Changes In Clinical Measures Research Articles

Validation of Quantitative Scores Derived From Motor Evoked Potentials in the Assessment of Primary Progressive Multiple Sclerosis: A Longitudinal Study.

Objective: To evaluate the sensitivity to change of differently calculated quantitative scores from motor evoked potentials (MEP) in patients with primary progressive multiple sclerosis (PPMS).Methods: Twenty patients with PPMS had MEP to upper and lower limbs at baseline, years 1 and 2 measured in addition to clinical assessment [Expanded Disability Status Scale (EDSS), ambulation score]; a subsample (n = 9) had a nine-hole peg test (NHPT) and a timed 25-foot walk (T25FW). Quantitative MEP scores for upper limbs (qMEP-UL), lower limbs (qMEP-LL), and all limbs (qMEP) were calculated in three different ways, based on z-transformed central motor conduction time (CMCT), shortest corticomuscular latency (CxM-sh), and mean CxM (CxM-mn). Changes in clinical measures and qMEP metrics were analyzed by repeated-measures analysis of variance (rANOVA), and a factor analysis was performed on change in qMEP metrics.Results: Expanded Disability Status Scale and ambulation score progressed in the rANOVA model (p < 0.05; post-hoc comparison baseline–year 2, p < 0.1). Lower limb and combined qMEP scores showed significant deterioration of latency (p < 0.01, MEP-LL_CxM-sh: p < 0.05) and in post-hoc comparisons (baseline–year 2, p < 0.05), qMEP_CxM-mn even over 1 year (p < 0.05). Effect sizes were higher for qMEP scores than for clinical measures, and slightly but consistently higher when based on CxM-mn compared to CxM-sh or CMCT. Subgroup analysis yielded no indication of higher sensitivity of timed clinical measures over qMEP scores. Two independent factors were detected, the first mainly associated with qMEP-LL, the second with qMEP-UL, explaining 65 and 29% of total variability, respectively.Conclusions: Deterioration in qMEP scores occurs earlier than EDSS progression in patients with PPMS. Upper and lower limb qMEP scores contribute independently to measuring change, and qMEP scores based on mean CxM are advantageous. The capability to detect subclinical changes longitudinally is a unique property of EP and complementary to clinical assessment. These features underline the role of EP as candidate biomarkers to measure effects of therapeutic interventions in PPMS.

Changes in clinical measures and tissue adaptations in collegiate swimmers across a competitive season

Competitive swimmers incur shoulder pain and injury. Physical characteristics such as shoulder range of motion (ROM) and endurance and tissue adaptations such as posterior capsule thickness (PCT) may be risk factors in addition to high training volume. 1) To identify the most provocative special test and prevalence of positive special tests for shoulder impingement tests in a group of collegiate swimmers, (2) to assess shoulder pain and disability, internal rotation (IR) and external rotation, and horizontal adduction (HADD) ROM and posterior shoulder endurance longitudinally over a competitive collegiate season, and (3) determine if there is a relationship between swimming yardage, supraspinatus tendon organization, and PCT. Thirty Division III swimmers were tested poolside at the beginning (T1), middle (T2), and end (T3) of their season. Dependent variables included pain and disability, shoulder ROM, Posterior Shoulder Endurance Test (PSET) value, and PCT. Analyses of variance with follow-up t tests compared measures over time, and Pearson correlation coefficients were performed. Despite increased swimming yardage, disability was reduced from T1 to T3 (P = .003). There was a reduction in bilateral IR and HADD ROM from T1 to T3. PSET values increased on the right from T1 to T3 (P = .014). There was a significant positive correlation between swimming yardage at T1 and T2 and PCT at T3 (P = .034, P = .028). A loss of shoulder IR and HADD was observed across the season concurrent with less swimming-related disability, which may indicate a favorable adaptation. Improved PSET scores over the season is consistent with prior research linking endurance and less pain and disability.

