Common Clinical Measures Research Articles

Fiberglass dermatitis: clinical presentations, prevention, and treatment - a review of literatures.

Fiberglass dermatitis is a common form of occupational irritant contact dermatitis. Individuals experience a negative reaction to fiberglass fragments because of mechanical irritation. This review comprehensively analyzes the information in the existing literature on fiberglass dermatitis. Recognizing the different environmental risks factors for acquiring fiberglass dermatitis is necessary for better diagnosis and prevention. In addition to the identification of high-risk populations exposed to fiberglass particles, the common clinical presentation and preventive measures that can reduce the risk of acquiring fiberglass dermatitis are thoroughly discussed.

Functional Gait Measures Prediction by Spatiotemporal and Gait Symmetry in Individuals Post Stroke

Hemiplegic individuals often exhibit gait impairments. Current technologies allow for simple and fast acquisition of spatiotemporal gait parameters and gait Symmetry Indices (SI). Gait SI have been associated with instability and fall risk. These data may therefore prove an important addition to the already common conventional clinical measures, e.g. the 10 Meter Walk Test (10MWT), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), Six Minute Walk Test (6MWT) and the Motor Functional Independence Measure (MFIM). However, the prediction of these conventional clinical measures using spatiotemporal gait parameters and gait SI for individuals post stroke, has yet to be thoroughly investigated. We aimed to evaluate the correlation between spatiotemporal gait parameters and commonly-used clinical gait test scores, and to predict common clinical measures by spatiotemporal gait parameters in patients post stroke. In this cross-sectional retrospective study, spatiotemporal data were collected from files of adult patients (n = 70) post stroke, who performed one or more of the aforementioned functional evaluations within 1 year following stoke. Correlations were also performed for 53 of these subjects who performed all the tests in the subacute stage. High correlations (>0.7) were found between 10MWT, 6MWT and TUG and between diverse spatiotemporal parameters. Spatiotemporal parameters significantly predicted the 6MWT (R2 = .743), TUG (R2 = .668), 10MWT (R2 = .552), MFIM (R2 = .513), and the BBS (R2 = .556). An objective computerized evaluation producing spatiotemporal and symmetry gait parameters is compatible with common functional gait measures and might prove more advantageous in patient evaluation, since it provides additional multiple data, easily and quickly acquired.

The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies.

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56-0.89).

Cell Therapies for Parkinson's Disease.

Cell Therapies for Parkinson's Disease.

From suppression to stereoacuity: a composite binocular function score for clinical research.

This study aimed to validate a binocular function score that is based on common clinical measures of visual function, providing a more complete analysis of binocular outcomes, against laboratory-based dichoptic tests of threshold stereoacuity and depth of suppression. Scores on a composite binocular function (BF) score derived from clinical stereoacuity measures (Randot Preschool Stereoacuity Test and Randot Butterfly) and the Worth 4 Dot test were determined in adults (n=20; age 24.8±7.2years) and children (N=77; age 8.3±1.7years) with abnormal binocular vision from strabismus or amblyopia. Adults had threshold stereoacuity measured with a novel, computerised dichoptic psychophysical test of stereopsis. Depth of suppression (dichoptic eye chart inter-ocular contrast balance test) was determined in both adults and children. Clinical Randot stereoacuity was measurable in 50% of adult and 61% of child participants. Threshold stereoacuity was measurable in 65% of the adult participants. The presence of suppression or simultaneous perception (flat fusion or diplopia) was measurable in all participants, enabling assignment of a BF score to all participants in both groups. In adults, the BF score was highly correlated with the psychophysical threshold stereoacuity measure (ρ=0.71; p<0.001). In both adults and children, there was also a high correlation between the BF score and inter-ocular contrast balance (adult ρ=0.90; child ρ=0.86; p<0.001). The composite BF score is a convenient and valid scale of binocularity that can be used to extend the stereoacuity measure in cohorts where nil stereoacuity is common and thus could be considered as an outcome measure in clinical trials.

Prediction of Insulin Resistance with Anthropometric and Clinical Laboratory Measures in Nondiabetic Teenagers.

