over time were not associated with disease progression, we demonstrated a link between DGM shape and the patients’ average disease severity as well as white matter lesion-load.

Rim lesions are demonstrated in early relapsing\u2013remitting multiple sclerosis using 3\xa0T-based susceptibility-weighted imaging in a multi-institutional setting

PurposeRim lesions, characterised by a paramagnetic rim on susceptibility-based MRI, have been suggested to reflect chronic inflammatory demyelination in multiple sclerosis (MS) patients. Here, we assess, through susceptibility-weighted imaging (SWI), the prevalence, longitudinal volume evolution and clinical associations of rim lesions in subjects with early relapsing–remitting MS (RRMS).MethodsSubjects (n = 44) with recently diagnosed RRMS underwent 3 T MRI at baseline (M0) and 1 year (M12) as part of a multi-centre study. SWI was acquired at M12 using a 3D segmented gradient-echo echo-planar imaging sequence. Rim lesions identified on SWI were manually segmented on FLAIR images at both time points for volumetric analysis.ResultsTwelve subjects (27%) had at least one rim lesion at M12. A linear mixed-effects model, with ‘subject’ as a random factor, revealed mixed evidence for the difference in longitudinal volume change between rim lesions and non-rim lesions (p = 0.0350 and p = 0.0556 for subjects with and without rim lesions, respectively). All 25 rim lesions identified showed T1-weighted hypointense signal. Subjects with and without rim lesions did not differ significantly with respect to age, disease duration or clinical measures of disability (p > 0.05).ConclusionWe demonstrate that rim lesions are detectable in early-stage RRMS on 3 T MRI across multiple centres, although their relationship to lesion enlargement is equivocal in this small cohort. Identification of SWI rims was subjective. Agreed criteria for defining rim lesions and their further validation as a biomarker of chronic inflammation are required for translation of SWI into routine MS clinical practice.

A smartphone sensor-based digital outcome assessment of multiple sclerosis

Background: Sensor-based monitoring tools fill a critical gap in multiple sclerosis (MS) research and clinical care. Objective: The aim of this study is to assess performance characteristics of the Floodlight Proof-of-Concept (PoC) app. Methods: In a 24-week study (clinicaltrials.gov: NCT02952911), smartphone-based active tests and passive monitoring assessed cognition (electronic Symbol Digit Modalities Test), upper extremity function (Pinching Test, Draw a Shape Test), and gait and balance (Static Balance Test, U-Turn Test, Walk Test, Passive Monitoring). Intraclass correlation coefficients (ICCs) and age- or sex-adjusted Spearman’s rank correlation determined test–retest reliability and correlations with clinical and magnetic resonance imaging (MRI) outcome measures, respectively. Results: Seventy-six people with MS (PwMS) and 25 healthy controls were enrolled. In PwMS, ICCs were moderate-to-good (ICC(2,1) = 0.61–0.85) across tests. Correlations with domain-specific standard clinical disability measures were significant for all tests in the cognitive (r = 0.82, p < 0.001), upper extremity function (|r|= 0.40–0.64, all p < 0.001), and gait and balance domains (r = −0.25 to −0.52, all p < 0.05; except for Static Balance Test: r = −0.20, p > 0.05). Most tests also correlated with Expanded Disability Status Scale, 29-item Multiple Sclerosis Impact Scale items or subscales, and/or normalized brain volume. Conclusion: The Floodlight PoC app captures reliable and clinically relevant measures of functional impairment in MS, supporting its potential use in clinical research and practice.

Real-world keystroke dynamics are a potentially valid biomarker for clinical disability in multiple sclerosis

Background: Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing. Objective: The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS. Methods: In total, 102 MS patients and 24 controls were included in this observational study. Keyboard interactions were obtained with the Neurokeys keyboard app. Eight timing-related keystroke features were assessed for reliability with intraclass correlation coefficients (ICCs); construct validity by analysing group differences (in fatigue, gadolinium-enhancing lesions on magnetic resonance imaging (MRI), and patients vs controls); and concurrent validity by correlating with disability measures. Results: Reliability was moderate in two (ICC = 0.601 and 0.742) and good to excellent in the remaining six features (ICC = 0.760–0.965). Patients had significantly higher keystroke latencies than controls. Latency between key presses correlated the highest with Expanded Disability Status Scale (r = 0.407) and latency between key releases with Nine-Hole Peg Test and Symbol Digit Modalities Test (ρ = 0.503 and r = −0.553, respectively), ps < 0.001. Conclusion: Keystroke dynamics were reliable, distinguished patients and controls, and were associated with clinical disability measures. Consequently, keystroke dynamics are a promising valid surrogate marker for clinical disability in MS.

