Daniel G. Whitney

Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy

INTRODUCTION Nonambulatory children with severe cerebral palsy (CP) have underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. MATERIALS AND METHODS Ambulatory children with mild spastic CP and typically developing children (4 to 11years; 12/group) were compared. Magnetic resonance imaging was used to estimate cortical bone, bone marrow and total bone volume and width, bone strength [i.e., section modulus (Z) and polar moment of inertia (J)], and bone marrow fat concentration in the midtibia, and muscle volume, intermuscular, subfascial, and subcutaneous adipose tissue (AT) volume and intramuscular fat concentration in the midleg. Accelerometer-based activity monitors worn on the ankle were used to assess physical activity. RESULTS There were no group differences in age, height, body mass, body mass percentile, BMI, BMI percentile or tibia length, but children with CP had lower height percentile (19th vs. 50th percentile) and total physical activity counts (44%) than controls (both p<0.05). Children with CP also had lower cortical bone volume (30%), cortical bone width in the posterior (16%) and medial (32%) portions of the shaft, total bone width in the medial-lateral direction (15%), Z in the medial-lateral direction (34%), J (39%) and muscle volume (39%), and higher bone marrow fat concentration (82.1±1.8% vs. 80.5±1.9%), subfascial AT volume (3.3 fold) and intramuscular fat concentration (25.0±8.0% vs. 16.1±3.3%) than controls (all p<0.05). When tibia length was statistically controlled, all group differences in bone architecture, bone strength, muscle volume and fat infiltration estimates, except posterior cortical bone width, were still present (all p<0.05). Furthermore, a higher intermuscular AT volume in children with CP compared to controls emerged (p<0.05). CONCLUSIONS Ambulatory children with mild spastic CP exhibit an underdeveloped bone architecture and low bone strength in the midtibia and a greater infiltration of fat in the bone marrow and surrounding musculature compared to typically developing children. Whether the deficit in the musculoskeletal system of children with CP is associated with higher chronic disease risk and whether the deficit can be mitigated requires further investigation.

The pattern of trabecular bone microarchitecture in the distal femur of typically developing children and its effect on processing of magnetic resonance images

INTRODUCTION Magnetic resonance imaging (MRI) is used to assess trabecular bone microarchitecture in humans; however, image processing can be labor intensive and time consuming. One aim of this study was to determine the pattern of trabecular bone microarchitecture in the distal femur of typically developing children. A second aim was to determine the proportion and location of magnetic resonance images that need to be processed to yield representative estimates of trabecular bone microarchitecture. MATERIALS AND METHODS Twenty-six high resolution magnetic resonance images were collected immediately above the growth plate in the distal femur of 6-12year-old typically developing children (n=40). Measures of trabecular bone microarchitecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the lateral aspect of the distal femur were determined using the twenty most central images (20IM). The average values for appBV/TV, appTb.N, appTb.Th and appTb.Sp from 20IM were compared to the average values from 10 images (10IM), 5 images (5IM) and 3 images (3IM) equally dispersed throughout the total image set and one image (1IM) from the center of the total image set using linear regression analysis. The resulting mathematical models were cross-validated using the leave-one-out technique. RESULTS Distance from the growth plate was strongly and inversely related to appBV/TV (r(2)=0.68, p<0.001) and appTb.N (r(2)=0.92, p<0.001) and was strongly and positively related to appTb.Sp (r(2)=0.86, p<0.001). The relationship between distance from the growth plate and appTb.Th was not linear (r(2)=0.06, p=0.28), but instead it was quadratic and statistically significant (r(2)=0.54, p<0.001). Trabecular bone microarchitecture estimates from 10IM, 5IM, 3IM and 1IM were not different from estimates from 20IM (p>0.05). However, there was a progressive decrease in the strength of the relationships as a smaller proportion of images were used to predict estimates from 20IM (r(2)=0.98 to 0.99 using 10IM, 0.94 to 0.96 using 5IM, 0.87 to 0.90 using 3IM and 0.66 to 0.72 using 1IM; all p<0.001). Using the resulting mathematical models and the leave-one-out cross-validation analysis, measures of trabecular bone microarchitecture estimated from the 10IM and 5IM partial image sets agreed extremely well with estimates from 20IM. CONCLUSIONS The findings indicate that partial magnetic resonance image sets can be used to provide reasonable estimates of trabecular bone microarchitecture status in the distal femur of typically developing children. However, because the relative amount of trabecular bone in the distal femur decreases with distance from the growth plate due to a decrease in trabecular number, careful positioning of the region of interest and sampling from throughout the region of interest is necessary.