Changes in Clinical Measures and Tissue Adaptations in Collegiate Swimmers Across a Competitive Season

Background: Due to high training volume, competitive swimmers incur shoulder pain and injury1, but certain physical characteristics, such as shoulder ROM and endurance, and tissue adaptations such as posterior capsule thickness (PCT) and supraspinatus tendon structure may also be risk factors. Decreased endurance and ROM have been found in competitive swimmers along with being related to pain2. However, no longitudinal studies have examined pain and disability, range of motion, training volume, shoulder endurance and tendon structure over the course of a competitive season.&#x0D; Purpose: The purpose of this study was to: 1) to assess shoulder pain and disability, internal rotation (IR) and external rotation (ER) and horizontal adduction (HADD) ROM, and posterior shoulder endurance longitudinally over a competitive collegiate season, and 2) determine if there is a relationship between swimming yardage, supraspinatus tendon organization and posterior capsule thickness.&#x0D; Methods: 17 male and 13 female Division III swimmers aged 19.6 ± 1.1 years participated. Pain and disability were assessed using the Penn Shoulder Score and the Disability of Arm Shoulder Hand sports module. Internal rotation (IR), external rotation (ER), and horizontal adduction (HA) were measured using a digital inclinometer. Shoulder endurance was measured using the Posterior Shoulder Endurance Test (PSET). Anterior, center, and posterior supraspinatus tendon images were collected by locating the anterior aspect of the tendon insertion and moving posteriorly. The ultrasound images were analyzed using custom MATlab software to quantify tissue organization. All measures were found in the beginning (T1), middle (T2), and end (T3) of the season. Repeated measure ANOVAs were used to compare longitudinal changes across time. If p-values were found to be ≤ 0.05, follow-up paired t-tests with Bonferroni corrections were used to compare T1, T2, and T3. This protocol was IRB-approved and participants signed a written consent form.&#x0D; Results: An increase in swimming yardage from T1 to T2 was followed by a significant decrease in yardage to finish the swimming season (Table 1). Disability decreased and endurance increased throughout the season with no observed changes in pain. IR and HA ROM decreased significantly between all timepoint comparisons. Tendon banding frequency did not change over time (Table 2).&#x0D; Discussion: Large amounts of IR during the pull phase and late initiation of ER during the recovery phase have been associated with a high risk of impingement4. The relationship between pain, disability, and range of motion may suggest that a reduction of IR could protect the swimmers’ shoulder by limiting impingement through the pull and recovery phases. However, further investigation is required to confirm. The lack of statistical significance longitudinally in tendon organization is not surprising since there were no changes in pain, a decrease in disability, and an increase in endurance.&#x0D; Conclusion/Clinical Relevance: Further research is required to understand the relationship between training volume, tendon organization, and disability. Collegiate swimmers demonstrate increased endurance and decreased disability over the course of the season. It may suggest that the loss of ROM is a positive adaptation and may be protective.

Amyloid Imaging and Longitudinal Clinical Progression in Dementia With Lewy Bodies

Significant amyloid deposition is present in approximately half of all cases of dementia with Lewy bodies (DLB). We sought to determine whether amyloid deposition was associated with more rapid clinical decline over 1 year. Twenty-eight participants had a baseline clinical assessment and amyloid PET scan, followed by a further clinical assessment after 1 year. Changes in clinical measures were compared with amyloid deposition assessed by visual rating and cortical standardized uptake value ratio. Amyloid deposition on visual rating was associated with greater decline in Mini-Mental State Examination and daily function over 1 year. There was no correlation between cortical standardized uptake value ratio and clinical measures. This study provides further evidence for a link between amyloid deposition and clinical progression in DLB. Pathologies such as amyloid, and their interaction with α-synuclein, remain possible treatment targets in DLB.

Longitudinal flortaucipir ([18F]AV-1451) PET imaging in primary progressive apraxia of speech

Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.