Adolescent obesity is an important risk factor for cardiovascular disease in part due to its relationship to type 2 diabetes. Therefore, screening for type 2 diabetes is recommended. However, since insulin resistance (IR) is an early precursor of diabetes, it would be beneficial if IR predictors from routine assessments could identify those at greatest metabolic risk before diabetes has developed. Adolescents aged 14-18 years with normal fasting plasma glucose (n = 252) were selected from the National Health and Nutrition Examination Survey 2013-2014. IR was estimated with homeostatic model assessment (HOMA). Multivariable linear/logistic regressions with demographic covariates assessed HOMA Index (HI)-determined IR associations with common clinical measurements. The constellation of body mass index (BMI) percentile (P < 0.0001), diastolic blood pressure (DBP, P = 0.0056), and serum alanine aminotransferase (ALT, P = 0.0295) predicted log-transformed HI; cholesterol, triglycerides, and high- and low-density lipoprotein cholesterol were not predictive. Secondary gender analyses indicated significant associations in males (BMI percentile, P = 0.0008; DBP, P = 0.0003; ALT, P = 0.0436), but only BMI percentile in females (P = 0.0001). After stratifying predictors at clinical thresholds, logistic regressions had increased specificity at HI's 85th percentile compared with its 75th [85th: area under curve (AUC) = 0.87, 75th: AUC = 0.80]. At the 85th HI percentile, IR was associated with these components [BMI percentile: adjusted odds ratio (aOR) = 34.31, 95% confidence interval (CI): 8.5-139.3; ALT: aOR = 11.36, 95% CI: 3.0-43.7; DBP: aOR = 7.73, 95% CI: 2.4-24.6]. In males, IR was associated with elevated BMI percentile (aOR 24.0) and ALT (aOR 23.9) and in females with elevated BMI percentile (aOR 45.8) and DBP (aOR 17.9). Three routine clinical assessments, BMI percentile, DBP, and ALT, predicted IR at HI's 75th and 85th percentiles in nondiabetic adolescents. Prospective validation may yield simple gender-specific screening identifying nondiabetic adolescents at greatest need of treatment intervention.

Characterization of Type 2 Diabetes into Five Sub-Types

This mini-review discuss the findings of Ahlqvist et al. [1] recently published results in Lancet, showing that they could further characterize type 2 diabetes into five subtypes. Participants with type 2 diabetes were from Scandinavia. Common clinical measures were used to stratify by clusters (e.g., age of onset, body mass index, A1c, glutamate acid decarboxylase antibodies, homeostatic model assessment2-insulin resistance and beta cell function).

Abstract A54: Multisystemic biologic risk index and cancer mortality: Differences by age group and race/ethnicity

Abstract Background: Multisystemic biologic risk is a clinically meaningful and practical surrogate for allostatic load, a metric of health risk used to express shared physiologic variance in multiple biologic systems, based on the hypothesis that recurrent exposure to external stressors leads to progressive dysregulation. Allostatic load and proxies capture the complex biologic cascade that occurs in cardiovascular, metabolic, and immune domains in response to chronic environmental and psychosocial stress. Previous research has demonstrated positive associations between higher indices of multisystemic biologic risk and declining cognition, physical function, and increased cardiovascular disease and mortality risk. However, we are not aware of any research testing the association between an index of multisystemic biologic risk and cancer outcomes. Aim: To examine the association of an index of multisystemic biologic risk (MSBRI) with cancer mortality using data from NHANES, and whether the association differed by race/ethnicity and age. Methods: In 8,996 participants in the NHANES III (year 1989-94), age ≥ 40 years with complete data, we created an index of MSBRI using biomarkers from domains of cardiovascular (pulse rate, blood pressure), metabolic (HOMA-IR, triglycerides, waist circumference), and immune (white blood cell count, c-reactive protein, fibrinogen level). Participants were assigned a score for each biomarker informed by clinical cut points, or based upon evidence in the literature indicating a threshold of risk for disease, and each marker within each domain was scored 0 (low), 1 (moderate), and 2 (high); a higher score represents hypothesized higher risk (range 0-14). Cancer mortality was ascertained from linkage to the National Death Index and participants were followed until 2011. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for overall cancer mortality risk with the MSBRI, adjusting for age, sex, education, income, U.S. region, insurance, physical activity, smoking, alcohol, and BMI. All models utilized the appropriate survey weights. Results: There were 621 cancer deaths during follow-up. Non-Hispanic black, Mexican-Americans, and women (overall) had higher average levels of the MSBRI. On a per-unit basis of the MSBRI, the HR (95% CI) for cancer mortality was 1.11 (1.02-1.21) for each unit of increase in score. Additionally, there was evidence that the association may differ by race/ethnicity. Among the non-Hispanic white sample, the per-unit HR (95% CI) for the MSBRI was 1.06 (1.00-1.12), whereas the HR (95% CI) for non-Hispanic Black, Mexican American, and “Other” (all other race ethnicities not including the aforementioned groups) were, respectively, 1.04 (0.95-1.13), 1.07 (0.98-1.18), and 1.23 (1.07-1.42). There was also evidence that the association may differ by age. The HR (95% CI) was 1.09 (0.97-1.24) for participants &amp;gt; 50 years of age, and 1.28 (1.05-1.56) for ages ≤ 50 years. Conclusions: There was strong, positive association between a higher score on an index of multisystemic biologic risk (proxy for allostatic load) and risk for cancer mortality in the NHANES III follow-up cohort. The results also suggest that the association may differ by race/ethnicity and age. These results are some of the first to link a proxy for allostatic load with a major cancer outcome, and because the formulation of the index relied upon common clinical measures, this index may have clinical utility for cancer prediction and thus clinical and population cancer prevention strategies. Citation Format: Teofilia Acheampong, Andrew Odegaard. Multisystemic biologic risk index and cancer mortality: Differences by age group and race/ethnicity [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A54.

