European Journal of Cardiovascular Medicine

The ligamentum flavum extends from C2-S1. The ligamentum flavum is composed of elastic fibres (80%) and collagen fibres (20%). It is attached to the under surface of the lamina above and the upper part of the lamina below. It has a capsular portion and inter laminar portion.^1,2 Ossified yellow ligament (OYL) is a representation of ageing of the vertebral ligaments and is linked to the systemic ossification trait. Usually, it occurs at the lower thoracic levels. It may occur in combination with ossified posterior longitudinal ligament (OPLL).

The cause of ossification of the yellow ligament is multifactorial ranging from heredity, abnormal glucose metabolism, abnormal calcium metabolism, abnormalities in the gender hormones, degeneration of the ligament etc.³ In degenerative conditions, the mechanical stress to the ligament especially at the capsular position, lead to OYL. Chondrocytes are activated by the stress of the ligament, this will lead to production of type- 2 collagen, which in turn gets transformed to type-1 collagen in the course of endochondral ossification of the yellow ligament. People with collagen 11 A2gene and 6A1 gene are shown to be predisposed for this development. Growth factors and transcription factors like cartilage derived morphogenic protein- 1, promyelocytic leukaemia zinc finger and tumour necrosis factor alpha stimulated gene 6 are related to the transformation of the undifferentiated mesenchymal cell to the osteoblastic cell.^4,5

In the lower thoracic spine, the kyphotic alignment with strong traction force and rotational movements, act on the ligamentum flavum and influence the ossification mechanism.^6,7 In the lordotic lumbar and cervical spines, the traction force doesn’t act strongly, so calcification tend to develop rather than ossification of trabecular structure.

All the cases of ossified yellow ligaments operated by the 1^st author from 2003 onwards till 2024 May are reviewed. 18 cases of OYL of different neurological status were operated. 11 of them were males and 7 were females. Age group ranged from 44 years to 91 years. OYL was seen more within 50-70 years age group.

8 patients were diabetic (3 males and 5 females), 4 patients were hypertensive, one had hypothyroidism, two among them had both hypertension and diabetes. 5 patients (3 males and 2 females) had associated ossified posterior longitudinal ligament (OPLL) at the same level as OYL or at different locations: mostly in the cervical spine.

One of the patients developed OYL and paraplegia 5 years after sustaining a traumatic disc prolapse with quadriplegia and recovery after surgery. The patients at admission were assessed neurologically and JOA scoring was applied. 6 patients out of 18 had bladder and bowel involvement.

The patients were evaluated with plain Xray of the spine and MRI. Once the diagnosis was made, CT scan of the level of interest was taken to look for the bony extent of the lesion and the presence of dural ossification. MRI depicted the extent of myelomalacia and thinning of the cord. Further evaluation was done to ensure the surgical fitness of these patients.

All patients had OYL in the thoracic spine. Some patients had OYL at multiple levels. 7 patients had OYL at D10-11 and 6 patients had OYL at D9-D10. Two patients had OYL at D8 to D10.

Associated OPLL was present in 4 patients at the cervical levels and thoracic levels. One had OPLL at C5-C6/C6-C7 and D12-L1, 2^nd patient had OPLL at C4-7 and D8-10, 3^rd patient had OPLL at C3-6 only and the 4^th patient had OPLL at D8-D10 and C4-C7: One patient had isolated OPLL in the thoracic spine along with thoracic OYL and the rest 3 patients had combination of thoracic and cervical OPLL along with thoracic OYL.

The neurological status was assessed using JOA scoring system.

Surgery

All patients underwent laminectomy and instrumented fusion. Wide laminectomy was done. Dural calcifications were addressed by floating technique. Diamond burr was used to thin out the calcified mass and left as such.  No dural tear was encountered. No neurological deterioration was noticed in the post operative period.

6 out of 18 patients had bowel/bladder dysfunction at admission. 5 of them recovered the bowel bladder dysfunction. One patient had no improvement of bladder function at 1 year post-surgery. 8 patients had JOA score zero at admission; 5 patients had score of one at admission. Another set of 5 patients had JOA score of 2 at admission. 4 patients with ‘0’ JOA score at admission were JOA score of 4 (completely recovered) at 1 year after surgery. 2 patients had JOA score ‘0’ at admission and improved to JOA score of 3 at 1 year post surgery. Another 2 patients had JOA score of ‘0” at admission and improved to JOA score 2. All patients with JA score 1 and 2 at admission improved to normalcy at 1 year (JOA score – 4).

So, out of the 18 patients, all patients with JOA score one and two (total 10 patients) recovered completely at 1 year post surgery. Of the 8 patients who presented with JOA score of zero, 4 of them recovered completely at 1 year (50%), two of them to JOA score of 3 and another 2 to JOA score of 2.