Improved walking function in laboratory does not guarantee increased community walking in stroke survivors: Potential role of gait biomechanics

Reduced daily stepping in stroke survivors may contribute to decreased functional capacity and increased mortality. We investigated the relationships between clinical and biomechanical walking measures that may contribute to changes in daily stepping activity following physical interventions provided to participants with subacute stroke. Following ≤40 rehabilitation sessions, 39 participants were categorized into three groups: responders/retainers increased daily stepping >500 steps/day post-training (POST) without decreases in stepping at 2–6 month follow-up (F/U); responders/non-retainers increased stepping at POST but declined >500 steps/day at F/U; and, non-responders did not change daily stepping from baseline testing (BSL). Gait kinematics and kinetics were evaluated during graded treadmill assessments at BSL and POST. Clinical measures of gait speed, timed walking distance, balance and balance confidence were measured at BSL, POST and F/U. Between-group comparisons and regression analyses were conducted to predict stepping activity from BSL and POST measurements. Baseline and changes in clinical measures of walking demonstrated selective associations with stepping, although kinematic measures appeared to better discriminate responders. Specific measures suggest greater paretic vs non-paretic kinematic changes in responders with training, although greater non-paretic changes predicted greater gains (i.e., smaller declines) in stepping in retainers at F/U. No kinetic variables were primary predictors of changes in stepping activity at POST or F/U. The combined findings indicate specific biomechanical assessments may help differentiate changes in daily stepping activity post-stroke.

Treatment monitoring as a component of psychologically informed physical therapy: A case series of patients at high risk for persistent low back pain related disability

BackgroundPsychologically Informed Physical Therapy (PIPT) aims to identify individuals at high risk for transitioning to chronicity and merge impairment-focused physical therapy with cognitive behavioral therapy principles. Treatment monitoring is an important part of PIPT and involves identifying changes in clinical measures to inform clinical decision making. ObjectivesThe purpose of this case series is to describe treatment monitoring using psychological and physical impairment measures for patients identified as ‘high-risk’ for persistent low back pain (LBP) related disability. DesignSecondary analysis of patients (n = 23) identified as ‘high-risk’ using the STarT Back Tool and enrolled in two-phased, sequential study that evaluated feasibility and generated preliminary PIPT treatment effects for 4-week clinical outcomes. MethodPhysical therapists (n = 5) used psychological [Fear-Avoidance Beliefs Questionnaire (FABQ-PA, FABQ-W), Tampa Scale for Kinesiophobia (TSK-11), Pain Catastrophizing Scale (PCS) and Fear of Daily Activities Questionnaire (FDAQ)] and the Physical Impairment Index (PII) measures for PIPT treatment monitoring. Clinical outcome measures [Numerical Pain Rating Scale (NPRS), Oswestry Disability Index (ODI)] were administered at intake and 4-weeks later. Linear regression models evaluated independent contribution of intake and 4-week changes in psychological measures and PII scores as predictors of 4-week NPRS and ODI scores. ResultsFABQ-PA and PCS changes provided largest contributions to prediction of 4-week ODI scores. Treatment monitoring measures did not explain additional variability in 4-week NPRS scores after baseline scores were considered. ConclusionsFor patients at high risk for persistent LBP psychological measures consistently performed better as treatment monitoring variables compared to physical impairment measures. Treatment monitoring for PIPT with psychological measures provides opportunities to refine prediction of disability outcomes. Findings from this exploratory case series should be interpreted with caution based on its small sample size and lack of statistical power which prohibits definitive conclusions to be made on any of the treatment monitoring measures.

The Health and economic effects of light rail lines: design, methods, and protocol for a natural experiment

