B. Ruth Clark

Gait and balance in essential tremor: Variable effects of bilateral thalamic stimulation†

Essential tremor (ET) is a multi‐faceted condition best known for postural and action tremor but also may include disordered gait and postural instability. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus provides substantial tremor reduction yet some patients with bilateral VIM DBS have gait and balance impairment. This study examines gait and balance performance in 13 participants with ET who have bilateral VIM DBS compared with a matched control group. Participants with ET were tested with their stimulators off (DBS OFF) and on (DBS ON). For both standard and tandem walking, participants with ET walked significantly more slowly than controls, with significantly lower cadence, spending a lower percentage of the gait cycle in single limb support and a higher percentage in double support compared with controls. Participants with ET also had significantly lower tandem and one leg stance times, Berg balance scores, balance confidence, and required significantly greater time to perform the Timed Up‐and‐Go relative to controls. There were no significant differences in any gait or balance measures in the DBS OFF versus DBS ON conditions, but the effects of DBS on gait and balance were highly variable among individuals. Future studies are needed to determine why some individuals experience gait and balance difficulties after bilateral thalamic DBS and others do not. A better understanding of the mechanisms underlying gait and balance impairments in those with bilateral DBS is critical to reduce falls and fractures in this group.

GDNF and IGF-I trophic factors delay hereditary Purkinje cell degeneration and the progression of gait ataxia

Neurotrophic factors GDNF and/or IGF-I were chronically infused into shaker mutant rats to rescue cerebellar Purkinje neurons from adult-onset heredodegeneration. The natural expression of the shaker mutation is characterized by spatially restricted degeneration of Purkinje cells that occurs earlier and faster in an anterior vermal compartment and slightly later and more slowly in a posterior vermal compartment. Gait ataxia and whole body tremor develop concomitant with the degeneration of Purkinje neurons. The number and spatial distribution of surviving Purkinje neurons, identified by cell-specific calbindin immunoreactivity, were quantitatively analyzed in mid-sagittal sections and correlated with quantitative movement analysis of hindlimb gait patterns. Compared to the number of surviving Purkinje cells in age-matched, non-infused, or saline-infused control mutants, 4 weeks of infusion of GDNF or IGF-I rescued many anterior compartment Purkinje cells from early degeneration. However, 2 and 4 weeks after cessation of GDNF or IGF-I infusion, respectively, the number and spatial distribution of surviving Purkinje cells was comparable to that observed in age-matched controls. Eight weeks of infusion of trophic factors did not support the continued survival of most anterior compartment Purkinje cells and was partially, and probably only transiently, neuroprotective for some posterior compartment Purkinje cells. When GDNF and IGF-I were infused together for 4 weeks the number of surviving Purkinje cells was additively greater than with either factor alone. Behaviorally, 4 weeks of infusion of trophic factors delayed the development of gait ataxia. Infused GDNF appeared to preserve hip stability, whereas IGF-I stabilized step length. Tremor was attenuated with 8 weeks of infusion of GDNF or IGF-I. GDNF-infused animals showed low power tremor frequencies, whereas IGF-I infusion resulted in a single large power peak with decreased numbers of low-amplitude frequencies. Collectively these findings indicate that exogenous trophic factors can delay the onset of hereditary Purkinje cell degeneration and gait ataxia. Quite surprisingly, GDNF and IGF-I appeared to act on disparate populations of mutant Purkinje cells, whose differential survival affected different aspects of locomotion.

Chronic intraventricular infusion of glial cell line-derived neurotrophic factor (GDNF) rescues some cerebellar Purkinje cells from heredodegeneration.

Cerebellar Purkinje cells degenerate in shaker mutant rats. Glia cell line-derived neurotrophic factor (GDNF) was chronically infused intraventricularly in an attempt to rescue mutant Purkinje cells from dying. Four weeks of chronic GDNF infusion delayed the degeneration of many but not all Purkinje cells. Surviving Purkinje cells formed spatially related groups interrupted by other groups of degenerated Purkinje cells. There was a positive correlation in GDNF-supported Purkinje cell survival and persistence of normal motor behaviors.