O 058 – The Foot – Gait Profile Score (Foot – GPS (OFM))

Daily ambulation with a prosthesis often involves turning to negotiate within the home and community environments, however how people with lower limb loss perform turns is infrequently studied. Administering a common clinical outcome measure to capture turn performance data provides a convenient means of assessing this ubiquitous activity.What temporal-spatial parameters are exhibited by people with unilateral lower limb amputation while performing a 180˚ turn task?Forty community-ambulating subjects with unilateral lower limb amputation (20 transtibial amputees, 20 transfemoral amputees) performed the Component Timed-Up-and-Go (cTUG) test turning once in each direction, both toward the intact and toward the prosthetic limb. An instrumented walkway captured temporal-spatial parameters during performance of the 180˚ turn task of the cTUG, while a custom iPad application recorded time and number of steps to perform the turn. Comparisons between turn direction and level of amputation during the cTUG and temporal-spatial results were assessed.People with lower limb amputation spent more time on their intact limb while turning than their prosthetic limb regardless of the position of the intact limb, and those with transfemoral amputation spent significantly more time over the intact limb than those with transtibial amputation. Additionally, subjects with transfemoral amputation performed the turn significantly faster when turning with an inner intact limb.Amputees use different movement strategies with altered temporal-spatial characteristics to turn depending on the direction of the turn and the level of amputation. Clinical use of the cTUG could provide evidence supporting prosthetic prescription practice and introduction of novel physical therapy interventions for individuals with lower limb amputation.

Temporal-Spatial Values During a 180° Step Turn in People with Unilateral Lower Limb Amputation

BackgroundDaily ambulation with a prosthesis often involves turning to negotiate within the home and community environments, however how people with lower limb loss perform turns is infrequently studied. Administering a common clinical outcome measure to capture turn performance data provides a convenient means of assessing this ubiquitous activity. Research questionWhat temporal-spatial parameters are exhibited by people with unilateral lower limb amputation while performing a 180˚ turn task? MethodsForty community-ambulating subjects with unilateral lower limb amputation (20 transtibial amputees, 20 transfemoral amputees) performed the Component Timed-Up-and-Go (cTUG) test turning once in each direction, both toward the intact and toward the prosthetic limb. An instrumented walkway captured temporal-spatial parameters during performance of the 180˚ turn task of the cTUG, while a custom iPad application recorded time and number of steps to perform the turn. Comparisons between turn direction and level of amputation during the cTUG and temporal-spatial results were assessed. ResultsPeople with lower limb amputation spent more time on their intact limb while turning than their prosthetic limb regardless of the position of the intact limb, and those with transfemoral amputation spent significantly more time over the intact limb than those with transtibial amputation. Additionally, subjects with transfemoral amputation performed the turn significantly faster when turning with an inner intact limb. SignificanceAmputees use different movement strategies with altered temporal-spatial characteristics to turn depending on the direction of the turn and the level of amputation. Clinical use of the cTUG could provide evidence supporting prosthetic prescription practice and introduction of novel physical therapy interventions for individuals with lower limb amputation.