The overall complete neurological improvement in our scores were 77.77%. JOA scores one and above at admission recovered completely at 1 year (100%). This is in agreement with Joji Inamasu et al, who stated that preoperative neurological status is a predictor of neurological recovery after surgery.⁸

The aetiology of OYL include trauma, diffuse idiopathic skeletal hyperostosis (DISH), ankylosing spondylitis, hemochromatosis, adenocarcinomatous metastasis, fluorosis and disorders of calcium and phosphorous metabolism.^9,10

Ossified yellow ligament (OYL) is one of the major reasons for thoracic myeloradiculopathy. 88.8% of the cases are seen in Japanese population followed by Caucasians (8.2%).¹¹ Bone morphogenic proteins and transforming growth factor β are shown to play a prominent role in the matrix hyperplasia and ossification of the yellow ligament.¹² Ossification of ligamentum flavum (OYL) of the spine is a common form of ectopic bone formation in the spinal ligaments with a high incidence in the families and run in races.^12,13 OYL is multifactorial and may share common etiopathology with OPLL and might often co-exist with it. According to different gene studies, it is shown that hereditary factors are involved in the pathogenesis of OYL.

Polymorphism of COL6A1 which is located in chromosome 21q22.3 is found to be associated with OYL and OPLL (ossified posterior longitudinal ligament).¹⁴ Along with genetic factors, dietary factors are also shown to be independent risk factors.^15,16 For unknown genetic reasons, OYL is associated with higher incidence of obesity and disturbance in the glucose metabolism.¹⁷ Subsequently increased levels of fibronectin, a glycoprotein in growth plate and essential factors in endochondral ossifications have been shown to be higher in patients with OYL and OPLL.¹⁸

Diagnosis is based on clinical and radiological parameters. Myelopathy due to OYL is caused by static or dynamic compression of the spinal cord. People may complain of stiffness of the back or constriction like discomfort due to irritation of the intercoastal nerves by OYL. Physical therapy and medicines are prescribed in this early part. Decompression surgery is recommended for patients with severe neural compression and resultant neurological deficits.

A laminectomy or laminoplasty may be done through a posterior approach. Ossified dura may be resected leaving the arachnoid behind. The dural gap may be reconstructed with graft/dural patch. Instrumentation is recommended when there is instability after wide resection of lamina and facets. Numbness of lower limbs and spastic gait hardly improves after surgery and may remain as such. Temporary neurological worsening after surgery is a possibility in severe cord compression. So informed consent on these aspects is a must before embarking on surgery.

The neurological recovery after OYL surgery is variable. Many papers reported temporary neurological deterioration after surgery for thoracic OYL. Bad predictors of neurological outcome include poor preoperative walking score, presence of intra operative dural tear, extradural haematoma, spinal cord injury, intraoperative drop of SSEP signal.¹⁹ The role of demographic factors, number of OYL segments, co-existing OPLL, presence of high signal activity in the cord, etc have shown inconsistent outcomes in different studies. One study reviewing the recent literature has shown pre operative duration of symptoms and pre operative neurological score as predictive factors for the neurological outcome.⁸

From this study, it is shown that OYL predominantly affects the dorsal spine. In our series, all the 18 cases were in the thoracic region, 6 of them at D9-D10 and 7 of them at D10-D11(mostly lower thoracic). 8 of the 18 patients were diabetic. Co-existing OPLL was found in 6 out of the 18 patients. Most of the patients 13/18 (72.22%) were between 51 and 70 years of age. Males predominated in our series with 11 out of 18. The dural calcification/ossification was addressed with floating technique. No dural tear occurred in any of the 18 cases. No neurological worsening occurred in the post operative period. Our series of 18 patients from 2003 to 2024 had excellent neurological recovery.