Noncommunicable disease and multimorbidity in young adults with cerebral palsy

Purpose Individuals with cerebral palsy (CP) are at increased risk for frailty and chronic disease due to factors experienced throughout the lifespan, such as excessive sedentary behaviors and malnutrition. However, little is known about noncommunicable diseases (NCDs) and multimorbidity profiles in young adults with CP. The study objective was to compare NCD and multimorbidity profiles between young adults with and without CP. Methods A clinic-based sample of adults (18–30 years) with (n=452) and without (n=448) CP was examined at the University of Michigan Medical Center. The prevalence and predictors of 13 NCDs were evaluated, including existing diagnoses or historical record of musculoskeletal, cardiometabolic, and pulmonary morbidities. The level of motor impairment was determined by the Gross Motor Function Classification System (GMFCS) and stratified by less vs more severe motor impairment (GMFCS I–III vs IV–V). Logistic regression was used to determine the odds of NCD morbidity and multimorbidity in adults with CP compared to adults without CP, and for GMFCS IV–V compared to GMFCS I–III in those with CP, after adjusting for age, sex, body mass index, and smoking. Results Adults with CP had a higher prevalence of osteopenia, osteoporosis, hypertension, myocardial infarction, hyperlipidemia, asthma, and multimorbidity compared to adults without CP, and higher odds of musculoskeletal (odds ratio [OR]: 6.97) and cardiometabolic morbidity (OR: 1.98), and multimorbidity (OR: 2.67). Adults with CP with GMFCS levels IV–V had a higher prevalence of osteopenia/osteoporosis, osteoarthritis, hypertension, other cardiovascular conditions, pulmonary embolism, and multimorbidity, and higher odds of musculoskeletal (OR: 3.41), cardiometabolic (OR: 2.05), pulmonary morbidity (OR: 1.42), and multimorbidity (OR: 3.45) compared to GMFCS I–III. Conclusion Young adults with CP have a higher prevalence of chronic NCDs and multimorbidity compared to young adults without CP, which is pronounced in those with more severe motor impairment. These findings reiterate the importance of early screening for prevention of NCDs in CP.

Site-Specific Transmission of a Floor-Based, High-Frequency, Low-Magnitude Vibration Stimulus in Children With Spastic Cerebral Palsy.

OBJECTIVE To determine the degree to which a high-frequency, low-magnitude vibration signal emitted by a floor-based platform transmits to the distal tibia and distal femur of children with spastic cerebral palsy (CP) during standing. DESIGN Cross-sectional study. SETTING University research laboratory. PARTICIPANTS Children with spastic CP who could stand independently (n=18) and typically developing children (n=10) (age range, 4-12y) participated in the study (N=28). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES The vibration signal at the high-frequency, low-magnitude vibration platform (approximately 33Hz and 0.3g), distal tibia, and distal femur was measured using accelerometers. The degree of plantar flexor spasticity was assessed using the Modified Ashworth Scale. RESULTS The high-frequency, low-magnitude vibration signal was greater (P<.001) at the distal tibia than at the platform in children with CP (.36±.06g vs .29±.05g) and controls (.40±.09g vs .24±.07g). Although the vibration signal was also higher at the distal femur (.35±.09g, P<.001) than at the platform in controls, it was lower in children with CP (.20±.07g, P<.001). The degree of spasticity was negatively related to the vibration signal transmitted to the distal tibia (Spearman ρ=-.547) and distal femur (Spearman ρ=-.566) in children with CP (both P<.05). CONCLUSIONS A high-frequency, low-magnitude vibration signal from a floor-based platform was amplified at the distal tibia, attenuated at the distal femur, and inversely related to the degree of muscle spasticity in children with spastic CP. Whether this transmission pattern affects the adaptation of the bones of children with CP to high-frequency, low-magnitude vibration requires further investigation.

Greater visceral fat but no difference in measures of total body fat in ambulatory children with spastic cerebral palsy compared to typically developing children