BackgroundThe health impacts of community design have been studied extensively over the past two decades. In particular, public transportation use is associated with more walking between transit stops and shops, work, home and other destinations. Change in transit access has been linked with physical activity and obesity but seldom to health outcomes and associated costs, especially within a causal framework. Health related fiscal impacts of transit investment should be a key consideration in major transit investment decisions.MethodsThe Rails & Health study is a natural experiment evaluating changes in clinical measures, health care utilization and health care costs among Kaiser Permanente Northwest (KPNW) members following the opening of a new light rail transit (LRT) line in Portland, Oregon. The study is prospectively following 3036 adults exposed to the new LRT line and a similar cohort of 4386 adults who do not live close to the new line. Individual-level outcomes and covariates are extracted from the electronic medical record at KPNW, including member demographics and comorbidities, blood pressure, body mass index, lipids, glycosylated hemoglobin, and health care utilization and costs. In addition, participants are surveyed about additional demographics, travel patterns, physical activity (PA), and perceived neighborhood walkability. In a subsample of the study population, we are collecting direct measures of travel-related behavior—physical activity (accelerometry), global positioning system (GPS) tracking, and travel diaries—to document mechanisms responsible for observed changes in health outcomes and cost. Comprehensive measures of the built environment at baseline and after rail construction are also collected. Statistical analyses will (1) examine the effects of opening a new LRT line on chronic disease indicators, health care utilization, and health care costs and (2) evaluate the degree to which observed effects of the LRT line on health measures and costs are mediated by changes in total and transportation-associated PA.DiscussionThe results of the Rails & Health study will provide urban planners, transportation engineers, health practitioners, developers, and decision makers with critical information needed to document how transit investments impact population health and related costs.

Objective Assessment of Disparity Vergence after Treatment of Symptomatic Convergence Insufficiency in Children.

SIGNIFICANCEThis first report of the use of objective measures of disparity vergence as outcome measures for symptomatic convergence insufficiency in children provides additional information that is not accessible with clinical tests. The study results also demonstrate that objective measures of vergence could be used in future randomized clinical trials of binocular vision disorders with children.PURPOSEThis study was designed to evaluate changes in objective measures of disparity vergence after office-based vergence/accommodative therapy (OBVAT) for convergence insufficiency in children 12 to 17 years old.METHODSIn this prospective trial, we recruited 10 participants with normal binocular vision and 12 with convergence insufficiency. All participants with convergence insufficiency were treated with 12 weeks of OBVAT. The primary outcome measure was average peak velocity for 4° symmetrical convergence steps. Other objective outcome measures of disparity vergence included time to peak velocity, latency, and accuracy. Changes in clinical measures (near point of convergence, positive fusional vergence at near) and symptoms were evaluated.RESULTSThere was a statistically significant increase in peak velocity and more accurate response amplitude to 4° symmetrical convergence step stimuli after OBVAT compared with baseline measurements. Near point of convergence, positive fusional vergence, and symptoms also statistically significantly improved after OBVAT. Ten of the 12 participants met clinical success criteria.CONCLUSIONSIn this prospective study on the treatment of symptomatic convergence insufficiency in children in which both clinical and objective eye movement measurements were used to evaluate the results of treatment, significant changes were found in symptoms and both clinical and objective measures of disparity vergence after completion of OBVAT in children with symptomatic convergence insufficiency.

5.38 Effects of Antidepressant Treatment on Clinical Measures of Attention in Adolescents With Depression

Previous studies have reported mixed findings on deficits in executive function and attention in youth with MDD. Moreover, longitudinal effects of SSRI on executive function and attention in adolescents with MDD are relatively unknown. This study aimed to investigate the changes in clinical measures of attention in youth with MDD treated with SSRI.

Does Glaucoma Alter Eye Movements When Viewing Images of Natural Scenes? A Between-Eye Study.