1. Hotta, Y. "Anatomical Study of the Yellow Ligament of the Spine with Special Reference to Its Ossification." Nihon Seikeigeka Gakkai Zasshi, vol. 59, no. 3, 1985, pp. 311-25.
2. Yong-Hing, K., Reilly, J., and Kirkaldy-Willis, W. H. "The Ligamentum Flavum." Spine, vol. 1, no. 4, 1976, pp. 226-34.
3. Hirabayashi, S. "Ossification of the Ligamentum Flavum." Spine Surgery and Related Research, vol. 1, no. 4, 2017, pp. 158-63.
4. Inoue, I., Ikeda, R., and Tsukahara, S. "Current Topics in Pharmacological Research on Bone Metabolism: Promyelotic Leukemia Zinc Finger (PLZF) and Tumor Necrosis Factor-α-Stimulated Gene 6 (TSG-6) Identified by Gene Expression Analysis Play Roles in the Pathogenesis of Ossification of the Posterior Longitudinal Ligament." Journal of Pharmacological Sciences, vol. 100, no. 3, 2006, pp. 205-10.
5. Nakase, T., Ariga, K., Yonenobu, K., Tsumaki, N., Luyten, F., Mukai, Y., et al. "Activation and Localization of Cartilage-Derived Morphogenetic Protein-1 at the Site of Ossification of the Ligamentum Flavum." European Spine Journal, vol. 10, 2001, pp. 289-94.
6. Kaneyama, S., Doita, M., Nishida, K., Shimomura, T., Maeno, K., Tamura, Y., et al. "Thoracic Myelopathy Due to Ossification of the Yellow Ligament in Young Baseball Pitchers." Clinical Spine Surgery, vol. 21, no. 1, 2008, pp. 68-71.
7. Yoshiiwa, T., Miyazaki, M., Kawano, M., Ikeda, S., and Tsumura, H. "Analysis of the Relationship Between Hypertrophy of the Ligamentum Flavum and Lumbar Segmental Motion with Aging Process." Asian Spine Journal, vol. 10, no. 3, 2016, pp. 528.
8. Inamasu, J., and Guiot, B. H. "A Review of Factors Predictive of Surgical Outcome for Ossification of the Ligamentum Flavum of the Thoracic Spine." Journal of Neurosurgery: Spine, vol. 5, no. 2, 2006, pp. 133-39.
9. Resnick, D., and Niwayama, G. "Entheses and Enthesopathy: Anatomical, Pathological, and Radiological Correlation." Radiology, vol. 146, no. 1, 1983, pp. 1-9.
10. Jayakumar, P. N., Devi, B. I., Bhat, D. I., and Das, B. S. "Thoracic Cord Compression Due to Ossified Hypertrophied Ligamentum Flavum." Neurology India, vol. 50, no. 3, 2002, pp. 286-89.
11. Pascal-Moussellard, H., Cabre, P., Smadja, D., and Catonné, Y. "Symptomatic Ossification of the Ligamentum Flavum: A Clinical Series from the French Antilles." Spine, vol. 30, no. 14, 2005, pp. E400-05.
12. Pascal-Moussellard, H., Smadja, D., Cabre, P., Raynaud, M., and Catonne, Y. "Ossification of the Ligamenta Flava with Severe Myelopathy in a Black Patient: A Case Report." Spine, vol. 23, no. 14, 1998, pp. 1607-08.
13. Vasudevan, A., and Knuckey, N. W. "Ossification of the Ligamentum Flavum." Journal of Clinical Neuroscience, vol. 9, no. 3, 2002, pp. 311-13.
14. Kong, Q., Ma, X., Li, F., Guo, Z., Qi, Q., Li, W., et al. "COL6A1 Polymorphisms Associated with Ossification of the Ligamentum Flavum and Ossification of the Posterior Longitudinal Ligament." Spine, vol. 32, no. 25, 2007, pp. 2834-38.
15. Moon, S. H., Park, S. R., Kim, H., Kwon, U. H., Kim, K. H., Kim, H. S., and Lee, H. M. "Biologic Modification of Ligamentum Flavum Cells by Marker Gene Transfer and Recombinant Human Bone Morphogenetic Protein-2." Spine, vol. 29, no. 9, 2004, pp. 960-65.
16. Okamoto, K., Kobashi, G., Washio, M., Sasaki, S., Yokoyama, T., Miyake, Y., et al. "Dietary Habits and Risk of Ossification of the Posterior Longitudinal Ligaments of the Spine (OPLL); Findings from a Case-Control Study in Japan." Journal of Bone and Mineral Metabolism, vol. 22, 2004, pp. 612-17.
17. Takeuchi, Y., Matsumoto, T., Takuwa, Y., Hoshino, Y., Kurokawa, T., Shibuya, N., et al. "High Incidence of Obesity and Elevated Serum Immunoreactive Insulin Level in Patients with Paravertebral Ligamentous Ossification: A Relationship to the Development of Ectopic Ossification." Journal of Bone and Mineral Metabolism, vol. 7, no. 1, 1989, pp. 17-21.
18. Fujii, Y., Yoshida, H., and Sakou, T. "Immunohistochemical Studies on Tenascin in Human Yellow Ligament." In Vivo (Athens, Greece), vol. 7, no. 2, 1993, pp. 143-46.
19. Tang, C. Y., Cheung, J. P., Samartzis, D., Leung, K. H., Wong, Y. W., Luk, K. D., and Cheung, K. M. "Predictive Factors for Neurological Deterioration After Surgical Decompression for Thoracic Ossified Yellow Ligament." European Spine Journal, vol. 26, 2017, pp. 2598-2605.