BACKGROUND Individuals with cerebral palsy (CP) are at increased risk for obesity and obesity-related complications. Studies of total body fat in those with CP are inconsistent and studies of abdominal fat are lacking in children with CP. The objective of this study was to determine if ambulatory children with spastic CP have greater central adiposity compared to typically developing children. METHODOLOGY Eighteen ambulatory children with spastic CP (n = 5 girls; 8.6 ± 2.9 yr) and 18 age-, sex-, and race-matched typically developing children (controls; 8.9 ± 2.1 yr) participated in this cross-sectional study. Children with CP were classified as I or II using the Gross Motor Function Classification System. Dual-energy X-ray absorptiometry assessed body composition, including total body, trunk and abdominal fat mass, fat-free mass, fat mass index (FMI), and fat-free mass index (FFMI). RESULTS There were no group differences in fat mass, fat-free mass, FMI, and FFMI in the total body, fat mass, fat-free mass, and FFMI in the trunk, or fat mass, visceral fat mass, and subcutaneous fat mass in the abdomen (p > 0.05). Compared to controls, children with CP had higher trunk FMI, abdominal FMI, and visceral FMI (p < 0.05). Although marginally insignificant (p = 0.088), children with CP had higher subcutaneous FMI. CONCLUSIONS Ambulatory children with spastic CP have elevated central adiposity, especially in the visceral region, despite no differences in measures of total body fat. How this relates to cardiometabolic disease progression in those with CP requires further investigation.

BMI does not capture the high fat mass index and low fat-free mass index in children with cerebral palsy and proposed statistical models that improve this accuracy

Background/objectivesChildren with cerebral palsy (CP) are at risk for having a misclassified overweight/obesity status based on BMI thresholds due to their lower fat-free mass and similar fat mass compared with typically developing children. The primary objective was to determine if BMI could predict fat mass index (FMI) and fat-free mass index (FFMI) in children with CP.Subjects/methodsForty-two children with CP and 42 typically developing children matched to children with CP for age and sex participated in the study. Dual-energy X-ray absorptiometry was used to assess body composition. Children with CP who could ambulate without assistance were considered ambulatory (ACP) and the rest were considered nonambulatory (NACP).ResultsChildren with CP had higher percent body fat (%Fat) and FMI and lower fat-free mass and FFMI than controls (p < 0.05) but no difference in fat mass (p = 0.10). When BMI was statistically controlled, NACP had higher %Fat, fat mass and FMI and lower FFMI than ACP and controls (p < 0.05). NACP also had lower fat-free mass than controls (p < 0.05). ACP had higher %Fat and FMI and lower fat-free mass and FFMI than controls (p < 0.05). BMI was a strong predictor of FMI (r2 = 0.83) and a moderately strong predictor of FFMI (r2 = 0.49) in children with CP (both p < 0.01). Prediction of FMI (R2 = 0.86) and FFMI (R2 = 0.66) from BMI increased (p < 0.05) when age, sex and ambulatory status were included.ConclusionCompared with typically developing children, children with CP have a higher FMI and lower FFMI for a given BMI, which is more pronounced in NACP than ACP. The finding suggests that the prevalence of overweight/obesity status may be underestimated in children with CP.

Mental health disorders and physical risk factors in children with cerebral palsy: a cross-sectional study

To examine the prevalence of mental health disorders among children with and without cerebral palsy (CP), and to examine how physical risk factors in children with CP might mitigate any elevated risk of mental health disorders in this population.

Age trajectories of musculoskeletal morbidities in adults with cerebral palsy

BACKGROUND Individuals with cerebral palsy (CP) are at an increased risk for age-related morbidities due to functional impairments, maladapted growth, and altered body composition. While musculoskeletal (MSK) deficits are present in children, little is understood about MSK morbidity throughout the lifespan in those with CP. The purpose of this study was to examine the age-related trajectories of MSK morbidity and multimorbidity throughout adulthood in those with CP. METHODS A clinic-based sample of adults with CP (n = 1395; ≥18 years) was examined to determine prevalence of MSK morbidities at the University of Michigan Medical Center. Logistic regression was used to determine the effects of age on individual MSK morbidities and multimorbidity (i.e., ≥2 morbidities) after adjusting for sex, race, weight, and smoking. RESULTS With the 18-30 year age group as the reference, the adjusted odds of osteopenia was lower in the 41-50 and >50 year age groups, the odds of osteoporosis and rheumatoid arthritis was higher in 41-50 and >50 year age groups, and the odds of osteoarthritis was higher in 31-40, 41-50, and >50 year age groups. The adjusted odds of MSK multimorbidity increased substantially with increasing age for 31-40 year olds (OR: 1.919; 95% CI 1.05-3.52), 41-50 year olds (OR: 4.30; 95% CI 2.40-7.69), and >50 year olds (OR: 6.05; 95% CI 3.56-10.27). CONCLUSIONS Adults with CP are at high risk for MSK morbidities across all ages. Future studies are needed to examine the global aging trajectories of MSK health among adults with CP. Study findings highlight the importance of maximizing MSK accretion, and developing programs to assist individuals with CP and their caregivers to maintain MSK mass and function throughout the lifespan.