Trunk and foot acceleration variability during walking relates to fall history and clinical disability in persons with multiple sclerosis

BackgroundPersons with multiple sclerosis are often at higher risk for falling, but clinical disability scales and fall risk questionnaires are subjective and don't provide specific feedback about why an individual is unstable. The purpose of this study was to determine how relationships between trunk and foot acceleration variability relate to physiological impairments, clinical disability scales, and mobility questionnaires in persons with multiple sclerosis. Methods15 fallers and 25 non-fallers with multiple sclerosis walked on a treadmill at normal walking speed while trunk and foot accelerations were recorded with wireless accelerometers and variability measures were extracted and used to calculate the gait stability index metrics as a ratio of trunk acceleration variability divided foot acceleration variability. Subjects' sensorimotor delays and lower extremity vibration sensitivity were tested. Subjects also completed clinical disability scales (Guy's Neurological Disability Scale and Patient Reported Expanded Disability Status Scale) and mobility questionnaires (Falls Efficacy Scale, Activities Balance Confidence Scale, 12 Item Multiple Sclerosis Walk Scale). FindingsMultiple gait stability index metrics were significantly correlated with clinical measures of disability and mobility in multiple sclerosis subjects (r = 0.354–0.528), but no correlations were found for sensorimotor delays or lower extremity sensation. Multiple gait stability indices performed at least as well as clinical questionnaires for separating fallers from non-fallers. InterpretationThe gait stability indices can potentially be used outside of a laboratory setting to measure walking characteristics related to fall history and disability level in people with multiple sclerosis.

Lumbar intervertebral disc characterization through quantitative MRI analysis: An automatic voxel-based relaxometry approach.

PurposeTo develop an automated pipeline based on convolutional neural networks to segment lumbar intervertebral discs and characterize their biochemical composition using voxel‐based relaxometry, and establish local associations with clinical measures of disability, muscle changes, and other symptoms of lower back pain.MethodsThis work proposes a new methodology using MRI (n = 31, across the spectrum of disc degeneration) that combines deep learning–based segmentation, atlas‐based registration, and statistical parametric mapping for voxel‐based analysis of T1ρ and T2 relaxation time maps to characterize disc degeneration and its associated disability.ResultsAcross degenerative grades, the segmentation algorithm produced accurate, high‐confidence segmentations of the lumbar discs in two independent data sets. Manually and automatically extracted mean disc T1ρ and T2 relaxation times were in high agreement for all discs with minimal bias. On a voxel‐by‐voxel basis, imaging‐based degenerative grades were strongly negatively correlated with T1ρ and T2, particularly in the nucleus. Stratifying patients by disability grades revealed significant differences in the relaxation maps between minimal/moderate versus severe disability: The average T1ρ relaxation maps from the minimal/moderate disability group showed clear annulus nucleus distinction with a visible midline, whereas the severe disability group had lower average T1ρ values with a homogeneous distribution.ConclusionThis work presented a scalable pipeline for fast, automated assessment of disc relaxation times, and voxel‐based relaxometry that overcomes limitations of current region of interest–based analysis methods and may enable greater insights and associations between disc degeneration, disability, and lower back pain.

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis

Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation −0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.

Should Sagittal Spinal Alignment Targets for Adult Spinal Deformity Correction Depend on Pelvic Incidence and Age?

Retrospective analysis. Determine whether deformity corrections should vary by pelvic incidence (PI). Alignment targets for deformity correction have been reported for various radiographic parameters. The T1 pelvic-angle (TPA) has gained in applications for adult spinal deformity (ASD) surgical-planning since it directly measures spinal alignment separate from pelvic- and lower-extremity compensation. Recent studies have demonstrated that ASD corrections should be age specific. A prospective database of consecutive ASD patients was analyzed in conjunction with a normative spine database. Clinical measures of disability included the Oswestry Disability Index (ODI) and Short Form 36 Survey (SF-36) Physical Component Score (PCS). Baseline relationships between TPA, age, PI, and ODI/SF-36 PCS scores were analyzed in the ASD and asymptomatic patients. Linear regression modeling was used to determine alignment targets based on PI and age-specific normative SF-36-PCS values. Nine hundred three ASD patients (mean 53.7 yr) and 111 normative subjects (mean 50.7 yr) were included. Patients were subanalyzed by PI: low, medium, high (<40, 40-75, >75); and age: elderly (>65 yr, n = 375), middle age (45-65 yr, n = 387), and young (18-45 yr, n = 141). TPA and SRS-Schwab parameters correlated with age and PI in ASD and normative subjects (r = 0.42, P < 0.0001). ODI correlated with PCS (r = 0.71, P < 0.0001). Linear regression analysis using age-normative SF-36-PCS values demonstrated that ideal spinopelvic alignment is less strict with increasing PI and age. Targets for ASD correction should vary by age and PI. This is demonstrated in both asymptomatic and ASD subjects. Using age-normative SF-36 PCS values, alignment targets are described for different age and PI categories. High-PI patients do not require as rigorous realignments to attain age-specific normative levels of health status. As such, sagittal spinal alignment targets increase with increasing age as well as PI. 3.

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study.

Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = −0.85, P = 0.021) and caudate nucleus (β = −0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures.

Clinical measures of disability in children and adolescents due to pathology of the musculoskeletal system and connective tissue in the Voronezh region in 2015–2017

The paper presents a brief review of the primary and recurrent disability of persons under the age of 18 in the Voronezh Region in comparison with data on the Central Federal District and the Russian Federation. The article draws attention to the urgency of the comprehensive approach to diagnostics and development of measures of multilevel prevention and medical and social rehabilitation of patients and disabled persons with this pathology. It highlights the great importance of rehabilitation and habilitation for the formation or recovery of their social and professional status.