X-linked transmission of the shaker mutation in rats with hereditary Purkinje cell degeneration and ataxia

This study reports on the mode of inheritance of the shaker mutation and the development of an inbred strain of the shaker rat mutation from Sprague Dawley outbred stock onto a Wistar Furth background. Neuroanatomical and behavioral expression of the affected phenotype, through seven generations of backcross and intercross breeding, has confirmed the mode of inheritance to be X-linked. Behaviorally, affected mutants present with a wide-based ataxic gait and whole body tremor. In affected mutants calbindin immunostaining for surviving cerebellar Purkinje cells revealed widespread degeneration in the anterior lobe and in limited areas of the posterior lobe. Fast Fourier transform analysis of the tremor revealed a frequency of 3-5 Hz. As predicted by X-linked inheritance, female descendants of an affected male are carriers for the genotype and the phenotype is expressed in one-half of her male offspring. There was spatially random and limited degeneration of Purkinje cells in carrier females, but they did not display overt clinical signs of ataxia and tremor. These data provide further support for using the shaker mutant rat as an animal model for studies of mechanisms underlying human heredodegenerative diseases.

Relationship Between Skin Intrinsic Fluorescence—an Indicator of Advanced Glycation End Products—and Upper Extremity Impairments in Individuals With Diabetes Mellitus

Background Accumulation of advanced glycation end products (AGEs) is thought to contribute to limited joint mobility in people with diabetes mellitus (DM), but the relationships among AGEs, shoulder structural changes, movement, and disability are not understood. Objective The purpose of this study was to determine the differences and relationships among skin intrinsic fluorescence (SIF), a proxy measure of AGEs, biceps and supraspinatus tendon thickness, upper extremity movement, and disability in groups with and without DM. Design This was a cross-sectional, case-control study. Methods Fifty-two individuals participated: 26 with type 2 DM and 26 controls matched for sex, age, and body mass index. The main outcome measures were: SIF; biceps and supraspinatus tendon thickness; 3-dimensional peak shoulder motion; and Disability of the Arm, Shoulder and Hand (DASH) questionnaire scores. Results Mean SIF measurements were 19% higher in the DM group compared with the control group (P<.05). Biceps tendons (mean and 95% confidence interval [CI]) (4.7 mm [4.4, 5.0] versus 3.2 mm [2.9, 3.5]) and supraspinatus tendons (6.4 mm [5.9, 6.8] versus 4.9 mm [4.4, 5.3]) were thicker and peak humerothoracic elevation (139° [135°, 146°] versus 150° [146°, 155°]) and glenohumeral external rotation (35° [26°, 46°] versus 51° [41°, 58°]) were reduced in the DM group compared with the control group (P<.05). In the DM group, SIF was correlated to biceps tendon thickness, DASH score, and shoulder motion (r=.44–.51, P<.05). The SIF score and shoulder strength explained 64% of the DASH scores (P<.01). Limitations Because this was a cross-sectional study design, a cause-effect relationship could not be established. Conclusions Accumulation of AGEs in the connective tissues of individuals with DM appears to be associated with increased tendon thickness and decreased shoulder joint mobility and upper extremity function. Physical therapists should be aware of these possible metabolic effects on structure, movement, and disability when treating people with diabetes.

Shoulder limited joint mobility in people with diabetes mellitus

BACKGROUND Limited joint mobility at the shoulder is an understudied problem in people with diabetes mellitus. The purpose of this study was to determine the differences in shoulder kinematics between a group with diabetes and those without diabetes. METHODS Fifty-two participants were recruited, 26 with diabetes and 26 non-diabetes controls (matched for age, BMI and sex). Three-dimensional position of the trunk, scapula and humerus were collected using electromagnetic tracking sensors during scapular plane elevation and rotation movements. FINDINGS Glenohumeral external rotation was reduced by 11.1°-16.3° (P<0.05) throughout the humerothoracic elevation range of motion, from neutral to peak elevation, in individuals with diabetes as compared to controls. Peak humerothoracic elevation was decreased by 10-14°, and peak external rotation with the arm abducted was decreased 22° in the diabetes group compared to controls (P<0.05). Scapulothoracic and glenohumeral internal rotation motions were not different between the two groups. INTERPRETATION Shoulder limited joint mobility, in particular decreased external rotation, was seen in individuals with diabetes as compared to control participants. Future research should investigate causes of diabetic limited joint mobility and strategies to improve shoulder mobility and prevent additional detrimental changes in movement and function.

