Microarray analysis for ligamentum flavum in lumbar developmental spinal stenosis

Grant Data
Project Title
Microarray analysis for ligamentum flavum in lumbar developmental spinal stenosis
Principal Investigator
Dr Cheung, Jason Pui Yin   (Principal investigator)
Dr Tam Vivian   (Co-Investigator)
Dr Leung Victor Yu Leong   (Co-Investigator)
Start Date
Completion Date
Conference Title
Presentation Title
Developmental Spinal Stenosis, Ligamentum flavum, MRI, Histology, Microarray
Orthopaedics/Traumatology,Genomic Biology
Block Grant Earmarked for Research (104)
HKU Project Code
Grant Type
Seed Funding Programme for Basic Research
Funding Year
One major contributor of neural compression in lumbar spinal stenosis is ligamentum flavum (LF) hypertrophy.[8] With narrowing of the bony spinal canal, there may be a lower threshold for the severity of LF hypertrophy. LF hypertrophy may be due to a fibrotic change[9,10], which is characterized by increased level of collagen fibers with reduced amount of elastin or degenerated elastin.[11] In lumbar spinal stenosis, LF has been reported to demonstrate both accelerated collagen synthesis as well as elastic fiber degradation.[12] An increased number of fibrocartilaginous cells are found, resulting in the proliferation of collagen fibers within a hypertrophic LF.[13] This is in comparison to normal LF which consists of 80% elastin and 20% collagen.[14] It is clear that both spinal canal diameter and LF thickness play crucial roles in the pathogenesis of spinal stenosis. However, the relationship between the two factors is unknown. Due to a pre-existing narrowed canal, the neural elements are more susceptible and milder degrees of LF hypertrophy may already cause symptoms. By comparison, in larger-sized canals, more fibrotic changes may be seen in symptomatic subjects. We performed a prospective study looking at 34 patients undergoing surgery for lumbar spinal stenosis, 110 LF specimens were retrieved for histology classification.[15] Patients were classified according to the canal size into DSS and non-DSS groups. The canal diameter was correlated with the grade and area of fibrosis seen on histology by the grading system (Grade 0-4) defined by Sairyo et al[16]. Grade 0 represents normal tissue with no fibrotic system, Grade 1 represents fibrosis less than or equal to 25% of the entire area, Grades 2 and 3 represent fibrosis occurs at between 25-50% and 50-75% of the entire area respectively, and Grade 4 represents fibrosis of more than or equal to 75% of the entire area. Although subjects with DSS is expected to exhibit a milder degree of LF hypertrophy due to its narrower spinal canal, interestingly, these subjects do not demonstrate thinner LF. Moreover, despite comparable LF thickness among all study groups, patients with narrower canals demonstrate a significant inverse relationship between LF thickness with the degree of fibrosis and fibrotic area. In contrast, subjects without canal narrowing demonstrate a positive relationship between LF thickness and fibrosis. Findings also suggest that patients without narrowing of the bony spinal canal has a greater degree of degeneration. With less degenerative processes in DSS subjects, the lack of fibrotic change on histology suggests that the pathomechanism of LF hypertrophy in DSS is not as simple as has been described. Since DSS is a disorder of development, the properties of LF in DSS may not be the same as those canals we see as a result of degeneration. Thus, to further investigate the rationale for causing thickening, the objective of this study is to determine the genetic and functional pathways leading to this disjunction between canal size and fibrosis in LF. To do this, microarray analysis of different histology patterns in lumbar spinal stenosis will be performed and results correlated with canal size and degree of LF fibrosis. Our hypothesis is that differences in LF expression can be visualized with developmental genes in the LF of DSS and degenerative genes in non-DSS.