Obesity Indices in Children With Spastic Cerebral Palsy

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URL: http://udspace.udel.edu/handle/19716/23077

PROQUEST: 1970798055

Abstract

Cerebral palsy (CP) results from damage or malformation of the developing brain and is the most common physical disability of childhood with approximately 80% of all CP cases having some degree of skeletal muscle spasticity. Children with CP have difficulties with neuromuscular tasks, such as gait, posture and balance, are prone to skeletal muscle weakness and are less physically active than their typically developing peers. Children with CP present with a weak and underdeveloped musculoskeletal system that gets progressively worse throughout growth, potentially increasing the risk for development of musculoskeletal and cardiometabolic diseases. Importantly, mobility and gait function declines as children with CP age into their adult years which may act to exacerbate musculoskeletal pathology, excessive fat accumulation, frailty and chronic disease risk. This is supported by a higher prevalence of age-related chronic diseases and multimorbidity in adults with CP compared to the general population. However, considering age-related chronic diseases often get their roots in childhood, cardiometabolic disease risk and factors associated with cardiometabolic disease risk, such as musculoskeletal health and indices of obesity, have not been examined in children with CP.

The first aim of this dissertation was to determine if ambulatory children with spastic CP have an altered fat distribution of the leg compared to typically developing children using magnetic resonance imaging at the mid-third of the leg. Compared to controls (n = 12), children with CP (n = 12) had no difference in total (p = 0.796) or subcutaneous (p = 0.868) fat, but had higher intermuscular (p = 0.036) and subfascial (p = 0.002) fat and intramuscular (p = 0.002) and tibia bone marrow (p = 0.004) fat concentration after statistically controlling for tibia length. These findings suggest that ambulatory children with spastic CP have an altered fat distribution profile of the leg that is favoring musculoskeletal depots as evidenced by no difference in total or subcutaneous fat, but higher fat infiltration of the skeletal muscle and bone marrow depots.

The second aim of this dissertation was to determine the volume and fat concentration profile of the 11 individual leg muscles and how it relates to muscle strength in ambulatory children with spastic CP using magnetic resonance imaging along the length of the tibia and a Biodex dynamometer to assess muscle strength. Compared to controls (n = 14), children with CP (n = 14) had lower volume of all muscles (all p < 0.05), except for the marginally insignificant peroneus longus (p = 0.052), ranging from 27 % (peroneus longus) to 44 % (tibialis anterior) and higher intramuscular fat of all muscles (all p < 0.05) ranging from 4.4 (tibialis posterior) to 10.1 (soleus) percentile units. The slopes for tibia length regressed on flexor digitorum longus volume and tibialis anterior volume were significantly different between groups (interaction, p = 0.040 and 0.005, respectively). There were positive relationships between plantar flexion strength regressed on gastrocnemius and soleus volume and dorsi flexion strength regressed on tibialis anterior volume in children with CP and controls (r² = 0.32 to 0.71, all p < 0.05). When intramuscular fat concentration was removed from muscle volume (corrected muscle volume), the relationships became slightly stronger (r² = 0.37 to 0.77, all p < 0.05). For all the uncorrected and corrected muscle volume-strength relationships, there was a significant difference in the yintercept between groups, but not the slope. These findings suggest that ambulatory children with spastic CP have smaller muscles that are highly infiltrated with fat and have weaker muscle strength per unit of muscle volume. The higher intramuscular fat of the gastrocnemius, soleus and tibialis anterior is contributing to muscle weakness in ambulatory children with spastic CP; albeit, to a small extent.

The third aim of this dissertation was to determine if ambulatory children with spastic CP have higher abdominal fat compared to typically developing children using dual-energy x-ray absorptiometry. There were no group differences in body mass index (BMI), BMI % or total body fat mass index (FMI; all p > 0.05). Compared to controls (n = 18), children with CP (n = 18) had higher trunk FMI (p = 0.019), abdominal FMI (p = 0.001) and visceral FMI (p = 0.001) but no difference in subcutaneous FMI (p = 0.088). These findings suggest that ambulatory children with spastic CP have a higher concentration of fat in the abdominal region compared to typically developing children, which is not captured by BMI or total body fat.

The fourth aim of this dissertation was to determine if BMI can estimate body composition in children with CP. There were no group differences in BMI or BMI % between all children with CP (n = 42) and controls (n = 42) or among nonambulatory (n = 18) and ambulatory (n = 24) children with CP and controls (all p > 0.05). Compared to controls, nonambulatory and ambulatory children with CP had higher FMI (p < 0.001 and 0.019, respectively) and lower fat-free mass index (FFMI; p < 0.001 and 0.036, respectively) after statistically controlling for BMI. BMI was a strong predictor of FMI and a moderately-strong predictor of FFMI in children with CP (r² = 0.59 and 0.47, respectively, both p < 0.001). The prediction of FMI (R² = 0.86) and FFMI (R² = 0.66) from BMI significantly increased (both R² change, p < 0.05) when age, sex and ambulatory status (i.e., either ambulatory or nonambulatory) were included in the regression model. These findings suggest that children with CP have a higher FMI and lower FFMI for a given BMI which is more pronounced in nonambulatory than ambulatory children with CP. Importantly, theprevalence of obesity may be even higher than reported. Fortunately, this aim developed validated statistical models to estimate FMI and FFMI from easily attainable measures.

The overall findings from this dissertation provides a comprehensive assessment of obesity indices in children with CP that often precede cardiometabolic disease. These findings suggest that children with CP are at a very high risk for an early and accelerated development of age-related chronic diseases. Future efforts are needed to monitor changes in these fat depots with age or in response to interventions and how these higher obesity indices related to cardiometabolic disease risk in children with CP.

Cited Works (15)

Year	Entry
2000	Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. January 21, 2000;100(2):197-207.
1971	Meunier P, Aaron J, Edouard C, Vignon G. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue: a quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res. October 1971;80:147-154.
2001	Hsieh Y, Robling AG, Ambrosius WT, Burr DB, Turner CH. Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location. J Bone Miner Res. December 2001;16(10):2291-2297.
2011	Cole JH, van der Meulen MCH. Whole bone mechanics and bone quality. Clin Orthop Relat Res. August 2011;469(8):2139-2149.
2004	Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res. March 2004;19(3):360-369.
2002	Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system. Cell. November 1, 2002;111(3):305-317.
2009	Andersen TL, Sondergaard TE, Skorzynska KE, Dagnaes-Hansen F, Plesner TL, Hauge EM, Plesner T, Delaisse J-M. A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol. January 2009;174(1):239-247.
1999	Turner CH. Toward a mathematical description of bone biology: the principle of cellular accommodation. Calcif Tiss Int. December 1999;65(6):466-471.
1990	Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM. Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res. August 1990;5(8):843-850.
2001	Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. September 2001;16(9):1575-1582.
2001	Turner CH, Burr DB. Experimental techniques for bone mechanics. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:7-1–7-35.
2001	Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. September 2001;2(3):165-171.
1995	Dobnig H, Turner RT. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology. August 1995;136(8):3632-3638.
2002	Turner CH, Robling AG, Duncan RL, Burr DB. Do bone cells behave like a neuronal network? Calcif Tiss Int. June 2002;70(6):435-442.
2007	David V, Martin A, Lafage-Proust M-H, Malaval L, Peyroche S, Jones DB, Vico L, Guignandon A. Mechanical loading down-regulates peroxisome proliferator-activated receptor γ in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis. Endocrinology. May 2007;148(5):2553-2562.