IN VITRO AND IN SILICO CHARACTERIZATION OF HUMAN NASAL EPITHELIAL ION AND LIQUID TRANSPORT MECHANISMS

IntroductionCystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, which codes for a widely expressed anion channel located in the apical membrane of epithelial cells. Loss of CFTR function results in an osmotic imbalance due to defective ion and water transport. Human bronchial epithelial cell cultures (HBE) are a well‐established experimental model of CF and show the same transport defects of the CF airway. More recently, human nasal epithelial cell cultures (HNE) have emerged as a novel alternative due to their accessibility and potential to allow for matched in vitro studies analogous to common clinical measurements. Here we implement a combination of experimental and computational approaches to facilitate the description of the ion and liquid transport functions of HNEs, and the role they may play in CF.MethodsWe have performed extensive characterization studies on well‐differentiated non‐CF HNE (n=9) and non‐CF HBE (n=12) to determine the extent of any possible physiological differences. This includes Ussing chamber studies to assess epithelial short‐circuit currents and resistance, apical volume regulation and paracellular flux assays, as measured by Tc99m‐DTPA (DTPA), to study response to volume challenges, and standard protein expression. We have also used this data to generate parametric fits of individual ion channel permeabilities, as predicted by a mathematical model of cell‐scale electrophysiology. Best parameter sets from each donor were estimated and compared against those from the opposite group to establish population differences according to a 2‐sample Kolmogorov‐Smirnov test.ResultsOur study shows HNE have a significant increase in the ENaC current (p&lt;0.05), and a decrease in stimulated CFTR current (p&lt;0.01) versus non‐CF HBEs. Similarly, thin film studies revealed significantly decreased DTPA retention, (p &lt; 0.05), as well as apical volume at 12 and 24 hrs following an apical volume challenge (p&lt;0.01). Donor‐specific parameter fits predicted statistically different parametric distributions for CFTR, ENaC, BKCa, and a basolateral Cl‐channel between the HBE and HNE population (p&lt;0.01). Of note are the increased basolateral Cl− and BKCA permeabilities relative to CFTR permeability.ConclusionOur studies showed non‐CF HNEs have higher liquid absorption rates than non‐CF HBEs. This behavior may be correlated with the lower CFTR dependent Cl− current also seen in HNE. It could suggest that HNEs operate at a different homeostatic level than HBEs due to environmental differences between the bronchi and the paranasal sinus, or perhaps it is the result of distinct functional levels of members of the epithelial electrophysiology network. Similar studies exploring the extent of these physiological differences in CF HNEs, and carriers of a single CF mutation, are currently underway.Support or Funding InformationSupported by NIH R01‐HL108929‐01, U01‐HL131046‐01, P30‐DK‐072506This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Statistical atlas-based descriptor for an early detection of optic disc abnormalities.

.Optic disc (OD) appearance in fundus images is one of the clinical indicators considered in the assessment of retinal diseases such as glaucoma. The cup-to-disc ratio (CDR) is the most common clinical measurement used to characterize glaucoma. However, the CDR only evaluates the relative sizes of the cup and the OD via their diameters. We propose to construct an atlas-based shape descriptor (ASD) to statistically characterize the geometric deformations of the OD shape and of the blood vessels’ configuration inside the OD region. A local representation of the OD region is proposed to construct a well-defined statistical atlas using nonlinear registration and statistical analysis of deformation fields. The shape descriptor is defined as being composed of several statistical measures from the atlas. Analysis of the average model and its principal modes of deformation are performed on a healthy population. The components of the ASD show a significant difference between pathological and healthy ODs. We show that the ASD is able to characterize healthy and glaucomatous OD regions. The deviation map extracted from the atlas can be used to assist clinicians in an early detection of deformation abnormalities in the OD region.