Exercise and Cardiometabolic Risk Factors in Graduate Students: A Longitudinal, Observational Study

Abstract Objective: To evaluate cardiometabolic risk of students longitudinally and compare them with age-matched national samples. Participants: Participants are 134 graduate students enrolled between August 2005 and May 2010. Methods: Students were assessed at the beginning and end of their 3-year curriculum. Comparative samples included 966 National Health and Nutrition Examination Survey participants and 5,154 National College Health Assessment respondents. Results: Most students had desirable weight, blood glucose, lipids, and fitness at both time points. However, 26.9% had elevated blood pressure, 29.9% performed aerobic exercise < 3 days/week, and 80.6% consumed < 5 fruits/vegetables daily. Relative to young adults nationwide, these students exhibited more favorable exercise patterns, dietary patterns, and cardiometabolic indices. Over time, increases in adiposity and decreases in exercise frequency correlated with adverse changes in lipid concentrations and fitness. Conclusions: Small changes in lifestyle behaviors and adiposity within a healthy cohort of young adults significantly influenced cardiometabolic indices during their graduate career.

Obesity and Aerobic Fitness among Urban Public School Students in Elementary, Middle, and High School.

Aims and Objectives To assess the prevalence of cardiovascular disease risk among urban public school students through a collaborative school district and university partnership. Methods Children and adolescents in grades K-12 from 24 urban public schools participated in measurements of height, weight, and other health metrics during the 2009–2010 school year. Body mass index (BMI) percentiles and z-scores were computed for 4673 students. President’s Challenge 1-mile endurance run was completed by 1075 students ages 9–19 years. Maximal oxygen consumption (⩒O2max) was predicted using an age-, sex-, and BMI-specific formula to determine health-related fitness. Resting blood pressure (BP) was assessed in 1467 students. Regression analyses were used to compare BMI z-scores, fitness, and age- and sex-specific BP percentiles across grade levels. Chi-square tests were used to explore the effect of sex and grade-level on health-related outcomes. Results Based on BMI, 19.8% were categorized as overweight and 24.4% were obese. Included in the obese category were 454 students (9.7% of sample) classified with severe obesity. Using FITNESSGRAM criteria, 50.2% of students did not achieve the Healthy Fitness Zone (HFZ); the proportion of students in the Needs Improvement categories increased from elementary to middle school to high school. Male students demonstrated higher fitness than female students, with 61.4% of boys and only 35.4% of girls meeting HFZ standards. Elevated BP was observed among 24% of 1467 students assessed. Systolic and diastolic BP z-scores revealed low correlation with BMI z-scores. Conclusions A community-university collaboration identified obesity, severe obesity, overweight, and low aerobic fitness to be common risk factors among urban public school students.

Physical Activity for Campus Employees: A University Worksite Wellness Program

BACKGROUND Workplaces provide ideal environments for wellness programming. The purpose of this study was to explore exercise self-efficacy among university employees and the effects of a worksite wellness program on physical activity, cardiorespiratory fitness, and cardiovascular disease (CVD) risk factors. METHODS Participants included 121 university employees (85% female). The worksite wellness program included cardiovascular health assessments, personal health reports, 8 weeks of pedometer-based walking and tracking activities, and weekly wellness sessions. Daily step count was assessed at baseline, Week 4, and Week 8. Exercise self-efficacy and CVD risk factors were evaluated at baseline and follow-up. RESULTS Daily step count increased from 6566 ± 258 (LSM ± SE) at baseline to 8605 ± 356 at Week 4 and 9107 ± 388 at Week 8 (P < .0001). Steps increased among normal weight, overweight, and obese subgroups. Exercise self-efficacy correlated with baseline steps (P < .05). Small improvements were observed in cardiorespiratory fitness, body mass index, blood pressure, blood glucose, total cholesterol, and triglycerides (all P < .01). CONCLUSIONS A worksite wellness program was effective for improving physical activity, cardiorespiratory fitness, and CVD risk factors among university employees. Exercise barriers and outcome expectations were identified and have implications for future worksite wellness programming.

Physical Activity During Recess Outdoors and Indoors Among Urban Public School Students, St. Louis, Missouri, 2010–2011

We measured the quantity and intensity of physical activity in 106 urban public school students during recess outdoors, recess indoors in the gym, and recess indoors in the classroom. Students in grades 2 through 5 wore accelerometer pedometers for an average of 6.2 (standard deviation [SD], 1.4) recess periods over 8 weeks; a subsample of 26 also wore heart rate monitors. We determined, on the basis of 655 recess observations, that outdoor recess enabled more total steps per recess period (P < .0001), more steps in moderate-to-vigorous physical activity (P < .0001), and higher heart rates than recess in the gym or classroom. To maximize physical activity quantity and intensity, school policies should promote outdoor recess.