To investigate whether glaucoma produces measurable changes in eye movements. Fifteen glaucoma patients with asymmetric vision loss (difference in mean deviation [MD] > 6 dB between eyes) were asked to monocularly view 120 images of natural scenes, presented sequentially on a computer monitor. Each image was viewed twice-once each with the better and worse eye. Patients' eye movements were recorded with an Eyelink 1000 eye-tracker. Eye-movement parameters were computed and compared within participants (better eye versus worse eye). These parameters included a novel measure: saccadic reversal rate (SRR), as well as more traditional metrics such as saccade amplitude, fixation counts, fixation duration, and spread of fixation locations (bivariate contour ellipse area [BCEA]). In addition, the associations of these parameters with clinical measures of vision were investigated. In the worse eye, saccade amplitude\(\def\upalpha{\unicode[Times]{x3B1}}\)\(\def\upbeta{\unicode[Times]{x3B2}}\)\(\def\upgamma{\unicode[Times]{x3B3}}\)\(\def\updelta{\unicode[Times]{x3B4}}\)\(\def\upvarepsilon{\unicode[Times]{x3B5}}\)\(\def\upzeta{\unicode[Times]{x3B6}}\)\(\def\upeta{\unicode[Times]{x3B7}}\)\(\def\uptheta{\unicode[Times]{x3B8}}\)\(\def\upiota{\unicode[Times]{x3B9}}\)\(\def\upkappa{\unicode[Times]{x3BA}}\)\(\def\uplambda{\unicode[Times]{x3BB}}\)\(\def\upmu{\unicode[Times]{x3BC}}\)\(\def\upnu{\unicode[Times]{x3BD}}\)\(\def\upxi{\unicode[Times]{x3BE}}\)\(\def\upomicron{\unicode[Times]{x3BF}}\)\(\def\uppi{\unicode[Times]{x3C0}}\)\(\def\uprho{\unicode[Times]{x3C1}}\)\(\def\upsigma{\unicode[Times]{x3C3}}\)\(\def\uptau{\unicode[Times]{x3C4}}\)\(\def\upupsilon{\unicode[Times]{x3C5}}\)\(\def\upphi{\unicode[Times]{x3C6}}\)\(\def\upchi{\unicode[Times]{x3C7}}\)\(\def\uppsy{\unicode[Times]{x3C8}}\)\(\def\upomega{\unicode[Times]{x3C9}}\)\(\def\bialpha{\boldsymbol{\alpha}}\)\(\def\bibeta{\boldsymbol{\beta}}\)\(\def\bigamma{\boldsymbol{\gamma}}\)\(\def\bidelta{\boldsymbol{\delta}}\)\(\def\bivarepsilon{\boldsymbol{\varepsilon}}\)\(\def\bizeta{\boldsymbol{\zeta}}\)\(\def\bieta{\boldsymbol{\eta}}\)\(\def\bitheta{\boldsymbol{\theta}}\)\(\def\biiota{\boldsymbol{\iota}}\)\(\def\bikappa{\boldsymbol{\kappa}}\)\(\def\bilambda{\boldsymbol{\lambda}}\)\(\def\bimu{\boldsymbol{\mu}}\)\(\def\binu{\boldsymbol{\nu}}\)\(\def\bixi{\boldsymbol{\xi}}\)\(\def\biomicron{\boldsymbol{\micron}}\)\(\def\bipi{\boldsymbol{\pi}}\)\(\def\birho{\boldsymbol{\rho}}\)\(\def\bisigma{\boldsymbol{\sigma}}\)\(\def\bitau{\boldsymbol{\tau}}\)\(\def\biupsilon{\boldsymbol{\upsilon}}\)\(\def\biphi{\boldsymbol{\phi}}\)\(\def\bichi{\boldsymbol{\chi}}\)\(\def\bipsy{\boldsymbol{\psy}}\)\(\def\biomega{\boldsymbol{\omega}}\)\(\def\bupalpha{\unicode[Times]{x1D6C2}}\)\(\def\bupbeta{\unicode[Times]{x1D6C3}}\)\(\def\bupgamma{\unicode[Times]{x1D6C4}}\)\(\def\bupdelta{\unicode[Times]{x1D6C5}}\)\(\def\bupepsilon{\unicode[Times