Association of Urinary Citrate With Acid-Base Status, Bone Resorption, and Calcium Excretion in Older Men and Women

Elevated urine net acid excretion (NAE), indicative of subclinical metabolic acidosis, has been associated with higher bone turnover. Urine citrate, which is a common clinical measure, changes in response to acid-base status but its association with bone turnover is uncertain. We evaluated the association between change in urine citrate and change in bone turnover and calcium excretion. A total of 233 healthy men and women ≥60 years old were randomly assigned to 1.0 mmol/kg/d potassium bicarbonate (KHCO3), 1.5 mmol/kg/d KHCO3, or placebo for 84 days. Urine citrate, NAE, N-telopeptide of collagen type-I (NTX), calcium excretion, and serum amino-terminal propeptide of type 1 procollagen (P1NP) were measured before and after intervention. Urine citrate increased dose dependently after KHCO3 supplementation (P trend < 0.001). The urine citrate change was significantly inversely associated with P1NP change (P = 0.021) but not with change in NTX (P = 0.051) or calcium excretion (P = 0.652). The NAE change was positively associated with change in NTX and calcium excretion (P ≤ 0.003) but not with change in P1NP (P = 0.051). When the urine citrate change and NAE change were included in the same model, the urine citrate change was not associated with change in NTX, calcium excretion, or serum P1NP (P ≥ 0.086), whereas change in NAE remained associated with change in NTX and calcium excretion (P ≤ 0.003). Urine citrate may not be a suitable alternative to NAE when assessing acid-base status in relation to bone turnover in older adults.

Systematic review of peer education intervention programmes among individuals with type 2 diabetes.

To systematically review published randomised controlled trials of peer education interventions among adults with type 2 diabetes. Systematic reviews have shown mixed results for peer support interventions to improve diabetes self-management. Given the effectiveness of diabetes education by healthcare professionals, peer education interventions may be a useful alternative approach. This review addressed that gap. Systematic review. A systematic search of published randomised controlled trials between 2006-2016 was conducted using the keywords diabetes, type 2 diabetes, randomised controlled trials, self-management, peer education and peer support. The methodological quality of each study was assessed using the Jadad scale. Seven studies were included in the final review, and the Jadad scores ranged from 8-10 of a possible 13 points. There was no consistent design, setting, or outcome measurement among the studies. There were two types of peer education interventions compared to traditional diabetes education: face-to-face or a combination of face-to-face and telephone/texting. The most common clinical outcome measure was HbA1c. Two of six studies showed statistically significant improvement in HbA1c between intervention and control groups. An increase in diabetes knowledge was also statistically significant in two of five studies. Peer education could be successful in improving clinical outcomes. No evidence was found indicating that healthcare provider education was superior in regard to clinical knowledge or behavioural or psychological outcome measures than peer education. HbA1c was statistically significantly lower in some peer education groups compared to control groups. There is evidence that peer education can be useful in achieving positive clinical outcomes such as decreasing HbA1c levels and increasing diabetes knowledge. A certified diabetes educator or a trained healthcare professional should not be overlooked though when using peer educators.

Research Techniques Made Simple: Cost-Effectiveness Analysis

Cost-effectiveness analysis (CEA) is a research method used to determine the clinical benefit-to-cost ratio of a given intervention. CEA offers a standardized means of comparing cost-effectiveness among interventions. Changes in quality-adjusted life-years, disability-adjusted life-years, or survival and mortality are some of the common clinical benefit measures incorporated into CEA. Because accounting for all associated costs and benefits of an intervention is complex and potentially introduces uncertainty into the analysis, sensitivity analyses can be performed to test the analytic model under varying conditions. CEA informs the identification of high-value clinical practices and can be used to evaluate preventative, diagnostic, and therapeutic interventions in dermatology.

Liver fibrosis scores predict liver disease mortality in the United States population.

In the United States population, higher liver fibrosis scores were associated with increased liver disease and overall mortality. Liver health management with common clinical measures of fibrosis risk stratification merits further investigation. (Hepatology 2017;66:84-95).

Reliability and Minimum Detectable Change for Common Clinical Physical Function Tests in Sarcopenic Men and Women.

