Urine hydroxyproline correlates with progression of spasticity in cerebral palsy
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Department of Orthopaedic and Traumatology, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
Department of Orthopaedic and Traumatology, Hospital Selayang, Kuala Lumpur, Malaysia
Tissue Engineering Centre, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
Online publication date: 2017-12-29
Publication date: 2017-12-29
Corresponding author
Ohnmar Htwe   

Consultant Rehabilitation Physician, Rehabilitation Unit, Department of Orthopedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaccob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur Phone: +6019-2207918.
Eur J Gen Med 2018;15(1):1-9
Most Cerebral Palsy (CP) patients develop muscle spasticity which is characterized by jerky movements and muscle and joint stiffness. This increase of muscle stiffness in spastic CP has been correlated with the accumulation of collagen in the muscle as detected by the increase in muscle hydroxyproline, a major component of collagen.

Material and Methods:
This was a cross sectional comparative study, conducted in the tertiary hospital, Malaysia from June’2012 to December’2014. Children with spastic CP (6 to 18 years) who were scheduled for muscle/tendon lengthening as part of the on going management and children with pure spasticity were included in this study. Normal children who are aged and sex matched to the CP children were included. Muscle biopsy and urine samples were collected for MH and UH analysis respectively.

A total of 48 children, aged 6 to 18 years (17 normal; 16 spastic CP without contracture, 15 spastic CP with contracture) were included in this study. Muscle biopsy (only for CP children with contracture) and urine samples were collected. A significant negative correlation was noted between the MH (261.894±69.077ng/ml) and UH (13.266±7.999ng/ml) levels (p=0.031). There was a statistically significant correlation between UH levels and the MAS score (p=0.01), and GMFCS score (p=0.015).

UH quantification may be an objective tool to estimate the severity and progression of spasticity in CP.

The objective of the study is to determine if there is any correlation between muscle and urine hydroxyproline levels in spastic CP. Further, to determine if Urine Hydroxyproline levels are different between spastic CP with and without contracture. Finally to determine if UH levels can be correlated with severity of CP as determined by Modified Ashworth Scale (MAS) and Gross Motor Function Classification System (GMFCS) scores.

Yeargin-Allsopp M, Braun KVN, Doernberg NS, Benedict RE, Kirby RS, Durkin MS. Prevalence of cerebral palsy in 8-year-old children in three areas of the United States in 2002: a multisite collaboration. Pediatrics. 2008;121(3):547-54.
Booth CM, Cortina‐Borja MJ, Theologis TN. Collagen accumulation in muscles of children with cerebral palsy and correlation with severity of spasticity. Developmental medicine & child Neurology 2001;43(5):314-20.
Kesava Reddy G, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clinical biochemistry. 1996;29(3):225-9.
Bruin MD, Smeulders MJ, Kreulen M, Huijing PA, Jaspers RT. Intramuscular Connective Tissue Differences in Spastic and Control Muscle: A Mechanical and Histological Study. PLOS One. 2014. doi: 10.1371/journal.pone.0101038.
Ito J-i, Araki A, Tanaka H, Tasaki T, Cho K, Yamazaki R. Muscle histopathology in spastic cerebral palsy. Brain Dev. 1996;18(4):299-303.
Smith LR, Lee KS, Ward SR, Chambers HG, Lieber RL. Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length. The Journal of Physiology. 2011;589(10):2625-39.
Smith LR, Chambers HG, Subramaniam S, Lieber RL. Transcriptional Abnormalities of Hamstring Muscle Contractures in Children with Cerebral Palsy. PLOS One. 2012;7(8):e40686.
Li Y, Foster W, Deasy BM, Chan Y, Prisk V, Tang Y, Cummins J, Huard J. Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am J Pathol. 2004;164:1007–19.
Adams E, Ramaswamy S, Lamon M. 3-Hydroxyproline content of normal urine. Journal of Clinical Investigation. 1978;61(6):1482.
Weiss PH, Klein L. The quantitative relationship of urinary peptide hydroxyproline excretion to collagen degradation. Journal of Clinical Investigation. 1969;48(1):1.
Ziff M, Kibrick A., Dresner E, Gribetz HJ. Excretion of hydroxyproline in patients with rheumatic and non-rheumatic diseases. J Clin Invest. 1956; 35: 579-587.
Meilman E, Urivetzky MM, Rapoport CM. Studies on urinary hydroxyproline peptides. J. Clin. Invest 1963;42:40-50.
Bohannon RW, Smith MB. Muscle Spasticity-Interrater Reliability of a Modified Ashworth Scale of muscle spasticity. Physther. 1987; 67:206-7.
Morris S. Ashworth and Tardieu scales: their clinical relevance for measuring spasticity in adult and pediatric neurological populations. Phys Ther Rev. 2002;7:53–62.
Hodgkinson I, Bérard C. Assessment of spasticity in pediatric patients. Operative Techniques in Neurosurgery. 2004;7(3):109-12.
Klein L, Curtiss PH. Urinary hydroxyproline as an index of bone metabolism. In: Dynamic studies of metabolic bone disease. Pearson, 0H, Joplin GF, eds. Oxford: Blackwell & Scientific Publications. 1964:201-24.
Sprott H, Muller A, Heine H. Collagen crosslinks in fibromyalgia. Arthritis Rheum. 1997;40:1450–4.
Watts NB. Clinical utility of biochemical markers of bone remodeling, Clinical Chemistry. 1999;45(8B):1359-68.
Barış Şimşek, Özgül Karacaer, İnci Karaca. Clinical Usefulness of Urinary Hydroxy proline as a Biochemical Marker of Bone Resorption. Dişhekimliği Fakültesi Dergisi. 2002; 3(1):17-9.
Kıvırıkko KI. Excretion of urinary hydroxyproline peptide in the assessment of bone collagen deposition and resorption, In: Clinical disorders of bone and mineral metabolism. Frame B, Potts JT Jr, eds. Amsterdam: Excerpta Medica. 1983:105-7.
Lowry M, Hall DE, Brosnan JJ. Hydroxyproline metabolism in the rat kidney distrubition of the renalenzimes of hydroxyproline catabolism and renal conversion of hydroxyproline to glisincine and serine, Metabolism. 1985; 34(10): 955-61.
Lieber RL, Fridén J. Functional and clinical significance of skeletal muscle architecture. Muscle & nerve. 2000;23:1647-66.
Lieber RL, Runesson E, Einarsson F, Fridén J. Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material. Muscle & nerve. 2003;28(4):464-71.
Purslow PP. Strain-induced reorientation of an intramuscular connective tissue network: implications for passive muscle elasticity. J Biomech. 1989;22(1):21-31.
Friden J, Lieber RL. Spastic muscle cells are shorter and stiffer than normal cells. Muscle Nerve. 2003;27:157–64.
Eyre DR. The specificity of collagen cross-links as markers of bone and connective tissue degradation. Acta Orthopaedica. 1995;66(S266):166-70.
Miller GR, Smith CA, Stauber WT. Determination of fibrosis from cryostat sections using high performance liquid chromatography: skeletal muscle. The Histochemical Journal. 1999;31(2):89-94.
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