Optical Coherence Tomography versus Visual Evoked Potentials for Detecting Visual Pathway Abnormalities in Patients with Neuromyelitis Optica Spectrum Disorder.

Background and PurposeOptical coherence tomography (OCT) and visual evoked potentials (VEPs) can be used to detect optic neuritis (ON). However, the comparative sensitivities of OCT and VEPs for detecting ON in neuromyelitis optica spectrum disorder (NMOSD) are unclear, and so we assessed these sensitivities.MethodsThis cross-sectional study included 73 patients with aquaporin-4 antibody-seropositive NMOSD, and 101 eyes with ON. The clinical characteristics, visual acuity (VA), Expanded Disability Status Scale (EDSS) scores, OCT peripapillary retinal nerve fiber layer (RNFL) thickness, and VEPs of the patients were evaluated.ResultsOCT and VEPs were abnormal in 68% and 73% of eyes with a history of ON, respectively, and in 2% and 9% of eyes without ON. Test sensitivities were influenced by the number of ON episodes: the OCT RNFL thickness and VEPs were abnormal in 50% and 67% of the eyes with first-ever ON episode, respectively (p=0.041), with the combination of both tests detecting abnormalities in up to 75% of the eyes. The sensitivities of the OCT RNFL thickness and VEPs increased to 95% and 83%, respectively, after the second or subsequent ON episode (p=0.06), with the combination of both tests detecting abnormalities in 95% of cases. The OCT RNFL thickness and VEP latency/amplitude were correlated with EDSS scores and VA.ConclusionsVEPs were superior for detecting subclinical or first-ever ON, while OCT was better for detecting eyes with multiple ON episodes. The correlations of OCT and VEPs with clinical disability measures indicate that these tests are potential markers of the disease burden in NMOSD.

MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.

Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission (r [9] = -0.78; P = .014) and at 3-month follow-up (r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment (r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord.

Robotic Quantification of Position Sense in Children With Perinatal Stroke

Background. Perinatal stroke is the leading cause of hemiparetic cerebral palsy. Motor deficits and their treatment are commonly emphasized in the literature. Sensory dysfunction may be an important contributor to disability, but it is difficult to measure accurately clinically. Objective. Use robotics to quantify position sense deficits in hemiparetic children with perinatal stroke and determine their association with common clinical measures. Methods. Case-control study. Participants were children aged 6 to 19 years with magnetic resonance imaging–confirmed unilateral perinatal arterial ischemic stroke or periventricular venous infarction and symptomatic hemiparetic cerebral palsy. Participants completed a position matching task using an exoskeleton robotic device (KINARM). Position matching variability, shift, and expansion/contraction area were measured with and without vision. Robotic outcomes were compared across stroke groups and controls and to clinical measures of disability (Assisting Hand Assessment) and sensory function. Results. Forty stroke participants (22 arterial, 18 venous, median age 12 years, 43% female) were compared with 60 healthy controls. Position sense variability was impaired in arterial (6.01 ± 1.8 cm) and venous (5.42 ± 1.8 cm) stroke compared to controls (3.54 ± 0.9 cm, P < .001) with vision occluded. Impairment remained when vision was restored. Robotic measures correlated with functional disability. Sensitivity and specificity of clinical sensory tests were modest. Conclusions. Robotic assessment of position sense is feasible in children with perinatal stroke. Impairment is common and worse in arterial lesions. Limited correction with vision suggests cortical sensory network dysfunction. Disordered position sense may represent a therapeutic target in hemiparetic cerebral palsy.

Subcortical grey matter volumes predict subsequent walking function in early multiple sclerosis

BackgroundAtrophy of subcortical grey matter structures has been reported to be associated with clinical measures of disability in multiple sclerosis (MS) patients. It is not clear if the degree of tissue loss in patients with very early MS is associated with changes in disability measures. ObjectiveTo study the association between subcortical grey matter structure volumes and clinical disability outcomes. MethodsRelapsing MS patients within 12months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36months of follow-up and serial brain MRI and clinical assessments. MRI metrics, including thalamic, putamen, caudate, pallidum and cerebellar cortical volume, were measured by an automated, custom-made FreeSurfer pipeline. Volumes were normalized for head size. Clinical measures included EDSS, MSFC scores and its components. Mixed model regression measured time trends and associations between imaging and clinical outcomes. Results42 patients with a mean follow-up of 30.6months were analyzed in this study. There was a statistically significant decrease in thalamus, caudate and putamen volumes, but not cerebellar cortical and pallidum volumes during the follow-up period. Baseline thalamus, caudate and putamen volumes predicted subsequent changes in the timed 25-ft walk test (p=0.036) and MSFC (p=0.024). There was a trend for an association between baseline caudate volume and subsequent change in the timed 25-ft walk test (p=0.084). No association between baseline imaging and subsequent EDSS changes were seen. ConclusionSubcortical grey matter volumes at early stages of MS are associated with subsequent changes in disability measures.