]{x1D6C6}}\)\(\def\bupvarepsilon{\unicode[Times]{x1D6DC}}\)\(\def\bupzeta{\unicode[Times]{x1D6C7}}\)\(\def\bupeta{\unicode[Times]{x1D6C8}}\)\(\def\buptheta{\unicode[Times]{x1D6C9}}\)\(\def\bupiota{\unicode[Times]{x1D6CA}}\)\(\def\bupkappa{\unicode[Times]{x1D6CB}}\)\(\def\buplambda{\unicode[Times]{x1D6CC}}\)\(\def\bupmu{\unicode[Times]{x1D6CD}}\)\(\def\bupnu{\unicode[Times]{x1D6CE}}\)\(\def\bupxi{\unicode[Times]{x1D6CF}}\)\(\def\bupomicron{\unicode[Times]{x1D6D0}}\)\(\def\buppi{\unicode[Times]{x1D6D1}}\)\(\def\buprho{\unicode[Times]{x1D6D2}}\)\(\def\bupsigma{\unicode[Times]{x1D6D4}}\)\(\def\buptau{\unicode[Times]{x1D6D5}}\)\(\def\bupupsilon{\unicode[Times]{x1D6D6}}\)\(\def\bupphi{\unicode[Times]{x1D6D7}}\)\(\def\bupchi{\unicode[Times]{x1D6D8}}\)\(\def\buppsy{\unicode[Times]{x1D6D9}}\)\(\def\bupomega{\unicode[Times]{x1D6DA}}\)\(\def\bupvartheta{\unicode[Times]{x1D6DD}}\)\(\def\bGamma{\bf{\Gamma}}\)\(\def\bDelta{\bf{\Delta}}\)\(\def\bTheta{\bf{\Theta}}\)\(\def\bLambda{\bf{\Lambda}}\)\(\def\bXi{\bf{\Xi}}\)\(\def\bPi{\bf{\Pi}}\)\(\def\bSigma{\bf{\Sigma}}\)\(\def\bUpsilon{\bf{\Upsilon}}\)\(\def\bPhi{\bf{\Phi}}\)\(\def\bPsi{\bf{\Psi}}\)\(\def\bOmega{\bf{\Omega}}\)\(\def\iGamma{\unicode[Times]{x1D6E4}}\)\(\def\iDelta{\unicode[Times]{x1D6E5}}\)\(\def\iTheta{\unicode[Times]{x1D6E9}}\)\(\def\iLambda{\unicode[Times]{x1D6EC}}\)\(\def\iXi{\unicode[Times]{x1D6EF}}\)\(\def\iPi{\unicode[Times]{x1D6F1}}\)\(\def\iSigma{\unicode[Times]{x1D6F4}}\)\(\def\iUpsilon{\unicode[Times]{x1D6F6}}\)\(\def\iPhi{\unicode[Times]{x1D6F7}}\)\(\def\iPsi{\unicode[Times]{x1D6F9}}\)\(\def\iOmega{\unicode[Times]{x1D6FA}}\)\(\def\biGamma{\unicode[Times]{x1D71E}}\)\(\def\biDelta{\unicode[Times]{x1D71F}}\)\(\def\biTheta{\unicode[Times]{x1D723}}\)\(\def\biLambda{\unicode[Times]{x1D726}}\)\(\def\biXi{\unicode[Times]{x1D729}}\)\(\def\biPi{\unicode[Times]{x1D72B}}\)\(\def\biSigma{\unicode[Times]{x1D72E}}\)\(\def\biUpsilon{\unicode[Times]{x1D730}}\)\(\def\biPhi{\unicode[Times]{x1D731}}\)\(\def\biPsi{\unicode[Times]{x1D733}}\)\(\def\biOmega{\unicode[Times]{x1D734}}\)\((P = 0.012; - 13\% \)) and BCEA \((P = 0.005; - 16\% )\) were smaller, while SRR was greater (\(P = 0.018; + 16\% \)). There was a significant correlation between the intereye difference in BCEA, and differences in MD values (\({\rm{Spearman^{\prime} s}}\ r = 0.65;P = 0.01\)), while differences in SRR were associated with differences in visual acuity (\({\rm{Spearman^{\prime} s}}\ r = 0.64;P = 0.01\)). Furthermore, between-eye differences in BCEA were a significant predictor of between-eye differences in MD: for every 1-dB difference in MD, BCEA reduced by 6.2% (95% confidence interval, 1.6%-10.3%). Eye movements are altered by visual field loss, and these changes are related to changes in clinical measures. Eye movements recorded while passively viewing images could potentially be used as biomarkers for visual field damage.

Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes

Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.

Tildrakizumab: monoclonal antibody against IL-23p19 for moderate to severe psoriasis.

Tildrakizumab is a monoclonal antibody that binds to the p19 subunit of interleukin (IL)-23. Studies examining affected skin in psoriatic patients showed significant changes in the cellular, cytokine and gene expression profiles of psoriatic lesions as a result of treatment with tildrakizumab, as well as significant changes in clinical measures of disease activity. These studies demonstrated significant clinical responses in psoriasis with significant improvements found in the percentage of patients achieving a Physician Global Assessment score of 0 or 1, and a 75%, 90% or 100% improvement in the Psoriasis Area and Severity Index (PASI 75, PASI 90, PASI 100). These changes were accompanied by a low frequency of adverse effects. This combination of efficacy and safety led to the approval of tildrakizumab in 2018 by the U.S. Food and Drug Administration (FDA) for use in adult patients with moderate to severe psoriasis.

Guselkumab: human monoclonal antibody against interleukin-23 for moderate to severe psoriasis.

Guselkumab is an antibody designed to bind to the p19 subunit of interleukin-23 (IL-23). Detailed studies of affected skin in patients with psoriasis demonstrated that guselkumab induced significant changes in the cellular, cytokine and gene expression profiles of psoriatic lesions accompanied by significant changes in clinical measures of disease activity. The significant clinical response in psoriasis was demonstrated in these studies by significant improvement as reflected in the percentage of patients achieving a Physicians Global Assessment score of 0 or 1, and a 90% or 100% improvement in the Psoriasis Area and Severity Index (PASI 90, PASI 100), as well as changes in quality of life measures. These changes were accompanied by a low frequency of adverse effects. The combination of efficacy and safety led to its approval by the Food and Drug Administration (FDA) for use in patients with moderate to severe psoriasis.

Objective Assessment of Vergence after Treatment of Concussion-Related CI: A Pilot Study.

To evaluate changes in objective measures of disparity vergence after office-based vision therapy (OBVT) for concussion-related convergence insufficiency (CI) and determine the feasibility of using this objective assessment as an outcome measure in a clinical trial. This was a prospective, observational trial. All participants were treated with weekly OBVT with home reinforcement. Participants included two adolescents and three young adults with concussion-related, symptomatic CI. The primary outcome measure was average peak velocity for 4° symmetrical convergence steps. Other objective outcome measures of disparity vergence included time to peak velocity, latency, accuracy, settling time, and main sequence. We also evaluated saccadic eye movements using the same outcome measures. Changes in clinical measures (near point of convergence, positive fusional vergence at near, Convergence Insufficiency Symptom Survey [CISS] score) were evaluated. There were statistically significant and clinically meaningful changes in all clinical measures for convergence. Four of the five subjects met clinical success criteria. For the objective measures, we found a statistically significant increase in peak velocity, response accuracy to 4° symmetrical convergence and divergence step stimuli, and the main sequence ratio for convergence step stimuli. Objective saccadic eye movements (5 and 10°) appeared normal pre-OBVT and did not show any significant change after treatment. This is the first report of the use of objective measures of disparity vergence as outcome measures for concussion-related convergence insufficiency. These measures provide additional information that is not accessible with clinical tests about underlying physiological mechanisms leading to changes in clinical findings and symptoms. The study results also demonstrate that patients with concussion can tolerate the visual demands (over 200 vergence and versional eye movements) during the 25-minute testing time and suggest that these measures could be used in a large-scale randomized clinical trial of concussion-related CI as outcome measures.

Progression of Regional Microstructural Degeneration in Parkinson's Disease: A Multicenter Diffusion Tensor Imaging Study.