To determine the test-retest reliability and minimum detectable change scores for seven common clinical measurements of muscle strength and physical function in a multiethnic sample of sarcopenic, malnourished men and women. Each participant visited the laboratory seven times over 25 to 26 weeks. Reliability was assessed for each measurement from Familiarization 1 to Familiarization 2 (R1), Familiarization 2 to baseline testing (R2), Familiarization 3 to 12-week testing (R3), and Familiarization 4 to 24-week testing (R4). Data were collected during a clinical trial at 23 sites in the United States, Belgium, Italy, Mexico, Poland, Spain, Switzerland, and the United Kingdom. Sarcopenic, malnourished, older adults (N = 257; n = 98 men aged 76.8 ± 6.3, n = 159 women aged 75.9 ± 6.6). During each visit, participants completed the Short Physical Performance Battery (SPBB) and isometric handgrip and isokinetic leg extensor and flexor strength testing at a slow (1.05 rad/s) and fast (3.15 rad/s) velocity. Handgrip strength, gait speed, SPPB score, and isokinetic leg extension and flexion peak torque (PT) had intraclass correlation coefficients (ICCs) that were significantly greater than 0 (all ≥0.59) at R1, R2, R3, and R4, although most of these variables demonstrated systematic increases at R1, and several exhibited systematic variability beyond the baseline testing session. The ICCs and standard errors of the measurement (SEMs) generally improved with familiarization, which emphasizes the need for at least one familiarization trial for these measurements in sarcopenic, malnourished older adults. A three tier-approach to interpreting the clinical importance of statistically significant results that includes null hypothesis testing, examination and interpretation of the effect magnitude, and comparison of individual changes with the SEM and minimum detectable change of the measurements used is recommended.

Central venous pressure up date: What is it good for?

Central venous pressure is a very common clinical measurement, but it is frequently misunderstood and misused. As with all hemodynamic measurements, it is important to understand its basic principles. Use of CVP for the estimating of cardiac preload and volume status requires an understanding of its determinants. Actually, CVP and cardiac output are determined by the interaction of two function curves: the cardiac function curve and the return curve. There are no data to support the widespread practice of using central venous pressure (CVP) to guide fluid therapy. But, CVP is readily available in many patients. The fact that an isolated measurement of CVP does not predict the response to a fluid bolus does not reduce its importance as a hemodynamic variable. CVP may be usefull taken in the context of the whole clinical picture and over time.

Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis.

At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology.Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0–6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging.Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were significantly related to corticospinal tract fractional anisotropy (r > 0.26; p < 0.04) and magnetization transfer ratio (r > 0.29; p < 0.03) measures. Although the Expanded Disability Status Scale was highly correlated with walking measures, it was not significantly related to either corticospinal tract fractional anisotropy or magnetization transfer ratio (p > 0.05). Walk velocity was a significant contributor to magnetization transfer ratio (p = 0.006) and fractional anisotropy (p = 0.011) in regression modeling that included both quantitative measures of function and basic clinical information.Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking along with tract-specific imaging methods may improve our ability to monitor disease change over time, with intervention, and provide needed guidelines for developing more effective targeted rehabilitation strategies.

Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury.

Restoration of walking ability is an area of great interest in the rehabilitation of persons with spinal cord injury. Because many cortical, subcortical, and spinal neural centers contribute to locomotor function, it is important that intervention strategies be designed to target neural elements at all levels of the neuraxis that are important for walking ability. While to date most strategies have focused on activation of spinal circuits, more recent studies are investigating the value of engaging supraspinal circuits. Despite the apparent potential of pharmacological, biological, and genetic approaches, as yet none has proved more effective than physical therapeutic rehabilitation strategies. By making optimal use of the potential of the nervous system to respond to training, strategies can be developed that meet the unique needs of each person. To complement the development of optimal training interventions, it is valuable to have the ability to predict future walking function based on early clinical presentation, and to forecast responsiveness to training. A number of clinical prediction rules and association models based on common clinical measures have been developed with the intent, respectively, to predict future walking function based on early clinical presentation, and to delineate characteristics associated with responsiveness to training. Further, a number of variables that are correlated with walking function have been identified. Not surprisingly, most of these prediction rules, association models, and correlated variables incorporate measures of volitional lower extremity strength, illustrating the important influence of supraspinal centers in the production of walking behavior in humans.