This study aimed to identify the utility of diffusion tensor imaging (DTI) in measuring the regional distribution of abnormal microstructural progression in patients with Parkinson’s disease who were enrolled in the Parkinson's progression marker initiative (PPMI). One hundred and twenty two de-novo PD patients (age = 60.5±9) and 50 healthy controls (age = 60.6±11) had DTI scans at baseline and 12.6±1 months later. Automated image processing included an intra-subject registration of all time points and an inter-subjects registration to a brain atlas. Annualized rates of DTI variations including fractional anisotropy (FA), radial (rD) and axial (aD) diffusivity were estimated in a total of 118 white matter and subcortical regions of interest. A mixed effects model framework was used to determine the degree to which DTI changes differed in PD relative to changes in healthy subjects. Significant DTI changes were also tested for correlations with changes in clinical measures, dopaminergic imaging and CSF biomarkers in PD patients. Compared to normal aging, PD was associated with higher rates of FA reduction, rD and aD increases predominantly in the substantia nigra, midbrain and thalamus. The highest rates of FA reduction involved the substantia nigra (3.6±1.4%/year from baseline, whereas the highest rates of increased diffusivity involved the thalamus (rD: 8.0±2.9%/year, aD: 4.0±1.5%/year). In PD patients, high DTI changes in the substantia nigra correlated with increasing dopaminergic deficits as well as with declining α-synuclein and total tau protein concentrations in cerebrospinal fluid. Increased DTI rates in the thalamus correlated with progressive decline in global cognition in PD. The results suggest that higher rates of regional microstructural degeneration are potential markers of PD progression.

P.4.a.006 - The role of genes encoding the transcription factors c-Fos, c-Jun and Ier5 in posttraumatic stress disorder

Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.

Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

ObjectiveThe decrease in verbal fluency in patients with Parkinson’s disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking.MethodsTo explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism.ResultsWe did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency.ConclusionsThese results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms.

Group cognitive behavioural treatment of youth anxiety in community based clinical practice: Clinical significance and benchmarking against efficacy

The efficacy of a group cognitive behavioural therapy (CBT) programme (Cool Kids) of youth anxiety has been demonstrated at university clinics in Australia and Denmark and similar CBT programmes have been found effective within community settings in other countries. However, most effectiveness studies of CBT for youth anxiety have either used a mixture of CBT guidelines, or translated protocols not previous tested in an efficacy trial. This study used a benchmarking strategy to compare outcomes from the same CBT programme used at a university research clinic (N=87) and community centres (N=82). There was a significant reduction on both clinical and self-report measures of youth anxiety over time with medium to large effect sizes within both samples. Treatment effects on self-report measures of youth anxiety were significantly larger within the university sample, while changes in clinical measures of youth anxiety were similar in the two samples. Overall these findings suggest that an efficacious CBT group treatment programme developed within research contexts is transportable to community centres. Despite being effective within the community, the results indicate that the treatment may lose some of its efficacy when disseminated to the community.

Robotic therapy for chronic stroke: general recovery of impairment or improved task-specific skill?

There is a great need to develop new approaches for rehabilitation of the upper limb after stroke. Robotic therapy is a promising form of neurorehabilitation that can be delivered in higher doses than conventional therapy. Here we sought to determine whether the reported effects of robotic therapy, which have been based on clinical measures of impairment and function, are accompanied by improved motor control. Patients with chronic hemiparesis were trained for 3 wk, 3 days a week, with titrated assistive robotic therapy in two and three dimensions. Motor control improvements (i.e., skill) in both arms were assessed with a separate untrained visually guided reaching task. We devised a novel PCA-based analysis of arm trajectories that is sensitive to changes in the quality of entire movement trajectories without needing to prespecify particular kinematic features. Robotic therapy led to skill improvements in the contralesional arm. These changes were not accompanied by changes in clinical measures of impairment or function. There are two possible interpretations of these results. One is that robotic therapy only leads to small task-specific improvements in motor control via normal skill-learning mechanisms. The other is that kinematic assays are more sensitive than clinical measures to a small general improvement in motor control.